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PMC11276146_p0
PMC11276146
sec[0]/p[0]
Differentiated microbiotic habitats originate in the oral cavity at the level of the hard tissues of the teeth and in the soft tissues of the gingival sulcus, the back of the tongue, the lips, the cheeks and the palate . The microhabitats inside the pediatric oral cavity differ significantly in the absolute abundance o...
en
1. Introduction
biomedical
study
4.082031
[ 0.99951171875, 0.00023865699768066406, 0.00019180774688720703 ]
[ 0.9677734375, 0.00971221923828125, 0.02215576171875, 0.0002980232238769531 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p1
PMC11276146
sec[0]/sec[0]/p[0]
Dental caries is an infectious, degenerative and destructive disease affecting the hard substances of the tooth (the enamel and dentine); if not treated, they progress in depth up to the dental pulp. It has a multifactorial etiology: bacterial plaque plays a crucial role in its pathogenesis, as does a diet rich in suga...
en
1.1. Etiology of Caries
biomedical
review
4.964844
[ 0.99609375, 0.0022735595703125, 0.001781463623046875 ]
[ 0.35009765625, 0.00472259521484375, 0.64306640625, 0.0021038055419921875 ]
0.999995
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p2
PMC11276146
sec[0]/sec[1]/p[0]
Dental caries can have a negative impact on the health and quality of the young patient due to the pain, which causes a reduction in the appetite with consequent weight loss due to difficulties in chewing food and hypersensitivity to cold, heat and thermal and chemical stimuli, as well as acid in sugary foods and drink...
en
1.2. Effects and Systemic Correlations of Dental Caries
biomedical
study
4.226563
[ 0.99951171875, 0.000377655029296875, 0.00028514862060546875 ]
[ 0.79248046875, 0.0033016204833984375, 0.2037353515625, 0.0005922317504882812 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p3
PMC11276146
sec[0]/sec[2]/p[0]
Microbial species, in particular bacteria, tend to organize themselves into biofilms to increase resistance to antibacterial agents, especially antibiotics, and ensure greater survival. Dental bacterial plaque is a biofilm formed by a polymicrobial aggregate that adheres to and colonizes the smooth surface of teeth, ro...
en
1.3. Dental Bacterial Plaque
biomedical
study
4.222656
[ 0.99951171875, 0.000400543212890625, 0.00017905235290527344 ]
[ 0.9404296875, 0.0303955078125, 0.0285491943359375, 0.0006971359252929688 ]
0.999996
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p4
PMC11276146
sec[0]/sec[3]/p[0]
The oral biofilm is able to alter the balance of the host microbiota, initiate oral dysbiosis and promote the onset of caries and periodontal diseases with reflections on systemic health .
en
1.4. Composition of Oral Bacterial Plaque
biomedical
other
2.945313
[ 0.998046875, 0.00113677978515625, 0.00098419189453125 ]
[ 0.027587890625, 0.95458984375, 0.01611328125, 0.0015916824340820312 ]
0.999998
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p5
PMC11276146
sec[0]/sec[3]/p[1]
Biofilm is considered a complex and effectively organized bacterial system responsible for the two most widespread oral diseases: tooth decay and gingival-periodontal diseases. The different oral environments presuppose a substantial difference in the bacterial species involved in biofilm formation; therefore, the supr...
en
1.4. Composition of Oral Bacterial Plaque
biomedical
study
4.644531
[ 0.9990234375, 0.0004875659942626953, 0.0005388259887695312 ]
[ 0.93505859375, 0.0012006759643554688, 0.06317138671875, 0.0003514289855957031 ]
0.999998
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p6
PMC11276146
sec[0]/sec[4]/p[0]
The oral district is populated by more than 700 species of microorganisms, including fungi, viruses and protozoa, where 58% have an official name, 16% are unnamed but have been cultivated and 26% are known only as uncultivated phylotypes . The tongue has the highest bacterial load of all oral tissues, hosting about two...
en
1.5. Bacterial Biofilm on the Tongue
biomedical
study
4.679688
[ 0.9990234375, 0.0005736351013183594, 0.0003609657287597656 ]
[ 0.99267578125, 0.0006623268127441406, 0.0064697265625, 0.0002493858337402344 ]
0.999996
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p7
PMC11276146
sec[1]/p[0]
The aim of this review is to examine the scientific literature to clarify whether the mechanical removal of bacterial biofilm from the posterior tongue can have a positive effect on caries prevention and on the reduction in salivary streptococcal CFU and whole-mouth plaque index (FMPS), in order to identify a preventiv...
en
2. Purpose of Work
biomedical
review
4.03125
[ 0.99072265625, 0.00643157958984375, 0.00279998779296875 ]
[ 0.005474090576171875, 0.0020465850830078125, 0.99169921875, 0.0006814002990722656 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p8
PMC11276146
sec[1]/sec[0]/p[0]
In order to provide a new guideline to healthcare professionals for the prevention of carious disease in pediatric patients, research was carried out on the inclusion of tongue cleaning in OH. We examined the English scientific literature, including literature reviews, case–control studies, cross-sectional studies and ...
en
2.1. Materials and Methods
biomedical
study
2.644531
[ 0.998046875, 0.0005931854248046875, 0.0013637542724609375 ]
[ 0.95068359375, 0.0247344970703125, 0.023712158203125, 0.0008821487426757812 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p9
PMC11276146
sec[1]/sec[0]/p[1]
The search for scientific articles was performed on 16 June 2024, in medical databases such as PubMed, Cochrane and Google Scholar. The data were extracted independently by two reviewers (C.M. and G.M.). A manual search was also performed to improve the pool of articles. The authors discussed the inclusion of each arti...
en
2.1. Materials and Methods
biomedical
review
2.679688
[ 0.99267578125, 0.0014410018920898438, 0.005901336669921875 ]
[ 0.37744140625, 0.03387451171875, 0.5869140625, 0.0015249252319335938 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p10
PMC11276146
sec[1]/sec[0]/p[2]
The keyword indicators used were “tongue cleaning in children” and “caries and systemic diseases and children”, for which inclusion and exclusion guidelines were drawn up. After preliminary screening and the removal of duplicates, the abstracts and titles of the articles were evaluated to include the articles and their...
en
2.1. Materials and Methods
biomedical
review
3.980469
[ 0.994140625, 0.0027332305908203125, 0.0031032562255859375 ]
[ 0.0125579833984375, 0.0014486312866210938, 0.98583984375, 0.00038886070251464844 ]
0.999998
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p11
PMC11276146
sec[2]/p[0]
The search revealed 28,580 total results. Initially, after removing duplicates, the titles and abstracts of the studies related to the keywords were considered to select the articles eligible for the reading of the full text. In total, 28,267 articles were excluded, and only 4 randomized studies, which met the search c...
en
3. Results
biomedical
review
3.828125
[ 0.98779296875, 0.004123687744140625, 0.0080718994140625 ]
[ 0.0092620849609375, 0.004108428955078125, 0.98583984375, 0.0005884170532226562 ]
0.999996
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p12
PMC11276146
sec[2]/p[1]
Overall, 183 children aged 9 to 12 years (mean age of 10.5 years) were involved in the included studies. The studies by Winnier et al. and Manju et al. , demonstrated that the total bacterial plaque index and CFU in S. mutans saliva were statistically significantly reduced in the OH groups with the brushing and scrapin...
en
3. Results
biomedical
study
4.113281
[ 0.9990234375, 0.00051116943359375, 0.0004715919494628906 ]
[ 0.9375, 0.0006699562072753906, 0.061431884765625, 0.00021791458129882812 ]
0.999996
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p13
PMC11276146
sec[2]/sec[0]/p[0]
The included works have a low risk of bias; the contribution of new studies will be necessary to confirm the initial endpoint. Table 3 shows the risk of bias of the main articles examined. This review has a relatively low risk of bias.
en
Risk of Bias
biomedical
review
2.484375
[ 0.9609375, 0.0053253173828125, 0.03369140625 ]
[ 0.01329803466796875, 0.0163726806640625, 0.96923828125, 0.0009613037109375 ]
0.999999
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p14
PMC11276146
sec[3]/p[0]
Among the causes attributable to the onset of caries disease are poor OH, an unhealthy diet and microbiota dysbiosis .
en
4. Discussion
biomedical
other
2.324219
[ 0.99609375, 0.001117706298828125, 0.00275421142578125 ]
[ 0.058929443359375, 0.92333984375, 0.0159759521484375, 0.0018568038940429688 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p15
PMC11276146
sec[3]/p[1]
An analysis of the literature shows that the most frequent form of oral pathology in children is associated with bacterial plaque and manifests itself as gingivitis and caries . The results of this review underline that the greatest reduction in the plaque index and CFU in the saliva of S. mutans can be obtained with m...
en
4. Discussion
biomedical
review
4.296875
[ 0.98876953125, 0.006244659423828125, 0.005126953125 ]
[ 0.01111602783203125, 0.0010280609130859375, 0.9873046875, 0.0005249977111816406 ]
0.999998
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p16
PMC11276146
sec[3]/p[2]
In the Report on the Global State of Oral Health , the WHO requested urgent action to give people with health problems the opportunity to be treated, above all to guarantee prevention, with one ambitious goal of meeting oral health needs globally by 2030. Untreated carious disease of permanent teeth is the most widespr...
en
4. Discussion
biomedical
review
3.890625
[ 0.99072265625, 0.003810882568359375, 0.005542755126953125 ]
[ 0.0092926025390625, 0.1737060546875, 0.81591796875, 0.0011930465698242188 ]
0.999998
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p17
PMC11276146
sec[4]/p[0]
Below, we propose OH protocols for the mucous membranes and tongue to be practiced with OH for a minimum of two times a day, not neglecting the time before bedtime.
en
5. Tongue-Cleaning Protocols
biomedical
other
2.011719
[ 0.9375, 0.050689697265625, 0.0117340087890625 ]
[ 0.003787994384765625, 0.9931640625, 0.0007777214050292969, 0.0024471282958984375 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p18
PMC11276146
sec[4]/sec[0]/p[0]
In the first months of the baby’s life, it is possible to use the appropriate wipes to clean the oral cavity after each feeding or, alternatively, to use sterile cotton gauze sufficiently soaked in physiological saline water.
en
5.1. Protocol for Hygiene of Tongue and Oral Cavity in Newborns
biomedical
other
1.993164
[ 0.90478515625, 0.0849609375, 0.01019287109375 ]
[ 0.00228118896484375, 0.9921875, 0.00047969818115234375, 0.004894256591796875 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p19
PMC11276146
sec[4]/sec[0]/p[1]
To clean a child’s oral cavity, the following steps are recommended: (1) Sit the child on your lap, facing one side. (2) Support their head with your arm and one hand. (3) Use the index finger and thumb of the hand supporting them to open their mouth. (4) Wrap the gauze around the index finger of the other hand. (5) Cl...
en
5.1. Protocol for Hygiene of Tongue and Oral Cavity in Newborns
biomedical
other
2.732422
[ 0.5947265625, 0.383056640625, 0.02203369140625 ]
[ 0.0014352798461914062, 0.98876953125, 0.0009069442749023438, 0.00890350341796875 ]
0.999998
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p20
PMC11276146
sec[4]/sec[1]/p[0]
After OH with an electric or manual toothbrush, place a tongue brush along the midline of the back of the tongue as far back as possible, avoiding reaching the point that could induce the gag reflex, then slide the toothbrush forward and backward with light pressure, in five sequences, from the back to the tip. Rinse t...
en
5.2. Tongue-Cleaning Protocol with Toothbrush
biomedical
other
3.333984
[ 0.88623046875, 0.10430908203125, 0.00957489013671875 ]
[ 0.0027751922607421875, 0.99267578125, 0.0007944107055664062, 0.003719329833984375 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p21
PMC11276146
sec[4]/sec[2]/p[0]
After OH with an electric or manual toothbrush, place the tongue cleaner at the most proximal point to the root of the tongue mantle and perform posterior–anterior movements, gentle but decisive. Repeat the sequence five times, taking care to clean the instrument with water, and finish with a vigorous rinse .
en
5.3. Tongue-Cleaning Protocol with Tongue Scraper
biomedical
other
2.585938
[ 0.7578125, 0.206298828125, 0.035736083984375 ]
[ 0.001628875732421875, 0.994140625, 0.0007252693176269531, 0.0036182403564453125 ]
0.999996
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
PMC11276146_p22
PMC11276146
sec[5]/p[0]
Primary prevention is recommended to maintain health and reduce the possibility of disease onset. Daily tongue hygiene, two times a day, during OH, could be considered the gold standard for the prevention of carious disease. Furthermore, this simple mechanical maneuver is assimilated naturally if proposed from birth. T...
en
6. Conclusions
biomedical
review
3.923828
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[ 0.0026454925537109375, 0.002925872802734375, 0.994140625, 0.00045943260192871094 ]
0.999997
[ "Giovanna Mosaico", "Mara Pinna", "Roberta Grassi", "Germano Orrù", "Andrea Scribante", "Carolina Maiorani", "Cinzia Casu", "Gianna Maria Nardi", "Andrea Butera" ]
https://doi.org/10.3390/children11070816
https://creativecommons.org/licenses/by/4.0/
39070602_p0
39070602
sec[0]/p[0]
Significant progress has been achieved over the last two decades in the development of tuberculosis treatment, with the discovery of new chemical entities and trials testing new combinations of drugs. This progress has resulted in substantial improvements in the treatment of tuberculosis, and the World Health Organizat...
en
Introduction
biomedical
review
3.869141
[ 0.990234375, 0.006145477294921875, 0.0035648345947265625 ]
[ 0.003238677978515625, 0.0164642333984375, 0.9794921875, 0.0007653236389160156 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p1
39070602
sec[0]/p[1]
The early 2000s brought the discovery of new chemical entities with new modes of action on tuberculosis bacilli, 5 , 6 such as the development of diarylquinolines and nitroimidazoles, and the repurposing of active compounds traditionally used against Gram-positive infections (oxazolidinones); 7 all these developments p...
en
Introduction
biomedical
review
3.962891
[ 0.9970703125, 0.0015926361083984375, 0.0012216567993164062 ]
[ 0.0201873779296875, 0.0139007568359375, 0.96533203125, 0.0007266998291015625 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p2
39070602
sec[0]/p[2]
In 2017, WHO published Target regimen profiles for treatment of tuberculosis , promoting an end-to-end process integrating the development of new drugs within the development of new regimens, and defining specific requirements that new regimens should meet. 10 In view of the ground-breaking progress in tuberculosis tre...
en
Introduction
biomedical
other
3.146484
[ 0.9873046875, 0.007656097412109375, 0.005168914794921875 ]
[ 0.006221771240234375, 0.86669921875, 0.1256103515625, 0.00141143798828125 ]
0.999993
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p3
39070602
sec[1]/p[0]
The revision of the target regimen profiles for tuberculosis treatment by WHO followed similar methods to those established for initial regimen development in 2016. The WHO Global Tuberculosis Programme established a Scientific Target Regimen Profile Development Group that included leading scientists and experts, publi...
en
Methods
biomedical
other
1.673828
[ 0.833984375, 0.010498046875, 0.155517578125 ]
[ 0.00440216064453125, 0.99267578125, 0.0027332305908203125, 0.0004191398620605469 ]
0.999994
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p4
39070602
sec[1]/p[1]
After a critical review of the 2016 document, our group retained the initial approach of classifying target regimen profiles for rifampicin-susceptible and rifampicin-resistant tuberculosis. Further, considering the possibility of developing a regimen composed of entirely new anti-tuberculosis drugs for which minimal o...
en
Methods
biomedical
study
4.097656
[ 0.9990234375, 0.00052642822265625, 0.000232696533203125 ]
[ 0.99560546875, 0.0005335807800292969, 0.003894805908203125, 0.00012624263763427734 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p5
39070602
sec[1]/p[2]
The target regimen profiles proposed here aim to guide the development of new tuberculosis treatment regimens, considering end-user needs and real-world conditions. We established a list of 13 characteristics – eight of which are common to all target regimen profiles (target population; populations of special interest;...
en
Methods
biomedical
study
4.015625
[ 0.99853515625, 0.0010318756103515625, 0.00021505355834960938 ]
[ 0.98193359375, 0.00904083251953125, 0.00861358642578125, 0.00033593177795410156 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p6
39070602
sec[1]/p[3]
Based on this preliminary work, we developed an initial draft document that was shared with the group for revision and comments. We then divided into three subgroups who worked through virtual consultative meetings on each of the target regimen profiles, leading to a new version that was posted by WHO for public commen...
en
Methods
other
other
1.330078
[ 0.252685546875, 0.00965118408203125, 0.73779296875 ]
[ 0.006366729736328125, 0.99072265625, 0.00225830078125, 0.0006546974182128906 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p7
39070602
sec[2]/sec[0]/p[0]
Regimens should be intended for all population groups, irrespective of age, site of disease, clinical severity and co-morbidities. The regimens must have an acceptable safety profile, be well tolerated and efficacious in all these groups (including neonates, infants, children, women of reproductive age, and pregnant an...
en
Target population
biomedical
other
3.855469
[ 0.93505859375, 0.0623779296875, 0.002471923828125 ]
[ 0.028717041015625, 0.94970703125, 0.01922607421875, 0.002140045166015625 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p8
39070602
sec[2]/sec[1]/p[0]
Human data indicate that the treatment does not cause any increased risk of structural abnormalities in the fetus, and the drugs are safe for women of childbearing potential, and pregnant and lactating women. The component drugs should be compatible with common forms of hormone-based birth control for women of reproduc...
en
Populations of special interest
biomedical
other
2.513672
[ 0.99462890625, 0.002513885498046875, 0.00272369384765625 ]
[ 0.018768310546875, 0.97021484375, 0.009674072265625, 0.0011816024780273438 ]
0.999995
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p9
39070602
sec[2]/sec[2]/p[0]
New chemical entities should have minimal or no drug–drug interaction with the other components of the regimen combination. For people living with human immunodeficiency virus undergoing antiretroviral therapy, drug–drug interaction studies should be initiated as soon as doses are known; ideally, no dose adjustments as...
en
Drug–drug interaction and metabolism
biomedical
other
3.507813
[ 0.9150390625, 0.08282470703125, 0.002277374267578125 ]
[ 0.007068634033203125, 0.9873046875, 0.002986907958984375, 0.002838134765625 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p10
39070602
sec[2]/sec[3]/p[0]
Imperfect adherence increases the risk of unfavourable treatment outcomes. 15 On this basis, forgiveness of a regimen, defined as “the degree to which regimen efficacy is unaffected by suboptimal adherence,” 11 was introduced as a new regimen characteristic. Because it can be challenging to ensure full daily drug admin...
en
Forgiveness of the regimen
biomedical
other
3.496094
[ 0.99560546875, 0.002391815185546875, 0.0021228790283203125 ]
[ 0.412109375, 0.52734375, 0.059539794921875, 0.0012273788452148438 ]
0.999998
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p11
39070602
sec[2]/sec[4]/p[0]
Regimens containing three to four drugs would provide the best balance to ensure high efficacy and minimize the risk of developing drug resistance. Further, limiting the number of component drugs in a regimen helps to minimize pill burden and safety risks, and facilitates drug coformulation.
en
Number of component drugs
biomedical
other
3.265625
[ 0.99169921875, 0.0057830810546875, 0.00254058837890625 ]
[ 0.00858306884765625, 0.984375, 0.006572723388671875, 0.0006337165832519531 ]
0.999998
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p12
39070602
sec[2]/sec[5]/p[0]
Formulation should be all-oral, with simple, age- or weight-based dose adjustment. Fixed-dose combination formulations as well as child-friendly formulations are strongly encouraged.
en
Formulation
biomedical
other
2.371094
[ 0.94677734375, 0.038482666015625, 0.01454925537109375 ]
[ 0.0012807846069335938, 0.99462890625, 0.0028133392333984375, 0.0011396408081054688 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p13
39070602
sec[2]/sec[6]/p[0]
Drugs included in the treatment regimen should protect each other against emergence of resistance; they should therefore have different targets, 16 have different pharmacokinetic–pharmacodynamic properties, be active and synergistic at the lesion site level, 17 and have half-lives that are well matched to reduce the ri...
en
Propensity to develop resistance
biomedical
other
3.849609
[ 0.99658203125, 0.00262451171875, 0.0006966590881347656 ]
[ 0.09393310546875, 0.88623046875, 0.018646240234375, 0.0010280609130859375 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p14
39070602
sec[2]/sec[7]/p[0]
Ideally, all component drugs should be stable for at least 5 years in climate zones III and IV (i.e. 30 °C and 75% relative humidity).
en
Stability and shelf life
biomedical
other
2.398438
[ 0.98681640625, 0.003376007080078125, 0.00988006591796875 ]
[ 0.01439666748046875, 0.984375, 0.0005764961242675781, 0.0004291534423828125 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p15
39070602
sec[3]/sec[0]/p[0]
Despite its wide availability, low cost and high efficacy, the current 6-month treatment of rifampicin-susceptible tuberculosis has several limitations, including adverse events, drug–drug interactions and adherence requirements. A 4-month regimen was recommended by WHO as non-inferior to the 6-month regimen in 2020, b...
en
Rifampicin-susceptible tuberculosis
biomedical
review
3.847656
[ 0.99560546875, 0.0031566619873046875, 0.0010471343994140625 ]
[ 0.0211639404296875, 0.028717041015625, 0.94921875, 0.0008826255798339844 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p16
39070602
sec[3]/sec[0]/sec[0]/p[0]
The rifampicin-susceptible tuberculosis regimen is indicated for patients with active tuberculosis disease caused by rifampicin-susceptible Mycobacterium tuberculosis strains, including forms with monoresistance to isoniazid, pyrazinamide and ethambutol (the other drugs included in the current 6-month treatment regimen...
en
Indication and drug susceptibility testing
biomedical
other
3.548828
[ 0.97900390625, 0.0196685791015625, 0.0013532638549804688 ]
[ 0.006999969482421875, 0.986328125, 0.0037689208984375, 0.0027599334716796875 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p17
39070602
sec[3]/sec[0]/sec[1]/p[0]
The current 6-month regimen of isoniazid, rifampicin, pyrazinamide and ethambutol has 90–95% efficacy under trial conditions. 18 The efficacy and duration targets aim to improve on the current 4-month WHO-recommended treatment (comprising the drugs isoniazid, rifapentine and moxifloxacin, with the addition of pyrazinam...
en
Efficacy and duration
biomedical
study
3.958984
[ 0.99853515625, 0.001171112060546875, 0.0002944469451904297 ]
[ 0.8408203125, 0.032867431640625, 0.1253662109375, 0.0008211135864257812 ]
0.999995
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p18
39070602
sec[3]/sec[0]/sec[2]/p[0]
Although serious adverse events with the current standards of care are uncommon, important tolerability issues affect adherence and, as a result, effectiveness. The safety and tolerability of a new rifampicin-susceptible regimen should be at least equal to, and ideally better than, the current standards of care. Demand...
en
Safety and tolerability
biomedical
other
3.701172
[ 0.9765625, 0.021270751953125, 0.001979827880859375 ]
[ 0.009307861328125, 0.9482421875, 0.04071044921875, 0.00177764892578125 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p19
39070602
sec[3]/sec[0]/sec[3]/p[0]
A regimen would ideally comprise just one pill per day; minimally, the pill burden should not be greater than for the 6-month regimen of isoniazid, rifampicin, pyrazinamide and ethambutol.
en
Pill burden
biomedical
other
3.074219
[ 0.9765625, 0.0201568603515625, 0.003078460693359375 ]
[ 0.004627227783203125, 0.9921875, 0.001934051513671875, 0.0013608932495117188 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p20
39070602
sec[3]/sec[1]/p[0]
In 2020, the global success rate for treatment of multidrug-resistant (MDR) tuberculosis (i.e. tuberculosis that is resistant to both rifampicin and isoniazid) was 60%. 20 Treatment typically lasted 9–18 months and included a large number of drugs, resulting in high pill burden and frequent side-effects that often led ...
en
Rifampicin-resistant tuberculosis
biomedical
review
3.927734
[ 0.9970703125, 0.002094268798828125, 0.0007567405700683594 ]
[ 0.03802490234375, 0.020172119140625, 0.94091796875, 0.0008254051208496094 ]
0.999995
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p21
39070602
sec[3]/sec[1]/sec[0]/p[0]
Under the minimal requirement, a rifampicin-resistant tuberculosis regimen is indicated for patients with active tuberculosis disease caused by rifampicin-resistant strains, with or without isoniazid resistance. Under the optimal requirement, the regimen is indicated for patients with active tuberculosis caused by eith...
en
Indication and drug susceptibility testing
biomedical
other
4.070313
[ 0.92822265625, 0.06964111328125, 0.002170562744140625 ]
[ 0.0191650390625, 0.93212890625, 0.0400390625, 0.00864410400390625 ]
0.999995
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p22
39070602
sec[3]/sec[1]/sec[1]/p[0]
The 2022 WHO tuberculosis treatment guideline update recommends the 6-month bedaquiline, pretomanid, linezolid and moxifloxacin regimen for most adult patients with tuberculosis that is MDR or rifampicin resistant. This regimen is approximately 90% efficacious. 25 Consequently, a new rifampicin-resistant-tuberculosis r...
en
Efficacy and duration
biomedical
other
3.908203
[ 0.9326171875, 0.06402587890625, 0.0034160614013671875 ]
[ 0.008941650390625, 0.77294921875, 0.2110595703125, 0.00728607177734375 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p23
39070602
sec[3]/sec[1]/sec[2]/p[0]
The minimum and optimum targets are identical: it is suggested that the incidence and severity of adverse events with any new MDR-tuberculosis regimen should be lower than for the current regimens to guarantee best tolerability, acceptability and effectiveness under programmatic conditions. In the pivotal trial of the ...
en
Safety and tolerability
biomedical
study
4.070313
[ 0.98876953125, 0.0106048583984375, 0.0004725456237792969 ]
[ 0.95947265625, 0.036041259765625, 0.003574371337890625, 0.000995635986328125 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p24
39070602
sec[3]/sec[1]/sec[3]/p[0]
A regimen would ideally comprise not more than four to five pills per day; minimally, the pill burden should not be greater than five to seven pills per day.
en
Pill burden
biomedical
other
2.580078
[ 0.9208984375, 0.06280517578125, 0.0160980224609375 ]
[ 0.0036487579345703125, 0.994140625, 0.0013027191162109375, 0.000972747802734375 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p25
39070602
sec[3]/sec[2]/sec[0]/p[0]
A regimen containing fully novel compounds with no cross-resistance could be used as a first-line tuberculosis regimen in individuals with tuberculosis disease without prior knowledge of the patient’s drug resistance profile. This approach would allow treatment to begin without delay while drug susceptibility testing i...
en
Indication and drug susceptibility testing
biomedical
other
3.970703
[ 0.9912109375, 0.00829315185546875, 0.0007305145263671875 ]
[ 0.07611083984375, 0.85546875, 0.064453125, 0.0037364959716796875 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p26
39070602
sec[3]/sec[2]/sec[1]/p[0]
Considering that a pan-tuberculosis regimen would be used to treat both rifampicin-susceptible and rifampicin-resistant tuberculosis, efficacy should be at least as good as the current rifampicin-susceptible tuberculosis regimen, with a duration of no more than 3–4 months. Optimally, efficacy should be better than the ...
en
Efficacy and duration
biomedical
other
3.976563
[ 0.99072265625, 0.00823211669921875, 0.0010356903076171875 ]
[ 0.060546875, 0.505859375, 0.429931640625, 0.0034236907958984375 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p27
39070602
sec[3]/sec[2]/sec[2]/p[0]
In line with the recommendations for the rifampicin-susceptible and rifampicin-resistant tuberculosis regimens, and considering that the pan-tuberculosis regimen will be provided to a larger proportion of patients with rifampicin-susceptible than rifampicin-resistant tuberculosis, it is expected that the incidence and ...
en
Safety and tolerability
biomedical
other
3.855469
[ 0.9892578125, 0.0096435546875, 0.0011835098266601562 ]
[ 0.04595947265625, 0.7998046875, 0.1519775390625, 0.001972198486328125 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p28
39070602
sec[3]/sec[2]/sec[3]/p[0]
A regimen would ideally comprise just one pill per day; minimally, the pill burden should not be greater than for the 6-month regimen of isoniazid, rifampicin, pyrazinamide and ethambutol.
en
Pill burden
biomedical
other
3.074219
[ 0.9765625, 0.0201568603515625, 0.003078460693359375 ]
[ 0.004627227783203125, 0.9921875, 0.001934051513671875, 0.0013608932495117188 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p29
39070602
sec[4]/p[0]
We discuss several key aspects that are relevant across all three regimens: drug susceptibility testing; adherence and forgiveness; treatment strategies; post-tuberculosis lung disease; and cost and access considerations.
en
Cross-cutting aspects
biomedical
review
2.953125
[ 0.9892578125, 0.005504608154296875, 0.00504302978515625 ]
[ 0.025970458984375, 0.2254638671875, 0.7451171875, 0.0035953521728515625 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p30
39070602
sec[4]/sec[0]/p[0]
Phenotypic or genotypic tests should be available at time of regimen introduction for both individual patient care and population-level surveillance. Drug developers need to support this by establishing minimum inhibitory concentration distributions and drug susceptibility testing interpretative criteria. To allow an u...
en
Drug susceptibility testing
biomedical
other
3.984375
[ 0.99267578125, 0.006702423095703125, 0.0006871223449707031 ]
[ 0.06585693359375, 0.9052734375, 0.026092529296875, 0.0026092529296875 ]
0.999997
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p31
39070602
sec[4]/sec[1]/p[0]
Poor adherence affects treatment outcomes and increases the risk of developing resistance, although uncertainty remains with regards to the magnitude of this effect. 26 A meta-analysis of trial participants receiving isoniazid, rifampicin, pyrazinamide and ethambutol suggested that those who missed 10% or more of treat...
en
Adherence and forgiveness
biomedical
study
4.015625
[ 0.99853515625, 0.0008587837219238281, 0.0006246566772460938 ]
[ 0.6328125, 0.0012235641479492188, 0.365478515625, 0.0004355907440185547 ]
0.999998
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p32
39070602
sec[4]/sec[2]/p[0]
Beyond the specific characteristics of treatment regimens, novel treatment strategies such as stratified medicine approaches may be implemented to maximize the benefits and minimize the harms of treatment. Re-analyses of clinical trial data suggest that a difficult-to-treat subset of patients with rifampicin-susceptibl...
en
Treatment strategies
biomedical
study
3.931641
[ 0.9990234375, 0.0007929801940917969, 0.00034046173095703125 ]
[ 0.560546875, 0.0075531005859375, 0.431396484375, 0.00069427490234375 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p33
39070602
sec[4]/sec[3]/p[0]
There is increasing recognition that pulmonary tuberculosis (both rifampicin-susceptible and rifampicin-resistant) may result in clinically significant lung injury and functional impairment, termed post-tuberculosis lung disease, even in patients whose treatment is otherwise successful. Developers are encouraged to inc...
en
Post-tuberculosis lung disease
biomedical
review
3.941406
[ 0.99853515625, 0.001155853271484375, 0.000423431396484375 ]
[ 0.2249755859375, 0.207763671875, 0.56591796875, 0.001567840576171875 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p34
39070602
sec[4]/sec[4]/p[0]
Given the significant role of public financing for tuberculosis research and development, new products should be appropriately priced to reflect overall investments by global public and public–private actors, including governments, philanthropists, and other research and product sponsors. Any resulting product should d...
en
Cost and access considerations
biomedical
study
4.007813
[ 0.99609375, 0.0015096664428710938, 0.0021533966064453125 ]
[ 0.56787109375, 0.1026611328125, 0.32861328125, 0.0008740425109863281 ]
0.999998
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p35
39070602
sec[5]/p[0]
The 2023 update of the WHO target regimen profiles for tuberculosis treatment highlights key priorities for the next generation of tuberculosis treatments. However, it might not be feasible to fully meet all requirements simultaneously; developers may have to prioritize one or several characteristics over others, takin...
en
Discussion
biomedical
review
3.769531
[ 0.99609375, 0.0019073486328125, 0.0021915435791015625 ]
[ 0.0740966796875, 0.4091796875, 0.51513671875, 0.0012464523315429688 ]
0.999996
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p36
39070602
sec[5]/p[1]
We undertook a modelling analysis to estimate the impact on health outcomes and costs of improving various regimen characteristics. 11 In this analysis, ease of adherence (defined as the proportion of prescribed doses that patients take effectively while still on treatment) had the greatest influence on proportion of p...
en
Discussion
biomedical
study
4.125
[ 0.9990234375, 0.0007066726684570312, 0.00023126602172851562 ]
[ 0.998046875, 0.0002791881561279297, 0.0015268325805664062, 0.00011479854583740234 ]
0.999995
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p37
39070602
sec[5]/p[2]
Drug developers should therefore consider the capacity of their proposed regimen under development to be best used in programmatic conditions. Indeed, beyond the intrinsic pharmacological and antibacterial characteristics of new regimens, their clinical and public health impact will also depend on operational and epide...
en
Discussion
biomedical
other
4.042969
[ 0.99609375, 0.0029430389404296875, 0.0009613037109375 ]
[ 0.2335205078125, 0.42822265625, 0.3359375, 0.0023040771484375 ]
0.999998
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p38
39070602
sec[5]/p[3]
This target regimen profile update also highlights the deleterious impact of drug resistance. Developers should work in partnership with reference laboratories and diagnostic manufacturers to identify protocols and standards for phenotypic and genotypic tests, providing the necessary tools (compounds, mutants if availa...
en
Discussion
biomedical
other
3.876953
[ 0.99365234375, 0.005084991455078125, 0.0010251998901367188 ]
[ 0.043365478515625, 0.81201171875, 0.14208984375, 0.0023670196533203125 ]
0.999995
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39070602_p39
39070602
sec[5]/p[4]
In conclusion, the revised target regimen profiles described here represent an important step towards the development of new regimens for the treatment of all forms of tuberculosis. These profiles are expected to serve as a reference for research consortia involving drug developers, academics, public health institution...
en
Discussion
biomedical
other
3.005859
[ 0.99462890625, 0.0017833709716796875, 0.003391265869140625 ]
[ 0.0151214599609375, 0.96826171875, 0.0163116455078125, 0.0005373954772949219 ]
0.999994
[ "Christian Lienhardt", "Kelly E Dooley", "Payam Nahid", "Charles Wells", "Theresa S Ryckman", "Emily A Kendall", "Gerry Davies", "Grania Brigden", "Gavin Churchyard", "Daniela Maria Cirillo", "Eugenia Di Meco", "Ramya Gopinath", "Carole Mitnick", "Cherise Scott", "Farhana Amanullah", "...
https://doi.org/10.2471/BLT.24.291881
https://creativecommons.org/licenses/by/3.0/igo/
39057070_p0
39057070
sec[0]/p[0]
The type 2 coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2) is an obligatory intracellular pathogen that kidnaps the cell machinery that it needs for its replicative cycle. Lipidic interactions are essential during the entrance of this virus to the host cell and afterward for the budding process o...
en
1. Introduction
biomedical
study
4.765625
[ 0.9990234375, 0.0006432533264160156, 0.0003864765167236328 ]
[ 0.990234375, 0.0020961761474609375, 0.007160186767578125, 0.0003600120544433594 ]
0.999996
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p1
39057070
sec[0]/p[1]
Lipids including phospholipids (PLs), fatty acids (FA), and cholesterol (CT) are essential nutrients that play important roles in anatomical and physiological functions such as cell signaling, death, and survival pathways in all cells. Furthermore, they are components of the bilipid plasma membrane and the membranes of...
en
1. Introduction
biomedical
study
4.886719
[ 0.9990234375, 0.0007066726684570312, 0.0005049705505371094 ]
[ 0.99169921875, 0.0027484893798828125, 0.00476837158203125, 0.0005693435668945312 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p2
39057070
sec[0]/p[2]
In addition to FAs, other lipids, such as CT, which are abundant in the lipid rafts of the membrane where the ACE2 receptor is anchored, are important in viral pathways, such as their biosynthesis and assembly . Therefore, an intricate disturbance in lipid metabolism might happen in the process of infection and replica...
en
1. Introduction
biomedical
study
4.382813
[ 0.9990234375, 0.0006213188171386719, 0.00023949146270751953 ]
[ 0.73046875, 0.00299072265625, 0.265625, 0.0010576248168945312 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p3
39057070
sec[0]/p[3]
On the other hand, tocopherol, also known as vitamin E (Vit E), is an essential micronutrient and fat-soluble antioxidant in mammals that prevents the oxidation of FAs of the cell membranes by radical oxygen species (ROS), thus contributing to an increased fluidity of membranes and a decrease in lipid peroxidation (LPO...
en
1. Introduction
biomedical
review
4.660156
[ 0.998046875, 0.001010894775390625, 0.0010433197021484375 ]
[ 0.2064208984375, 0.004192352294921875, 0.7880859375, 0.00102996826171875 ]
0.999996
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p4
39057070
sec[0]/p[4]
Vit E supplementation (60 mg/7 day) decreased the LPO index in blood plasma and in the lung and liver in male mice with influenza . However, only a limited number of human trials have shown the effects of Vit E on resistance against infectious diseases, such as sepsis, compared to those performed in animals . The focus...
en
1. Introduction
biomedical
study
4.140625
[ 0.99951171875, 0.0003294944763183594, 0.0001252889633178711 ]
[ 0.9990234375, 0.0004203319549560547, 0.00064849853515625, 0.00010156631469726562 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p5
39057070
sec[1]/sec[0]/p[0]
Ethical approval was obtained on 19 August 2020 . The protocol was registered . The Research and Ethics Committee of our institution approved the research protocol . This study was carried out according to the international ethical standards and the General Health Law, as well as the Helsinki Declaration, modified at t...
en
2.1. Ethical Considerations
biomedical
other
1.469727
[ 0.9794921875, 0.00667572021484375, 0.01398468017578125 ]
[ 0.18603515625, 0.80908203125, 0.0012722015380859375, 0.0036945343017578125 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p6
39057070
sec[1]/sec[1]/p[0]
This was a prospective, analytical, open, and longitudinal (before–after) study run on 22 patients with COVID-19 who received Vit E treatment. The group before treatment with Vit E was compared with 23 healthy subjects (HSs), who constitute the control group. Inclusion criteria were patients with SARS-CoV-2 infection, ...
en
2.2. Population of this Study
biomedical
study
4.167969
[ 0.982421875, 0.01708984375, 0.00045490264892578125 ]
[ 0.9912109375, 0.006969451904296875, 0.0007390975952148438, 0.0012598037719726562 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p7
39057070
sec[1]/sec[1]/p[1]
Treatment with Vit E was applied during the 2020 pandemic between the months of August and September and consisted of Vit E (α-tocopheryl acetate) capsules of 400 IU equivalent to 800 mg that were administered every 12 h/5 days. The patients were not vaccinated against SARS-CoV-2 because a vaccine had not yet been appr...
en
2.2. Population of this Study
biomedical
study
4.148438
[ 0.75390625, 0.2449951171875, 0.0013141632080078125 ]
[ 0.8251953125, 0.134033203125, 0.01209259033203125, 0.0287017822265625 ]
0.999996
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p8
39057070
sec[1]/sec[2]/p[0]
A total of 15 men and 8 women matched by age and gender who were negative for SARS-CoV-2 infection were included in the group of healthy subjects (HSs) and served as the controls. Autoimmune diseases, thyroid disease, obesity, overweight, dyslipidemia, arterial hypertension, diabetes mellitus, and inflammatory and dege...
en
2.3. Healthy Subjects
biomedical
study
4.007813
[ 0.9990234375, 0.0006742477416992188, 0.0002340078353881836 ]
[ 0.99951171875, 0.00031304359436035156, 0.0002281665802001953, 0.00008594989776611328 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p9
39057070
sec[1]/sec[3]/p[0]
Swab samples were collected from COVID-19 patients to apply the Paired Technique (nasopharyngeal and saliva). Samples were considered positive for SARS-CoV-2 when both the N1 and N2 protein primer presets were detected. Specific probes to detect the virus and the real-time reverse transcriptase polymerase chain reactio...
en
2.4. Detection of SARS-CoV-2 by a Real-Time Reverse Transcriptase Polymerase Chain Reaction
biomedical
study
4.0625
[ 0.99951171875, 0.0003223419189453125, 0.00016438961029052734 ]
[ 0.9990234375, 0.0008282661437988281, 0.00028061866760253906, 0.00008535385131835938 ]
0.999995
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p10
39057070
sec[1]/sec[4]/p[0]
A total of 10 mL of peripheral blood per patient were collected by venopuncture. The blood was centrifuged for 20 min at 936 g and 4 °C. The red blood cell pellet was discarded; the serum was recovered and collected in polypropylene tubes of 400 μL and stored at −30 °C until use. Interleukin-6 (IL-6), CRPs, TGs, HDLs, ...
en
2.5. Peripheral Blood Samples
biomedical
study
4.097656
[ 0.9990234375, 0.0006537437438964844, 0.00016629695892333984 ]
[ 0.9990234375, 0.00044846534729003906, 0.0002529621124267578, 0.00010859966278076172 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p11
39057070
sec[1]/sec[5]/p[0]
The LPO index was measured indirectly through malondialdehyde MDA, and it was measured with a UV-2100 spectrophotometer at 532 nm (United Products and Instruments, Inc., 182-E Ridge Road Dayton, NJ, USA). A total of 100 μL of serum were used for this determination. Methanol with BHT at 4% (100 μL) and a KH 2 PO 4 buffe...
en
2.6. Determination of Markers of Lipid Peroxidation
biomedical
study
4.109375
[ 0.99951171875, 0.00022912025451660156, 0.0002053976058959961 ]
[ 0.99853515625, 0.0009899139404296875, 0.00025725364685058594, 0.00008147954940795898 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p12
39057070
sec[1]/sec[6]/p[0]
A total of 50 μL of serum were used for these determinations. The quantification of 8-isoprostane , thromboxane B 2 (TXB 2 ) , PGE 2 , and 6-keto-PGF 1α were provided by Cayman chemical , and IL-6 was provided by R&D systems as a biotechne and was measured at a wavelength range of 450–492 nm using a visible light micro...
en
2.7. 8-Isoprostane, TXB 2 , PGE 2 , 6-keto-PGF 1α , and IL-6 Determinations
biomedical
study
3.984375
[ 0.99951171875, 0.00015032291412353516, 0.00019180774688720703 ]
[ 0.998046875, 0.00165557861328125, 0.00031828880310058594, 0.00008630752563476562 ]
0.999996
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p13
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sec[1]/sec[7]/p[0]
For the extraction and derivatization of Vit E, saline solution 0.09% (1 mL respectively) and hexane (3 mL) were added to 100 µL of serum diethyl ether, and the samples were shaken with a vortex for 30 s and centrifuged at 3000 rpm for 4 min. The organic phase was recovered and evaporated under a stream of nitrogen. Th...
en
2.8. Vitamin E Quantification in Serum
biomedical
study
4.167969
[ 0.99951171875, 0.00030517578125, 0.00018477439880371094 ]
[ 0.99853515625, 0.0011157989501953125, 0.00038242340087890625, 0.0001081228256225586 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p14
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sec[1]/sec[8]/p[0]
For the extraction and derivatization of the TFA, 100 µL of serum were used according to the method described by Folch et al. in the presence of 50 µg of margaric acid (C17:0) as an internal standard. Then, 1 mL of a saline solution (0.09%) was added and mixed for 15 s, and then 2 mL of a methanol chloroform mixture (2...
en
2.9. Total Fatty Acid (TFA) Determination
biomedical
study
4.269531
[ 0.99951171875, 0.0003612041473388672, 0.00018739700317382812 ]
[ 0.99853515625, 0.0008082389831542969, 0.0005807876586914062, 0.00012254714965820312 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p15
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sec[1]/sec[9]/p[0]
For fatty acid analysis in an acetone insoluble phospholipid fraction (FAAIPF) extraction, 200 μL of serum were used in the presence of 50 μg of L-γ-phosphatidylcholine-di-heptadecanoyl acid as internal standard plus acetone (1 mL) and 1 mL of saline solution (0.09%). The mixture was shaken 30 s and centrifuged at 1145...
en
2.10. Fatty Acid Analysis in an Acetone Insoluble Phospholipid Fraction (FAAIPF) Determination in Serum
biomedical
study
4.152344
[ 0.99951171875, 0.000232696533203125, 0.000202178955078125 ]
[ 0.998046875, 0.001491546630859375, 0.0003108978271484375, 0.00009876489639282227 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p16
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sec[1]/sec[10]/p[0]
The TPL determination in the serum was made with 100 µL of serum by a colorimetric assay through an enzymatic method utilizing N-ethyl-N-(2,hydroxy-3-sulfopropyl)-3,5-domethoxyaniline, according to the manufacturer’s recommendations (Fujifilm . The absorbance was measured at 600 nm. This method is able to detect lecith...
en
2.11. Total Phospholipids (TPLs)
biomedical
study
4.085938
[ 0.99951171875, 0.00019824504852294922, 0.0001766681671142578 ]
[ 0.99609375, 0.0035152435302734375, 0.00041985511779785156, 0.00012826919555664062 ]
0.999999
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p17
39057070
sec[1]/sec[11]/p[0]
TFAs and PLs are expressed as a percentage. Categorical variables were expressed as frequencies and percentages. Continuous variables were compared with the Mann–Whitney U rank-sum test followed by the normality test (Shapiro–Wilk) between HSs vs. before treatment with Vit E in the COVID-19 patients and by the Kruskall...
en
2.12. Statistical Analysis
biomedical
study
4.089844
[ 0.99951171875, 0.00046634674072265625, 0.0002052783966064453 ]
[ 0.9990234375, 0.0006303787231445312, 0.00020444393157958984, 0.00007331371307373047 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p18
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sec[2]/sec[0]/p[0]
A total of nineteen men (86%) and three (14%) women were included in the group of patients, with a median age of 55 years and a body mass index of 28. The comorbidities they presented were diabetes mellitus (27%), hypertension (14%), dyslipidemia (46%), overweight (41%), and morbid obesity (36%). Furthermore, the gasom...
en
3.1. Demographic Characteristics of the Patients with COVID-19
biomedical
study
3.564453
[ 0.98779296875, 0.01158905029296875, 0.0004069805145263672 ]
[ 0.99609375, 0.0025043487548828125, 0.000392913818359375, 0.0011682510375976562 ]
0.999996
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p19
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sec[2]/sec[1]/p[0]
A total of fifteen men (55%) and eight (35%) women were included in the HS group, with a median age of 60 years, adding to a total of 23 individuals. The values of the levels of glucose, Ca 2+ , uric acid, creatinine, CT, HDLs, LDLs, TGs, and CRPs in these subjects are shown in Table 2 . The same variables in the serum...
en
3.2. Blood Biochemical Characteristics of the Healthy Subjects and COVID-19 Patients
biomedical
study
4.03125
[ 0.9990234375, 0.0004878044128417969, 0.00031065940856933594 ]
[ 0.99951171875, 0.00022113323211669922, 0.00018548965454101562, 0.00005894899368286133 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p20
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sec[2]/sec[1]/p[1]
Table 3 shows the values of IL-6 and CRP in the HS and COVID-19 patients before and after treatment with Vit E. COVID-19 patients before treatment with Vit E showed an increase in these pro-inflammatory markers in comparison with HSs ( p = 0.001), but a decrease in both variables ( p = 0.01) was observed after treatmen...
en
3.2. Blood Biochemical Characteristics of the Healthy Subjects and COVID-19 Patients
biomedical
study
4.082031
[ 0.9990234375, 0.0005826950073242188, 0.00022280216217041016 ]
[ 0.99951171875, 0.00031566619873046875, 0.00025463104248046875, 0.00008231401443481445 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p21
39057070
sec[2]/sec[2]/p[0]
Figure 2 A shows that the Vit E concentration in COVID-19 patients was decreased ( p = 0.005) in comparison to HSs. However, treatment with Vit E favored an increase in these patients ( p = 0.04). Figure 2 B shows that the TPLs determined by colorimetry, which are represented by lecithin, lysolecithin, and the sphingom...
en
3.3. Vit E and Total Phospholipids
biomedical
study
4.101563
[ 0.99951171875, 0.0003352165222167969, 0.0002263784408569336 ]
[ 0.99951171875, 0.00019669532775878906, 0.00030875205993652344, 0.000057816505432128906 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p22
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sec[2]/sec[3]/p[0]
Table 4 shows the percentage of TFAs in the serum of the HSs and patients with COVID-19. The PA, palmitoleic, and stearic, ( p ≤ 0.04) acids were decreased, but OA was increased ( p = 0.001) in patients with COVID-19 in comparison to HSs. The AA and EPA showed a tendency to increase but did not reaching a significant d...
en
3.4. Total Fatty Acids and Fatty Acids in an Acetone Insoluble Phospholipid Fraction (FAAIPF) in Serum
biomedical
study
4.101563
[ 0.99951171875, 0.00035834312438964844, 0.00025200843811035156 ]
[ 0.99951171875, 0.00018262863159179688, 0.0002532005310058594, 0.00005358457565307617 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p23
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sec[2]/sec[3]/p[1]
Table 5 shows the composition of the saturated (SFA), monounsaturated (MUFA), and polyunsaturated-3, -6 (PUFA) acids in the serum in the patients with COVID-19 before and after treatment with Vit E and in the serum in the HSs. The total SFA decreased ( p = 0.02) and the MUFA increased ( p = 0.02) in patients with COVID...
en
3.4. Total Fatty Acids and Fatty Acids in an Acetone Insoluble Phospholipid Fraction (FAAIPF) in Serum
biomedical
study
4.09375
[ 0.99951171875, 0.0003821849822998047, 0.0002033710479736328 ]
[ 0.99951171875, 0.00026416778564453125, 0.00028777122497558594, 0.00006747245788574219 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p24
39057070
sec[2]/sec[3]/p[2]
Table 6 shows the desaturation indexes, including the palmitoleic/PA ratio, which was decreased ( p = 0.01), and the stearic/OA, ratio which was increased ( p = 0.001). These ratios are usually used as indexes of ∆ 9 —the activity of desaturation. The ratio of γ-linoleic/linoleic that is used as an index of the desatur...
en
3.4. Total Fatty Acids and Fatty Acids in an Acetone Insoluble Phospholipid Fraction (FAAIPF) in Serum
biomedical
study
4.125
[ 0.99951171875, 0.000278472900390625, 0.00022912025451660156 ]
[ 0.99951171875, 0.000186920166015625, 0.00028014183044433594, 0.00005942583084106445 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p25
39057070
sec[2]/sec[3]/p[3]
Table 7 shows the FAAIPF percentage in the serum from the HSs and patients with COVID-19. The PA and stearic ( p = 0.002 and p = 0.01, respectively) increased, but OA and D-γ-LA tended to increase ( p = 0.07), and LA acid decreased, ( p = 0.001) in patients with COVID-19 in comparison to HSs. But, treatment with Vit E ...
en
3.4. Total Fatty Acids and Fatty Acids in an Acetone Insoluble Phospholipid Fraction (FAAIPF) in Serum
biomedical
study
4.089844
[ 0.99951171875, 0.0002505779266357422, 0.0002434253692626953 ]
[ 0.99951171875, 0.00020372867584228516, 0.00023448467254638672, 0.0000508427619934082 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p26
39057070
sec[2]/sec[3]/p[4]
Table 8 shows the composition of the SFA, MUFA, and PUFA-3 and -6 in the FAAIPF in serum in the patients with COVID-19 before and after treatment with Vit E and in the HSs. The total SFAs increased ( p = 0.002), but the PUFA-3 decreased ( p = 0.002). However, treatment with Vit E favored an increase in the PUFA-6 ( p =...
en
3.4. Total Fatty Acids and Fatty Acids in an Acetone Insoluble Phospholipid Fraction (FAAIPF) in Serum
biomedical
study
4.125
[ 0.99951171875, 0.0004239082336425781, 0.00021946430206298828 ]
[ 0.99951171875, 0.0002789497375488281, 0.0002658367156982422, 0.0000655055046081543 ]
0.999996
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p27
39057070
sec[2]/sec[3]/p[5]
Table 9 shows the desaturation index in the FAAIPF. The stearic/OA ratio decreased ( p = 0.03) in COVID-19 patients in comparison to HSs, but treatment with Vit E in the COVID-19 patients tended to increase the index of the ∆ 5 desaturase through the DHA/EPA ratio, but there was no significant difference ( p = 0.07).
en
3.4. Total Fatty Acids and Fatty Acids in an Acetone Insoluble Phospholipid Fraction (FAAIPF) in Serum
biomedical
study
4.105469
[ 0.99951171875, 0.0002918243408203125, 0.0002472400665283203 ]
[ 0.99951171875, 0.0002396106719970703, 0.00018703937530517578, 0.00005626678466796875 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p28
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sec[2]/sec[4]/p[0]
Figure 3 A shows the concentration of PGE 2 in the serum of the experimental groups; there was a significant increase in patients with COVID-19 in comparison with HSs ( p = 0.03), and after treatment with Vit E ( p = 0.01), it decreased. The same tendency was observed with the TXB 2 concentration in the patients with C...
en
3.5. Prostaglandins and Interleukin Concentration
biomedical
study
4.09375
[ 0.99951171875, 0.00037097930908203125, 0.0002448558807373047 ]
[ 0.99951171875, 0.0002237558364868164, 0.00025010108947753906, 0.00005805492401123047 ]
0.999995
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p29
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sec[2]/sec[5]/p[0]
Figure 4 A shows that the LPO index and 8-isoprostane were significantly increased in the serum of the COVID-19 patients in comparison with HSs ( p = 0.001) after treatment with Vit E ( p = 0.001).
en
3.6. Lipid Peroxidation and 8-Isoprostene
biomedical
study
4.03125
[ 0.99951171875, 0.0003352165222167969, 0.0002751350402832031 ]
[ 0.99951171875, 0.0003039836883544922, 0.00022423267364501953, 0.000060439109802246094 ]
0.999999
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p30
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sec[3]/p[0]
The SARS-CoV-2 virus responsible for the COVID-19 pandemic that devastated the world between 2020 and 2021 continues to mutate and still claims the lives of millions of people around the world. Although there are already different vaccines provided by different pharmaceutical companies against this virus (13.590 millio...
en
4. Discussion
biomedical
study
4.25
[ 0.99951171875, 0.0004239082336425781, 0.0001493692398071289 ]
[ 0.99853515625, 0.0004642009735107422, 0.00079345703125, 0.00014412403106689453 ]
0.999994
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p31
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sec[3]/p[1]
Our results show a decrease in Vit E levels in the serum of patients with COVID-19, which confirms the previously mentioned reports and suggests that in the infectious process caused by SARS-CoV-2, there is a depletion of molecules with antioxidant capacity, such as Vit E, which contributes to the progression of the in...
en
4. Discussion
biomedical
study
4.375
[ 0.99951171875, 0.0004737377166748047, 0.00016176700592041016 ]
[ 0.99853515625, 0.0003342628479003906, 0.0010156631469726562, 0.00015425682067871094 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p32
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sec[3]/p[2]
Moreover, high levels of LPO are present in the inflammatory process, and these are in part the result of ferroptosis present in these patients . Our results showed an increase in the LPO index in patients with COVID-19 in comparison to HSs. Moreover, treatment with Vit E favored a decrease. This suggests that Vit E su...
en
4. Discussion
biomedical
study
4.132813
[ 0.99951171875, 0.00028514862060546875, 0.00016760826110839844 ]
[ 0.99951171875, 0.00019943714141845703, 0.00037407875061035156, 0.00007492303848266602 ]
0.999999
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p33
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sec[3]/p[3]
The increase in LPO in COVID-19 suggests that an oxidizing background in the SARS-CoV-2 infection has already been documented . This situation favors the oxidation of the AA to 8-isoprostanes, which are molecules considered markers of LPO and oxidative injury. For this reason, this molecule has been considered an ideal...
en
4. Discussion
biomedical
study
4.105469
[ 0.99951171875, 0.00026726722717285156, 0.00014853477478027344 ]
[ 0.9990234375, 0.0002810955047607422, 0.00040602684020996094, 0.00007975101470947266 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p34
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sec[3]/p[4]
Regarding the results of the TPL fractions obtained (lecithin, lysolecithin, and sphingomyelin), the patients with COVID-19 showed a significant decrease in serum. Different studies in COVID-19 have demonstrated an alteration in the profile of the lipid metabolism in this disease . Therefore, the rescheduling of the FA...
en
4. Discussion
biomedical
study
4.332031
[ 0.99951171875, 0.00038814544677734375, 0.00020456314086914062 ]
[ 0.9990234375, 0.00026416778564453125, 0.0005059242248535156, 0.00010162591934204102 ]
0.999997
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
39057070_p35
39057070
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In addition, the desaturation process constitutes an important step in the metabolism of FAs, and desaturases are key enzymes in the biosynthesis of the MUFA from the SFA. These enzymes introduce a cis-double bond into the SFA, which is very important in the control of the structural, fluidity, and disorders of the mem...
en
4. Discussion
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study
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[ 0.99951171875, 0.0004131793975830078, 0.0002073049545288086 ]
[ 0.998046875, 0.0004401206970214844, 0.0012178421020507812, 0.0001628398895263672 ]
0.999998
[ "María Elena Soto", "Linaloe Manzano-Pech", "Verónica Guarner-Lans", "Adrían Palacios-Chavarría", "Rafael Ricardo Valdez-Vázquez", "Raúl Martínez-Memije", "Mohammed El-Hafidi", "Félix Leao Rodríguez-Fierros", "Israel Pérez-Torres" ]
https://doi.org/10.3390/cimb46070429
https://creativecommons.org/licenses/by/4.0/
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Biomed-Enriched

Biomed-Enriched: A Biomedical Dataset Enriched with LLMs for Pretraining and Extracting Rare and Hidden Content

Dataset Authors

Rian Touchent, Nathan Godey & Eric de la Clergerie
Sorbonne Université, INRIA Paris

Overview

Biomed-Enriched is a PubMed-derived dataset created using a two-stage annotation process. Initially, Llama 3.1 70B Instruct annotated 400K paragraphs for document type, domain, and educational quality. These annotations were then used to fine-tune a smaller model, which propagated the labels across the entire PubMed Central Open Access corpus. This process yielded 2M clinical case paragraphs, with over 450K high-quality paragraphs licensed for commercial use. This dataset provides a large-scale, openly available alternative to private clinical text. In continual pre-training experiments with OLMo2, curated subsets showed targeted improvements: clinical upsampling boosted MMLU ProfMed scores by ~5%, and educational quality filtering improved MedQA and MedMCQA by ~1%. Combining these methods achieved similar performance compared to standard continual-pretraining with just one-third of the training tokens, highlighting the potential for more efficient biomedical pretraining.

The dataset is structured into two primary splits:

  • Commercial
  • Non-Commercial

Dataset Structure

Commercial Split

  • text: Textual content of the paragraphs.
  • path: Precise XML path referencing original paragraph locations.
  • license_url: URL linking to the license.
  • authors: Comprehensive list of authors per paragraph for proper attribution compliance.

Non-Commercial Split

  • path: Precise XML path referencing original paragraph locations.
  • license_url: URL linking to the license.
  • authors: Comprehensive list of authors per paragraph for proper attribution compliance.

Note: The non-commercial split does not contain text data due to licensing restrictions. However, we provide scripts to populate the text field from a local PMC Open Access XML dump. See below for installation and usage instructions.

pip install biomed-enriched

With Python

from biomed_enriched import populate

DATASET_DIR = "/path/to/biomed-enriched"  # input dataset
PMC_XML_ROOT = "/path/to/pmc/non-comm/xml"          # PMC XML dump
OUTPUT_DIR = "/path/to/populated-biomed-enriched"  # drop arg to overwrite in-place

populate(DATASET_DIR, PMC_XML_ROOT, output_path=OUTPUT_DIR, splits="noncommercial", num_proc=1)

The call overwrites the dataset in-place, adding a new text column as the third column (after article_id, path).

With CLI

biomed-enriched \
  --input /path/to/biomed-enriched \
  --xml-root /path/to/pmc/non-comm/xml \
  --num-proc 8

Add --output DIR if you prefer writing to a new directory instead of overwriting.

Annotation Process

The dataset was created using a two-stage annotation framework:

  1. Initial Annotation by Large Language Model:
  • Annotated a subset of paragraphs for the following categories:
  • Document Type: Categorizes the structure and purpose of the content.
    • Clinical Case: Detailed report of symptoms, diagnosis, treatment, and follow-up of individual patients.
    • Study: Research paragraph with methods, results, and discussion of experiments or observations.
    • Review: Summary or synthesis of current knowledge on a specific topic.
    • Other: Content not fitting above categories (editorials, commentaries, policy paragraphs).
  • Domain: Identifies the subject area focus.
    • Clinical: Content relating to patient care, clinical trials, case reports, or practice guidelines.
    • Biomedical: Scientific aspects of medicine and biology.
    • Other: Content mentioning biomedical topics but focusing on administrative, policy, or general communications.
  • Educational Quality: Assesses pedagogical value for college-level biomedical learning on a scale from 1 (minimal value) to 5 (exceptional value) inspired by FineWeb-edu.
    • Score 1: Basic information relevant to biomedical topics, may contain irrelevant content.
    • Score 2: Addresses biomedical education elements but with limitations in coherence or depth.
    • Score 3: Appropriate for college-level curricula, introduces key concepts with reasonable coherence.
    • Score 4: Highly relevant educational content with clear writing style, minimal irrelevant information.
    • Score 5: Outstanding educational value, detailed reasoning with profound insights for college-level learning.
  1. Annotation Scaling via Model Distillation:
  • These annotations were distilled into a XLM-RoBERTa-base model, enabling scalability to the entire PMC dataset.

Annotation Statistics

Here is the distribution of educational scores per domain:

Educational Score Biomedical (n=116 221 134) Clinical (n=2 182 784) Other (n=15 213 051)
1 1.8 % 6.0 % 60.1 %
2 9.4 % 23.4 % 29.4 %
3 10.9 % 26.6 % 8.3 %
4 75.3 % 44.0 % 2.1 %
5 2.6 %

Here is the distribution of educational scores per document type:

Educational Score Study (n=100 387 809) Review (n=6 811 226) Clinical case (n=2 122 403) Other (n=24 295 531)
1 0.7 % 0.3 % 4.0 % 43.4 %
2 7.9 % 1.6 % 14.4 % 30.9 %
3 10.0 % 5.0 % 24.6 % 14.6 %
4 78.7 % 86.9 % 57.0 % 11.1 %
5 2.6 % 6.1 % 0.0 % 0.0 %

Language Distribution

Language Articles Paragraphs Clinical Case Paragraphs % Clinical Cases
en 4,113,275 131,579,445 2,113,185 1.61
es 4,339 181,779 1,235 0.68
zh-cn 3,649 59,719 0 0.00
fr 3,410 173,325 2,586 1.49
de 2,976 248,608 51 0.02
it 2,708 274,819 521 0.19
pt 934 85,242 4,540 5.33
ko 636 25,535 0 0.00
ru 222 10,553 0 0.00
id 189 91,865 15 0.02

Key Applications

  • Improve efficiency in biomedical pretraining by focusing on high-quality, specific content.
  • Create new biomedical subsets tailored to specific research needs based on document type and domain.

Evaluation

Our evaluation focuses on isolating the effects of data curation rather than pursuing state-of-the-art scores on benchmarks. A more powerful foundation model would likely yield higher absolute scores but would obscure the precise impact of our dataset. We therefore selected OLMo2-7B-stage1 as our foundation model, as this intermediate checkpoint provides strong baseline capabilities while allowing for a clear attribution of performance gains to our enrichment strategies. This model has already developed strong language modeling capabilities but precedes the knowledge-intensive tuning of stage 2, providing an ideal balance without the risk of catastrophic forgetting of instruction-following abilities during domain adaptation. Notably, the data mix used in phase 1 includes DCLM, a dataset filtered from web data using a classifier trained on instruction data, which gives OLMo2-7B relatively strong question-answering capabilities even after stage 1.

Each Biomed-Enriched variant was trained for exactly 33.6 billion tokens using identical hyperparameters. We follow the annealing strategy of OLMo2 used in the mid-training phase. By maintaining strict parameter parity across experiments, we created a controlled environment focused solely on measuring the effectiveness of different data curation strategies.

These experiments are designed to illustrate how our granular annotations enable targeted improvements in model capabilities. For instance, by specifically upsampling clinical content (BE-Clinical and BE-ClinicalCase variants), we expect to see a notable increase in performance on the MMLU Professional Medicine benchmark, underscoring the dataset's potential for developing specialized models.

The following variants were created for this evaluation:

  • BE-Base: The complete unmodified PMC Open Access Subset serving as baseline.
  • BE-Educational: Preserves all articles but removes paragraphs with educational quality scores below 3.
  • BE-Clinical: Replicates articles with predominantly clinical domain content 10× in the training mix.
  • BE-ClinicalCase: Replicates articles containing at least one clinical case paragraph 10× to increase exposure to clinical narratives.
  • BE-Prefix: Prefixes each paragraph with its predicted annotations to allow modeling of metadata-content relationships.
  • BE-French: Upsamples articles containing French text 10× to address language imbalance.
  • BE-All: Combines quality filtering (score ≥ 3), upsampling of clinical content, French text, and clinical cases, plus metadata prefixing.

Performance Results

SOTA Models for reference

Model MedQA MedMCQA PubMedQA Anat Clin Bio Med Gen Prof Avg
Llama-3-8B 59.70 57.47 74.80 68.89 74.72 78.47 61.85 83.00 70.22 69.90
Meditron-70B 57.10 46.80 76.60 53.30 66.70 76.30 63.00 69.00 71.60 64.49

Benchmark Results by Dataset Variant (continual pre-training of OLMo2-7B-stage1)

Variant MedQA MedMCQA PubMedQA Anat Clin Bio Med Gen Prof Avg
OLMo2-7B-stage1 45.33 41.14 75.60 54.81 63.40 69.44 53.18 69.00 59.93 59.09
BE-Base 44.85 41.91 76.40 57.04 64.15 70.83 59.54 69.00 59.93 60.41
BE-Clinical 41.95 39.35 76.60 53.33 63.40 65.28 58.38 66.00 63.97 58.70
BE-ClinicalCase 42.11 39.52 76.60 57.04 64.91 66.67 59.54 69.00 62.87 59.81
BE-Prefix 45.72 41.76 77.80 57.04 64.53 68.75 57.23 66.00 61.76 60.07
BE-Educational 45.64 43.08 77.00 57.04 65.28 68.06 56.65 71.00 58.82 60.29
BE-All 47.21 42.79 76.60 60.00 65.66 68.06 58.96 69.00 61.40 61.08

Note: The first three columns represent Medical QA benchmarks. The following six (Anat, Clin, Bio, Med, Gen, Prof) are sub-tasks from MMLU Medical. MMLU abbreviations: Anat=Anatomy, Clin=Clinical Knowledge, Bio=College Biology, Med=College Medicine, Gen=Medical Genetics, Prof=Professional Medicine.

Results Analysis

Overall performance. BE-All achieved the highest average performance across benchmarks at 61.08%, surpassing BE-Base (60.41%) by a small but consistent margin (+0.67 pts, see table above). Its strongest improvements appeared in MedQA (47.21%), MMLU Anatomy (60.00%), and Clinical Knowledge (65.66%), suggesting the effectiveness of combining multiple targeted enrichment strategies.

Clinical enrichment. Clinical enrichment (BE-Clinical) significantly boosted performance on MMLU Professional Medicine benchmark (63.97%, +4.04 pts vs. BE-Base, Figure 2). This improvement was stable from early training, highlighting how clinical narratives enhance the model’s clinical reasoning abilities efficiently.

Educational filtering. Educational filtering (BE-Educational) consistently improved performance on medical question-answering tasks, notably Medical Genetics (71.00%, +2 pts), MedMCQA (43.08%, +1.17 pts), and PubMedQA (77.00%, +0.6 pts). These tasks likely benefit from the knowledge present in educationally high-quality paragraphs (Figure 2).

Metadata prefixing. Metadata prefixing (BE-Prefix) specifically improved performance on PubMedQA (77.80%, +1.4 pts vs. BE-Base). Providing explicit paragraph-level metadata helped primarily with structured document comprehension, but it had limited benefits for other tasks.

General biomedical knowledge trade-off. BE-Base performed better on College Biology (70.83%) than others. Building a biology variant (BE-Bio) could be an interesting future direction, as the current dataset does not specifically target this domain.

Non-English enrichment. BE-French showed clear improvements in French medical QA (FrenchMedMCQA), achieving 40.5% accuracy, significantly surpassing BE-Base and the OLMo2-7B-stage1 baseline (38.32%, Figure 1). These results illustrate effective adaptation to non-English contexts without modifying the underlying model architecture.

Benchmark Results

Data efficiency and training stability. As shown in Figure 2, BE-All reached robust benchmark performance using roughly one-third of the tokens required by BE-Base. Individual enrichments (Educational, Clinical) also displayed early and stable improvements, underscoring potential reductions in training time and computational cost.

Benchmark Results

Licensing

The Biomed-Enriched annotations (document type, domain, educational quality scores, and metadata) are released under the MIT License.

The textual content licensing depends on the individual article licenses from PubMed Central Open Access. Each paragraph includes a license_url field pointing to the specific license. Users must comply with the respective license terms when using the textual data.

How to Cite

Please cite Biomed-Enriched using:

@misc{touchent2025biomedenrichedbiomedicaldatasetenriched,
      title={Biomed-Enriched: A Biomedical Dataset Enriched with LLMs for Pretraining and Extracting Rare and Hidden Content}, 
      author={Rian Touchent and Nathan Godey and Eric de la Clergerie},
      year={2025},
      eprint={2506.20331},
      archivePrefix={arXiv},
      primaryClass={cs.CL},
      url={https://arxiv.org/abs/2506.20331}, 
}

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