Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving the explainability of Random Forest classifier - user centered approach

Machine Learning (ML) methods are now influencing major decisions about patient care, new medical methods, drug development and their use and importance are rapidly increasing in all areas. However, these ML methods are inherently complex and often difficult to understand and explain resulting in barriers to their adoption and validation. Our work (RFEX) focuses on enhancing Random Forest (RF) classifier explainability by developing easy to interpret explainability summary reports from trained RF classifiers as a way to improve the explainability for (often non-expert) users. RFEX is implemented and extensively tested on Stanford FEATURE data where RF is tasked with predicting functional sites in 3D molecules based on their electrochemical signatures (features). In developing RFEX method we apply user-centered approach driven by explainability questions and requirements collected by discussions with interested practitioners. We performed formal usability testing with 13 expert and non-expert users to verify RFEX usefulness. Analysis of RFEX explainability report and user feedback indicates its usefulness in significantly increasing explainability and user confidence in RF classification on FEATURE data. Notably, RFEX summary reports easily reveal that one needs very few (from 2-6 depending on a model) top ranked features to achieve 90% or better of the accuracy when all 480 features are used.
Profile of Brazilian smokers in the National Program for Tobacco Control.

OBJECTIVE The treatment of tobacco addiction in Brazil has expanded in recent years; however, we must increase knowledge about the characteristics of individuals who adhere to cessation programs in order to adjust treatments to specific characteristics of the target population that favor success. The aim of this study was to describe the characteristics of smokers who present to Brazilian public health units seeking help to quit smoking based on the experience of a primary health care unit that covers a poor community in the city of Rio de Janeiro. METHODS Data were collected at a Teaching Health Center from January 03 2012 to January 03 2014. RESULTS Mean patient age was 49.32 ± 11.82 years, and 71% were women. About half of the participants successfully quit smoking (n=125, 51%). Higher levels of nicotine dependence were associated with lower levels of smoking cessation. There was a notable decrease in the probability of remaining smoking throughout the first month of treatment. After 3 weeks of treatment, only 19% had not quit smoking. The probability of quitting smoking decreases by 2% for every additional year of age. CONCLUSION There is a need to revise and expand current strategies to make them more effective in preventing smoking since childhood.
A cluster-randomized trial to reduce cesarean delivery rates in Quebec.

BACKGROUND In Canada, cesarean delivery rates have increased substantially over the past decade. Effective, safe strategies are needed to reduce these rates. METHODS We conducted a cluster-randomized, controlled trial of a multifaceted 1.5-year intervention at 32 hospitals in Quebec. The intervention involved audits of indications for cesarean delivery, provision of feedback to health professionals, and implementation of best practices. The primary outcome was the cesarean delivery rate in the 1-year postintervention period. RESULTS Among the 184,952 participants, 53,086 women delivered in the year before the intervention and 52,265 women delivered in the year following the intervention. There was a significant but small reduction in the rate of cesarean delivery from the preintervention period to the postintervention period in the intervention group as compared with the control group (change, 22.5% to 21.8% in the intervention group and 23.2% to 23.5% in the control group; odds ratio for incremental change over time, adjusted for hospital and patient characteristics, 0.90; 95% confidence interval [CI], 0.80 to 0.99; P=0.04; adjusted risk difference, -1.8%; 95% CI, -3.8 to -0.2). The cesarean delivery rate was significantly reduced among women with low-risk pregnancies (adjusted risk difference, -1.7%; 95% CI, -3.0 to -0.3; P=0.03) but not among those with high-risk pregnancies (P=0.35; P = 0.03 for interaction). The intervention group also had a reduction in major neonatal morbidity as compared with the control group (adjusted risk difference, -0.7%; 95% CI, -1.3 to -0.1; P=0.03) and a smaller increase in minor neonatal morbidity (adjusted risk difference, -1.7%; 95% CI, -2.6 to -0.9; P<0.001). Changes in minor and major maternal morbidity did not differ significantly between the groups. CONCLUSIONS Audits of indications for cesarean delivery, feedback for health professionals, and implementation of best practices, as compared with usual care, resulted in a significant but small reduction in the rate of cesarean delivery, without adverse effects on maternal or neonatal outcomes. The benefit was driven by the effect of the intervention in low-risk pregnancies. (Funded by the Canadian Institutes of Health Research; QUARISMA Current Controlled Trials number, ISRCTN95086407.).
Steroids for symptom control in infectious mononucleosis.

BACKGROUND Glandular fever (infectious mononucleosis) is associated with fatigue, fever, sore throat and swollen lymph nodes. The severity of symptoms can vary. In extreme cases, breathing difficulties because of swelling in the throat and other complications can require hospitalization. The duration of symptoms is also variable; in some instances they can last for months. There are few treatments available. There are no universal criteria for using steroids in glandular fever. While their use is generally reserved for severe complications, there are reports of practitioners treating most symptomatic people with steroids. As glandular fever often affects young people at a time in their studies where they need to be continually productive, the potential duration of the condition is perhaps a key factor in prescribing such a potent drug for symptom control. OBJECTIVES To determine the efficacy and safety of steroid therapy for symptom control in glandular fever. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005); MEDLINE (January 1966 to November 2005); EMBASE (January 1974 to November 2005); and the UK National Research Register (November 2005). SELECTION CRITERIA Randomised controlled trials (RCTs) that compared the effectiveness for symptom control of a steroid to placebo or to another intervention for people of any age with documented glandular fever were included. DATA COLLECTION AND ANALYSIS Authors independently assessed trial inclusion according to predetermined criteria. Results are presented separately for each symptom and, where possible, it was intended to combine results in a meta-analysis. MAIN RESULTS Seven trials were included. The diagnosis, steroid regime, outcomes and methodological quality varied between trials. The sample size ranged from 24 to 94. For sore throat the results of two studies suggest a benefit at 12 hours of steroid therapy over placebo; however this benefit was not maintained. The evidence from one trial suggests a longer benefit when the steroid is combined with an antiviral drug. There was evidence from one trial that steroids may improve resolution of fatigue around four weeks; however it is unclear if this is only in combination with an antiviral. Two trials reported severe complications in participants in the steroid group. AUTHORS' CONCLUSIONS There is insufficient evidence - the trials were few, heterogeneous and some were of poor quality, to recommend steroid treatment for symptom control in glandular fever. There is also a lack of research on the side effects, potential adverse effects or complications, particularly in the long term.
Post-Tonsillectomy Hemorrhage: Results of a 3-Month Follow-Up

Episodes of post-tonsillectomy hemorrhage are unpredictable and potentially life-threatening. Primary post-tonsillectomy hemorrhage (<24 hr postoperatively) is generally considered to be more common and more serious than secondary hemorrhage (>24 hr). Therefore, recent studies have focused on the control of primary hemorrhage in order to determine the appropriate length of postoperative observation. The issue of follow-up is becoming more important in light of the increasing popularity of outpatient tonsillectomy. We undertook a prospective study to evaluate the incidence of post-tonsillectomy hemorrhage over the short and long term (3 mo). We studied 602 patients, aged 23 months to 89 years (mean: 20.6 yr), who had undergone inpatient tonsillectomy in 1999 and who had been hospitalized for at least 5 days. Our goal was to ascertain the number of episodes of postoperative hemorrhage that required surgical treatment under general anesthesia. We were able to contact 601 of these patients (or their parents) by telephone 3 months postoperatively to inquire about any instances of delayed secondary bleeding. In all, 16 patients (2.7%) had experienced post-tonsillectomy bleeding that required surgically achieved hemostasis under general anesthesia. Of this group, 11 patients (68.8%) had experienced primary hemorrhage and were treated immediately, and five (31.3%) experienced secondary hemorrhage. One patient in the latter group experienced excessive bleeding 38 days postoperatively, which we believe is the latest episode of secondary bleeding reported to date. Based on the findings of this study, we believe that a postoperative follow-up period of 10 days is sufficient to identify all but the most rare cases of post-tonsillectomy hemorrhage.
Sex‐Steroid Induction of Endogenous Opioid Inhibition on Oxytocin Secretory Responses to Stress

In pregnancy, endogenous opioids inhibit enhanced basal and stressor‐stimulated oxytocin neurone activity and secretion. By contrast, stress responses of the hypothalamo‐pituitary‐adrenal (HPA) axis are reduced in pregnancy. We investigated whether the high levels of oestradiol and progesterone of pregnancy could induce these changes. Silastic capsules containing oestradiol or progesterone (or control capsules) were implanted s.c. in virgin female rats for 16 or 17 days, with or without progesterone removal on day 15 to mimic the progesterone withdrawal seen at the end of pregnancy. Plasma concentrations of oxytocin, adrenocorticotrophic hormone (ACTH) and corticosterone were measured in jugular vein blood samples from conscious rats. Under basal conditions, naloxone (5 mg/kg) increased oxytocin secretion in all groups, but had no greater effect in sex‐steroid treated rats, and did not induce Fos expression in the supraoptic nucleus. Forced swimming, a stressor, increased oxytocin secretion at 5 min in vehicle‐injected controls, and this response was slightly attenuated in the sex‐steroid treated groups. Pretreatment with naloxone greatly enhanced the response in the sex‐steroid treated rats, and was less effective in the controls. In rats treated with oestradiol alone, naloxone prolonged the response. Thus, the combined sex‐steroid treatment enhanced the responsiveness of oxytocin neurones to the stressor, while simultaneously restraining oxytocin secretion via endogenous opioid inhibition. In the same rats, ACTH and corticosterone secretion was also stimulated by the stressor, but the hypothalamo‐pituitary‐adrenal (HPA) axis response was not attenuated in sex‐steroid treated rats. Naloxone weakly reduced the HPA axis response in controls and was ineffective in the sex‐steroid treated rats. We conclude that oestradiol and progesterone may be responsible for inducing the opioid restraint and enhanced oxytocin neurone responsiveness in pregnancy.
Understanding the benefits and challenges of community engagement in the development of community mental health services for common mental disorders: Lessons from a case study in a rural South African subdistrict site

Against the backdrop of a large treatment gap for mental disorders in low- to middle-income countries (LMICs), the 2007 Lancet series on global mental health calls for a scaling up of mental health services. Community participation is largely harnessed as one strategy to facilitate this call. Using a participatory implementation framework for the development of mental health services for common mental disorders (CMDs) in a rural subdistrict in South Africa as a case study, this study sought to understand the benefits and challenges of community participation beyond that of scaling up. Qualitative process evaluation involving interviews with service providers and users was employed. The results suggest that in addition to promoting mobilization of resources and actions for scaling up mental health services, community participation can potentially contribute to more culturally competent services and personal empowerment of recipients of care. In addition, community participation holds promise for engendering community-led public health actions to ameliorate some of the social determinants of mental ill health. Challenges include that community members involved in these activities are mainly marginalized women, who have limited power to achieve structural change, including cultural practices that may be harmful to the mental health of women and children. We conclude that in addition to contributing to scaling up mental health services, community participation can potentially promote the development of culturally competent mental health services and greater community control of mental health.
A Diversity-Covering Approach to Immunization with Plasmodium falciparum Apical Membrane Antigen 1 Induces Broader Allelic Recognition and Growth Inhibition Responses in Rabbits

ABSTRACT Plasmodium falciparum apical membrane antigen 1 (PfAMA1), a candidate malaria vaccine, is polymorphic. This polymorphism is believed to be generated predominantly under immune selection pressure and, as a result, may compromise attempts at vaccination. Alignment of 355 PfAMA1 sequences shows that around 10% of the 622 amino acid residues can vary between alleles and that linkages between polymorphic residues occur. Using this analysis, we have designed three diversity-covering (DiCo) PfAMA1 sequences that take account of these linkages and, when taken together, on average incorporate 97% of amino acid variability observed. For each of the three DiCo sequences, a synthetic gene was constructed and used to transform the methylotrophic yeast Pichia pastoris, allowing recombinant expression. All three DiCo proteins were reactive with the reduction-sensitive monoclonal antibody 4G2, suggesting the DiCo sequences had conformations similar to those of naturally occurring PfAMA1. Rabbits were immunized with FVO strain PfAMA1 or with the DiCo proteins either individually or as a mixture. Antibody titers and the ability to inhibit parasite growth in vitro were determined. Animals immunized with the DiCo mix performed similarly to animals immunized with FVO AMA1 when measured against FCR3 strain parasites but outperformed animals immunized with FVO AMA1 when assessed against other strains. The levels of growth inhibition (∼70%) induced by the mix of three DiCo proteins were comparable for FVO, 3D7, and HB3, suggesting that a considerable degree of diversity in AMA1 is adequately covered. This suggests that vaccines based upon the DiCo mix approach provide a broader functional immunity than immunization with a single allele.
FMR1 and the fragile X syndrome: Human genome epidemiology review

The fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is one of the most common forms of inherited mental retardation. The cognitive, behavioral, and physical phenotype varies by sex, with males being more severely affected because of the X-linked inheritance of the mutation. The disorder-causing mutation is the amplification of a CGG repeat in the 5′ untranslated region of FMR1 located at Xq27.3. The fragile X CGG repeat has four forms: common (6–40 repeats), intermediate (41–60 repeats), premutation (61–200 repeats), and full mutation (>200–230 repeats). Population-based studies suggest that the prevalence of the full mutation, the disorder-causing form of the repeat, ranges from 1/3,717 to 1/8,918 Caucasian males in the general population. The full mutation is also found in other racial/ethnic populations; however, few population-based studies exist for these populations. No population-based studies exist for the full mutation in a general female population. In contrast, several large, population-based studies exist for the premutation or carrier form of the disorder, with prevalence estimates ranging from 1/246 to 1/468 Caucasian females in the general population. For Caucasian males, the prevalence of the premutation is ∼1/1,000. Like the full mutation, little information exists for the premutation in other populations. Although no effective cure or treatment exists for the fragile X syndrome, all persons affected with the syndrome are eligible for early intervention services. The relatively high prevalence of the premutation and full mutation genotypes coupled with technological advances in genetic testing make the fragile X syndrome amenable to screening. The timing as well as benefits and harms associated with the different screening strategies are the subject of current research and discussion.
Association between chronic oral inflammatory burden and physical fitness in males: a cross‐sectional observational study

AIM To evaluate the association between chronic oral inflammatory burden (OIB) - as the combination of periodontal and endodontic disease load - and physical fitness. METHODOLOGY One hundred and twelve nonsmoker male police officers who performed a standardized physical fitness test (PFT) were analysed. Participants underwent oral clinical and periapical radiographic examinations. Periodontal disease was assessed by probing depth (PD) and clinical attachment loss (AL). For radiographic analysis, both apical periodontitis (AP) and root canal treatment (RCT) variables were analysed. Endodontic Burden (EB) was calculated merging the total number of teeth with AP and/or RCT per individual. OIB was calculated combining EB and AL. The outcome of physical fitness was dichotomized according to whether the highest PFT score was 'achieved' or 'not-achieved'. Multivariable logistic regression models were adjusted for age, body mass index and frequency of daily exercise. RESULTS There was no significant association between AP, RCT and EB with physical fitness whereas PD, AL and OIB were significantly associated with low physical fitness (P < 0.05). Multivariate regression analysis revealed that individuals with OIB = EB ≥ 3 and AL ≥ 4 mm had a 81% lower chance of reaching the highest PFT score (OR = 0.19, 95%CI = 0.04-0.87, P = 0.03) compared to individuals with EB < 3 and and no AL ≥ 4 mm. Individuals with unfavourable periodontal parameters but with low EB (OIB = EB < 3 & AL ≥ 4 mm) showed no significant differences on the chance to reach the highest PFT score compared to participants with favourable periodontal status and low EB (OIB = EB < 3 & no AL ≥ 4 mm). CONCLUSIONS The OIB - higher levels of EB in periodontal patients - was independently associated with poor physical fitness in males.
Collagen Integrin Receptors Regulate Early Osteoblast Differentiation Induced by BMP‐2

Studies in several cell types indicate that the actions of integrin receptors for extracellular matrix and receptors for growth factors are synergistic in regulating cellular differentiation and function. We studied the roles of the α1β1 and α2β1 integrin collagen receptors in regulating the differentiation of 2T3 osteoblastic cells in response to bone morphogenetic protein (BMP)‐2. The immortalized 2T3 cell line was established from the calvaria of mice transgenic for a BMP‐2 promoter driving SV40 T‐antigen. These cells require exogenous BMP‐2, as well as ascorbic acid and β‐glycerolphosphate, for expression of a mature osteoblast phenotype and formation of a mineralized matrix. To determine how integrin receptors for collagen‐I affect BMP‐2 signaling, function‐perturbing anti‐rat α1 and/or α2 integrin subunit, or anti‐type I collagen (Col‐I), antibodies were added to human recombinant (hr)BMP‐2–treated 2T3 cultures at confluence (C0) or at 4 or 8 days postconfluence (C4, C8). After 4 days of exposure to the antibodies, cultures were assayed for alkaline phosphatase (ALP) mRNA levels and enzyme activity and for cAMP production in response to parathyroid hormone. Addition of anti‐Collagen‐I or both anti–integrin‐α1 and ‐α2 antibodies to C0 cultures blocked expression of these early osteoblast markers by more than 90%, and also blocked mineralization (0.5–1.8% control) of these cells. In all cases, adding anti‐α1 or anti‐α2 antibodies separately produced partial effects, while their combined effect approached that of anti‐Collagen‐I. When antibodies were added to more differentiated 2T3 cells, the inhibitory effects decreased. 2T3 cells carrying constitutively active BMP receptor (caBMPR‐IB) showed elevated ALP activity without hrBMP‐2; this constitutive activity was also suppressed by α1 and α2 integrin antibodies and by anti‐Col‐I antibody. Together, our data suggest that a signal(s) from collagen integrin receptors regulates the response to BMP downstream of BMPR‐IB and upstream of the regulation of ALP mRNA and other early markers of osteoblast differentiation.
Hydrogen Sulfide Induces Oxidative Damage to RNA and DNA in a Sulfide‐Tolerant Marine Invertebrate

Hydrogen sulfide acts as an environmental toxin across a range of concentrations and as a cellular signaling molecule at very low concentrations. Despite its toxicity, many animals, including the mudflat polychaete Glycera dibranchiata, are periodically or continuously exposed to sulfide in their environment. We tested the hypothesis that a broad range of ecologically relevant sulfide concentrations induces oxidative stress and oxidative damage to RNA and DNA in G. dibranchiata. Coelomocytes exposed in vitro to sulfide (0–3 mmol L−1 for 1 h) showed dose‐dependent increases in oxidative stress (as 2′,7′‐dichlorofluorescein fluorescence) and superoxide production (as dihydroethidine fluorescence). Coelomocytes exposed in vitro to sulfide (up to 0.73 mmol L−1 for 2 h) also acquired increased oxidative damage to RNA (detected as 8‐oxo‐7,8‐dihydroguanosine) and DNA (detected as 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine). Worms exposed in vivo to sulfide (0–10 mmol L−1 for 24 h) acquired elevated oxidative damage to RNA and DNA in both coelomocytes and body wall tissue. While the consequences of RNA and DNA oxidative damage are poorly understood, oxidatively damaged deoxyguanosine bases preferentially bind thymine, causing G‐T transversions and potentially causing heritable point mutations. This suggests that sulfide can be an environmental mutagen in sulfide‐tolerant invertebrates.
Interrater agreement of visual analysis in single-subject decisions: quantitative review and analysis.

The empirical literature examining the interrater agreement for visual analysis of single-subject data was examined using the technique of meta-analysis. Aggregated study results revealed an overall interrater agreement value of . 58 for 14 studies representing a total of 789 raters. Additional analyses revealed that the interrater agreement values did not vary across raters based on previous experience or level of expertise. Characteristics of the graphs, including whether the data were hypothetical or real, or whether designs were the simple AB format or more complex (ABAB) designs, did not significantly influence the interrater agreement values. The only graphic characteristic related to increased interrater agreement was the presence of a trend (regression) line. Trend lines appeared to improve interrater agreement if the raters were familiar with their method of computation and interpretation. Simply including a trend line in the graphs produced only a marginal improvement in interrater agreement.