Miracle-dz/UniFAR-FTUs huggingface dataset:
A Workshop Report on the Causes and Consequences of Sleep Health Disparities.

Sleep deficiencies, which include insufficient or long sleep duration, poor sleep quality, and irregular timing of sleep, are disproportionately distributed among populations that experience health disparities in the United States. Sleep deficiencies are associated with a wide range of suboptimal health outcomes, high risk health behaviors, and poorer overall functioning and wellbeing. This report focuses on sleep health disparities (SHDs), which is defined as differences in one or more dimensions of sleep health on a consistent basis that adversely affects designated disadvantaged populations. SHDs appear to share many of the same determinants and causal pathways observed for health outcomes with well-known disparities. There also appears to be common behavioral and biological mechanisms that connect sleep with poorer health outcomes, suggesting a link between SHDs and other health disparities observed within these designated populations. In 2018, the National Institute on Minority Health and Health Disparities, the National Heart, Lung, and Blood Institute, and the Office of Behavioral and Social Sciences Research convened a workshop with experts in sleep, circadian rhythms, and health disparities to identify research gaps, challenges, and opportunities to better understand and advance research to address SHDs. The major strategy to address SHDs is to promote integration between health disparity causal pathways and sleep and circadian-related mechanisms in research approaches and study designs. Additional strategies include developing a comprehensive, integrative conceptual model, building transdisciplinary training and research infrastructure, and designing as well as testing multilevel, multifactorial interventions to address SHDs.
Genome–scale approach to study the genetic relatedness among Brucella melitensis strains

Brucellosis is an important zoonotic disease that affects both humans and animals. To date, laboratory surveillance is still essentially based on the traditional MLVA-16 methodology and the associated epidemiological information is frequently scarce. Our goal was to contribute to the improvement of Brucella spp. surveillance through the implementation of a whole genome sequencing (WGS) approach. We created a curated ready-to-use species-specific wgMLST scheme enrolling a panel of 2656 targets (http://doi.org/10.5281/zenodo.3575026) and used this schema to perform a retrospective analysis of the genetic relatedness among B. melitensis strains causing human infection in Portugal (a country where brucellosis is an endemic disease) from 2010 to 2018. The strains showed a phylogenetic clustering within genotype II (25 out of 36) and IV (4 out of 36), and shared clades with strains isolated from countries with which Portugal has intense food trading, tourism and similar eating habits, such as Spain, Italy and Greece. In addition, our results point to the identification of strong associations between B. melitensis strains, likely underlying missed “outbreaks” as 22 out of the 36 strains showed genetic linkage with others. In fact, the applied gene-by-gene approach grouped these strains into six genetic clusters each one containing putative epidemiological links. Nevertheless, more studies will be needed in order to define the appropriate range of cut-offs (probable non-static cut-offs) that best illustrate the association between genetic linkage and epidemiological information and may serve as alerts for the health authorities. The release of this freely available and scalable schema contributes to the required technological transition for laboratorial surveillance of brucellosis and will facilitate the assessment of ongoing and future outbreaks in order to prevent the transmission spread.
Physalis peruviana L. Pulp Prevents Liver Inflammation and Insulin Resistance in Skeletal Muscles of Diet-Induced Obese Mice

A chronic high-fat diet (HFD) produces obesity, leading to pathological consequences in the liver and skeletal muscle. The fat in the liver leads to accumulation of a large number of intrahepatic lipid droplets (LD), which are susceptible to oxidation. Obesity also affects skeletal muscle, increasing LD and producing insulin signaling impairment. Physalis peruviana L. (PP) (Solanaceae) is rich in peruvioses and has high antioxidant activity. We assessed the ability of PP to enhance insulin-dependent glucose uptake in skeletal muscle and the capacity to prevent both inflammation and lipoperoxidation in the liver of diet-induced obese mice. Male C57BL/6J mice were divided into groups and fed for eight weeks: control diet (C; 10% fat, 20% protein, 70% carbohydrates); C + PP (300 mg/kg/day); HFD (60% fat, 20% protein, 20% carbohydrates); and HFD + PP. Results suggest that PP reduces the intracellular lipoperoxidation level and the size of LD in both isolated hepatocytes and skeletal muscle fibers. PP also promotes insulin-dependent skeletal muscle glucose uptake. In conclusion, daily consumption of 300 mg/kg of fresh pulp of PP could be a novel strategy to prevent the hepatic lipoperoxidation and insulin resistance induced by obesity.
Evaluation of the sensitivity of the Express View function in the Mirocam® capsule endoscopy software

Abstract Background: A new computer algorithm called Express-View has recently been introduced by Mirocam, but data concerning its application and efficacy are scarce. Objective: To evaluate the lesion detection rate, per-patient sensitivity and the diagnostic accuracy using Express-View. Methods: All patients who performed CE between January 2018 and June 2019, whose indication was obscure gastrointestinal bleeding (OGIB) and with findings on CE, were included. Lesions identified in conventional reading were selected and considered as reference. Results: Eighty-nine patients were included, 50.6% male, with a mean age of 68.4 years-old (±12.3). The Express-View mode detected 85.5% of lesions previously detected by conventional reading (524 out of 613). There were 89 missed lesions, mainly erosions or ulcers (44.9%) and angioectasias (38.2%). The lesion detection rate was found to be lower in the jejunum and ileum compared to extra-small bowel locations and duodenum (p = .04). Although Express-View had a per-patient sensitivity for all lesions of 56.2% and a per-patient sensitivity for all clinically significant lesions of 83.1%, it achieved a diagnostic accuracy of 91%. Conclusions: The per-patient sensitivity for all lesions was shown to be below expectations, although the lesion detection rate, the per-patient sensitivity for all clinically significant lesions, and the diagnostic accuracy were shown to be higher.
A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population

This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in paediatrics and to identify the sources of variability in its disposition. PubMed, ISI Web of Science, SCOPUS and Science Direct databases were searched from inception to January 2019. All paediatric population pharmacokinetic studies of digoxin that utilized the nonlinear mixed‐effect modelling approach were incorporated in this review, and data were synthesized descriptively. After application of the inclusion–exclusion criteria 8 studies were included. Most studies described digoxin pharmacokinetics as a 1‐compartment model with only 1 study describing its pharmacokinetics as 2‐compartments. Age was an important predictor of clearance in studies involving neonates or infants, other predictors of clearance were weight, height, serum creatinine, coadministration of spironolactone and presence of congestive heart failure. Congestive heart failure was also associated with an increased volume of distribution in 1 study. The estimated value of apparent clearance in a typical individual standardized by mean weight ranged between 0.24 and 0.56 L/h/kg, the interindividual variability in clearance ranged between 7.0 and 35.1%. Half of the studies evaluated the performance of their developed models via external evaluation. In conclusion, substantial predictors of digoxin pharmacokinetics in the paediatric population in addition to model characteristics and evaluation techniques are presented. For clinicians, clearance could be predicted using age especially in neonates or infants, weight, height, serum creatinine, coadministration of medications and disease status. For future researchers, designing pharmacokinetic studies that allow 2‐compartment modelling and linking pharmacokinetics with pharmacodynamics is recommended.
Evaluation of growth hormone co-treatment in in vitro fertilization in patients responding better to the GnRH antagonist short protocol

Objective The present study aims at evaluating the results obtained after in vitro fertilization in bad responders, using controlled ovarian hyperstimulation together with the use of gonadotrophin releasing hormone (GnRH) antagonist (cetrorelix acetate) in a short protocol. Methods This is an analytical, longitudinal, retrospective and controlled study involving patients who underwent in vitro fertilization (IVF) procedures in the assisted reproduction program of the Reproferty clinic, in the municipality of São José dos Campos/SP, from January 2012 to December 2016. We collected the data obtained from the medical records of patients considered to have undergone controlled ovarian hyperstimulation using GnRH antagonist (cetrorelix acetate) and Growth Hormone (GH) in a short cycle protocol. The patients considered controls were those submitted to the same hyperstimulation process, without using GH. Results There were significant differences in the following analyzed parameters: gonadotrophin regimen dose, stimulation duration, and estradiol levels on the day of HCG administration, number of follicles, number of retrieved oocytes, number of mature oocytes and number of good-quality embryos. On the other hand, the GH administration was not significant in the number of cycles that achieved transfer, the number of embryos transferred and the number of frozen cycles. In the case group, there was no increase in the number of cycles that reached pregnancy rate βhCG+; however, the clinical pregnancy rates and live birth rates were significant. Conclusion The present investigation demonstrated that GH administration as a supplement in poor responders improves the majority of the parameters to achieve a full term pregnancy in these patients.
What’s Hot in HIV in 2019—A Basic and Translational Science Summary for Clinicians From IDWeek 2019

Abstract The field of HIV research is constantly evolving, and every year brings advances that draw us closer to ending the HIV epidemic. Here, we present a nonexhaustive overview of select notable studies in HIV prevention, cure, and treatment, published in the last year as presented at IDWeek 2019: What’s Hot in HIV Basic Science. The past year brought interesting results on the use of broadly neutralizing antibodies for treatment and prevention, gene-editing approaches to HIV cure, and new ways to measure the HIV reservoir. We also saw encouraging results on novel HIV vaccine delivery strategies and how these may influence effective immune responses. Lastly, in the area of inflammation, some mechanistic insights were made into the contribution of cotrimoxazole prophylaxis and potential new targets to reduce HIV-associated chronic inflammation. The future from where we stand is bright for HIV research, with much more to look forward to in 2020.
The role of partner support, ego-resiliency, prenatal attitudes towards maternity and pregnancy in psychological well-being of women in high-risk and low-risk pregnancy

ABSTRACT We have shown by multiple regression analyses that partner support (as an external source of support) and ego-resiliency (as a personality trait and internal source of support) are significant factors contributing to pregnant women’s satisfaction with many different domains of psychological well-being (PWB), such as positive relations with others, self-acceptance, and environmental mastery, facilitating better psychological adaptation to pregnancy and motherhood. Type of pregnancy (high-risk or low-risk) is important for two areas of PWB of pregnant women, namely positive relations with others and self-acceptance. The attitudes towards maternity and pregnancy are weaker predictor than ego-resiliency and partner support and they are significant only for one PWB dimension – autonomy. Positive or negative attitudes towards motherhood and the unborn child depend on the education level. They are less stable factors than ego-resiliency. Empirical evidence is found for the moderating role of the pregnancy type (low- vs. high-risk) in the relationships between support from partner and two dimensions of PWB: positive relations with others and purpose in life. The received partner support helps women in high-risk pregnancy with positive psychological functioning, especially in maintaining the belief that their life is purposeful and in sustaining quality relationships with others.
Current Endoscopic Management of Malignant Biliary Stricture

Biliary and pancreatic cancers occur silently in the initial stage and become unresectable within a short time. When these diseases become symptomatic, biliary obstruction, either with or without infection, occurs frequently due to the anatomy associated with these cancers. The endoscopic management of these patients has changed, both with time and with improvements in medical devices. In this review, we present updated and integrated concepts for the endoscopic management of malignant biliary stricture. Endoscopic biliary drainage had been indicated in malignant biliary obstruction, but the concept of endoscopic management has changed with time. Although routine endoscopic stenting should not be performed in resectable malignant distal biliary obstruction (MDBO) patients, endoscopic biliary drainage is the treatment of choice for palliation in unresectable MDBO patients. Self-expanding metal stents (SEMS) have better stent patency and lower costs compared with plastic stents (PS). For malignant hilum obstruction, PS and uncovered SEMS yield similar short-term outcomes, while a covered stent is not usually used due to a potential unintentional obstruction of contralateral ducts.
The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Background: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. Objective: To estimate the length of the incubation period of COVID-19 and describe its public health implications. Design: Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. Setting: News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. Participants: Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. Measurements: Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. Results: There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. Limitation: Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. Conclusion: This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. Primary Funding Source: U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.
Evaluating the diagnostic accuracy of maximal aortic diameter, length and volume for prediction of aortic dissection

Objective Management of thoracic aortic aneurysms (TAAs) comprises regular diameter follow-up until the indication criterion for prophylactic surgery is reached. However, this approach is unable to predict the majority of acute type A aortic dissections (ATAADs). The current study aims to evaluate the diagnostic accuracy of ascending aortic diameter, length and volume for occurrence of ATAAD. Methods This two-centre observational cohort study retrospectively screened 477 consecutive patients who presented with ATAAD between 2009 and 2018. Of those, 25 (5.2%) underwent CT angiography (CTA) within 2 years before dissection onset. Aortic diameter, length and volume of these patients (‘pre-ATAAD’) were compared with those of TAA controls (n=75). Receiver operating curve analysis was performed to evaluate the predictive accuracy of the three different measurements. Results 96% of patients with pre-ATAAD did not meet the surgical diameter threshold of 55 mm before dissection onset. Maximal aortic diameters (45 (40–49) mm vs 46 (44–49) mm, p=0.075) and volume (126 (95–157) cm3 vs 124 (102–136) cm3, p=0.909) were comparable between patients with pre-ATAAD and TAA controls. Conversely, ascending aortic length (84±9 mm vs 90±16 mm, p=0.031) was significantly larger in patients with pre-ATAAD. All three parameters had an area under the curve of >0.800. At the 55 mm cut-off point, the maximal diameter yielded a positive predictive value (PPV) of 20%. While maintaining same specificity levels, measurements of aortic volume and length showed superior diagnostic accuracy (PPV 55% and 70%, respectively). Conclusion Measurements of aortic volume and length have superior diagnostic accuracy compared with the maximal diameter and could improve the timely identification of patients at risk for ATAAD.
Intein mediated high throughput screening for bispecific antibodies

ABSTRACT Bispecific antibodies comprise extremely diverse architectures enabling complex modes of action, such as effector cell recruitment or conditional target modulation via dual targeting, not conveyed by monospecific antibodies. In recent years, research on bispecific therapeutics has substantially grown. However, evaluation of binding moiety combinations often leads to undesired prolonged development times. While high throughput screening for small molecules and classical antibodies has evolved into a mature discipline in the pharmaceutical industry, dual-targeting antibody screening methodologies lack the ability to fully evaluate the tremendous number of possible combinations and cover only a limited portion of the combinatorial screening space. Here, we propose a novel combinatorial screening approach for bispecific IgG-like antibodies to extenuate screening limitations in industrial scale, expanding the limiting screening space. Harnessing the ability of a protein trans-splicing reaction by the split intein Npu DnaE, antibody fragments were reconstituted within the hinge region in vitro. This method allows for fully automated, rapid one-pot antibody reconstitution, providing biological activity in several biochemical and functional assays. The technology presented here is suitable for automated functional and combinatorial high throughput screening of bispecific antibodies.
Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines—Recommendations on the use of biologicals in severe asthma

Dupilumab, a fully human monoclonal antibody against interleukin‐4 receptor α, is approved as add‐on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma‐related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24‐52 weeks of follow‐up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45‐0.59) and the percentage use of oral corticosteroid use (mean difference (MD) −28.2 mg/d; 95% CI −40.7 to −15.7). Asthma control (ACQ‐5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ‐5 MD −0.28 (95% CI −0.39 to −0.17); AQLQ MD +0.28 (95% CI 0.20‐0.37); and rescue medication MD −0.35 (95% CI −0.73 to +0.02). FEV1 increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab‐related adverse events (AEs) (moderate certainty) and of drug‐related serious AEs (low certainty). The incremental cost‐effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long‐term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.
Developing equity-focused interventions for maternal and child health in Nigeria: an evidence synthesis for policy, based on equitable impact sensitive tool (EQUIST)

Introduction Among the most critical health systems components that requires strengthening to improve maternal, newborn and child health (MNCH) outcomes in Nigeria is the concept of equity. UNICEF has designed the equitable impact sensitive tool (EQUIST) to enable policymakers improve equity in MNCH and reduce disparities between the most marginalized mothers and young children and the better-off. Methods Using the latest available DHS data sets, we conducted EQUIST situation and scenario analysis of MNCH outcomes in Nigeria by sub-national categorization, wealth and by residence. We then identified the intervention package, the bottlenecks and strategies to address them and the number of deaths avertible. Results EQUIST profile analysis showed that the number of under-five deaths was considerably higher among the poorest and rural population in Nigeria, and was highest in North-West region. Neonatal causes, malaria, pneumonia and diarrhoea were responsible for most of the under-five deaths. Highest maternal mortality was recorded in the North-West Nigeria. Ante-partum, intrapartum and postpartum haemorrhages and hypertensive disorder, were responsible for highest maternal deaths. EQUIST scenario analysis showed that an intervention package of insecticide treated net can avert more than 20,000 under-five deaths and delivery by skilled professionals can avert nearly 17,000 under-five deaths. While as many as 3,370 maternal deaths can be averted by deployment of skilled professionals. Conclusion Scaling up integrated packages of essential interventions across the continuum of care, addressing the human resource shortages in rural area and economic/social empowerment of women are policy recommendations that can improve MNCH outcomes in Nigeria.