Miracle-dz/UniFAR-FTUs huggingface dataset:
T-Cell Expression of Angiotensin-Converting Enzyme 2 and Binding of Severe Acute Respiratory Coronavirus 2

Abstract The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not completely understood. SARS-CoV-2 infection frequently causes significant immune function consequences including reduced T cell numbers and enhanced T cell exhaustion that contribute to disease severity. The extent to which T cell effects are directly mediated through infection or indirectly result from infection of respiratory-associated cells is unclear. We show that primary human T cells express sufficient levels of angiotensin converting enzyme 2 (ACE-2), the SARS-CoV-2 receptor, to mediate viral binding and entry into T cells. We further show that T cells exposed to SARS-CoV-2 particles demonstrate reduced proliferation and apoptosis compared to uninfected controls, indicating that direct interaction of SARS-CoV-2 with T cells may alter T cell growth, activation, and survival. Regulation of T cell activation and/or turnover by SARS-CoV-2 may contribute to impaired T cell function observed in patients with severe disease.
Nursing students admitted through the affirmative action system display similar performance in professional and academic trajectories to those from the regular path in a public school in Brazil

Objectives Affirmative action providing higher education access for socially vulnerable students has been implemented in several countries. However, these policies remain controversial. This study compares the performance of students admitted through the regular path and social quota systems, during and after completion of nursing education, in a public nursing school in Brazil. Methods This retrospective cohort study included all students admitted to nursing school at the School of Health Sciences (ESCS), Brazil, between 2009 and 2014, who were followed until May 2020. The first phase involved document analysis from the ESCS academic management system and Brazilian government agencies. In the second phase, a survey was conducted among the alumni. The social quota system criterion was public school attendance across all primary and secondary education levels. Results Of the 448 students included in the study, 178 (39.7%) were from the affirmative action and 270 (60.3%) from the regular path systems. Affirmative action students were older at the time of nursing school admission (p < 0.001) and took longer to be admitted to the nursing school (p < 0.001) after completing high school. There were no significant differences in the dropout rates and years to complete nursing school. In the second phase, 108 alumni answered the survey. No significant differences were found in their participation in the undergraduate scientific research program and university extension projects, attending residency programs, getting a master’s degree and doctoral degree, monthly income, teaching activity, joining public service through a government job competition process, participation in management activities in the private and public health sector, and degree of job satisfaction. Conclusion Our results revealed that affirmative action is a policy that contributes to the reduction of inequalities and guarantees the training of nursing professionals with a similar professional qualification received through affirmative action and regular path systems.
THE EFFECT OF CROSSING ROMANIAN SHEEP BREEDS WITH RAMS OF MEAT BREEDS OVER THE SPECIFIC INDICATORS OF MEAT PRODUCTION

The purpose of the research was to investigate new solutions for the production of increased sheep meat quantities. The opportunity to carry out these surveys is because Romania has a very good position among the countries with large herds of sheep and that at European Union level requirements for sheep meat are not assured. In order to achieve the objectives set out above we included in the scheme for the production of the biological material for recovery for the main breeds in Romania, namely the Merinos de Palas and Tigaie, at which we add the Bluefaced Leicester and Suffolk. Biological material intended for fattening was a hybrid produced from crossing trirasial females mixed-race F1 (Bluefaced Leiceste x races) with Suffolk rams. Weaning lambs was made at the age of 85 days, and to remove the influence of the age was taken into account that differences in this parameter to be less than 25 days. The technology was applied to fattening of intensive type, and had a total duration of 90 days. Intensity analysis of fattening each batch was weighed at the beginning of each phase, weaning, fattening and started at the end of fattening, and to compare the results, control groups were made. In the case of consignments composed by using the breed of Merinos de Palas, the weight of the control group was lower by 5.2% as compared to the performance by the group composed of hybrid terminals, from which the final live weight was 40 kg. For the following experimental formats by using the Tigaie, the control batch though has the onset of fattening a bodyweight with 8.64 percent compared with the batch composed of trirasial hybrids, final live weight was more than 20% higher in the experimental batch. The results obtained at the fattening, and the quality of the carcasses being much better at experimental batches justifies the practicing of this type of crossing.
The impact of user characteristics of smallholder farmers on user experiences with collaborative map applications

In the future, farmers will have increasing opportunities to use collaborative smartphone applications for agricultural management. Geospatial information in combination with agricultural-relevant information is a great source of knowledge for farmers. Including maps in collaborative mobile agriculture applications benefits communication processes related to agricultural-relevant questions. Ensuring a positive user experience with map interfaces depends on their design. To develop design guidelines for map-oriented mobile agricultural applications, this study evaluates 24 different map design variations (varying in their elements and degrees of complexity) and characterizes their user experience with 72 coffee farmers as study participants. Our findings show that the most crucial factors for a positive user experience were restricted interactivity, simple tasks to conduct (selecting single point features), and a simplified base map style, highlighting relevant landmarks. Since our farmers consisted primarily of less-experienced smartphone and map users, our findings may also be helpful for users in general, sharing similar user characteristics. While empirical, in-situ studies pose many challenges, they provide relevant insights into the real use situation and user behavior of mobile map applications. Our findings help establish some basic principles for designing map adaptations, serving as a guideline for creating effective mapping applications, which adapt to the farmers’ contextual factors. Based on our study results, we suggest future research for continuing conceptualizing principles of map design adaptation and support this effort through empirical, in-situ studies for relating contextual user factors to the adaptation behavior of map applications.
In silico predictions of the human pharmacokinetics/toxicokinetics of 65 chemicals from various classes using conformal prediction methodology

Abstract Pharmacokinetic/toxicokinetic (PK/TK) information for chemicals in humans is generally lacking. Here we applied machine learning, conformal prediction and a new physiologically-based PK/TK model for prediction of the human PK/TK of 65 chemicals from different classes, including carcinogens, food constituents and preservatives, vitamins, sweeteners, dyes and colours, pesticides, alternative medicines, flame retardants, psychoactive drugs, dioxins, poisons, UV-absorbents, surfactants, solvents and cosmetics. About 80% of the main human PK/TK (fraction absorbed, oral bioavailability, half-life, unbound fraction in plasma, clearance, volume of distribution, fraction excreted) for the selected chemicals was missing in the literature. This information was now added (from in silico predictions). Median and mean prediction errors for these parameters were 1.3- to 2.7-fold and 1.4- to 4.8-fold, respectively. In total, 59 and 86% of predictions had errors <2- and <5-fold, respectively. Predicted and observed PK/TK for the chemicals was generally within the range for pharmaceutical drugs. The results validated the new integrated system for prediction of the human PK/TK for different chemicals and added important missing information. No general difference in PK/TK-characteristics was found between the selected chemicals and pharmaceutical drugs.
Multicentric analysis of the perceptions and knowledge of digital health amongst undergraduate medical students

Introduction Digital health (DH) is continuously evolving by use of information and communications technology to improve healthcare provision, thereby reshaping systems and clinical practices. Recent studies identified an overwhelming lack of awareness of DH within the profession. This study aimed to analyse student perceptions and knowledge of DH to assess confidence in its use to develop greater DH awareness and literacy. Methods Students enrolled in undergraduate medical degrees were invited to take part in an online survey assessing aspects of DH including demography, familiarity, attitudes, level of knowledge and confidence. Anonymised data was collated and subsequently analysed to review DH awareness. Results A total of 143 students participated from nine British universities with 28.7% of respondents admitting low levels of familiarity of DH concepts. Students anticipated negative repercussions of DH including reduced data security (42.7%) and deterioration in doctor-patient relationship (30%); while improvements in healthcare access and health-outcomes are expected by 89.5% and 68.5%, respectively. 71.4% of participants believed they had minimal experience of exposure to DH and 76% believed they did not possess the necessary skills to utilise DH. Only 3.5% of students had some exposure to DH teaching during their course. Conclusion There is an important requirement to address the lack of knowledge and exposure of students to DH, particularly as the world targets the COVID-19 pandemic. DH is forming the basis of the ‘new normal’ in healthcare, however the full potential of DH cannot be achieved unless there is an increase in its teaching incorporated into medical school curricula.
Deep learning guided optimization of human antibody against SARS-CoV-2 variants with broad neutralization

Significance SARS-CoV-2 continues to evolve through emerging variants, more frequently observed with higher transmissibility. Despite the wide application of vaccines and antibodies, the selection pressure on the Spike protein may lead to further evolution of variants that include mutations that can evade immune response. To catch up with the virus’s evolution, we introduced a deep learning approach to redesign the complementarity-determining regions (CDRs) to target multiple virus variants and obtained an antibody that broadly neutralizes SARS-CoV-2 variants.
Healthcare Utilization Survey in the Hybrid Model of the Surveillance for Enteric Fever in India (SEFI) Study: Processes, Monitoring, Results, and Challenges

Abstract Background Lack of reliable data in India drove the “Surveillance of Enteric Fever in India” (SEFI) concept. Hybrid surveillance, combining facility-based surveillance for the crude incidence, and a community-based healthcare utilization survey (HCUS) to calculate the factor needed to arrive at the adjusted incidence, was used in 6 sites. The HCUS aimed to determine the percentage of utilization of study facilities by the catchment population for hospitalizations due to febrile illness. Methods Population proportional to size sampling and systematic random sampling, in 2 stages, were used to survey 5000 households per site. Healthcare utilization was assessed. Results Febrile illness accounted for 20% of admissions among 137 990 individuals from 30 308 households. Only 9.6%–38.3% of those admitted with febrile illness sought care in the study hospitals. The rate of rural utilization of the private sector for hospitalization was 67.6%. The rate of hospitalization for febrile illness, per 1000 population, ranged from 2.6 in Manali to 9.6 in Anantapur; for 25.8% of the deaths associated with febrile illness, no facility was used before death. Conclusions One in 5 hospitalizations were associated with fever. Rural utilization of the private sector for hospitalization due to febrile illness was more than that of the public sector. Healthcare utilization patterns for hospital admissions due to febrile illness varied across sites. A meticulously performed HCUS is pivotal for accurate incidence estimation in a hybrid surveillance. Clinical Trials Registration ISRCTN72938224.
Full transparency of ticagrelor trials in coronary artery disease should be warranted

Cardiology department, Service de cardiologie, Centre Hospitalier Universitaire Henri Mondor, Créteil, France; Medizinische Fakultät, Department Public Health (DPH), Universität Basel, Basel, Switzerland; University Heart and Vascular Institute, New Orleans, LA, USA; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark
Sampling alternative conformational states of transporters and receptors with AlphaFold2

Equilibrium fluctuations and triggered conformational changes often underlie the functional cycles of membrane proteins. For example, transporters mediate the passage of molecules across cell membranes by alternating between inward- and outward-facing states, while receptors undergo intracellular structural rearrangements that initiate signaling cascades. Although the conformational plasticity of these proteins has historically posed a challenge for traditional de novo protein structure prediction pipelines, the recent success of AlphaFold2 (AF2) in CASP14 culminated in the modeling of a transporter in multiple conformations to high accuracy. Given that AF2 was designed to predict static structures of proteins, it remains unclear if this result represents an underexplored capability to accurately predict multiple conformations and/or structural heterogeneity. Here, we present an approach to drive AF2 to sample alternative conformations of topologically diverse transporters and G-protein-coupled receptors that are absent from the AF2 training set. Whereas models of most proteins generated using the default AF2 pipeline are conformationally homogeneous and nearly identical to one another, reducing the depth of the input multiple sequence alignments by stochastic subsampling led to the generation of accurate models in multiple conformations. In our benchmark, these conformations spanned the range between two experimental structures of interest, with models at the extremes of these conformational distributions observed to be among the most accurate (average template modeling score of 0.94). These results suggest a straightforward approach to identifying native-like alternative states, while also highlighting the need for the next generation of deep learning algorithms to be designed to predict ensembles of biophysically relevant states.
Further Characterization of SMC1A Loss of Function Epilepsy Distinct From Cornelia de Lange Syndrome

Cornelia de Lange syndrome is a rare developmental malformation syndrome characterized by small stature, limb anomalies, distinctive facial features, developmental delays, and behavioral issues. The diagnosis of Cornelia de Lange syndrome is made clinically or on the basis of an identified variant in one of the genes associated with Cornelia de Lange syndrome. SMC1A variants are the cause of 5% of the cases of Cornelia de Lange syndrome. SMC1A is located on the X-chromosome and is thought to escape X-inactivation in some females. Patients with SMC1A variants are being increasingly identified through panel testing or exome sequencing without prior clinical suspicion of Cornelia de Lange syndrome. In general, intractable epilepsy is not considered a prominent feature of Cornelia de Lange syndrome, yet this is found in these patients with SMC1A variants. Here we report on a series of patients with SMC1A variants and intractable epilepsy. In contrast to patients with typical SMC1A-associated Cornelia de Lange syndrome, all of the identified patients were female, and when available, X-inactivation studies were highly skewed with truncating variants. We describe the medical involvement and physical appearance of the participants, compared to the diagnostic criteria used for classical Cornelia de Lange syndrome. We also report on the clinical characteristics of the epilepsy, including age of onset, types of seizures, electroencephalographic (EEG) findings, and response to various antiepileptic medications. These findings allow us to draw conclusions about how this population of patients with SMC1A variants fit into the spectrum of Cornelia de Lange syndrome and the broader spectrum of cohesinopathies and allow generalizations that may impact clinical care and, in particular, epilepsy management.
Using arterial spin labeling to measure cerebrovascular reactivity in Moyamoya disease: Insights from simultaneous PET/MRI

Cerebrovascular reactivity (CVR) reflects the CBF change to meet different physiological demands. The reference CVR technique is PET imaging with vasodilators but is inaccessible to most patients. DSC can measure transit time to evaluate patients suspected of stroke, but the use of gadolinium may cause side-effects. Arterial spin labeling (ASL) is a non-invasive MRI technique for CBF measurements. Here, we investigate the effectiveness of ASL with single and multiple post labeling delays (PLD) to replace PET and DSC for CVR and transit time mapping in 26 Moyamoya patients. Images were collected using simultaneous PET/MRI with acetazolamide. CVR, CBF, arterial transit time (ATT), and time-to-maximum (Tmax) were measured in different flow territories. Results showed that CVR was lower in occluded regions than normal regions (by 68 ± 12%, 52 ± 5%, and 56 ± 9%, for PET, single- and multi-PLD PCASL, respectively, all p < 0.05). Multi-PLD PCASL correlated slightly higher with PET (CCC = 0.36 and 0.32 in affected and unaffected territories respectively). Vasodilation caused ATT to reduce by 4.5 ± 3.1% (p < 0.01) in occluded regions. ATT correlated significantly with Tmax (R2 > 0.35, p < 0.01). Therefore, multi-PLD ASL is recommended for CVR studies due to its high agreement with the reference PET technique and the capability of measuring transit time.
Incidence of Enteric Fever in a Pediatric Cohort in North India: Comparison with Estimates from 20 Years Earlier

Abstract Background An earlier cohort in 1995–1996 showed a very high burden of typhoid in Delhi. Our aim was to estimate the current overall and age-specific incidence of culture-confirmed enteric fever among children aged 6 months to 15 years in Delhi. Methods We enrolled a cohort of 6000 children aged 6 months to <14 years in South Delhi and followed them up weekly for 24 months or until 15 completed years of child age, whichever was earlier. Blood culture to confirm enteric fever was done in children with ≥3 consecutive days of fever. Results We recorded a total of 14 650 episodes of fever in the 11 510 person-years (PY) of follow-up. A total of 81 fever episodes were positive for enteric fever. The incidence (95% confidence interval) of all enteric fever was 703.7 (560.5–874.7) per 100 000 PY. The incidences of typhoid and paratyphoid fevers were 608.1 (95% confidence interval, 481.1–768.7) and 111.7 (59.5–191.1) per 100 000 PY, respectively, highest among children aged 10–15 years. Conclusions Despite a 35% reduction in incidence compared with the 1995–1996 cohort, our study suggested a substantial burden of enteric fever in the population. Continued efforts to improve water, sanitation, and hygiene parameters along with implementation of novel vaccination strategies and disease surveillance can help achieve the goal of disease elimination.
Routine lung volume recruitment in boys with Duchenne muscular dystrophy: a randomised clinical trial

Background Impaired cough results in airway secretion retention, atelectasis and pneumonia in individuals with Duchenne muscular dystrophy (DMD). Lung volume recruitment (LVR) stacks breaths to inflate the lungs to greater volumes than spontaneous effort. LVR is recommended in DMD clinical care guidelines but is not well studied. We aimed to determine whether twice-daily LVR, compared with standard of care alone, attenuates the decline in FVC at 2 years in boys with DMD. Methods In this multicentre, assessor-blinded, randomised controlled trial, boys with DMD, aged 6–16 years with FVC >30% predicted, were randomised to receive conventional treatment or conventional treatment plus manual LVR twice daily for 2 years. The primary outcome was FVC % predicted at 2 years, adjusted for baseline FVC % predicted, age and ambulatory status. Secondary outcomes included change in chest wall distensibility (maximal insufflation capacity minus FVC) and peak cough flow. Results Sixty-six boys (36 in LVR group, 30 in control) were evaluated (median age (IQR): 11.5 years (9.5–13.5), median baseline FVC (IQR): 85% predicted (73–96)). Adjusted mean difference in FVC between groups at 2 years was 1.9% predicted (95% CI −6.9% to 10.7%; p=0.68) in the direction of treatment benefit. We found no differences in secondary outcomes. Conclusion There was no difference in decline in FVC % predicted with use of twice-daily LVR for boys with DMD and relatively normal lung function. The burden associated with routine LVR may outweigh the benefit. Benefits of LVR to maintain lung health in boys with worse baseline lung function still need to be clarified. Trial registration number NCT01999075.
A Residual Movement Classification Based User Interface for Control of Assistive Devices by Persons With Complete Tetraplegia

Objective: Complete tetraplegia can deprive a person of hand function. Assistive technologies may improve autonomy but needs for ergonomic interfaces for the user to pilot these devices still persist. Despite the paralysis of their arms, people with tetraplegia may retain residual shoulder movements. In this work we explored these movements as a mean to control assistive devices. Methods: We captured shoulder movement with a single inertial sensor and, by training a support vector machine based classifier, we decode such information into user intent. Results: The setup and training process take only a few minutes and so the classifiers can be user specific. We tested the algorithm with 10 able body and 2 spinal cord injury participants. The average classification accuracy was 80% and 84%, respectively. Conclusion: The proposed algorithm is easy to set up, its operation is fully automated, and achieved results are on par with state-of-the-art systems. Significance: Assistive devices for persons without hand function present limitations in their user interfaces. Our work presents a novel method to overcome some of these limitations by classifying user movement and decoding it into user intent, all with simple setup and training and no need for manual tuning. We demonstrate its feasibility with experiments with end users, including persons with complete tetraplegia without hand function.