Miracle-dz/UniFAR-FTUs huggingface dataset:
Trends in prevalence of guideline‐based use of lipid‐lowering therapy in a large health system

The 2013 ACC/AHA (American College of Cardiology/American Heart Association) cholesterol guidelines provided an evidence‐based rationale for the allocation of lipid‐lowering therapy based on risk for atherosclerotic cardiovascular disease (ASCVD). Adoption of these guidelines was initially suboptimal but whether this has improved over time remains unclear.
Surgery in the 2020s: Implications of advancing technology for patients and the workforce

ABSTRACT As the surgical workforce, surgical techniques and patient expectations change, the Royal College of Surgeons of England is actively engaged in taking forward the recommendations of its Future of Surgery Commission. Here the commission's chair articulates the implications for smaller hospitals and the need for achieving interoperability and safe sharing of patient data across different systems, so enabling immediate access to patients' records across healthcare organisations; extension of regulation to surgical care practitioners, reflecting the recent decision to regulate physician associates and physician assistants; introducing a UK-wide registry of surgical devices, with tracking for implantable devices; implementing a robotics strategy to help the NHS plan and purchase new surgical robotics, as well as monitor their use and the effect on outcomes; and investing in genomic medicine and artificial intelligence for diagnostics, and in stem-cell research for treatment.
The immunologic Warburg effect: Evidence and therapeutic opportunities in autoimmunity

Pro‐inflammatory signals induce metabolic reprogramming in innate and adaptive immune cells of both myeloid and lymphoid lineage, characterized by a shift to aerobic glycolysis akin to the Warburg effect first described in cancer. Blocking the switch to aerobic glycolysis impairs the survival, differentiation, and effector functions of pro‐inflammatory cell types while favoring anti‐inflammatory and regulatory phenotypes. Glycolytic reprogramming may therefore represent a selective vulnerability of inflammatory immune cells, providing an opportunity to modulate immune responses in autoimmune disease without broad toxicity in other tissues of the body. The mechanisms by which aerobic glycolysis and the balance between glycolysis and oxidative phosphorylation regulate immune responses have only begun to be understood, with many additional insights expected in the years to come. Immunometabolic therapies targeting aerobic glycolysis include both pharmacologic inhibitors of key enzymes and glucose‐restricted diets, such as the ketogenic diet. Animal studies support a role for these pharmacologic and dietary therapies for the treatment of autoimmune diseases, and in a few cases proof of concept has been demonstrated in human disease. Nonetheless, much more work is needed to establish the clinical safety and efficacy of these treatments.
Use of Statins in Patients With and Without Liver Disease

First isolated from Penicillium citrum by Akira Endo and colleagues, statins were a breakthrough drug class of serum low-density lipoprotein (LDL)-lowering agents, subsequently demonstrating efficacy in prevention of cardiovascular disease and mortality. As other LDL-lowering therapies showed more modest benefits in patientcentered outcomes, data have emerged showing a range of pleiotropic effects that drive these benefits.
Autism-related traits and suicide risk among active duty U.S. military service members.

Suicide rates within the U.S. military are elevated. The interpersonal theory of suicide, supported within military samples, suggests that social disconnectedness confers risk for suicide. Autism spectrum disorder (ASD) is characterized by symptoms-difficulties in social communication/interaction (SCI) and restricted and repetitive behaviors (RRBs)-that contribute to social disconnectedness. To our knowledge, no study has examined ASD-related traits and suicide risk among active duty U.S. military service members. Participants included 292 active duty U.S. military service members (M [SD] age = 28.67 [7.40] years, 68.5% male, 78.1% White). The Autism Spectrum Quotient, Repetitive Behaviours Questionnaire-2 for Adults, Self-Injurious Thoughts and Behaviors Interview-Short Form, and Interpersonal Needs Questionnaire assessed for SCI difficulties, RRBs, suicidal symptoms, and interpersonal theory of suicide constructs (i.e., perceived burdensomeness, thwarted belongingness), respectively. Elevated levels of SCI difficulties and RRBs were associated with increased odds of reporting suicidal thoughts and behaviors occurring since joining the military, controlling for the number of years of service and suicidal symptoms occurring prior to joining the military. Perceived burdensomeness and thwarted belongingness statistically accounted for the relationship between ASD-related traits and suicidal ideation occurring since joining the military; a rival mediator, emotion dysregulation, was not a significant mediator. Among active duty U.S. military service members, greater ASD-related traits were associated with an increased likelihood of reporting suicidal thoughts and behaviors occurring since joining the military. Clinical efforts targeting perceived burdensomeness and thwarted belongingness might reduce suicide risk among military service members with elevated ASD-related traits. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
The distribution of hepatitis B virus surface antigen polymorphisms at positions associated with vaccine escape

Hepatitis B virus (HBV) infects over 250 million people worldwide. Vaccination is effective at preventing infection, although several mutations within the “a” determinant region of the HBV surface antigen (HBsAg) are associated with vaccine escape. We evaluated the frequency, genotype, and global distribution of polymorphisms at sites associated with vaccine escape in 4244 unique full‐length HBV genomes. The “a” determinant within the Surface gene was inspected for polymorphisms at sites identified previously associated with vaccine escape. Nearly, 268 (6.3%) sequences from 36 countries contained a polymorphism at a site associated with vaccine escape including 22 genotype A, 99 genotype B, 93 genotype C, 32 genotype D, 14 genotype E, 3 genotype F, 2 genotype G, and 3 genotype I. In genotype A, the most common polymorphism occurred at M133. In genotype B, Q129 and M133 occurred 45 and 51 times, respectively, accounting for 94% of polymorphisms. Polymorphisms at G145 were most frequent in genotype C, while P120 was most common in genotype D. Among all genotypes, polymorphisms at M133 were the most common and accounted for 30.9% of polymorphisms. Polymorphisms at T116, P120, F134, K141, and P142 occurred in geographically diverse locations, whereas polymorphisms at Q129, M133, D144, and G145 were concentrated in East Asia. While the sample size is large, this approach relied on convenience sampling within each country, and many countries have no data available, thereby highlighting the need for additional routine surveillance of surface antigen mutations associated with vaccine escape.
Evolutionary anatomy of the plantar aponeurosis in primates, including humans

The plantar aponeurosis in the human foot has been extensively studied and thoroughly described, in part, because of the incidence of plantar fasciitis in humans. It is commonly assumed that the human plantar aponeurosis is a unique adaptation to bipedalism that evolved in concert with the longitudinal arch. However, the comparative anatomy of the plantar aponeurosis is poorly known in most mammals, even among non‐human primates, hindering efforts to understand its function. Here, we review previous anatomical descriptions of 40 primate species and use phylogenetic comparative methods to reconstruct the evolution of the plantar aponeurosis and its relationship to the plantaris muscle in primates. Ancestral state reconstructions suggest that the overall organization of the human plantar aponeurosis is shared with chimpanzees and that a similar anatomical configuration evolved independently in different primate clades as an adaptation to terrestrial locomotion. The presence of a plantar aponeurosis with clearly developed lateral and central bands in the African apes suggests that this structure is not prohibitive to suspensory locomotion and that these species possess versatile feet adapted for both terrestrial and arboreal locomotion. This plantar aponeurosis configuration would have been advantageous in enhancing foot stiffness for bipedal locomotion in the earliest hominins, prior to the evolution of a longitudinal arch. Hominins may have subsequently evolved thicker and stiffer plantar aponeuroses alongside the arch to enable a windlass mechanism and elastic energy storage for bipedal walking and running, although this idea requires further testing.
Patients with Liver Cirrhosis as Frequent Attenders of Emergency Departments

Objectives Frequent attendance for nonemergency problems to emergency departments (EDs) contributes to ED overcrowding, resulting in medical care delays, increased medical errors, and social and economic burdens. Most studies regarding frequent attenders of EDs examine general patients without classifying certain subgroups. This study aimed to investigate patients with liver cirrhosis who present repeatedly to the ED. Methods This was a retrospective, observational cohort study of adult patients with a history of liver cirrhosis presenting to the ED from January 2011 to December 2015. We included patients with cirrhosis whose first ED visit occurred during the study period. We went far back for 20 years and excluded patients with any ED visits (including both cirrhosis and noncirrhosis-related ones) before the study period. We categorized frequent attenders as patients with more than 4 ED visits within 12 months after the first ED visit; infrequent attenders were those who did not meet this criterion. Results A total of 3513 patients with cirrhosis were included in this retrospective cohort study. Compared with the infrequent attenders, frequent attenders had a higher rate of presentations due to hepatic encephalopathy (15.2% vs 13.7%, P < 0.001) and ascites (10% vs 4%, P < 0.001) and ascites (10% vs 4%, P < 0.001) and ascites (10% vs 4%, Conclusions Hepatic encephalopathy and ascites account for more ED visits in frequent than in infrequent attenders. Our findings provide information for those planning outpatient support for patients with cirrhosis. Further research is warranted.
Analysis of Lung Gene Expression Reveals a Role for Cl- channels in Diisocyanate Induced Airway Eosinophilia in a Mouse Model of Asthma Pathology.

RATIONALE Diisocyanates are well-recognized causes of asthma. However, hypersensitive workers frequently lack diisocyanate-specific IgE, which complicates diagnosis and suggests the disease involves IgE-independent mechanisms. OBJECTIVES Utilize a mouse model of methylene diphenyl diisocyanate (MDI) asthma to identify biological pathways that may contribute to asthma pathogenesis. METHODS MDI sensitization and respiratory tract exposure was performed in Balb/c, transgenic B-cell (e.g. IgE) deficient mice, and a genetic background (C57BL/6)-matched strain. Eosinophils in airway fluid were quantitated by flow cytometry. Lung tissue gene expression was assessed using whole genome mRNA microarrays. Informatic software was used to identify biological pathways affected by respiratory tract exposure and potential targets for disease intervention. MEASUREMENTS AND MAIN RESULTS Airway eosinophilia and changes (>1.5-fold; p value < 0.05) in expression of 192 genes occurred in all 3 mouse strains tested, with enrichment in chemokines and a pattern associated with alternatively activated monocytes/macrophages (AAMs). The calcium-activated chloride channel regulator 1 (CLCA1) was the most upregulated gene transcript (>100-fold) in all exposed mouse lungs vs. controls, followed closely by SLC26A4, another transcript involved in Cl- conductance. Crofelemer, a U.S. Food and Drug Administration (FDA) approved Cl- channel inhibitor, reduced MDI exposure induction of airway eosinophilia, mucus, CLCA1 and other asthma-associated gene transcripts. CONCLUSIONS Expression changes in a core set of genes occurs independent of IgE in a mouse model of chemical-induced airway eosinophilia. In addition to chemokines and AAMs, the data suggest a crucial role for Cl- channels in diisocyanate asthma pathology and as a possible target for intervention.
Mathematically Modeling Anhedonia in Schizophrenia: A Stochastic Dynamical Systems Approach.

OBJECTIVE Anhedonia, traditionally defined as a diminished capacity for pleasure, is a core symptom of schizophrenia (SZ). However, modern empirical evidence indicates that hedonic capacity may be intact in SZ and anhedonia may be better conceptualized as an abnormality in the temporal dynamics of emotion. METHOD To test this theory, the current study used ecological momentary assessment (EMA) to examine whether abnormalities in one aspect of the temporal dynamics of emotion, sustained reward responsiveness, were associated with anhedonia. Two experiments were conducted in outpatients diagnosed with SZ (n = 28; n = 102) and healthy controls (n = 28; n = 71) who completed EMA reports of emotional experience at multiple time points in the day over the course of several days. Markov chain analyses were applied to the EMA data to evaluate stochastic dynamic changes in emotional states to determine processes underlying failures in sustained reward responsiveness. RESULTS In both studies, Markov models indicated that SZ had deficits in the ability to sustain positive emotion over time, which resulted from failures in augmentation (ie, the ability to maintain or increase the intensity of positive emotion from time t to t+1) and diminution (ie, when emotions at time t+1 are opposite in valence from emotions at time t, resulting in a decrease in the intensity of positive emotion over time). Furthermore, in both studies, augmentation deficits were associated with anhedonia. CONCLUSIONS These computational findings clarify how abnormalities in the temporal dynamics of emotion contribute to anhedonia.
A comparison of pre-school versus school-age orthoptic screening programmes in the North-East of England

Aim: Following changes to the age at which our primary vision screening programmes are delivered we aimed to assess the impact of this change of practice on final vision outcomes. Methods: This is a retrospective notes review of visual outcomes of children failing from two primary vision screening programmes: group A who were screened at pre-school age (3.5 years old) and group B who were screened at school entry age (4–5 years old). Results: Group A: coverage at screening 2742/4567 (60%), start visual acuity (VA) 0.516 logMAR (range 0.175–1.500), end VA 0.195 logMAR (range 0.00– 0.800). Group B: coverage at screening 5842/6082 (96%), start VA 0.514 logMAR (range 0.225–1.500), end VA 0.209 logMAR (range 0.00–1.200). Conclusion: Children in group B achieved the same visual outcome as group A in a shorter episode length and with a larger proportion of the target group screened.
Beyond antibiotics for pulmonary nontuberculous mycobacterial disease.

PURPOSE OF REVIEW Pulmonary nontuberculous mycobacterial disease (NTM) remains a significant clinical challenge with suboptimal therapy. This review focuses on recent understandings around the pathogenesis of NTM disease and nonantibiotic therapeutic approaches that are being pursued. RECENT FINDINGS The absence of animal models that truly replicate human disease remains a major problem for NTM research with most findings coming from tuberculosis or tuberculosis-like studies. Recent research reiterates the known key roles of interferon gamma (IFNγ), tumor necrosis factor, interleukin-12 and granulocyte-macrophage colony stimulation factor (GM-CSF) in immunity to NTM. Autoantibodies to some of these factors may be important. Recent nonantibiotic research has focused on either boosting the immune response to NTM (e.g. with IFNγ or GM-CSF) or using other compounds to kill these pathogens (e.g. inhaled NO, gallium, etc.). SUMMARY Our poor understanding of the immune deficit leading to NTM disease continues to hinder the development of highly effective therapies. New approaches are promising but need significant validation before being considered viable therapeutic options.
Effects of Beetroot Juice Ingestion on Physical Performance in Highly Competitive Tennis Players

Beetroot juice (BJ) contains high levels of inorganic nitrate (NO3−) and its intake has good evidence in increasing blood nitrate/nitrite concentrations. The ingestion of BJ has been associated with improvements in physical performance of endurance sports, however the literature in intermittent sports is scarce. The aim of this study was to investigate whether BJ could improve physical performance in tennis players. Thirteen well-trained tennis players (25.4 ± 5.1 years) participated in the study during their preparatory period for the tennis season. Subjects were randomly divided into two groups and performed a neuromuscular test battery after either BJ or placebo (PLA) consumption. Both trials were executed on two separate days, in randomized order, with one week of wash out period. The test battery consisted of serve velocity test (SVT), countermovement jump (CMJ), isometric handgrip strength (IHS), 5-0-5 agility test (5-0-5), and 10 m sprint (10-m). No significant differences were found in SVT (1.19%; p = 0.536), CMJ (0.96%; p = 0.327), IHS (4.06%; p = 0.069), 5-0-5 dominant and nondominant side (1.11–2.02%; p = 0.071–0.191) and 10-m (1.05%; p = 0.277) when comparing BJ and PLA ingestion. Thus, our data suggest that low doses of BJ (70 mL) consumption do not enhance tennis physical performance.
Cardiac rehabilitation of elderly patients in eight rehabilitation units in western Europe: Outcome data from the EU-CaRE multi-centre observational study

Aims The European Cardiac Rehabilitation in the Elderly (EU-CaRE) HORIZON 2020 project compares the sustainable effects of cardiac rehabilitation (CR) in elderly patients. Methods and results A total of 1633 patients with coronary artery disease (CAD) or heart valve replacement (HVR), with or without revascularization, aged 65 or above, who participated in CR were included. Peak oxygen uptake (VO2peak), smoking, body mass index, diet, physical activity, serum lipids, psychological distress and medication were assessed before and after CR (T0 and T1) and after 12 months (T2). Patients undergoing coronary artery bypass surgery or surgical HVR had lower VO2peak at T0 and a greater increase to T1 and T2 (2.8 and 4.4 ml/kg/min, respectively) than CAD patients undergoing percutaneous or no revascularization (1.6 and 1.4 ml/kg/min, respectively). After multivariable adjustment, earlier CR uptake was associated with greater improvements in VO2peak. The proportion of CAD patients with three or more uncontrolled risk factors declined from 58.4% at T0 to 40.1% at T2 (p < 0.0001). Psychological distress scores all improved and adherence to medication was overall good at all sites. There were significant differences in risk factor burden across sites, but no CR program was superior to others. Conclusions The outcomes of VO2peak in CR programs across Europe seemed mainly determined by timing of uptake and were maintained or even further improved at 1-year follow-up. Despite significant improvements, 40.1% of CAD patients still had three or more risk factors not at target after 1 year. Differences across sites could not be ascribed to characteristics of the CR programs offered.
Stability Study of Isoniazid and Rifampicin Oral Solutions Using Hydroxypropyl-Β-Cyclodextrin to Treat Tuberculosis in Paediatrics

(1) Background: First-line antituberculosis treatment in paediatrics entails the administration of Isoniazid, Pyrazinamide, and Rifampicin. This study examines the possibility of developing a combined dose liquid formulation for oral use that would facilitate dose adjustment and adherence to treatment for younger children. (2) Methods: The active pharmaceutical ingredients stability under in vitro paediatric digestive pH conditions have been checked. The samples were studied as individual or fixed combined paediatric dosages to determine the pH of maximum stability. The use of hydroxypropyl-β-cyclodextrin to improve Rifampicin solubility and the use of ascorbic acid to increase the stability of the formulation have been studied. (3) Results: Maximum stability of combined doses was determined at pH 7.4, and maximum complexation at pH 8.0. Taking this into account, formulations presented the minimum dose of two active pharmaceutical ingredients dissolved. The addition of ascorbic acid at 0.1% w/v enables the detection of a higher remaining quantity of both drugs after three days of storage at 5 °C. (4) Conclusions: a formulation which combines the minimum paediatric dosages dissolved recommended by WHO for Isoniazid and Rifampicin has been developed. Future assays are needed to prolong the stability of the formulation with the aim of incorporating Pyrazinamide to the solution.
Potential Use of Marine Seaweeds as Prebiotics: A Review

Human gut microbiota plays an important role in several metabolic processes and human diseases. Various dietary factors, including complex carbohydrates, such as polysaccharides, provide abundant nutrients and substrates for microbial metabolism in the gut, affecting the members and their functionality. Nowadays, the main sources of complex carbohydrates destined for human consumption are terrestrial plants. However, fresh water is an increasingly scarce commodity and world agricultural productivity is in a persistent decline, thus demanding the exploration of other sources of complex carbohydrates. As an interesting option, marine seaweeds show rapid growth and do not require arable land, fresh water or fertilizers. The present review offers an objective perspective of the current knowledge surrounding the impacts of seaweeds and their derived polysaccharides on the human microbiome and the profound need for more in-depth investigations into this topic. Animal experiments and in vitro colonic-simulating trials investigating the effects of seaweed ingestion on human gut microbiota are discussed.