Miracle-dz/UniFAR-FTUs huggingface dataset:
Pupillary fluctuation amplitude before target presentation reflects short-term vigilance level in Psychomotor Vigilance Tasks

Our daily activities require vigilance. Therefore, it is useful to externally monitor and predict our vigilance level using a straightforward method. It is known that the vigilance level is linked to pupillary fluctuations via Locus Coeruleus and Norepinephrine (LC-NE) system. However, previous methods of estimating long-term vigilance require monitoring pupillary fluctuations at rest over a long period. We developed a method of predicting the short-term vigilance level by monitoring pupillary fluctuation for a shorter period consisting of several seconds. The LC activity also fluctuates at a timescale of seconds. Therefore, we hypothesized that the short-term vigilance level could be estimated using pupillary fluctuations in a short period and quantified their amplitude as the Micro-Pupillary Unrest Index (M-PUI). We found an intra-individual trial-by-trial positive correlation between Reaction Time (RT) reflecting the short-term vigilance level and M-PUI in the period immediately before the target onset in a Psychomotor Vigilance Task (PVT). This relationship was most evident when the fluctuation was smoothed by a Hanning window of approximately 50 to 100 ms (including cases of down-sampled data at 100 and 50 Hz), and M-PUI was calculated in the period up to one or two seconds before the target onset. These results suggest that M-PUI can monitor and predict fluctuating levels of vigilance. M-PUI is also useful for examining pupillary fluctuations in a short period for elucidating the psychophysiological mechanisms of short-term vigilance.
A literature review of microvascular proliferation in arteriovenous malformations of skin and soft tissue

Background and Aim: Arteriovenous malformations (AVM) are defined as being quiescent vascular masses composed of mature vessels. However, recent studies reported areas of microvascular proliferation (MVP) in AVM, indicating a process of angiogenesis. As this finding questions the previous definition, the primary objective of this review was to evaluate whether angiogenesis occurs in vascular malformations of skin and soft tissue, and second, to identify potential factors involved in MVP. Method: Due to the multifaceted nature of this subject, a hermeneutic methodology was used to select articles that were likely to provide a deeper understanding of MVP in vascular malformations. Through citation tracking and database searching in PubMed and Web of Science, relevant articles were identified. All study designs concerning occurrence of MVP in AVM of skin and soft tissue in all age groups were included in the study. The Newcastle-Ottawa scale was used for quality assessment. Results: 16 studies were included in this review which reported occurrence of MVP areas in between the otherwise mature vessels of vascular malformations. In these studies, angiogenesis was reported only in AVM-type of vascular malformations. Increased levels of pro-angiogenic factors were also reported and proliferation was found most prominently during adolescence. Finally, several types of hormone receptors also have been described in tissues of AVM. Conclusion: Overall, the reviewed data support occurrence of active angiogenesis, highlighted by the presence of MVP in the arteriovenous type of vascular malformations, and a possible concurrent lesion progression towards a higher Schobinger stage of clinical severity. The relative scarcity of data at present implies that further research is required to elucidate the nature of MVP in AVM, which could have implications for developing targeted pharmacotherapy. Relevance for Patients: Active angiogenesis caused by MVP in AVM patients is known to be correlating to clinical symptoms and contributing to the progression of the disease, recurrence rate, and patient’s quality of life.
Comparison of three different exercise training modalities (aerobic, strength and mixed) in patients with schizophrenia: study protocol for a multicentre randomised wait-list controlled trial

Introduction Numerous studies support the practice of different physical exercise modalities as an effective treatment to address the problems associated with schizophrenia, reporting that they result in improvements in patient symptoms and quality of life. Given the lack of studies comparing different types of training in controlled environments, the aim of this proposed study will be to compare the effects of three physical exercise programmes (strength, aerobic and mixed) on the symptoms, body composition, level of physical activity and health-related quality of life of patients with schizophrenia. Methods and analysis A multicentre, single-blinded (evaluator), randomised, wait-list controlled (ratio 2:2:2:1) trial will be conducted with 105 patients recruited from different psychosocial care centres. The participants will be randomised into three 16-week training groups comprising 48 sessions lasting 1 hour each, or to the wait-list control group. The training groups will complete aerobic, strength or mixed (aerobic+strength) training. The participants will be assessed before, immediately after and 6 months after the end of the intervention. The patients in the wait-list control group (n=15) will receive one of the three trainings immediately after the intervention. The study variables will include positive, negative and general symptomology (Positive and Negative Syndrome Scale) as the primary outcome; as secondary outcome: body composition (by assessing body mass index, body fat mass and waist circumference), physical activity levels (International Physical Activity Questionnaire-Short Form) and quality of life (abbreviated WHO Quality of Life questionnaire). Ethics and dissemination This study was approved by the ethics committees for Biomedical Research at the CEU Cardenal Herrera University of Valencia, Spain (CEI18/215). Participants will be fully informed of the purpose and procedures of the study, and written informed consent will be obtained. The results from this study will be published in peer-reviewed journals and presented in scientific conferences. Trial registration number NCT04987151.
A systematic scoping review of undergraduate medical ethics education programs from 1990 to 2020

Abstract Introduction Ensuring medical students are equipped with essential knowledge and portable skills to face complex ethical issues underlines the need for ethics education in medical school. Yet such training remains variable amidst evolving contextual, sociocultural, legal and financial considerations that inform training across different healthcare systems. This review aims to map how undergraduate medical schools teach and assess ethics. Methods Guided by the Systematic Evidence-Based Approach (SEBA), two concurrent systematic scoping reviews were carried out, one on ethics teaching and another on their assessment. Searches were conducted on PubMed, Embase, PsycINFO and ERIC between 1 January 1990 and 31 December 2020. Data was independently analysed using thematic and content analysis. Results Upon scrutinising the two sets of full-text articles, we identified 141 articles on ethics teaching and 102 articles on their assessments. 83 overlapped resulting in 160 distinct articles. Similar themes and categories were identified, these include teaching modalities, curriculum content, enablers and barriers to teaching, assessment methods, and their pros and cons. Conclusion This review reveals the importance of adopting an interactive, multimodal and interdisciplinary team-teaching approach to ethics education, involving community resource partners and faculty trained in ethics, law, communication, professionalism, and other intertwining healthcare professions. Conscientious effort should also be put into vertically and horizontally integrating ethics into formal medical curricula to ensure contextualisation and application of ethics knowledge, skills and attitudes, as well as protected time and adequate resources. A stage-based multimodal assessment approach should be used to appropriately evaluate knowledge acquisition, application and reflection across various practice settings. To scaffold personalised development plans and remediation efforts, multisource evaluations may be stored in a centralised portfolio. Whilst standardisation of curricula content ensures cross-speciality ethical proficiency, deliberative curriculum inquiry performed by faculty members using a Delphi approach may help to facilitate the narrowing of relevant topics.
Virus infection modulates male sexual behaviour in Caenorhabditis elegans

Mating dynamics follow from natural selection on mate choice and individuals maximizing their reproductive success. Mate discrimination reveals itself by a plethora of behaviours and morphological characteristics, each of which can be affected by pathogens. A key question is how pathogens affect mate choice and outcrossing behaviour. Here we investigated the effect of Orsay virus on the mating dynamics of the androdiecious (male and hermaphrodite) nematode Caenorhabditis elegans. We tested genetically distinct strains and found that viral susceptibility differed between sexes in a genotype‐dependent manner with males of reference strain N2 being more resistant than hermaphrodites. Males displayed a constitutively higher expression of intracellular pathogen response (IPR) genes, whereas the antiviral RNAi response did not have increased activity in males. Subsequent monitoring of sex ratios over 10 generations revealed that viral presence can change mating dynamics in isogenic populations. Sexual attraction assays showed that males preferred mating with uninfected rather than infected hermaphrodites. Together our results illustrate for the first time that viral infection can significantly affect male mating choice and suggest altered mating dynamics as a novel cause benefitting outcrossing under pathogenic stress conditions in C. elegans.
Inactivation mode of sodium channels defines the different maximal firing rates of conventional versus atypical midbrain dopamine neurons

Two subpopulations of midbrain dopamine (DA) neurons are known to have different dynamic firing ranges in vitro that correspond to distinct projection targets: the originally identified conventional DA neurons project to the dorsal striatum and the lateral shell of the nucleus accumbens, whereas an atypical DA population with higher maximum firing frequencies projects to prefrontal regions and other limbic regions including the medial shell of nucleus accumbens. Using a computational model, we show that previously identified differences in biophysical properties do not fully account for the larger dynamic range of the atypical population and predict that the major difference is that originally identified conventional cells have larger occupancy of voltage-gated sodium channels in a long-term inactivated state that recovers slowly; stronger sodium and potassium conductances during action potential firing are also predicted for the conventional compared to the atypical DA population. These differences in sodium channel gating imply that longer intervals between spikes are required in the conventional population for full recovery from long-term inactivation induced by the preceding spike, hence the lower maximum frequency. These same differences can also change the bifurcation structure to account for distinct modes of entry into depolarization block: abrupt versus gradual. The model predicted that in cells that have entered depolarization block, it is much more likely that an additional depolarization can evoke an action potential in conventional DA population. New experiments comparing lateral to medial shell projecting neurons confirmed this model prediction, with implications for differential synaptic integration in the two populations.
Lesser Known Uses of γ‐Aminobutyric Acid Analogue Medications in Otolaryngology

In otolaryngology, γ‐aminobutyric acid (GABA) analogues have been previously analyzed for their roles in neuropathic pain, chronic cough, tinnitus, and perioperative analgesia. The primary aim of this study is to comprehensively summarize and synthesize the existing evidence for lesser known uses of gabapentin and pregabalin in otolaryngology.
Topology Automated Force-Field Interactions (TAFFI): A Framework for Developing Transferable Force Fields

Force-field development has undergone a revolution in the past decade with the proliferation of quantum chemistry based parametrizations and the introduction of machine learning approximations of the atomistic potential energy surface. Nevertheless, transferable force fields with broad coverage of organic chemical space remain necessary for applications in materials and chemical discovery where throughput, consistency, and computational cost are paramount. Here, we introduce a force-field development framework called Topology Automated Force-Field Interactions (TAFFI) for developing transferable force fields of varying complexity against an extensible database of quantum chemistry calculations. TAFFI formalizes the concept of atom typing and makes it the basis for generating systematic training data that maintains a one-to-one correspondence with force-field terms. This feature makes TAFFI arbitrarily extensible to new chemistries while maintaining internal consistency and transferability. As a demonstration of TAFFI, we have developed a fixed-charge force-field, TAFFI-gen, from scratch that includes coverage for common organic functional groups that is comparable to established transferable force fields. The performance of TAFFI-gen was benchmarked against OPLS and GAFF for reproducing several experimental properties of 87 organic liquids. The consistent performance of these force fields, despite their distinct origins, validates the TAFFI framework while also providing evidence of the representability limitations of fixed-charge force fields.
Differential requirement for the Polycomb repressor complex 2 in dendritic cell and tissue-resident myeloid cell homeostasis

Description PRC2 is essential for the self-renewal of tissue-resident macrophages but dispensable for dendritic cell development and function. Parsing Polycomb in myeloid cells The Polycomb repressive complex 2 (PRC2) is responsible for trimethylation of histone H3 on lysine-27 (H3K27me3), an epigenetic modification associated with transcriptional repression. The activity of PRC2 is dysregulated in certain cancers, but its function in myeloid cell development is not known. Using mice with myeloid-specific genetic deletion of core PRC2 proteins, Zhan et al. demonstrate a selective requirement for PRC2 activity in tissue-resident macrophages but not dendritic cells (DCs). Whereas activity of the EZH2 methyltransferase was broadly dispensable for myeloid cell homeostasis, PRC2 activity was essential for maintaining alveolar macrophage self-renewal by regulating expression of cell cycle and DNA replication genes. These results demonstrate a dichotomy in myeloid cell reliance on PRC2, highlighting differences in the epigenetic mechanisms regulating DC and macrophage homeostasis. Dendritic cells (DCs) and macrophages are at the forefront of immune responses, modifying their transcriptional programs in response to their tissue environment or immunological challenge. Posttranslational modifications of histones, such as histone H3 lysine-27 trimethylation (H3K27me3) by the Polycomb repressive complex 2 (PRC2), are tightly associated with epigenetic regulation of gene expression. To explore whether H3K27me3 is involved in either the establishment or function of the mononuclear phagocyte system, we selectively deleted core components of PRC2, either EZH2 or SUZ12, in CD11c-expressing myeloid cells. Unexpectedly, EZH2 deficiency neither prevented the deposition and maintenance of H3K27me3 in DCs nor hindered DC/macrophage homeostasis. In contrast, SUZ12 deficiency markedly impaired the capacity of DCs and macrophages to maintain H3K27me3. SUZ12 ablation induced a rapid loss of the alveolar macrophage and Langerhans cell networks under both steady state and inflammatory conditions because these cells could no longer proliferate to facilitate their self-renewal. Despite the reduced H3K27me3, DC development and function were unaffected by SUZ12 ablation, suggesting that PRC2-mediated gene repression was dispensable for DC homeostasis. Thus, the role of SUZ12 highlights the fundamentally different homeostatic mechanisms used by tissue-resident myeloid cells versus DCs.
The molecular architecture of Drosophila melanogaster defense against Beauveria bassiana explored through evolve and resequence and quantitative trait locus mapping

Abstract Little is known about the genetic architecture of antifungal immunity in natural populations. Using two population genetic approaches, quantitative trait locus (QTL) mapping and evolve and resequence (E&R), we explored D. melanogaster immune defense against infection with the fungus Beauveria bassiana. The immune defense was highly variable both in the recombinant inbred lines from the Drosophila Synthetic Population Resource used for our QTL mapping and in the synthetic outbred populations used in our E&R study. Survivorship of infection improved dramatically over just 10 generations in the E&R study, and continued to increase for an additional nine generations, revealing a trade-off with uninfected longevity. Populations selected for increased defense against B. bassiana evolved cross resistance to a second, distinct B. bassiana strain but not to bacterial pathogens. The QTL mapping study revealed that sexual dimorphism in defense depends on host genotype, and the E&R study indicated that sexual dimorphism also depends on the specific pathogen to which the host is exposed. Both the QTL mapping and E&R experiments generated lists of potentially causal candidate genes, although these lists were nonoverlapping.
Direct endoscopic ultrasound-guided gastroenterostomy using a feeding-tube waterjet system: a teaching video to facilitate understanding of the technique

To facilitate the safe and simple introduction of an endoscopic ultrasound (EUS)guided gastroenterostomy technique, we present a step-by-step teaching video of a variant technique for direct EUSguided gastroenterostomy using a feeding tube (▶Video 1). The stages involved are as follows. 1. Preparation: orotracheal intubation, positioning the patient in the left lateral position (maintain water at the Treitz angle), and use of a spasmolytic are recommended. 2. A therapeutic gastroscope is used to pass a 0.035-inch guidewire and endoscopic retrograde cholangiopancreatography catheter across the stricture until just distal to the Treitz angle. 3. Oroenteric catheter insertion: a radiopaque through-the-scope feeding tube (NJ-8; Cook Medical) is advanced over the guidewire, through the stenosis, and is positioned at the proximal jejunum using fluoroscopic guidance. 4. The gastroscope is carefully removed, maintaining the position of the feeding tube. The guidewire is removed once the scope is out. 5. Enteral loop distension: the feeding tube is connected to a waterjet system (saline and contrast) for continuous infusion into the jejunum until stent deployment. 6. An echoendoscope is advanced following the mesenteric vein (to the mid-stomach body), turning clockwise to identify the Treitz area with the first jejunal loop containing the feeding tube, which is visualized by EUS and fluoroscopy (▶Fig. 1). 7. Enteral access (the crucial point): the duodenal–jejunal loop (fixed at the Treitz angle) must be positioned in a longitudinal plane and in line with the working channel tract (▶Fig. 2). 8. Stent deployment: the direct “freehand” method using an electrocautery-enhanced lumen-apposing metal stent (LAMS; HotAxios; 20×10mm) and high settings (pure cut; 160W) is used. After the release of the distal stent flange, a guidewire is advanced. The LAMS is then completely deployed as described. 9. Intra-LAMS dilation up to 12–15mm. Spontaneous water drainage, and visualization of the enteral lumen (and usually, the feeding tube) to confirm the successful gastroenterostomy (▶Fig.3).
Dose optimisation of antibiotics used for meningitis

Purpose of review Central nervous system (CNS) infections such as ventriculitis and meningitis are associated with significant morbidity and mortality. In part, this may be due to increased difficulties in achieving a therapeutic antibiotic concentration at the site of infection due to both the pharmacokinetic (PK) changes observed during critical illness and the reduced antibiotic penetration through the blood brain barrier. This paper reviews the pharmacodynamics (PD) and CNS PKs of antibiotics used for Gram-negative bacterial CNS infections to provide clinicians with practical dosing advice. Recent findings Recent PK studies have shown that currently used intravenous antibiotic dosing regimens may not achieve a therapeutic exposure within the CNS, even for reportedly ‘susceptible’ bacteria per the current clinical meningitis breakpoints. Limited data exist for new β-lactam antibiotic/β-lactamase inhibitor combinations, which may be required for multidrug resistant infections. Intraventricular antibiotic administration, although not a new concept, has further evidence demonstrating improved patient outcomes compared with intravenous therapy alone, despite the ongoing paucity of PK studies guiding dosing recommendations. Summary Clinicians should obtain the bacterial minimum inhibitory concentration when treating patients with CNS Gram-negative bacterial infections and consider the underlying PK/PD principles when prescribing antibiotics. Therapeutic drug monitoring, where available, should be considered to guide dosing. Intraventricular therapy should also be considered for patients with ventricular drains to optimise clinical outcomes.
Quality, health, and spending in Medicare Advantage and traditional Medicare.

OBJECTIVES To compare Medicare Advantage (MA) and traditional Medicare (TM) performance on quality, health, and cost outcomes in peer-reviewed literature published since 2010. STUDY DESIGN Systematic review of peer-reviewed papers published between January 1, 2010, and May 1, 2020. METHODS To identify relevant research papers, we searched MEDLINE, EBSCO, and ProQuest. We excluded any studies that did not meet several inclusion criteria. Titles, abstracts, and full-text articles were independently reviewed by 1 author and several trained research assistants. Disagreements were resolved through discussion. We also reviewed the bibliographies of included studies and consulted subject matter experts to identify additional papers.For each eligible study, we extracted the first author, year published, study design, data sources, study years, sample sizes, relevant measures, and study quality. To ensure consistent and complete data extraction, each article was reviewed by 2 reviewers. Study quality was assessed using a modified Newcastle-Ottawa Scale. RESULTS Thirty-five studies including 208 analyses were included. All included studies were observational. Two-thirds of studies were of high methodological quality for observational studies, and 49% addressed selection bias. Analyses compared quality of care (41%), health outcomes (44%), and spending (15%). Overall, 65% of analyses found a statistically significant relationship: 52% favored MA and 13% favored TM. CONCLUSIONS More than half of recent analyses comparing MA and TM find that MA delivers significantly better quality of care, better health outcomes, and lower costs compared with TM.