Miracle-dz/UniFAR-FTUs huggingface dataset:
Reliance is key to effective access and oversight of medical products in case of public health emergencies

ABSTRACT Introduction Responding to new threats and public health emergencies (PHE) creates serious challenges to regulators. The pandemic due to SARS-CoV-2 has been the catalyzer for change in global and local regulatory practices. Intensified collaboration, rapid and coordinated actions, and reliance mechanisms were key elements of the regulators’ response to COVID-19 for all regulatory functions. Areas covered This article presents how collaboration and reliance among regulators were crucial tools for the regulatory responses to COVID-19, describes the reliance approaches for authorization of COVID-19 vaccines and other commodities, and the importance of reliance for other regulatory functions to avoid duplication and save resources where possible. This article also presents the results of a follow-up survey of reliance approaches in case of public health emergencies conducted between the International Pharmaceutical Regulators Programme (IPRP) members and discusses the forward-looking potential of reliance, analyzing the journey from theoretical concepts to real-life implementation. Expert opinion Regulatory reliance is an essential tool for regulators to act quickly and collectively in times of public health emergencies. Reliance approaches facilitate regulatory approvals and allow a more efficient use of resources, ultimately serving patients by facilitating earlier access to quality assured, safe and effective medicines.
Evidence of climate‐driven selection on tree traits and trait plasticity across the climatic range of a riparian foundation species

Selection on quantitative traits by heterogeneous climatic conditions can lead to substantial trait variation across a species range. In the context of rapidly changing environments, however, it is equally important to understand selection on trait plasticity. To evaluate the role of selection in driving divergences in traits and their associated plasticities within a widespread species, we compared molecular and quantitative trait variation in Populus fremontii (Fremont cottonwood), a foundation riparian distributed throughout Arizona. Using SNP data and genotypes from 16 populations reciprocally planted in three common gardens, we first performed QST‐FST analyses to detect selection on traits and trait plasticity. We then explored the environmental drivers of selection using trait‐climate and plasticity‐climate regressions. Three major findings emerged: (1) There was significant genetic variation in traits expressed in each of the common gardens and in the phenotypic plasticity of traits across gardens, both of which were heritable. (2) Based on QST‐FST comparisons, there was evidence of selection in all traits measured; however, this result varied from no effect in one garden to highly significant in another, indicating that detection of past selection is environmentally dependent. We also found strong evidence of divergent selection on plasticity across environments for two traits. (3) Traits and/or their plasticity were often correlated with population source climate (R2 up to .77 and .66, respectively). These results suggest that steep climate gradients across the Southwest have played a major role in shaping the evolution of divergent phenotypic responses in populations and genotypes now experiencing climate change.
Isolated Metastasis to Fallopian Tube Mucosa by Low-Grade Appendiceal Mucinous Neoplasm: Report of Two Cases

Isolated metastases from non-gynecological cancers to the fallopian tube are rare. Recent literature suggests that mucosal alterations of the fallopian tube should be considered primary tubal lesions. This has led to a paradigm shift in the classification of ovarian tumors with studies proposing tubal origin for these tumors, and clinicians advocating distal salpingectomy to decrease rates of ovarian cancer. This is based on the theory that sole presence of tubal mucosal disease is evidence of tubal origin. We present two patients with isolated mucosal metastases to the fallopian tube from appendiceal tumors. Two 36- and 72-year-old women presented with adnexal masses. Both had a history of right hemicolectomy for low-grade appendiceal mucinous neoplasms. The tubes in both cases were distended with mucin. Microscopic examination showed multifocal low-grade mucinous epithelium with papillations and tufting, interspersed by normal tubal epithelium. The mucinous epithelium was diffusely positive for keratin 20 and CDX2, focally positive for keratin 7, and negative for ER and PAX8 in both cases. Ovaries showed acellular mucin pools. Based on morphology and immunohistochemical features, it is likely that these tumors are of primary appendiceal origin metastatic to fallopian tube mucosa. These cases are unique in that no other organs were involved by metastases raising the possibility of an in-situ lesion or benign tubal mucinous metaplasia. These cases bring up an important point that mucosal metastasis can occur and question the current practice of assigning primary origin of a tumor to the fallopian tube in the presence of “intraepithelial” tumor.
The Proportion of Long-term Response to Anti-N IgG Antibody after 12 Months for COVID-19 Subclinical Infections and a Longitudinal Survey for COVID-19 Subclinical Infections in 2021

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.
Enhancing trainee clinical scientists' self‐regulated learning in the workplace

Trainee health professionals must be competent self‐regulated learners, particularly when learning in busy, unpredictable clinical settings. Whilst research indicates self‐regulated learning (SRL) is influenced both by learners' individual actions and their interactions with others, how these combine to foster SRL requires further exploration. We have used Zimmerman's learner‐focused SRL model and the situative perspective of communities of practice (CoPs) to investigate how UK trainee clinical scientists regulate their learning. Our aims were to develop a holistic understanding of SRL in the clinical workplace incorporating both individual and social aspects and to suggest ways of maximising learning for trainee clinical scientists and other health professionals.
An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS)

Objective: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. Background: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. Methods: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. Results: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. Conclusions: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.
Bibliometric and systemic review of the state of the art of occupational risk management in the construction industry

Objectives. The objective of this study is to use bibliometric and systemic terms to select and analyze a set of articles dealing with occupational risk management in the civil construction industry. Methods . Knowledge development process – constructivist (ProKnow-C) methodology was used as an intervention instrument to guide the selection of the bibliographic portfolio and to support systemic analysis. Results. The bibliographic portfolio was created and included 20 articles. Bibliometric highlights were relevant articles, authors, countries of origin, journals and keywords. Systemic analysis showed opportunities to contribute to the state of the art in all areas of knowledge, enabling the researcher to understand theoretical bases, gaps and research opportunities for the theme and thus establish their research question in accordance with the established knowledge vision. Conclusions. The systemic analysis of each article in the bibliographic portfolio based on the decision support model and areas of knowledge present in each stage of its construction measures the amplitude of the knowledge at each stage, and therefore the completeness of or gaps in each article. This clarifies the overall state of and gaps in the field, showing opportunities for new research.
Foramen magnum decompression for Chiari malformation type I – UK surgical practice

Abstract Background: Symptomatic Chiari 1 malformation (CM1) is a common condition in Neurosurgery. Surgery involves hindbrain decompression and restoration of CSF flow through different surgical approaches. No Class 1 evidence exists to suggest the superiority of any of the surgical techniques. Aims: To investigate current surgical practice for symptomatic CM1 patients in the United Kingdom (UK) and determine the willingness to participate in a randomised controlled trial (RCT) comparing different surgical techniques. Methods: An electronic survey was sent to consultant members of the Society of British Neurological Surgeons and the British Chiari-Syringomyelia Group. The questions covered pre-operative and intra-operative management, presence of equipoise/uncertainty in optimal technique and willingness to participate in an RCT. Results: 98 responses were received. 67% operate on adults. 30% on adult and paediatric patients. There is variation in routine pre-operative use of: ICP monitoring (18%), flexion/extension x-rays (16%), venography (20%) and ophthalmology assessment (26%). 18% of neurosurgeons would not offer foramen magnum decompression when the presenting symptom is only refractory cough/sneeze headache. 15% routinely perform bony decompression alone in adults vs 8% in children. In 68% of adult cases, durotomy is performed routinely (46% of them leave the dura open, 54% perform a type of duroplasty) and 16% routinely resect the cerebellar tonsils. Only 17% leave the dura open in children. The most common indicators for durotomy are syringomyelia and intra-operative ultrasound findings. 61% believe there is equipoise/uncertainty in the optimal strategy for decompression and would be willing to participate in an RCT. Comments also mention the heterogeneity of CM1 and that treatment should be tailored to each patient. Conclusion: There is wide variation in pre- and intra-operative management of CM1 patients in the UK and the majority of neurosurgeons would be willing to participate in an RCT comparing bony decompression alone vs dural opening with/without duroplasty.
Simultaneous Measurement of Patellofemoral Joint Kinematics and Contact Mechanics in Intact Knees: A Cadaveric Study

Patellofemoral kinematics and contact mechanics are important measurements for the assessment of patellofemoral joint (PFJ) problems. Simultaneously measuring PFJ contact pressures and kinematics is a challenging task. The purpose of this study was to simultaneously measure the kinematics and mean/peak contact pressures in the PFJs of cadaveric knees.
Ergodic Properties of Geodesic Flows on Closed Riemannian Manifolds of Negative Curvature

Citation in format AMSBIB \Bibitem{Ano67} \by D. ~V. ~Anosov \paper Geodesic flows on closed Riemannian manifolds of negative curvature \serial Trudy Mat. Inst. Steklov. \yr 1967 \vol 90 \pages 3--210 \mathnet{http://mi.mathnet. ru/tm2795} \mathscinet{http://www.ams. org/mathscinet-getitem? mr=0224110} \zmath{https://zbmath.org/? q=an:0163.43604|0176.19101} \transl \jour Proc. Steklov Inst. Math. \yr 1967 \vol 90 \pages 1--235
CREST: clinical bleeding and risk evaluation in hematology–oncology patients: a systematic review and meta-analysis of thromboelastography's role

Thrombocytopenia and bleeding are common complications of hematologic malignancies. Often, prophylactic platelets are administered to minimize bleeding risk, based on total platelet count (TPC). However, TPC is a poor predictor, and does not provide rapid information. This review presents a novel prospective in the use of point-of-care viscoelastic studies to assess bleeding risk and guide transfusion therapy in a haematological oncological population, where its use can be extended to a ward level as a bedside test. Monitoring TEG maximum amplitude trends may be useful to guide transfusion protocols, especially for patients with total platelet counts ranging 30–100 × 109/l. Fibrinogen assessment in this group of patients may identify other blood components that require replacing to reduce bleeding risk. Normal maximum amplitude parameters for patients with low platelet counts can be a reassuring sign. This meta-analysis serves to remind the reader that absolute platelet quantity does not equate to the quality of clot formation.
Visual snow: A systematic review and a case series

Background Visual Snow Syndrome is a recently recognized neurological condition presenting, continuous, tiny dots across the entire visual field, accompanied by nyctalopia, photophobia and palinopsia that persist for months. It may be part of migraine aura spectrum, yet its definition is still questionable. Diagnostic criteria for Visual Snow Syndrome are included in the supplemental material of ICHD-3. We aimed to summarize recent data to improve the understanding of Visual Snow Syndrome. Methods After presenting four new cases, we conducted a PRISMA systematic search in PubMed/MEDLINE and Embase databases using the keyword “visual snow” with specific inclusion and exclusion criteria. Results From the 855 articles identified 30 were included for the qualitative analysis. These reports covered five aspects related to Visual Snow Syndrome: epidemiology, clinical features, comorbidities, pathophysiology, and treatment. We found limited data concerning Visual Snow Syndrome’s epidemiology (one study). Clinical presentation (22 articles) and the comorbidities (migraine with aura and tinnitus most often, five reports) are described in detail. The pathophysiology of Visual Snow Syndrome is only approached with hypotheses, but several neuroimaging studies have been identified (seven articles). Treatment is based on single case reports only. Conclusion Data for Visual Snow Syndrome are few and not strong enough to support Visual Snow Syndrome as a medical identity. Further investigation is needed.
Simultaneous Prediction of Wrist and Hand Motions via Wearable Ultrasound Sensing for Natural Control of Hand Prostheses

Simultaneous prediction of wrist and hand motions is essential for the natural interaction with hand prostheses. In this paper, we propose a novel multi-out Gaussian process (MOGP) model and a multi-task deep learning (MTDL) algorithm to achieve simultaneous prediction of wrist rotation (pronation/supination) and finger gestures for transradial amputees via a wearable ultrasound array. We target six finger gestures with concurrent wrist rotation in four transradial amputees. Results show that MOGP outperforms previously reported subclass discriminant analysis for both predictions of discrete finger gestures and continuous wrist rotation. Moreover, we find that MTDL has the potential to improve the accuracy of finger gesture prediction compared to MOGP and classification-specific deep learning, albeit at the expense of reducing the accuracy of wrist rotation prediction. Extended comparative analysis shows the superiority of ultrasound over surface electromyography. This paper prioritizes exploring the performance of wearable ultrasound on the simultaneous prediction of wrist and hand motions for transradial amputees, demonstrating the potential of ultrasound in future prosthetic control. Our ultrasound-based adaptive prosthetic control dataset (Ultra-Pro) will be released to promote the development of the prosthetic community.
Healthcare Use Prior to Diabetes Diagnosis in Children Before and During COVID.

During COVID-19, healthcare systems reorganized with less ambulatory care and a shift to virtual care (1). There was an increase in diabetic ketoacidosis (DKA), a preventable, life-threatening condition, at diabetes onset in children during COVID-19 (2). DKA at diabetes onset has been attributed to delays in seeking care, missed diagnosis or delays in referral following a primary healthcare contact (3). Reasons for the recent increase in DKA may relate to hesitancy to seek care, providers failing to recognize diabetes symptoms due to cognitive bias focusing on COVID-19, or limitations of virtual care. To explore these potential mechanisms, we compared in-person and virtual primary care and emergency department (ED) visits in children four weeks prior to diagnosis, before and during COVID-19. If increased DKA rates during COVID-19 were due to more missed diagnoses, possibly related to virtual visits, children with DKA would be more likely to have visits during vs. pre-COVID-19. If families were hesitant to seek or unable to access care during COVID-19, then among those with no visits, there would be a higher proportion with DKA.
Two decades of tuberculosis surveillance reveal disease spread, high levels of exposure and mortality, and marked variation in disease progression in wild meerkats.

Infections with Tuberculosis (TB)-causing agents of the Mycobacterium tuberculosis complex threaten human, livestock, and wildlife health globally due to the high capacity to cross trans-species boundaries. Tuberculosis is a cryptic disease characterized by prolonged, sometimes lifelong subclinical infections, complicating disease monitoring. Consequently, our understanding of infection risk, disease progression, and mortality across species affected by TB remains limited. The TB agent Mycobacterium suricattae was first recorded in the late 1990s in a wild population of meerkats inhabiting the Kalahari in South Africa and has since spread considerably, becoming a common cause of meerkat mortality. This offers an opportunity to document the epidemiology of naturally spreading TB in a wild population. Here, we synthesize more than 25 years-worth of TB reporting and social interaction data across 3,420 individuals to track disease spread, and quantify rates of TB social exposure, progression, and mortality. We found that most meerkats had been exposed to the pathogen within eight years of first detection in the study area, with exposure reaching up to 95% of the population. Approximately one quarter of exposed individuals progressed to clinical TB stages, followed by physical deterioration and death within a few months. Since emergence, 11.6% of deaths were attributed to TB, although the true toll of TB-related mortality is likely higher. Lastly, we observed marked variation in disease progression among individuals, suggesting inter-individual differences in both TB susceptibility and resistance. Our results highlight that TB prevalence and mortality could be higher than previously reported, particularly in species or populations with complex social group dynamics. Long-term studies, such as the present one, allow us to assess temporal variation in disease prevalence and progression and quantify exposure, which is rarely measured in wildlife. Long-term studies are highly valuable tools to explore disease emergence and ecology, and study host-pathogen co-evolutionary dynamics in general, and its impact on social mammals. This article is protected by copyright. All rights reserved.
Changes in cellular Ca2+ and Na+ regulation during the progression towards heart failure

In adapting to disease and loss of tissue, the heart shows great phenotypic plasticity that involves changes to its structure, composition and electrophysiology. Together with parallel whole body cardiovascular adaptations, the initial decline in cardiac function resulting from the insult is compensated. However, in the long term, the heart muscle begins to fail and patients with this condition have a very poor prognosis, with many dying from disturbances of rhythm. The surviving myocytes of these hearts gain Na+, which is positively inotropic because of alterations to Ca2+ fluxes mediated by the Na+/Ca2+ exchange, but compromises Ca2+‐dependent energy metabolism in mitochondria. Uptake of Ca2+ into the sarcoplasmic reticulum (SR) is reduced because of diminished function of SR Ca2+ ATPases. The result of increased Ca2+ influx and reduced SR Ca2+ uptake is an increase in the diastolic cytosolic Ca2+ concentration, which promotes spontaneous SR Ca2+ release and induces delayed afterdepolarisations. Action potential duration prolongs because of increased late Na+ current and changes in expression and function of other ion channels and transporters increasing the probability of the formation of early afterdepolarisations. There is a reduction in T‐tubule density and so the normal spatial arrangements required for efficient excitation–contraction coupling are compromised and lead to temporal delays in Ca2+ release from the SR. Therefore, the structural and electrophysiological responses that occur to provide compensation do so at the expense of (1) increasing the likelihood of arrhythmogenesis; (2) activating hypertrophic, apoptotic and Ca2+ signalling pathways; and (3) decreasing the efficiency of SR Ca2+ release.