Miracle-dz/UniFAR-FTUs huggingface dataset:
ROBUST MACHINE LEARNING BY MEDIAN-OF-MEANS: THEORY AND PRACTICE

Median-of-means (MOM) based procedures have been recently introduced in learning theory (Lugosi and Mendelson (2019); Lecué and Lerasle (2017)). These estimators outperform classical least-squares estimators when data are heavy-tailed and/or are corrupted. None of these procedures can be implemented, which is the major issue of current MOM procedures ( Ann. Statist. 47 (2019) 783–794). In this paper, we introduce minmax MOM estimators and show that they achieve the same sub-Gaussian deviation bounds as the alternatives (Lugosi and Mendelson (2019); Lecué and Lerasle (2017)), both in small and high-dimensional statistics. In particular, these estimators are efﬁcient under moments assumptions on data that may have been corrupted by a few outliers. Besides these theoretical guarantees, the deﬁnition of minmax MOM estimators suggests simple and systematic modiﬁcations of standard algorithms used to approximate least-squares estimators and their regularized versions. As a proof of concept, we perform an extensive simulation study of these algorithms for robust versions of the LASSO.
Autoimmune anti‐D in an RhD‐positive young infant: Learning from a rare case

Anti‐D is usually immune in nature and is formed in individuals lacking D antigen or having variants/altered D phenotypes. In the Indian population, 93.8% are RhD positive, and R1R1 is the commonest Rh phenotype. Here we report a rare and interesting case of autoimmune anti‐D in an RhD‐positive 3‐month‐old infant leading to warm autoimmune haemolytic anaemia.
Cognitive behavioural therapy for neurologists

In neurological practice, we take pride in accurate diagnosis and using neuroscience to develop novel disease-modifying therapies, but we sometimes neglect symptom management and the treatment of distress. Most patients with neurological disorders report that their mental health needs are not being met. Of the many forms of psychological therapy, cognitive behavioural therapy (CBT) is the most likely to be available to our patients. This article sets out to answer the following questions: (1) What is CBT? (2) What will patients experience if they have CBT? (3) Is CBT effective for people with neurological disorders? (4) Who is most suitable for CBT? (5) How and where can a neurologist refer their patients for CBT? (6) Can we as neurologists use aspects of the CBT model in our own consultations?
ESYT1 tethers the ER to mitochondria and is required for mitochondrial lipid and calcium homeostasis

A protein complex composed of the outer mitochondrial membrane protein SYNJ2BP and the endoplasmic reticulum protein ESYT1 tethers the two organelles to facilitate calcium and lipid transfer. Mitochondria interact with the ER at structurally and functionally specialized membrane contact sites known as mitochondria–ER contact sites (MERCs). Combining proximity labelling (BioID), co-immunoprecipitation, confocal microscopy and subcellular fractionation, we found that the ER resident SMP-domain protein ESYT1 was enriched at MERCs, where it forms a complex with the outer mitochondrial membrane protein SYNJ2BP. BioID analyses using ER-targeted, outer mitochondrial membrane-targeted, and MERC-targeted baits, confirmed the presence of this complex at MERCs and the specificity of the interaction. Deletion of ESYT1 or SYNJ2BP reduced the number and length of MERCs. Loss of the ESYT1–SYNJ2BP complex impaired ER to mitochondria calcium flux and provoked a significant alteration of the mitochondrial lipidome, most prominently a reduction of cardiolipins and phosphatidylethanolamines. Both phenotypes were rescued by reexpression of WT ESYT1 and an artificial mitochondria–ER tether. Together, these results reveal a novel function for ESYT1 in mitochondrial and cellular homeostasis through its role in the regulation of MERCs.
PICKLE RELATED 2 is a Neofunctionalized Gene Duplicate Under Positive Selection With Antagonistic Effects to the Ancestral PICKLE Gene on the Seed Transcriptome

Abstract The evolution and diversification of proteins capable of remodeling domains has been critical for transcriptional reprogramming during cell fate determination in multicellular eukaryotes. Chromatin remodeling proteins of the CHD3 family have been shown to have important and antagonistic impacts on seed development in the model plant, Arabidopsis thaliana, yet the basis of this functional divergence remains unknown. In this study, we demonstrate that genes encoding the CHD3 proteins PICKLE (PKL) and PICKLE-RELATED 2 (PKR2) originated from a duplication event during the diversification of crown Brassicaceae, and that these homologs have undergone distinct evolutionary trajectories since this duplication, with PKR2 fast evolving under positive selection, while PKL is subject to purifying selection. We find that the rapid evolution of PKR2 under positive selection reduces the encoded protein's intrinsic disorder, possibly suggesting a tertiary structure configuration which differs from that of PKL. Our whole genome transcriptome analysis in seeds of pkr2 and pkl mutants reveals that they act antagonistically on the expression of specific sets of genes, providing a basis for their differing roles in seed development. Our results provide insights into how gene duplication and neofunctionalization can lead to differing and antagonistic selective pressures on transcriptomes during plant reproduction, as well as on the evolutionary diversification of the CHD3 family within seed plants.
Machine learning models to predict surgical case duration compared to current industry standards: scoping review

Abstract Background Surgical waiting lists have risen dramatically across the UK as a result of the COVID-19 pandemic. The effective use of operating theatres by optimal scheduling could help mitigate this, but this requires accurate case duration predictions. Current standards for predicting the duration of surgery are inaccurate. Artificial intelligence (AI) offers the potential for greater accuracy in predicting surgical case duration. This study aimed to investigate whether there is evidence to support that AI is more accurate than current industry standards at predicting surgical case duration, with a secondary aim of analysing whether the implementation of the models used produced efficiency savings. Method PubMed, Embase, and MEDLINE libraries were searched through to July 2023 to identify appropriate articles. PRISMA extension for scoping reviews and the Arksey and O’Malley framework were followed. Study quality was assessed using a modified version of the reporting guidelines for surgical AI papers by Farrow et al. Algorithm performance was reported using evaluation metrics. Results The search identified 2593 articles: 14 were suitable for inclusion and 13 reported on the accuracy of AI algorithms against industry standards, with seven demonstrating a statistically significant improvement in prediction accuracy (P < 0.05). The larger studies demonstrated the superiority of neural networks over other machine learning techniques. Efficiency savings were identified in a RCT. Significant methodological limitations were identified across most studies. Conclusion The studies suggest that machine learning and deep learning models are more accurate at predicting the duration of surgery; however, further research is required to determine the best way to implement this technology.
DiSignAtlas: an atlas of human and mouse disease signatures based on bulk and single-cell transcriptomics

Abstract Molecular signatures are usually sets of biomolecules that can serve as diagnostic, prognostic, predictive, or therapeutic markers for a specific disease. Omics data derived from various high-throughput molecular biology technologies offer global, unbiased and appropriately comparable data, which can be used to identify such molecular signatures. To address the need for comprehensive disease signatures, DiSignAtlas (http://www.inbirg.com/disignatlas/) was developed to provide transcriptomics-based signatures for a wide range of diseases. A total of 181 434 transcriptome profiles were manually curated from studies involving 1836 nonredundant disease types in humans and mice. Then, 10 306 comparison datasets comprising both disease and control samples, including 328 single-cell RNA sequencing datasets, were established. Furthermore, a total of 3 775 317 differentially expressed genes in humans and 1 723 674 in mice were identified as disease signatures by analysing transcriptome profiles using commonly used pipelines. In addition to providing multiple methods for the retrieval of disease signatures, DiSignAtlas provides downstream functional enrichment analysis, cell type analysis and signature correlation analysis between diseases or species when available. Moreover, multiple analytical and comparison tools for disease signatures are available. DiSignAtlas is expected to become a valuable resource for both bioscientists and bioinformaticians engaged in translational research.
Soan Tool Types from Ghila Kalan

THE assemblage described in this paper consists of 216 pieces of fractured stone collected from the exposed surface of a boulder conglomerate at the Soan River site called Ghila Kalan. The collection was made in 1964 by Elden Johnson from a localized area adjacent to a weathering loess cap on the most northerly section of the second terrace at Ghila Kalan. An area measuring approximately 50 m square furnished this sample and all stone showing any fracturing was collected. Almost all of the stones in the assemblage are of quartzite, usually light yellow-brown and with a cortex typically 5 or 6 mm thick. Patination on fractured surfaces is very slight, as seen from a few recent chippings. Fracturing qualities of the quartzite are fairly good, judging from the workmanship, and very few internal impurities were noted. Other materials include a more cherty or flintlike finer grained material, sometimes almost white but occasionally including reds or yellows. Such material is rare and does not tend to occur with any emphasis in any particular type of tool. All of the collected stones appear clearly to be of human workmanship. In some cases a chip or more may be of natural origin as indicated by greater patination, but almost all have been worked to some degree toward some intended form. The few exceptions to this last statement are a small group (19) of flakes which do not conform to any type noted in the collection, or elsewhere for that matter. These flakes can easily be ascribed to accidents of flaking not intended by the tool makers, but were of some potential utility anyway. An interesting aspect of this collection is that virtually all of the specimens are usable tools, and there are no manufacturing wastes. This clearly does not represent a workshop site in any sense. Had it been so, the collector would have noted, if not collected, waste flakes of no utility which should have far outnumbered finished tools. Also, many unfinished, broken and rejected tools, hammerstones, and cores
An Improved Method for Purification of the Residual Bodies from the Seminiferous Tubules of Mice

Human fertility is declining in Western countries, and it is becoming increasingly clear that male infertility plays a pivotal role in the overall fertility decline. To understand the process that drives successful male germ cell maturation, the study of spermatogenesis of model organisms, such as mice, is essential. Residual bodies (RBs) play an important role in the last stages of spermatogenesis. They are formed at the time when post‐meiotic spermatids undergo sequential differentiation steps so that the acrosome and flagellum are developed, the nucleus is markedly condensed, and the cytoplasm is lost. The masses of lost cytoplasm become RBs. Our recent work has shown that RB dynamics are highly sensitive to even small fertility defects. It was also noted that the transcriptome and proteome of RBs changes in response to spermatogenic defects. Thus, RBs represent an excellent and highly sensitive entity for studying male fertility. Previously published protocols for RB purification had some major limitations: they produced an RB fraction that was heavily contaminated with spermatozoa and erythrocytes or required tens of grams of starting material. In addition, most of the available protocols were developed for purification of RBs from rat testes. Here, we present a protocol that allows the isolation of 2.5‐3 × 106 RBs from mouse testes with a purity of 98% from only 1 g of starting material. The purified material can be used for various downstream applications to study male fertility, such as transcriptome and proteome analyses, super‐resolution microscopy, and electron and cryo‐electron microscopy, amongst many others. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.
Anticonvulsant effect of equilibrative nucleoside transporters 1 inhibitor in a mouse model of Dravet syndrome

There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1aE1099X/+ mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1aE1099X/+ mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post‐synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia‐induced seizures in Scn1aE1099X/+ mice. This effect possibly acts on presynaptic A1R‐mediated signaling modulation in granule cells.
Hydrographic Correlates of Winter Dunlin Abundance and Distribution in a Temperate Estuary

From 1989 to 1999,1 examined intra-seasonal and annual changes in the abundance and local dis­ tribution of two groups ofwintering Dunlin (Calidris alpina) occupying different positions along hydrographic gra­ dients in the Tomales Bay estuary, California. Reciprocal translocation of color-banded Dunlin indicated a discrete separation of wintering Dunlin between the north and south of Tomales Bay. Local abundance in both groups was significantly associated with cumulative seasonal rainfall within and among years. Increased variation in annual and intra-seasonal abundance was related to reduced tidal circulation, greater freshwater stream flow, and increased sa­ linity variation. On average, winter Dunlin use peaked later but declined earlier in the southern part of the bay (near the head of the bay) than in the northern part of the bay (near the mouth of the bay), Shifts in distribution associated with changes in hydrographic conditions and weather revealed consistent intra-seasonal changes in hab­ itat preference on temporal scales other than tidal cycles. In the northern part of the bay, changes in habitat pref­ erence by Dunlin corresponded to thresholds of 20-25 cm cumulative rainfall and 0.5-1.0 m" sec" stream flow, whereas in the south bay changes were relatively continuous. Rainfall, wind velocity and direction, and temperature also influenced habitat preferences. Flocking beha\~or dominated over habitat choice at low levels of Dunlin abun­ dance, resulting in contrasting patterns of habitat use relative to overall trends. These patterns suggested the loss of habitat quality as the criterion for patch use. In general, this study indicates that winter shorebird use of temper­ ate estuaries can be predicted by differences in weather and hydrographic regimes, including rates and variances of freshwater inflow, estuarine circulation, and water residence times unique to each system. Received 4 February
Deleterious and Adaptive Mutations in Plant Germplasm Conserved Ex Situ

Abstract Conserving more than 7 million plant germplasm accessions in 1,750 genebanks worldwide raises the hope of securing the food supply for humanity for future generations. However, there is a genetic cost for such long-term germplasm conservation, which has been largely unaccounted for before. We investigated the extent and variation of deleterious and adaptive mutations in 490 individual plants representing barley, wheat, oat, soybean, maize, rapa, and sunflower collections in a seed genebank using RNA-Seq technology. These collections were found to have a range of deleterious mutations detected from 125 (maize) to 83,695 (oat) with a mean of 13,537 and of the averaged sample-wise mutation burden per deleterious locus from 0.069 to 0.357 with a mean of 0.200. Soybean and sunflower collections showed that accessions acquired earlier had increased mutation burdens. The germplasm with more years of storage in several collections carried more deleterious and fewer adaptive mutations. The samples with more cycles of germplasm regeneration revealed fewer deleterious and more adaptive mutations. These findings are significant for understanding mutational dynamics and genetic cost in conserved germplasm and have implications for long-term germplasm management and conservation.
Direct measurement of over pressure of a volcanic blast on the June 1991 eruption at Unzen Volcano, Japan

Over pressure of a volcanic blast has been measured for the first time by a lead-plate blastmeter at Unzen Volcano, Kyushu, Japan. The over pressure of the volcanic blast on June 8 was 0.28 bar at 2700 m distance from the crater, and that was less than 0.06 bar at 4400 m distance. The estimated explosive yield of the explosion accompanied by the blast was 1.1 × 107 kg TNT (5 × 1020 erg) calculated based on the over pressure and distribution of the blast effect. The explosion energy is as much as 1/600 of that of the blast at Mount St. Helens on 18 May 1980. The lead-plate of the blastmeter at 2700 m has also recorded the collision with some accretionary lapillis. The maximum particle velocity of the blast was estimated to be about 75 m/sec based on the trace of the collision. The significance of over pressure for the prediction of volcanic hazards is also discussed briefly.
Anxious to detect deceit: an empirical investigation of social defense theory

ABSTRACT Social Defense Theory (SDT) states that anxious attachment reflects an adaptive sentinel strategy, whereby anxious people should be better able to detect lies than secure people. Existing research on this issue, however, has not been able to evaluate whether heightened lie detection among anxious individuals is due to an actual ability or a bias to assume that others are lying (one that pays off when others are, in fact, lying). We addressed this issue in a study in which 254 adults had to determine whether people in videos were lying or telling the truth about their experiences. Contrary to the predictions of SDT, highly anxious people did not have a heightened ability to separate lies from truths, but were biased to assume that others were lying regardless of the authenticity of their statements.
Cost-effectiveness analysis of low-dose prophylaxis versus on-demand treatment for moderate-to-severe hemophilia A in India

ABSTRACT Aim Hemophilia A (HA) is an inherited bleeding disorder caused by a deficiency of clotting factor VIII in the blood. In resource-limited settings like India, affordability is a significant challenge in managing patients with severe HA. This study aims to assess the cost-effectiveness of intermediate-dose prophylaxis versus on-demand factor therapy in adult and pediatric populations with moderate-to-severe congenital HA without inhibitors in India. Method We conducted a prospective cost-effectiveness analysis from a societal perspective, categorizing patients into a base state and a joint disease state (patients with Hemophilia suffering extensive bleeds leading to chronic joint disease). Using targeted literature search and primary market research, we developed a Markov model measuring the total cost of Hemophilia treatment and health outcomes, including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER). The model extended over a lifetime horizon of 70 years with a one-year cycle length. Sensitivity analyses assessed study robustness. Results Low-dose prophylactic therapy was cost-effective for adults (>18 years) and pediatric populations (<18 years), yielding better health outcomes (adults: 0.15 LYs and 2.43 QALYs gained; pediatric: 0.40 LYs and 3.12 QALYs gained). Intermediate-dose prophylaxis showed positive net monetary benefits in terms of Quality-Adjusted Life Years (QALYs) for both adult and pediatric populations, with dominant ICER and ICUR values in both cases. Conclusion Using intermediate-dose prophylactic factor VIII therapy is a cost-effective approach that improves clinical outcomes compared to on-demand therapy in the Indian adult and pediatric HA populations without inhibitors.
Evolutionary “Crowdsourcing”: Alignment of Fitness Landscapes Allows for Cross-species Adaptation of a Horizontally Transferred Gene

Abstract Genes that undergo horizontal gene transfer (HGT) evolve in different genomic backgrounds. Despite the ubiquity of cross-species HGT, the effects of switching hosts on gene evolution remains understudied. Here, we present a framework to examine the evolutionary consequences of host-switching and apply this framework to an antibiotic resistance gene commonly found on conjugative plasmids. Specifically, we determined the adaptive landscape of this gene for a small set of mutationally connected genotypes in 3 enteric species. We uncovered that the landscape topographies were largely aligned with minimal host-dependent mutational effects. By simulating gene evolution over the experimentally gauged landscapes, we found that the adaptive evolution of the mobile gene in one species translated to adaptation in another. By simulating gene evolution over artificial landscapes, we found that sufficient alignment between landscapes ensures such “adaptive equivalency” across species. Thus, given adequate landscape alignment within a bacterial community, vehicles of HGT such as plasmids may enable a distributed form of genetic evolution across community members, where species can “crowdsource” adaptation.
A normative model of brain responses to social scenarios reflects the maturity of children and adolescents’ social–emotional abilities

Abstract The rapid brain maturation in childhood and adolescence accompanies the development of socio-emotional functioning. However, it is unclear how the maturation of the neural activity drives the development of socio-emotional functioning and individual differences. This study aimed to reflect the age dependence of inter-individual differences in brain responses to socio-emotional scenarios and to develop naturalistic imaging indicators to assess the maturity of socio-emotional ability at the individual level. Using three independent naturalistic imaging datasets containing healthy participants (n = 111, 21 and 122), we found and validated that age-modulated inter-individual concordance of brain responses to socio-emotional movies in specific brain regions. The similarity of an individual’s brain response to the average response of older participants was defined as response typicality, which predicted an individual’s emotion regulation strategies in adolescence and theory of mind (ToM) in childhood. Its predictive power was not superseded by age, sex, cognitive performance or executive function. We further showed that the movie’s valence and arousal ratings grounded the response typicality. The findings highlight that forming typical brain response patterns may be a neural phenotype underlying the maturation of socio-emotional ability. The proposed response typicality represents a neuroimaging approach to measure individuals’ maturity of cognitive reappraisal and ToM.