julilili42/papers huggingface dataset:
Prior-Dependent Allocations for Bayesian Fixed-Budget Best-Arm Identification in Structured Bandits
2024-02-09

We study the problem of Bayesian fixed-budget best-arm identification (BAI) in structured bandits. We propose an algorithm that uses fixed allocations based on the prior information and the structure of the environment. We provide theoretical bounds on its performance across diverse models, including the first prior-dependent upper bounds for linear and hierarchical BAI. Our key contribution is introducing new proof methods that result in tighter bounds for multi-armed BAI compared to existing methods. We extensively compare our approach to other fixed-budget BAI methods, demonstrating its consistent and robust performance in various settings. Our work improves our understanding of Bayesian fixed-budget BAI in structured bandits and highlights the effectiveness of our approach in practical scenarios.
Agency, institutions, and welfare chauvinism: Tracing the exclusion of European Union migrant citizens from social assistance in Germany
2024-02-10

What explains welfare chauvinistic policy reform, that is, targeted exclusion of non-citizens from welfare? Existing research suggest that contextual factors like far-right party success, perceived immigration pressures, party ideologies and institutions could spur such reform, but the processes behind reforms remain understudied. This article draws on public policy literature to call attention the critical role of agency and institutions in welfare chauvinist reform. It focuses on a law excluding migrant EU citizens from social assistance in Germany. Through process tracing and inductive reconstruction of the policy process, based on political documents, interviews, media reporting and descriptive statistics, we show that the policy proposal originated from German city administrations; that the city of Hamburg was key in pushing for exclusions; and that Hamburg’s success in doing so crucially depended on the city’s mayor. Several comparable German cities (in terms of party politics and levels of immigration) were equally concerned with ‘welfare immigration’ and complained about problem pressure, but only Hamburg had a committed mayor with the right political networks and institutional resources to lobby for welfare exclusions at the federal level.
Genome-wide association study reveals different T cell distributions in peripheral blood of healthy individuals at high genetic risk of type 1 diabetes and long COVID
2024-02-11

Abstract The immune system plays a crucial role in many human diseases. In this context, genome-wide association studies (GWAS) offer valuable insights to elucidate the role of immunity in health and disease. The present multi-omics study aimed to identify genetic determinants of immune cell type distributions in the blood of healthy individuals and to assess whether the distributions of these cells may play a role for autoimmune and COVID-19 disease risk. To this end, the frequencies of different immune cells in 483 healthy individuals from the Berlin Aging Study II were quantified using flow cytometry, and GWAS was performed for 92 immune cell phenotypes. Additionally, we performed linear regression analyses of immune cell distributions using polygenic risk scores (PRS) based on prior GWAS for five autoimmune diseases as well as for COVID-19 infection and post-COVID syndrome (“long COVID”). We validated seven previously described immune loci and identified 13 novel loci showing genome-wide significant (α=5.00E-8) association with different immune cell phenotypes. The most significant novel signal was conferred by the SLC52A3 locus, encoding for a riboflavin transporter protein, which was associated with naïve CD57+ CD8+ T cells (p=4.13E-17) and colocalized with SLC52A3 expression. Several novel loci contained immunologically plausible candidate genes, e.g., variants near TBATA and B3GAT1 representing genes associated with T cell phenotypes. The PRS of type 1 diabetes were significantly associated with CD8+ T cells at different differentiation states (p≤7.02E-4), and PRS of long COVID were associated with early-differentiated CD4+ T cells (p≤1.54E-4). In conclusion, our extensive immune cell GWAS analyses highlight several novel genetic loci of likely relevance for immune system function. Furthermore, our PRS analyses point to a shared genetic basis between immune cell distributions in healthy adults and T1D (CD8+ T cells) as well as long COVID (CD4+ T cells).
Dynamic parallel imaging at 9.4 T using reconfigurable receive coaxial dipoles
2024-02-11

Parallel imaging is one of the key MRI technologies that allow reduction of image acquisition time. However, the parallel imaging reconstruction commonly leads to a signal‐to‐noise ratio (SNR) drop evaluated using a so‐called geometrical factor ( g ‐factor). The g ‐factor is minimized by increasing the number of array elements and their spatial diversity. At the same time, increasing the element count requires a decrease in their size. This may lead to insufficient coil loading, an increase in the relative noise contribution from the RF coil itself, and hence SNR reduction. Previously, instead of increasing the channel number, we introduced the concept of electronically switchable time‐varying sensitivities, which was shown to improve parallel imaging performance. In this approach, each reconfigurable receive element supports two spatially distinct sensitivity profiles. In this work, we developed and evaluated a novel eight‐element human head receive‐only reconfigurable coaxial dipole array for human head imaging at 9.4 T. In contrast to the previously reported reconfigurable dipole array, the new design does not include direct current (DC) control wires connected directly to the dipoles. The coaxial cable itself is used to deliver DC voltage to the PIN diodes located at the ends of the antennas. Thus, the novel reconfigurable coaxial dipole design opens a way to scale the dynamic parallel imaging up to a realistic number of channels, that is, 32 and above. The novel array was optimized and tested experimentally, including in vivo studies. It was found that dynamic sensitivity switching provided an 8% lower mean and 33% lower maximum g ‐factor (for R y × R z = 2 × 2 acceleration) compared with conventional static sensitivities.
Vertical and horizontal reading training in patients with hemianopia and its effect on reading eye movements
2024-02-12

Abstract Vertical reading training (VRTr) increases reading speed (RS) significantly in patients with hemianopic field defects (HFD). We ask, how eye movements (EM) contribute to this improvement and whether EM-behavior is affected by the side of HFD. Twenty-one patients, randomly assigned to VRTr or horizontal RTr, trained reading single lines from a screen at home, for 4 weeks. In the clinic, we recorded EM while reading short sentences aloud from a screen before training (T1), directly (T2) and 4 weeks afterwards (T3). RS-screen was correlated with RS during reading printed paragraphs (RS-print) to assess the transfer to everyday life. RS-screen and RS-print correlated positively (horizontal: r &gt; 0.8, vertical: r &gt; 0.9) at all times. Vertical RS did not exceed horizontal RS. We found significant negative correlations of EM-variables and RS-print: in right-HFD with the number of forward saccades (T1: r = − 0.79, T2: r = − 0.94), in left-HFD with the steps during return sweeps (T1: r = − 0.83, T2: r = − 0.56). Training effects remained stable at T3. EM-improvement was specific for the RTr and the side of the HFD: in right-HFD fewer forward saccades after VRTr, in left-HFD fewer steps during return sweeps after HRTr. RTr on a screen transfers to reading printed text in real-life situations. Trial registration: The study was retrospectively registered in the German Clinical Trials register: DRKS-ID: DRKS00018843, March 13th, 2020.
Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)
2024-02-12

Introduction Colorectal cancer (CRC) is the third most common cancer worldwide in men and women. In the metastasized stage, treatment options and prognosis are limited. To address the high medical need of this patient population, we generated a CD276xCD3 bispecific antibody termed CC-3. CD276 is expressed on CRC cells and on tumor vessels, thereby allowing for a “dual” anticancer effect. Methods and analysis This first-in-human clinical study is planned as a prospective multicenter trial, enrolling patients with metastatic CRC after three lines of therapy. During the dose-escalation part, initially, an accelerated titration design with single-patient cohorts is employed. Here, each patient will receive a fixed dose level (starting with 50 μg for the first patient); however, between patients, dose level may be increased by up to 100%, depending on the decision of a safety review committee. Upon occurrence of any adverse events (AEs) grade ≥2, dose-limiting toxicity (DLT), or reaching a dose level of ≥800 μg, the escalation will switch to a standard 3 + 3 dose design. After maximum tolerated dose (MTD) has been determined, defined as no more than one of the six patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD level in the dose-expansion phase. Primary endpoints are incidence and severity of AEs, as well as the best objective response to the treatment according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetic investigations. Ethics and dissemination The CD276xCD3 study was approved by the Ethics Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf and the Paul-Ehrlich-Institut (P00702). Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00).
SARS-CoV-2 and Adolescent Psychiatric Emergencies at the Tübingen University Hospital: Analyzing Trends, Diagnoses, and Contributing Factors
2024-02-12

Psychiatric emergencies have increased in recent decades, particularly with the onset of the SARS-CoV-2 pandemic, and far too little is known about the backgrounds of these emergencies. In this study, we investigated the extent to which the number of psychiatric emergencies changed during and in the aftermath of the SARS-CoV-2 pandemic at the Child and Adolescent Psychiatry (CAP) Tübingen. We considered age and psychiatric diagnoses. Additionally, we evaluated the backgrounds of the emergencies. We applied a mixed- (quantitative and qualitative) methods approach to data on emergency presentations at the CAP Tübingen from the pre-SARS-CoV-2 pandemic period (October 2019–January 2020) to Restriction Phase 1 (October 2020–January 2021), Restriction Phase 2 (October 2021–January 2022), and endemic phase (October 2022–January 2023). The total number of emergencies and those with eating disorders and affective disorders increased, while obsessive–compulsive disorders, expansive disorders and anxiety disorders decreased. The patients presenting in the pre-SARS-CoV-2 pandemic period were younger than those in the subsequent periods. We content-coded the reasons behind the emergency presentations. We also identified four areas of stressors and personality characteristics associated with the emergency presentations. In light of the increasing number of psychiatric emergencies, the long-term aim should be to meet the growing demands and create options for prevention.
Liquid footprinting: A novel approach for DNA footprinting using short double-stranded cell-free DNA from plasma
2024-02-12

Abstract The diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not been recognized, yet. Here, we present a method for enrichment of double-stranded cfDNA with an average length of about 40 base pairs from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we found significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA-methylation, positively with H3K4me3 histone modifications and gene transcription. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic with post-operative controls, we identified 731 and 1,107 differentially enriched loci, respectively. Using these differentially enriched loci, the disease types can be clearly distinguished by principal component analysis demonstrating the diagnostic potential of short double-stranded cfDNA signals as a new class of biomarkers for liquid biopsies.
Influence of insulin sensitivity on food cue evoked functional brain connectivity in children
2024-02-12

Abstract Objective Insulin resistance during childhood is a risk factor for developing type 2 diabetes and other health problems later in life. Studies in adults have shown that insulin resistance affects regional and network activity in the brain which are vital for behavior, e.g. ingestion and metabolic control. To date, no study has investigated whether brain responses to food cues in children are associated with peripheral insulin sensitivity. Methods We included 53 children (36 girls) between the age of 7-11 years, who underwent an oral Glucose Tolerance Test (oGTT) to estimate peripheral insulin sensitivity (ISI). Brain responses were measured using functional magnetic resonance imaging (fMRI) before and after glucose ingestion. We compared food-cue task-based activity and functional connectivity (FC) between children with low and high ISI, adjusted for age and BMIz. Results Independent of prandial state (i.e., glucose ingestion), children with lower ISI showed higher FC between the anterior insula and caudate and lower FC between the posterior insula and mid temporal cortex than children with higher ISI. Sex differences were found based on prandial state and peripheral insulin sensitivity in the insular FC. No differences were found on whole-brain food-cue reactivity. Conclusions Children with low peripheral insulin sensitivity showed differences in food cue evoked response particularly in insula functional connectivity. These differences might influence eating behavior and future risk of developing diabetes.
Natural variation in infection specificity ofCaenorhabditis briggsaeisolates by two RNA viruses
2024-02-12

Abstract Antagonistic relationships such as host-virus interactions potentially lead to rapid evolution and specificity in interactions. The Orsay virus is so far the only horizontal virus naturally infecting the nematode C. elegans . In contrast, several related RNA viruses infect its congener C. briggsae , including Santeuil (SANTV) and Le Blanc (LEBV) viruses. Here we focus on the host’s intraspecific variation in sensitivity to these two intestinal viruses. Many temperate-origin C. briggsae strains, including JU1264 and JU1498, are sensitive to both, while many tropical strains, such as AF16, are resistant to both. Interestingly, some C. briggsae strains exhibit a specific resistance, such as the HK104 strain, specifically resistant to LEBV. The viral sensitivity pattern matches the strains’ geographic and genomic relationships. The heavily infected strains mount a seemingly normal small RNA response that is insufficient to suppress viral infection, while the resistant strains show no small RNA response, suggesting an early block in viral entry or replication. We use a genetic approach from the host side to map genomic regions participating in viral resistance polymorphisms. Using Advanced Intercrossed Recombinant Inbred Lines (RILs) between virus-resistant AF16 and SANTV-sensitive HK104, we detect Quantitative Trait Loci (QTLs) on chromosomes IV and III. Building RILs between virus-sensitive JU1498 and LEBV-resistant HK104 followed by bulk segregant analysis, we identify a chromosome II QTL. In both cases, further introgressions of the regions confirmed the QTLs. This diversity provides an avenue for studying virus entry, replication, and exit mechanisms, as well as host-virus specificity and the host response to a specific virus infection.
Numerical simulation of long-range open quantum many-body dynamics with tree tensor networks
2024-02-13

Open quantum systems provide a conceptually simple setting for the exploration of collective behavior stemming from the competition between quantum effects, many-body interactions, and dissipative processes. They may display dynamics distinct from that of closed quantum systems or undergo nonequilibrium phase transitions which are not possible in classical settings. However, studying open quantum many-body dynamics is challenging, in particular, in the presence of critical long-range correlations or long-range interactions. Here, we make progress in this direction and introduce a numerical method for open quantum systems, based on tree tensor networks. Such a structure is expected to improve the encoding of many-body correlations and we adopt an integration scheme suited for long-range interactions and applications to dissipative dynamics. We test the method using a dissipative Ising model with power-law decaying interactions and observe signatures of a first-order phase transition for power-law exponents smaller than 1.
Selection-Dependent Differences in Youth Elite Basketball Players’ Relative Age, Maturation-Related Characteristics, and Motor Performance
2024-02-13

<b>Purpose</b>: The aim of the present study was to investigate the influence of players' relative age, maturation-related characteristics, and motor performance tests on two different stages of talent selection (regional and national level) in youth elite basketball. <b>Methods</b>: Relative age, maturation-related variables (height, weight, maturity offset, maturity timing) and motor performance (Countermovement jump, Standing long jump, Modified agility T-test, Linear sprint 20 m) of <i>N</i> = 68 male youth basketball players (<i>M</i><sub><i>age</i></sub> = 14.39 ± 0.28 years) were assessed during the initial selection tournament for the German U15 national team. Pre-selection biases regarding relative age and maturity timing on the regional level were investigated utilizing one-sample <i>t</i>-tests. Differences in relative age, maturation-related characteristics and motor performance between players selected (<i>n</i> = 27) and non-selected (<i>n</i> = 41) for the youth national team were examined via independent samples' <i>t</i>-tests and logistic regression analyses. <b>Results</b>: Strong pre-selection biases toward early-born and early-maturing players were confirmed on the regional level. Significant advantages in height and weight and higher values in maturity offset and maturity timing were found for selected players. Among the motor variables, only Countermovement jump performance was significantly better in selected players. When controlling for relative age and biological maturation regression models including motor performance variables did not significantly discriminate players' selection status. <b>Conclusion</b>: Coaches working in national, but also preceding selection stages (regional and club level) should raise their awareness to relative age and biological maturation when evaluating players' potential and current (motor) performance.
Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction
2024-02-13

Abstract The 313-variant polygenic risk score (PRS 313 ) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS 313 across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS 313 across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank. The mean PRS 313 differed markedly across European countries, being highest in south-eastern Europe and lowest in north-western Europe. Using the overall European PRS 313 distribution to categorise individuals leads to overestimation and underestimation of risk in some individuals from south-eastern and north-western countries, respectively. Adjustment for principal components explained most of the observed heterogeneity in mean PRS. Country-specific PRS distributions may be used to calibrate risk categories in individuals from different countries.
Discovery of a Small Molecule Activator of Slack (Kcnt1) Potassium Channels That Significantly Reduces Scratching in Mouse Models of Histamine‐Independent and Chronic Itch
2024-02-13

Abstract Various disorders are accompanied by histamine‐independent itching, which is often resistant to the currently available therapies. Here, it is reported that the pharmacological activation of Slack (Kcnt1, K Na 1.1), a potassium channel highly expressed in itch‐sensitive sensory neurons, has therapeutic potential for the treatment of itching. Based on the Slack‐activating antipsychotic drug, loxapine, a series of new derivatives with improved pharmacodynamic and pharmacokinetic profiles is designed that enables to validate Slack as a pharmacological target in vivo. One of these new Slack activators, compound 6, exhibits negligible dopamine D 2 and D 3 receptor binding, unlike loxapine. Notably, compound 6 displays potent on‐target antipruritic activity in multiple mouse models of acute histamine‐independent and chronic itch without motor side effects. These properties make compound 6 a lead molecule for the development of new antipruritic therapies targeting Slack.
Analysis and modelling of profiles to understand fractionation processes for contaminations with polychlorinated biphenyls observed in fish
2024-02-13

Polychlorinated biphenyls (PCB) both continue to spread into the environment and to bioaccumulate from primary urban and industrial sources as well as from secondary sources such as soils and the oceans. Fractions of congeners in PCB mixtures, i.e. PCB profiles, can be used as fingerprints to trace contamination pathways from sources to sinks because PCB mixtures fractionate during transport due to congener specific phase changes and degradation. Using a statistical analysis of a total of 8584 PCB profiles with seven congeners (CB28, CB52, CB101, CB118, CB138, CB153, CB180) for contaminated fish from two international datasets as well as a modelling of profiles, two major fractionation processes related to distinct contamination pathways were identified: (1) A relative enrichment of lighter congeners (CB28, CB52, CB101) in seawater fish due to a predominantly atmospheric transport, whereas freshwater and some coastal fish had higher fractions of heavier congeners (CB138, CB153) because those were mainly contaminated by particle-sorbed PCB from surface runoff. (2) A temperature driven fractionation tended to affect congeners with a medium molecular weight (CB118) as well as the heaviest congeners (CB180), a fractionation process which was conceptually associated with transport of PCB from secondary sources. Specifically, medium chlorinated PCB is sufficiently volatile and persistent for a preferred transport into cooler waters. In warmer climates, only the highest chlorinated congeners are persistent enough to ultimately accumulate in fish. Our analysis and modelling provide a starting point for the development of systems to trace - better than before - sources of PCB contaminations observed in fish.