Areeba Patel, Kirsten Göbel, Sebastian Ille, Felix Hinz, Natalie Schoebe, Henri Bogumil, Jochen Meyer, Michelle Brehm, Helin Kardo, Daniel Schrimpf, Artem Lomakin, Michael Ritter, Pauline Göller, Paul Kerbs, Lisa Pfeifer, Stefan Hamelmann, Christina Blume, Franziska M. Ippen, Natalie Berghaus, Philipp Euskirchen, Leonille Schweizer, Claus Hultschig, Nadine Van Roy, Jo Van Dorpe, Joni Van der Meulen, Siebe Loontiens, Franceska Dedeurwaerdere, Henning Leske, Skarphéðinn Halldórsson, Graeme Fox, Simon Deacon, Inswasti Cahyani, Nadine Holmes, Satrio Wibowo, Rory Munro, Dan Martin, Abid Sharif, Mark Housley, Robert Goldspring, Sebastian Brandner, Somak Roy, Jürgen Hench, Stephan Frank, Andreas Unterberg, Violaine Goidts, Natalie Jäger, Simon Paine, Stuart Smith, Christel Herold-Mende, Wolfgang Wick, Stefan M. Pfister, Einar O. Vik-Mo, Andreas von Deimling, Sandro Krieg, David TW Jones, Matthew Loose, Matthias Schlesner, Martin Sill, Felix Sahm <<<

Hesham ElAbd, Mitchell Pesesky, Gabriel Innocenti, Brian K. Chung, Aya K. H. Mahdy, Valeriia Kriukova, Laila Kulsvehagen, Dennis Strobbe, Claudia Stühler, Gabriele Mayr, Damon H. May, Melanie Prinzensteiner, Tim A. Steiert, Florian Tran, Michel V. Hadjihannas, Rainer Günther, Elisa Rosati, Sören Mucha, Wolfgang Lieb, Malte Ziemann, Astrid Dempfle, Felix Braun, Trine Folseraas, Johannes R. Hov, Espen Melum, Petra Bacher, Martina Sterneck, Tobias J. Weismüller, Henrike Lenzen, Bernd Bokemeyer, Bryan Howie, Harlan S. Robins, Christoph Röcken, Stefan Schreiber, Nina Khanna, Anne-Katrin Pröbstel, Christoph Schramm, Thomas Vogl, Tom H. Karlsen, Andre Franke <<<

Abstract Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC. A substantial fraction of these clonotypes was restricted to known PSC human leukocyte antigen susceptibility alleles and known to target Epstein–Barr virus (EBV) epitopes. We further utilized phage-immunoprecipitation sequencing to determine antibody epitope repertoires of 120 individuals with PSC and 202 healthy controls, which showed a higher burden of anti-EBV responses in PSC than controls. EBV-specific monoclonal antibodies isolated from B cells in PSC livers corroborated convergent B and T cell responses against EBV. By analyzing electronic health records of >116 million people, we identified an association between infectious mononucleosis and PSC (odds ratio, 12; 95% confidence interval, 6.3–22.9), suggesting a link between EBV and PSC. <<<

Rajappa S. Kenchappa, Laszlo Radnai, Erica J. Young, Natanael Zarco, Li Lin, Athanassios Dovas, Christian T. Meyer, Ashley Haddock, Alice Hall, Katalin Toth, Peter Canoll, Naveen K.H. Nagaiah, Gavin Rumbaugh, Michael D. Cameron, Theodore M. Kamenecka, Patrick R. Griffin, Courtney A. Miller, Steven S. Rosenfeld <<<

Ensuring that large language models (LLMs) generate outputs aligned withhuman preferences is important for safe and effective AI interactions. WhileDirect Preference Optimization (DPO) employs an implicit reward function tooptimize the policy model, however, it and its related variants overlook thedifferential importance of individual tokens and are sensitive to judgmentnoise in preference datasets during generation. Although recent methods attemptto assess the important weight of tokens via probability prediction orsimplistic weighting schemes, these evaluation methods are prone to biases andstill cannot fully address these issues. To solve this problem, we propose theToken-Importance Guided Direct Preference Optimization (TI-DPO), whichintroduces two key innovations: the gradient-based token-importance weightsthat dynamically prioritize critical tokens, and a triple loss that explicitlyguides model outputs to approach human-preferred responses and stay away fromnon-preferred responses. Experimental results show that TI-DPO achieves higheraccuracy and stronger generative diversity, providing more stable andcomputationally efficient solutions compared with DPO and other RLHF methods. <<<

William M. Schultz, Heval M. Kelli, John C. Lisko, Tina Varghese, Jia Shen, Pratik Sandesara, Arshed A. Quyyumi, Herman A. Taylor, Martha Gulati, John G. Harold, Jennifer H. Mieres, Keith C. Ferdinand, George A Mensah, Laurence S. Sperling <<<

Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment. <<<

Binjie Guo, Hanyu Zheng, Guowei Su, Ru Zhang, Haohan Jiang, Xurong Lin, Hongyan Wei, Aisheng Mo, Jie Li, Zhiyuan Qian, Zhuhao Zhang, Xiaoyuan Cheng <<<

Recent years have witnessed significant progress in reinforcement learning,especially with Zero-like paradigms, which have greatly boosted thegeneralization and reasoning abilities of large-scale language models.Nevertheless, existing frameworks are often plagued by high implementationcomplexity and poor reproducibility. To tackle these challenges, we presentAlphaZero-Edu, a lightweight, education-focused implementation built upon themathematical framework of AlphaZero. It boasts a modular architecture thatdisentangles key components, enabling transparent visualization of thealgorithmic processes. Additionally, it is optimized for resource-efficienttraining on a single NVIDIA RTX 3090 GPU and features highly parallelizedself-play data generation, achieving a 3.2-fold speedup with 8 processes. InGomoku matches, the framework has demonstrated exceptional performance,achieving a consistently high win rate against human opponents. AlphaZero-Eduhas been open-sourced at https://github.com/StarLight1212/AlphaZero_Edu,providing an accessible and practical benchmark for both academic research andindustrial applications. <<<

Progressive age-induced deterioration in the structure and function of the cardiovascular system involves cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, and endothelial dysfunction. These changes are driven by complex processes that are interconnected, such as oxidative stress, mitochondrial dysfunction, autophagy, inflammation, fibrosis, and telomere dysfunction. In recent years, the advances in research of cardiovascular aging, including the wide use of animal models of cardiovascular aging, elucidated an abundance of cell signaling pathways involved in these processes and brought into sight possible interventions, which span from pharmacological agents, such as metformin, sodium-glucose cotransporter 2-inhibitors, rapamycin, dasatinib and quercetin, to lifestyle changes. <<<

AbstractDirectional tongue movements are crucial for feeding and speech, ensuring proper food positioning for chewing and swallowing, as well as accurate sound production. While directional tuning in the arm region of the sensorimotor cortex during reaching tasks is well-studied, little is known about how 3D tongue direction is encoded in the orofacial sensorimotor cortex (OSMCx) during natural behaviors. Understanding this neural representation has important implications for rehabilitating individuals with orolingual dysfunctions. This study examines the directional tuning and population dynamics in OSMCx during naturalistic feeding and drinking, and how these are affected by sensory loss. Using biplanar videoradiography, we tracked implanted tongue markers in behaving rhesus macaques (Macaca mulatta) and simultaneously recorded 3D positional data with spiking activity from chronically implanted microelectrode arrays in primary motor (MIo) and somatosensory (SIo) areas of the orofacial cortex. In some sessions, tasks were preceded by bilateral nerve block injections to the sensory branches of the trigeminal nerve. Modulation to 3D tongue direction during feeding and drinking was found in most MIo and SIo neurons. Directional information in both individual- and population-level was higher in feeding and was more robust in MIo. Following sensory loss, alterations in tongue kinematics were accompanied by changes in directional information in MIo and SIo, manifesting as modifications in both individual neuron tuning characteristics and the broader dynamics of population-level neural activity. Overall, this study advances our understanding of how OSMCx contributes to complex, coordinated control of naturalistic tongue movements. It expands our current knowledge of orofacial control to three dimensions and demonstrates the specificity and adaptability of population activity in MIo and SIo in response to different behavioral contexts. <<<