The Dyson equalizer: adaptive noise stabilization for low-rank signal detection and recovery.

Detecting and recovering a low-rank signal in a noisy data matrix is a fundamental task in data analysis. Typically, this task is addressed by inspecting and manipulating the spectrum of the observed data, e.g.

Circulating tumor-reactive KIRCD8 T cells suppress anti-tumor immunity in patients with melanoma.

Effective anti-tumor immunity is driven by cytotoxic CD8 T cells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8 T cells that are tumor-antigen-specific and can be identified by KIR expression but paradoxically impair anti-tumor immunity in patients with melanoma.

Nerve-associated macrophages control adipose homeostasis across lifespan and restrain age-related inflammation.

Age-related inflammation or inflammaging is a key mechanism that increases disease burden and may control lifespan. How adipose tissue macrophages (ATMs) control inflammaging is not well understood in part because the molecular identities of niche-specific ATMs are incompletely known. Using intravascular labeling to exclude circulating myeloid cells and subsequent single-cell sequencing with orthogonal validation, we define the diversity and alterations in niche resident ATMs through lifespan.

Strategies to prevent blood loss and reduce transfusion in emergency general surgery, WSES-AAST consensus paper.

Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation.

IL-4 Licenses B Cell Activation Through Cholesterol Synthesis.

Lymphocyte activation involves a transition from quiescence and associated catabolic metabolism to a metabolic state with noted similarities to cancer cells such as heavy reliance on aerobic glycolysis for energy demands and increased nutrient requirements for biomass accumulation and cell division . Following antigen receptor ligation, lymphocytes require spatiotemporally distinct "second signals". These include costimulatory receptor or cytokine signaling, which engage discrete programs that often involve remodeling of organelles and increased nutrient uptake or synthesis to meet changing biochemical demands .

Supervised fine-tuning of pre-trained antibody language models improves antigen specificity prediction.

Antibodies play a crucial role in adaptive immune responses by determining B cell specificity to antigens and focusing immune function on target pathogens. Accurate prediction of antibody-antigen specificity directly from antibody sequencing data would be a great aid in understanding immune responses, guiding vaccine design, and developing antibody-based therapeutics. In this study, we present a method of supervised fine-tuning for antibody language models, which improves on previous results in binding specificity prediction to SARS-CoV-2 spike protein and influenza hemagglutinin.

Intractable Postoperative Pancreatic Fistula: Undefined Type of Pancreatic Fistula Managed by Puestow-Like Procedure.

Pancreatoduodenectomy (PD) is a very complex and highly challenging operation for surgeons worldwide. It is the surgical procedure of choice for the management of benign and malignant diseases of the periampullary region. Although mortality rate following this complicated surgery has fallen to 1-3%, morbidity rate following PD remains high, with almost 30-40% of patients developing at least one complication.

HIV-1-infected T cell clones are shared across cerebrospinal fluid and blood during ART.

The central nervous system HIV reservoir is incompletely understood and is a major barrier to HIV cure. We profiled people with HIV (PWH) and uninfected controls through single-cell transcriptomic and T cell receptor (TCR) sequencing to understand the dynamics of HIV persistence in the CNS. In PWH on ART, we found that most participants had single cells containing HIV-1 RNA, which was found predominantly in CD4 central memory T cells, in both cerebrospinal fluid (CSF) and blood.

Gene trajectory inference for single-cell data by optimal transport metrics.

Single-cell RNA sequencing has been widely used to investigate cell state transitions and gene dynamics of biological processes. Current strategies to infer the sequential dynamics of genes in a process typically rely on constructing cell pseudotime through cell trajectory inference. However, the presence of concurrent gene processes in the same group of cells and technical noise can obscure the true progression of the processes studied.

Three-Dimensional Reconstruction Pre-Training as a Prior to Improve Robustness to Adversarial Attacks and Spurious Correlation.

Ensuring robustness of image classifiers against adversarial attacks and spurious correlation has been challenging. One of the most effective methods for adversarial robustness is a type of data augmentation that uses adversarial examples during training. Here, inspired by computational models of human vision, we explore a synthesis of this approach by leveraging a structured prior over image formation: the 3D geometry of objects and how it projects to images.

Circulating Tumor Reactive KIR+CD8+ T cells Suppress Anti-Tumor Immunity in Patients with Melanoma.

Effective anti-tumor immunity is largely driven by cytotoxic CD8 T cells that can specifically recognize tumor antigens. However, the factors which ultimately dictate successful tumor rejection remain poorly understood. Here we identify a subpopulation of CD8 T cells which are tumor antigen-specific in patients with melanoma but resemble KIRCD8 T cells with a regulatory function (Tregs).

Fulminant Emphysematous Pancreatitis: Diagnosis Time Counts.

Emphysematous pancreatitis (EP), a severe form of necrotizing infection of the pancreas, is an extremely rare medical emergency with high rates of mortality. It is characterized by intraparenchymal pancreatic or peri-pancreatic air due to either monomicrobial or polymicrobial infection with gas-forming bacteria or due to entero-pancreatic fistula. EP is classified according to timing from disease onset when air bubble signs were detected on computed tomography (CT) scan, as early onset (within 2 weeks from disease onset) or late (more than 2 weeks from disease onset).

IL-10 constrains sphingolipid metabolism to limit inflammation.

Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types. Loss of IL-10 signalling results in life-threatening inflammatory bowel disease in humans and mice-however, the exact mechanism by which IL-10 signalling subdues inflammation remains unclear. Here we find that increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10 deficiency.

Are we ready for "green surgery" to promote environmental sustainability in the operating room? Results from the WSES STAR investigation.

Background: The importance of environmental sustainability is acknowledged in all sectors, including healthcare. To meet the United Nations Sustainable Development Goals 2030 Agenda, healthcare will need a paradigm shift toward more environmentally sustainable practices that will also impact clinical decision-making. The study investigates trauma and emergency surgeons' perception, acceptance, and employment of environmentally friendly habits.

SORBET: Automated cell-neighborhood analysis of spatial transcriptomics or proteomics for interpretable sample classification via GNN.

Spatially resolved transcriptomics or proteomics data have the potential to contribute fundamental insights into the mechanisms underlying physiologic and pathological processes. However, analysis of these data capable of relating spatial information, multiplexed markers, and their observed phenotypes remains technically challenging. To analyze these relationships, we developed SORBET, a deep learning framework that leverages recent advances in graph neural networks (GNN).

The Operating Room management for emergency Surgical Activity (ORSA) study: a WSES international survey.

Background: Despite advances and improvements in the management of surgical patients, emergency and trauma surgery is associated with high morbidity and mortality. This may be due in part to delays in definitive surgical management in the operating room (OR). There is a lack of studies focused on OR prioritization and resource allocation in emergency surgery.

Language model-based B cell receptor sequence embeddings can effectively encode receptor specificity.

High throughput sequencing of B cell receptors (BCRs) is increasingly applied to study the immense diversity of antibodies. Learning biologically meaningful embeddings of BCR sequences is beneficial for predictive modeling. Several embedding methods have been developed for BCRs, but no direct performance benchmarking exists.

Cesena guidelines: WSES consensus statement on laparoscopic-first approach to general surgery emergencies and abdominal trauma.

Background: Laparoscopy is widely adopted across nearly all surgical subspecialties in the elective setting. Initially finding indication in minor abdominal emergencies, it has gradually become the standard approach in the majority of elective general surgery procedures. Despite many technological advances and increasing acceptance, the laparoscopic approach remains underutilized in emergency general surgery and in abdominal trauma.

Scaling deep identifiable models enables zero-shot characterization of single-cell biological states.

How to identify true biological differences across samples while overcoming batch effects has been a persistent challenge in single-cell RNA-seq data analysis, hindering analyses across datasets for transferable biological findings. In this work, we show that scaling up deep identifiable models leads to a surprisingly effective solution for this challenging task. We developed scShift, a deep variational inference framework with theoretical support in disentangling batch-dependent and independent variations.

LMD: Cluster-Independent Multiscale Marker Identification in Single-cell RNA-seq Data.

Identifying accurate cell markers in single-cell RNA-seq data is crucial for understanding cellular diversity and function. Localized Marker Detector (LMD) is a novel tool to identify "localized genes" - genes exclusively expressed in groups of highly similar cells - thereby characterizing cellular diversity in a multi-resolution and fine-grained manner. LMD constructs a cell-cell affinity graph, diffuses the gene expression value across the cell graph, and assigns a score to each gene based on its diffusion dynamics.

A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better.

Background: Stimulating inflammatory tumor associated macrophages can overcome resistance to PD-(L)1 blockade. We previously conducted a phase I trial of cabiralizumab (anti-CSF1R), sotigalimab (CD40-agonist) and nivolumab. Our current purpose was to study the activity and cellular effects of this three-drug regimen in anti-PD-1-resistant melanoma.