Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants.

Background: Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase 1 clinical trial of Treg therapy in living donor renal transplantation, the ONE Study (ClinicalTrials.gov: NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression.

Tranexamic acid for postpartum bleeding: a systematic review and individual patient data meta-analysis of randomised controlled trials.

Background: Tranexamic acid is a recommended treatment for women with a clinical diagnosis of postpartum haemorrhage, but whether it can prevent bleeding is unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials to assess the effects of tranexamic acid in women giving birth.

Methods: In this systematic review and IPD meta-analysis, we searched the WHO International Clinical Trials Registry Platform from database inception to Aug 4, 2024 for randomised trials that assessed the effects of tranexamic acid in women giving birth.

Pathology of IgA nephropathy: A global perspective.

Worldwide adoption of the Oxford Classification of IgA nephropathy (IgAN) has enabled comparison of pathology data from clinicopathological studies in different regions of the world. It is apparent that the frequency of Oxford Classification MEST-C scores shows geographic variations. These in part reflect differences in the stage of disease at diagnosis, criteria for performing biopsies and inclusion in clinical studies, and pathologist reporting practice.

What factors influence cellular pathologists' confidence in case reporting?

Histopathology is a challenging interpretive discipline, and the level of confidence a pathologist has in their diagnosis is known to vary, which is conveyed descriptively in pathology reports. There has been little study to accurately quantify pathologists' diagnostic confidence or the factors that influence it. In this study involving sixteen pathologists from six NHS trusts, we assessed diagnostic confidence across multiple variables and four specialties.

Bacterial aggregation facilitates internalin-mediated invasion of .

Dissemination of food-borne in the host relies on internalin-mediated invasion, but the underlying invasion strategies remain elusive. Here we use live-cell microscopy to follow single cell interactions between individual human cells and and elucidate mechanisms associated with internalin B (InlB)-mediated invasion. We demonstrate that whilst a replicative invasion of nonphagocytic cells is a rare event even at high multiplicities of invasion, overcomes this by utilising a strategy relaying on PrfA-mediated ActA-based aggregation.

An experimentally validated approach to automated biological evidence generation in drug discovery using knowledge graphs.

Explaining predictions for drug repositioning with biological knowledge graphs is a challenging problem. Graph completion methods using symbolic reasoning predict drug treatments and associated rules to generate evidence representing the therapeutic basis of the drug. Yet the vast amounts of generated paths that are biologically irrelevant or not mechanistically meaningful within the context of disease biology can limit utility.

When Are Pregnant Patients Receiving Tranexamic Acid during Delivery Hospitalization in the United States?

Objective:  The World Health Organization recommends tranexamic acid (TXA) in the management of postpartum hemorrhage (PPH). However, the role of TXA in PPH prevention and the optimal timing of TXA administration remain unknown. Our objective was to describe the timing of TXA administration, differences in timing of TXA administration by mode of delivery, and current trends in TXA administration in the United States.

Electrical signaling in three-dimensional bacterial biofilms using an agent-based fire-diffuse-fire model.

Agent-based models were used to describe electrical signaling in bacterial biofilms in three dimensions. Specifically, wavefronts of potassium ions in Escherichia coli biofilms subjected to stress from blue light were modeled from experimental data. Electrical signaling occurs only when the biofilms grow beyond a threshold size, which we have shown to vary with the K^{+} ion diffusivity, and the K^{+} ion threshold concentration, which triggered firing in the fire-diffuse-fire model.

How bad becomes good: A neurocomputational model of affect-informed choice.

People often draw on their current affective experience to inform their decisions, yet little is known about the underlying mechanisms of this process. Understanding them has important implications for many big questions in both the affective and decision sciences. Do the same neural circuits that generate affect generate value? What differentiates people who have greater contextual flexibility in their reliance on affect? Do affective choices invoke processes that are distinct from less affective choices? To investigate these questions, we developed a neurocomputational model of affect-informed choice, in which people convert subjective affect into context-sensitive decision value through a process of weighted evidence accumulation.

Population pharmacokinetic modelling and simulation of tranexamic acid in adult trauma patients.

Aims: The aim of this study is to describe the disposition of tranexamic acid (TXA) in adult trauma patients and derive a dosing regimen that optimizes exposure based on a predefined exposure target.

Methods: We performed a population pharmacokinetic (popPK) analysis of participants enrolled in the Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI) trial (≥18 years with traumatic injury, given ≥1 blood product and/or requiring immediate transfer to the operating room) who were randomized to a single dose of either 2 or 4 g of TXA ≤2 h from time of injury. PopPK analysis was conducted using nonlinear mixed-effects modelling (NONMEM).

Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody.

Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy.

Evidence from the Oxford IgA nephropathy (IgAN) cohort supports the clinical value of subclassifying focal segmental glomerulosclerosis lesions (S1). Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidney outcome and response to immunosuppressive therapy. All biopsies were evaluated for glomeruli with segmental capillary occlusion by matrix ("not otherwise specified", NOS lesion), simple capsular adhesion without capillary occlusion (Adh), tip lesions, and podocyte hypertrophy (PH).

Do machine learning methods lead to similar individualized treatment rules? A comparison study on real data.

Identifying patients who benefit from a treatment is a key aspect of personalized medicine, which allows the development of individualized treatment rules (ITRs). Many machine learning methods have been proposed to create such rules. However, to what extent the methods lead to similar ITRs, that is, recommending the same treatment for the same individuals is unclear.

Electrical Impedance Spectroscopy with Bacterial Biofilms: Neuronal-like Behavior.

Negative capacitance at low frequencies for spiking neurons was first demonstrated in 1941 (K. S. Cole) by using extracellular electrodes.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.

Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists.

Digital pathology for reporting histopathology samples, including cancer screening samples - definitive evidence from a multisite study.

Aims: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples.

Methods: A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings.

A novel combination treatment for fragile X syndrome predicted using computational methods.

Fragile X syndrome is a neurodevelopmental disorder caused by silencing of the fragile X messenger ribonucleotide gene. Patients display a wide spectrum of symptoms ranging from intellectual and learning disabilities to behavioural challenges including autism spectrum disorder. In addition to this, patients also display a diversity of symptoms due to mosaicism.

Detection of PatIent-Level distances from single cell genomics and pathomics data with Optimal Transport (PILOT).

Although clinical applications represent the next challenge in single-cell genomics and digital pathology, we still lack computational methods to analyze single-cell or pathomics data to find sample-level trajectories or clusters associated with diseases. This remains challenging as single-cell/pathomics data are multi-scale, i.e.