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.

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease.

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences.

Regulatory cell therapy for kidney transplantation and autoimmune kidney diseases.

Regulatory cell therapies, including regulatory T cells and mesenchymal stromal cells, have shown promise in early clinical trials for reducing immunosuppression burden in transplantation. While regulatory cell therapies may also offer potential for treating autoimmune kidney diseases, data remains sparse, limited mainly to preclinical studies. This review synthesises current literature on the application of regulatory cell therapies in these fields, highlighting the safety and efficacy shown in existing clinical trials.

Multiscale topology classifies cells in subcellular spatial transcriptomics.

Spatial transcriptomics measures in situ gene expression at millions of locations within a tissue, hitherto with some trade-off between transcriptome depth, spatial resolution and sample size. Although integration of image-based segmentation has enabled impactful work in this context, it is limited by imaging quality and tissue heterogeneity. By contrast, recent array-based technologies offer the ability to measure the entire transcriptome at subcellular resolution across large samples.

The evolution of raw data archiving and the growth of its importance in crystallography.

The hardware for data archiving has expanded capacities for digital storage enormously in the past decade or more. The IUCr evaluated the costs and benefits of this within an official working group which advised that raw data archiving would allow ground truth reproducibility in published studies. Consultations of the IUCr's Commissions ensued via a newly constituted standing advisory committee, the Committee on Data.

Late Treatment With Autologous Expanded Regulatory T-cell Therapy After Alemtuzumab Induction Is Safe and Facilitates Immunosuppression Minimization in Living Donor Renal Transplantation.

Background: The TWO Study (Transplantation Without Overimmunosuppression) aimed to investigate a novel approach to regulatory T-cell (Treg) therapy in renal transplant patients, using a delayed infusion protocol at 6 mo posttransplant to promote a Treg-skewed lymphocyte repopulation after alemtuzumab induction. We hypothesized that this would allow safe weaning of immunosuppression to tacrolimus alone. The COVID-19 pandemic led to the suspension of alemtuzumab use, and therefore, we report the unique cohort of 7 patients who underwent the original randomized controlled trial protocol.

Perceptions of Wearable Health Tools Post the COVID-19 Emergency in Low-Income Latin Communities: Qualitative Study.

Background: Mobile health (mHealth) wearable devices are increasingly being adopted by individuals to help manage and monitor physiological signals. However, the current state of wearables does not consider the needs of racially minoritized low-socioeconomic status (SES) communities regarding usability, accessibility, and price. This is a critical issue that necessitates immediate attention and resolution.

A feasibility study on the use of audio-based ecological momentary assessment with persons with aphasia.

We describe a smartphone/smartwatch system to evaluate anomia in individuals with aphasia by using audio-recording-based ecological momentary assessments. The system delivers object-naming assessments to a participant's smartwatch, whereby a prompt signals the availability of images of these objects on the watch screen. Participants attempt to speak the names of the images that appear on the watch display out loud and into the watch as they go about their lives.

Decoding mTOR signalling heterogeneity in the tumour microenvironment using multiplexed imaging and graph convolutional networks.

Evaluating the contribution of the tumour microenvironment (TME) in tumour progression has proven a complex challenge due to the intricate interactions within the TME. Multiplexed imaging is an emerging technology that allows concurrent assessment of multiple of these components simultaneously. Here we utilise a highly multiplexed dataset of 61 markers across 746 colorectal tumours to investigate how complex mTOR signalling in different tissue compartments influences patient prognosis.

SmokeMon: Unobtrusive Extraction of Smoking Topography Using Wearable Energy-Efficient Thermal.

Smoking is the leading cause of preventable death worldwide. Cigarette smoke includes thousands of chemicals that are harmful and cause tobacco-related diseases. To date, the causality between human exposure to specific compounds and the harmful effects is unknown.

Electrocatalytic on-site oxygenation for transplanted cell-based-therapies.

Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host. Previous exogenous oxygenation strategies have been bulky and had limited oxygen production or regulation. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy under hypoxic stress and at high cell densities.

Use of Stroke Alert Sticker in the Field Decreases Time to Acute Interventions for Ischemic Stroke Patients.

BACKGROUND: Stroke is a medical emergency requiring timely intervention to optimize patient outcomes. The only treatments currently Food and Drug Administration approved for acute stroke are intravenous (IV) thrombolytics, which require obtaining specific medical history to be administered safely. This medical history may be overlooked in the prehospital setting or lost during patient handoff between emergency medical services (EMS) personnel and hospital staff, delaying treatment.

Automated Insulin Delivery with Remote Real-Time Continuous Glucose Monitoring for Hospitalized Patients with Diabetes: A Multicenter, Single-Arm, Feasibility Trial.

Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units.

Integrated In Silico Analysis of Proteogenomic and Drug Targets for Pancreatic Cancer Survival.

Pancreatic cancer remains a major health concern, being among the deadliest forms of cancer with over 80% of the patients presenting with metastatic disease. According to the American Cancer Society, for all stages of pancreatic cancer combined, the 5-year survival rate is less than 10%. Genetic research on pancreatic cancer has generally been focused on familial pancreatic cancer, which is only 10% of all pancreatic cancer patients.

Rationale and design of the SenseWhy project: A passive sensing and ecological momentary assessment study on characteristics of overeating episodes.

Objectives: Overeating interventions and research often focus on single determinants and use subjective or nonpersonalized measures. We aim to (1) identify automatically detectable features that predict overeating and (2) build clusters of eating episodes that identify theoretically meaningful and clinically known problematic overeating behaviors (e.g.

Opportunities for High-plex Spatial Transcriptomics in Solid Organ Transplantation.

The last 5 y have seen the development and widespread adoption of high-plex spatial transcriptomic technology. This technique detects and quantifies mRNA transcripts in situ, meaning that transcriptomic signatures can be sampled from specific cells, structures, lesions, or anatomical regions while conserving the physical relationships that exist within complex tissues. These methods now frequently implement next-generation sequencing, enabling the simultaneous measurement of many targets, up to and including the whole mRNA transcriptome.

Barriers to Treg therapy in Europe: From production to regulation.

There has been an increased interest in cell based therapies for a range of medical conditions in the last decade. This explosion in novel therapeutics research has led to the development of legislation specifically focused on cell and gene based therapies. In Europe, the European medicines agency (EMA) designates any medicines for human use which are based on genes, tissues, or cells as advanced therapy medicinal products or advanced therapy medicinal products (ATMPs).

Pre-Visit Digital Messaging Improves Patient-Reported Outcome Measure Participation Prior to the Orthopaedic Ambulatory Visit: Results from a Double-Blinded, Prospective, Randomized Controlled Trial.

Background: Patient-reported outcome measures (PROMs) are metrics that assess physical health, mental health, pain, and satisfaction. However, PROM collection in orthopaedic clinics presents numerous logistical and financial challenges. These challenges are reduced when PROMs are completed before clinic encounters, relieving the workflow constraints of in-office PROM collection.

Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury.

Severe lung damage resulting from COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways, and genes present across the spectrum of histopathological damage in COVID-19-affected lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from 46 areas of interest covering more than 62,000 cells within well-preserved lung samples from 3 patients.

Impacts of Image Obfuscation on Fine-grained Activity Recognition in Egocentric Video.

Automated detection and validation of fine-grained human activities from egocentric vision has gained increased attention in recent years due to the rich information afforded by RGB images. However, it is not easy to discern how much rich information is necessary to detect the activity of interest reliably. Localization of hands and objects in the image has proven helpful to distinguishing between hand-related fine-grained activities.

ActiSight: Wearer Foreground Extraction Using a Practical RGB-Thermal Wearable.

Wearable cameras provide an informative view of wearer activities, context, and interactions. Video obtained from wearable cameras is useful for life-logging, human activity recognition, visual confirmation, and other tasks widely utilized in mobile computing today. Extracting foreground information related to the wearer and separating irrelevant background pixels is the fundamental operation underlying these tasks.

launches Raw Data Letters.

A new category of articles - Raw Data Letters - is introduced to .

Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism.

Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking. The mechanism for Crohn's disease-like inflammation, lung fibrosis, and macrophage lipid accumulation in these patients remains enigmatic. The aim of this study is to understand the cellular basis of inflammation in HPS-1.

Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection.

Low-dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due to the cytokine's preferential expansion of immunosuppressive regulatory T cells (Tregs). However, off-target immune cell activation and short serum half-life limit the clinical potential of IL-2 treatment. Recent work showed that complexes comprising hIL-2 and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating Tregs over immune effector cells.