Conserved patterns of transcriptional dysregulation, heterogeneity, and cell states in clear cell kidney cancer.

Clear cell kidney cancers are characterized both by conserved oncogenic driver events and by marked intratumor genetic and phenotypic heterogeneity, which help drive tumor progression, metastasis, and resistance to therapy. How these are reflected in transcriptional programs within the cancer and stromal cell components remains an important question with the potential to drive novel therapeutic approaches to treating cancer. To better understand these programs, we perform single-cell transcriptomics on 75 multi-regional biopsies from kidney tumors and normal kidney.

Low Vision Rehabilitation Referral Characteristics for Patients with Neovascular Age-Related Macular Degeneration.

: Despite evidence that low vision rehabilitation (LVR) services can improve visual function in patients with neovascular age-related macular degeneration (nAMD), many patients are not directed to access these resources. This study was conducted to determine factors associated with LVR referral and to assess the visual outcomes from completed evaluations. : The study comprised a retrospective, cross-sectional analysis of patients with nAMD.

Low-dose methotrexate in Rheumatology: A reinvented drug.

Low-dose methotrexate (LD-MTX) is the anchor drug used in the treatment of various rheumatological illnesses. There are a lot of misconceptions associated with the long-term use of MTX in the minds of practitioners. The origin of most of these myths stems from the ill effects associated with high-dose MTX used in cancer chemotherapy.

Modeling Malignant Mesothelioma in Genetically Engineered Mice.

Mesothelioma is a lethal cancer of the serosal lining of the body cavities. Risk factors include environmental and genetic factors. Asbestos exposure is considered the principal environmental risk factor, but other carcinogenic mineral fibers, such as erionite, also have a causal role.

A protocol to study the effect of targeted parental education intervention to identify early childhood development disorder - multisite interventional study.

Background: In India, approximately 3.5 million children are affected by Developmental Delay (DD), often stemming from preterm births. These delays contribute to neurological and motor development delays, placing a significant financial burden on families.

Ongoing replication stress tolerance and clonal T cell responses distinguish liver and lung recurrence and outcomes in pancreatic cancer.

Patients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype.

Analysis of time to regulatory approval in an exception from informed consent trial in trauma patients.

Background: The interactive media-based approach to community consultation and public disclosure (CC/PD), a key step when conducting exception from informed consent (EFIC) clinical trials, is intended to be completed in 4 months. This analysis characterizes the process, from initiation of CC/PD activities to institutional review board approval, to better understand the barriers and how these can be mitigated.

Methods: This is a retrospective post hoc analysis of data collected as part of the CC/PD campaigns conducted for a large trial involving up to 90 trauma centers in the United States.

Screening for cardiac sarcoidosis: diagnostic approach and long-term follow-up in a tertiary centre.

Background: Cardiac sarcoidosis (CS) is associated with poor prognosis, making early diagnosis and treatment important. This study evaluated the results of a diagnostic approach in patients with known sarcoidosis and suspected cardiac involvement in a tertiary centre and their long-term outcomes.

Methods: We included 180 patients with sarcoidosis and a clinical suspicion of CS.

Impact of Heart Transplant Allocation Changes on Waitlist Mortality and Clinical Practice in Pediatric and Adult Patients With Congenital Heart Disease and Cardiomyopathy.

Background: The United Network of Organ Sharing made changes to the priority for allocation of hearts for transplantation (HT) in 2016 for pediatric patients and 2018 for adult patients. Although recent work has evaluated the impact of the revised allocation systems on mechanical circulatory support practices and waitlist outcomes, there are limited data that focus more specifically on the impact of the allocation changes on patients with congenital heart disease (CHD) or cardiomyopathy and how these relationships might differ in pediatric and adult patients.

Methods: The United Network of Organ Sharing database was queried for pediatric (<18 years of age) and adult (18-50 years of age) patients with a CHD or cardiomyopathy diagnosis listed for HT.

A rare PRIMER cell state in plant immunity.

Plants lack specialized and mobile immune cells. Consequently, any cell type that encounters pathogens must mount immune responses and communicate with surrounding cells for successful defence. However, the diversity, spatial organization and function of cellular immune states in pathogen-infected plants are poorly understood.

Establishing reference curves for vital tissue perfusion using quantitative near-infrared fluorescence imaging with indocyanine green.

Purpose: Assessment of tissue perfusion using near-infrared fluorescence (NIR) with indocyanine green (ICG) is gaining popularity, however reliable and objective interpretation remains a challenge. Therefore, this study aimed to establish reference curves for vital tissue perfusion across target tissues using this imaging modality.

Methods: Data from five prospective study cohorts conducted in three Dutch academic medical centres between December 2018 and June 2023 was included.

Development and validation of computable social phenotypes for health-related social needs.

Objective: Measurement of health-related social needs (HRSNs) is complex. We sought to develop and validate computable phenotypes (CPs) using structured electronic health record (EHR) data for food insecurity, housing instability, financial insecurity, transportation barriers, and a composite-type measure of these, using human-defined rule-based and machine learning (ML) classifier approaches.

Materials And Methods: We collected HRSN surveys as the reference standard and obtained EHR data from 1550 patients in 3 health systems from 2 states.

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.

Angiogenic factors versus fetomaternal Doppler for fetal growth restriction at term: an open-label, randomized controlled trial.

Small fetuses, with estimated fetal weight (EFW) below the tenth percentile, are classified as fetal growth restriction (FGR) or small for gestational age (SGA) based on prenatal ultrasound. FGR fetuses have a greater risk of stillbirth and perinatal complications and may benefit from serial ultrasound scans to guide early delivery. Abnormal serum angiogenic factors, such as the soluble fms-like tyrosine kinase-1 (sFlt-1):placental growth factor (PlGF) ratio, have shown potential to more accurately distinguish FGR from SGA, with fewer false positives.

Effects of early, late and self-selected time-restricted eating on visceral adipose tissue and cardiometabolic health in participants with overweight or obesity: a randomized controlled trial.

The optimal eating window for time-restricted eating (TRE) remains unclear, particularly its impact on visceral adipose tissue (VAT), which is associated with cardiometabolic morbidity and mortality. We investigated the effects of three TRE schedules (8 h windows in the early day, late day and participant-chosen times) combined with usual care (UC, based on education about the Mediterranean diet) versus UC alone over 12 weeks in adults with overweight or obesity. The primary outcome was VAT changes measured by magnetic resonance imaging.

A case study on using a large language model to analyze continuous glucose monitoring data.

Continuous glucose monitors (CGM) provide valuable insights about glycemic control that aid in diabetes management. However, interpreting metrics and charts and synthesizing them into linguistic summaries is often non-trivial for patients and providers. The advent of large language models (LLMs) has enabled real-time text generation and summarization of medical data.

Do low-risk patients really need follow-up after a pulmonary embolism?

Background: The British Thoracic Society recommend that pulmonary embolism (PE) patients with low-risk Pulmonary Embolism Severity Index (PESI) scores are considered for outpatient (OP) management, in settings where robust pathways for follow-up and monitoring exist.

Methods: Retrospective cohort study. We reviewed the electronic records of 109 consecutive PE patients considered appropriate for OP management.

Skin adaptation in lower limb amputees assessed through Raman spectroscopy and mechanical characterization.

Following lower limb amputation residuum skin from the lower leg is used to reconstruct the residual limb. Unlike skin on the sole of the foot (plantar skin), leg skin is not inherently load bearing. Despite this, leg skin is required to be load bearing in the prosthetic socket.

Optimizing contact tracing for avian influenza in poultry flocks.

Contact tracing is commonly used to manage infectious diseases of both humans and animals. It aims to detect early and control potentially infected individuals or farms that had contact with infectious cases. Because it is very resource-intensive, contact tracing is usually performed on a pre-defined time window, based on previous knowledge of the duration of the incubation period.

State-space modelling using wastewater virus and epidemiological data to estimate reported COVID-19 cases and the potential infection numbers.

The current situation of COVID-19 measures makes it difficult to accurately assess the prevalence of SARS-CoV-2 due to a decrease in reporting rates, leading to missed initial transmission events and subsequent outbreaks. There is growing recognition that wastewater virus data assist in estimating potential infections, including asymptomatic and unreported infections. Understanding the COVID-19 situation hidden behind the reported cases is critical for decision-making when choosing appropriate social intervention measures.

Sex Differences in Participation Restriction in Social Activities Among Older Stroke Survivors: A Nationwide Study.

Background: Women experience more poststroke physical activity limitations, but sex differences in social activity participation, an important patient-reported outcome for stroke recovery, remain uncertain.

Methods: Incident stroke survivors aged ≥65 years were identified from the US NHATS (National Health and Aging Trends Study), 2011-2022. Participants were asked to report restricted participation in the past month in 2 formal activities (religious services and clubs/classes) and 2 informal activities (visiting friends/family and going out for enjoyment) in the year of stroke onset.

Novel Lipid Formulation Increases Absorption of Oral Cannabidiol (CBD).

: Cannabidiol (CBD) is an approved treatment for childhood epilepsies and a candidate treatment for several other CNS disorders. However, it has poor oral bioavailability. We investigated the effect of a novel lipid formulation on its absorption in humans and on its tissue distribution in mice.

Translocation: A Common Tumor Driver of Distinct Human Neoplasms.

Cancer is among the leading causes of mortality in developed countries due to limited available therapeutic modalities and high rate of morbidity. Although malignancies might show individual genetic landscapes, recurring aberrations in the neoplastic genome have been identified in the wide range of transformed cells. These include translocations of frequently affected loci of the human genetic material like the Ewing sarcoma breakpoint region 1 () of chromosome 22 that results in malignancies with mesodermal origin.