Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.

Development of MHz X-ray phase contrast imaging at the European XFEL.

We report on recent developments that enable megahertz hard X-ray phase contrast imaging (MHz XPCI) experiments at the Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) instrument of the European XFEL facility (EuXFEL). We describe the technical implementation of the key components, including an MHz fast camera and a modular indirect X-ray microscope system based on fast scintillators coupled through a high-resolution optical microscope, which enable full-field X-ray microscopy with phase contrast of fast and irreversible phenomena. The image quality for MHz XPCI data showed significant improvement compared with a pilot demonstration of the technique using parallel beam illumination, which also allows access to up to 24 keV photon energies at the SPB/SFX instrument of the EuXFEL.

Biomechanical changes in the lumbar and hip joint after curved periacetabular osteotomy.

Background: The alignment of the spine and pelvis significantly impacts overall body balance; therefore, alterations in hip and lumbar spine biomechanics following curved acetabular osteotomy (CPO) can help surgeons optimize acetabular correction. To achieve this goal, we conducted patient-specific finite element analyses to compare hip and lumbar disc contact pressure (CP) between patients with developmental dysplasia of the hip (DDH) and healthy individuals. Additionally, we examined the influence of CPO on the CP of both the hip and lumbar discs in patients with DDH.

Distribution and predictors of haemophilia-related costs in the United Kingdom: analysis of the CHESS I and CHESS II burden of illness studies.

Background: Few studies have evaluated direct medical or societal costs of haemophilia in the United Kingdom (UK), and how patient characteristics impact future costs is uncertain. Cost predictors were identified and examined using cross-sectional data from the CHESS I and II studies.

Methods: Patient- and physician-reported outcomes were analysed for UK adult males aged ≤ 65, with haemophilia A or B and no recent clinical trial participation.

Generalized XY model with competing antiferromagnetic and antinematic interactions.

I study effects of q-order antinematic (AN_{q}) interactions on the critical behavior of the antiferromagnetic (AF) XY model on a square lattice. It is found that the evolution of the phase diagram topology of such AF-AN_{q} models with the parameter q does not follow the same line as for the corresponding FM-N_{q} models with the ferromagnetic (FM) and q-order nematic (N_{q}) interactions. Their phase diagrams are similar only for odd values of the parameter q.

An iterative approach for estimating domain-specific cognitive abilities from large scale online cognitive data.

Online cognitive tasks are gaining traction as scalable and cost-effective alternatives to traditional supervised assessments. However, variability in peoples' home devices, visual and motor abilities, and speed-accuracy biases confound the specificity with which online tasks can measure cognitive abilities. To address these limitations, we developed IDoCT (Iterative Decomposition of Cognitive Tasks), a method for estimating domain-specific cognitive abilities and trial-difficulty scales from task performance timecourses in a data-driven manner while accounting for device and visuomotor latencies, unspecific cognitive processes and speed-accuracy trade-offs.

Combining interferon-γ release assays and metagenomic next-generation sequencing for diagnosis of pulmonary tuberculosis: a retrospective study.

Background: Rapid diagnosis of pulmonary tuberculosis (PTB) is urgently needed. We aimed to improve diagnosis rates by combining tuberculosis-interferon (IFN)-γ release assays (TB-IGRA) with metagenomic next-generation sequencing (mNGS) for PTB diagnosis.

Methods: A retrospective study of 29 PTB and 32 non-TB patients from our hospital was conducted between October 2022 and June 2023.

Understanding tumour growth variability in breast cancer xenograft models identifies PARP inhibition resistance biomarkers.

Understanding the mechanisms of resistance to PARP inhibitors (PARPi) is a clinical priority, especially in breast cancer. We developed a novel mathematical framework accounting for intrinsic resistance to olaparib, identified by fitting the model to tumour growth metrics from breast cancer patient-derived xenograft (PDX) data. Pre-treatment transcriptomic profiles were used with the calculated resistance to identify baseline biomarkers of resistance, including potential combination targets.

Association Between Sociodemographic Factors and Self-Reported Diabetic Retinopathy: A Cross-sectional, Population-Based Analysis.

Purpose: This study aimed to investigate the relationship between sociodemographic and healthcare access factors with self-reported diabetic retinopathy (DR) prevalence in a nationally representative sample of the United States.

Design: This is a population based, cross-sectional analysis.

Methods: Data from those who answered the question, "Have you ever been told by a doctor or other health professional that you had diabetic retinopathy?" from the 2017 National Health Interview Survey (NHIS) was analyzed through logistic regression to examine the association between DR prevalence and social determinants of health (SDH).

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

A comprehensive review on Chinese honeysuckle (): A Traditional Chinese plant.

According to Chinese Medicine system, Chinese honeysuckle have a lot of valuable metabolites which have a various potential like anti-inflammatory action, antidiabetic, analgesics, antipyretic, eliminates pollutants etc. According to Chinese Medicinal System, the plant is mentioned to cure various diseases like peptic ulcer, diabetes, inflammation etc. It is frequently given for patients with colds that include fever, headaches, and sore throats, but it may also be used to help people who are overheated or under stress chill down.

Combinatorial effector targeting (COMET) for transcriptional modulation and locus-specific biochemistry.

Understanding how human gene expression is coordinately regulated by functional units of proteins across the genome remains a major biological goal. Here, we present COMET, a high-throughput screening platform for combinatorial effector targeting for the identification of transcriptional modulators. We generate libraries of combinatorial dCas9-based fusion proteins, containing two to six effector domains, allowing us to systematically investigate more than 110,000 combinations of effector proteins at endogenous human loci for their influence on transcription.

Sex-Related Differences in Speaker Introductions at Ophthalmology Grand Rounds.

Purpose: Sex bias remains a pervasive reality in academic medicine, often reflected in subtle linguistic choices, which can skew perceptions of competence and perpetuate workplace inequity. This study aims to investigate the relationship between host sex, speaker sex, and speaker introduction practices in ophthalmology grand rounds events.

Design: Cross-sectional study.

Innovative hypertension treatments: Transitioning from conventional therapies to siRNA-based solutions.

Hypertension remains a critical global health issue, despite significant advancements in treatment, management and preventive approaches. Current antihypertensive drugs have limitations, such as low adherence, renin-angiotensin-aldosterone system reactivation, and drug resistance,. Ongoing preclinical and clinical studies for siRNA therapies show promising results, demonstrating significant blood pressure reductions and their potential as effective, durable treatments.

Pharmacokinetics of Enteral Lormetazepam in Mechanically Ventilated ICU Patients with COVID-19: An Adjunct Sedative Study.

Background And Objective: During the coronavirus disease 2019 (COVID-19) pandemic, sedative prescriptions surged, leading to shortages of midazolam. This study investigates lormetazepam as an adjunct sedative alternative to midazolam for mechanically ventilated patients with COVID-19. We aimed to determine the clinical pharmacokinetics (PK) of enterally administered lormetazepam and provide dosing recommendations.

Cerebral Infarct Growth: Pathophysiology, Pragmatic Assessment, and Clinical Implications.

Cerebral ischemic injury occurs when blood flow drops below a critical level, resulting in an energy failure. The progressive transformation of hypoperfused viable tissue, the ischemic penumbra, into infarction is a mechanism shared by patients with ischemic stroke if timely reperfusion is not achieved. Yet, the pace at which this transformation occurs, known as the infarct growth rate (IGR), exhibits remarkable heterogeneity among patients, brain regions, and over time, reflecting differences in compensatory collateral flow and ischemic tolerance.

Prebiotics in food and dietary supplements: a roadmap to EU health claims.

Numerous studies have established that prebiotic ingredients in foods and dietary supplements may play a role in supporting human health. Over the three decades that have passed since prebiotics were first defined as a concept, research has revealed a complex universe of prebiotic-induced changes to the human microbiota. There are strong indications of a direct link between these prebiotic-induced changes and specific health benefits.