Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.

Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (Ra) treatment, but their association with treatment outcomes is unclear.

Methods: For patients with metastatic castration-resistant prostate cancer treated with Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).

The TRIPOD-LLM reporting guideline for studies using large language models.

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion.

Usefulness of Aortic Valve Calcification in Patients With Low-Flow Aortic Stenosis.

Background: Aortic valve calcification (AVC) has been shown to be a powerful assessment of aortic stenosis (AS) severity and a predictor of adverse outcomes. However, its accuracy in patients with low-flow AS has not yet been proven. The objective of the study was to assess the predictive value of AVC in patients with classical low-flow (CLF, that is, low-flow reduced left ventricular ejection fraction) or paradoxical low-flow (PLF, that is, low-flow preserved left ventricular ejection fraction) AS.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Encompassing view of spatial and single-cell RNA sequencing renews the role of the microvasculature in human atherosclerosis.

Atherosclerosis is a pervasive contributor to ischemic heart disease and stroke. Despite the advance of lipid-lowering therapies and anti-hypertensive agents, the residual risk of an atherosclerotic event remains high, and developing therapeutic strategies has proven challenging. This is due to the complexity of atherosclerosis with a spatial interplay of multiple cell types within the vascular wall.

Transcriptomic profiling of thyroid eye disease orbital fat demonstrates differences in adipogenicity and IGF-1R pathway.

Despite recent advances in the treatment of thyroid eye disease thyroid-related eye disease (TED), marked gaps remain in our understanding of the underlying molecular mechanisms, particularly concerning the insulin-like growth factor-1 receptor (IGF-1R) pathway. To dissect the pathophysiology of TED, we used single-nucleus RNA-Seq to analyze orbital fat specimens from both patients with TED and matched individuals acting as controls. The analysis demonstrated a marked increase in the proportion of fibroblasts transitioning to adipogenesis in the orbital fat of patients with TED compared with that in control patients.

Immune changes in pregnancy: associations with pre-existing conditions and obstetrical complications at the 20th gestational week-a prospective cohort study.

Background: Pregnancy is a complex biological process and serious complications can arise when the delicate balance between the maternal and semi-allogeneic fetal immune systems is disrupted or challenged. Gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth, and low birth weight pose serious threats to maternal and fetal health. Identification of early biomarkers through an in-depth understanding of molecular mechanisms is critical for early intervention.

PyAMARES, an Open-Source Python Library for Fitting Magnetic Resonance Spectroscopy Data.

: Magnetic resonance spectroscopy (MRS) is a valuable tool for studying metabolic processes in vivo. While numerous quantification methods exist, the advanced method for accurate, robust, and efficient spectral fitting (AMARES) is among the most used. This study introduces pyAMARES, an open-source Python implementation of AMARES, addressing the need for a flexible, user-friendly, and versatile MRS quantification tool within the Python ecosystem.

Psychosocial and physical wellbeing in women and male partners undergoing immediate versus postponed modified natural cycle frozen embryo transfer after ovarian stimulation and oocyte pick-up: a sub-study of a randomized controlled trial.

Study Question: Are there differences in psychosocial and physical wellbeing among women and male partners undergoing modified natural cycle (mNC) frozen embryo transfer (FET) in immediate compared to postponed cycles after ovarian stimulation (OS) and oocyte pick-up (OPU)?

Summary Answer: Significantly more women in the immediate group reported physical symptoms than women in the postponed group whilst fewer were emotionally affected by waiting time, although the latter difference lost statistical significance after adjustment for multiple testing.

What Is Known Already: Infertility and fertility treatment are known to cause psychosocial distress in women and couples longing for a child. The treatment may be long-term and delayed for various reasons, such as the elective postponement of FET after a fresh transfer without pregnancy or an elective freeze-all cycle, possibly further increasing the level of distress.

Enhancing intestinal absorption of a macromolecule through engineered probiotic yeast in the murine gastrointestinal tract.

Oral administration of therapeutic peptides is limited by poor intestinal absorption. Use of engineered microorganisms as drug delivery vehicles can overcome the challenges faced by conventional delivery methods. The potential of engineered microorganisms to act synergistically with the therapeutics they deliver opens new horizons for noninvasive treatment modalities.

Red flags for potential serious pathologies in people with neck pain: a systematic review of clinical practice guidelines.

Introduction: We conducted a systematic review of clinical practice guidelines to identify red flags for serious pathologies in neck pain mentioned in clinical practice guidelines, to evaluate agreement in red flag recommendations across guidelines, and to investigate the level of evidence including what study type the recommendations are based on.

Methods: We searched for guidelines focusing on specific and nonspecific neck pain in MEDLINE, EMBASE, and PEDro up to June 9, 2023. Additionally, we searched for guidelines through citation tracking strategies, by consulting experts in the field, and by checking guideline organization databases.

Artificial intelligence-aided data mining of medical records for cancer detection and screening.

The application of artificial intelligence methods to electronic patient records paves the way for large-scale analysis of multimodal data. Such population-wide data describing deep phenotypes composed of thousands of features are now being leveraged to create data-driven algorithms, which in turn has led to improved methods for early cancer detection and screening. Remaining challenges include establishment of infrastructures for prospective testing of such methods, ways to assess biases given the data, and gathering of sufficiently large and diverse datasets that reflect disease heterogeneities across populations.

Associations of perceived neighbourhood and home environments with sedentary behaviour among adolescents in 14 countries: the IPEN adolescent cross sectional observational study.

Background: Understanding environmental correlates of sedentary behaviour (SB) among young people is important as such data can identify approaches to limit sedentary time. This paper estimates associations of parent-reported neighbourhood and adolescent-reported home environments with SB among adolescents aged 11-19 years from 14 countries.

Methods: In the International Physical activity and the Environment Network (IPEN) Adolescent Study (an observational, cross-sectional multi-country study), adolescents wore a triaxial accelerometer for seven days that assessed sedentary time (ST).

Susceptibility to and severity of SARS-CoV-2 infection according to prescription drug use-an observational study of 46,506 Danish healthcare workers.

It is not well investigated whether exposure to specific drug classes is associated with COVID-19. We investigated the risk of SARS-CoV-2 infection and severe COVID-19 among healthcare workers according to prescription drug use. We conducted an observational study among Danish healthcare workers.

Adult Phenotype of -Associated Disorders.

Background And Objectives: Pathogenic variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with variants.

Functional Outcome Measures to Optimize Drug Development in Spinal and Bulbar Muscular Atrophy: Results From a Meta-Analysis of the Global SBMA Dataset.

Background And Objectives: Spinal and bulbar muscular atrophy (SBMA) is a rare, slowly progressive, and debilitating disease without effective treatments available. Lack of reliable biomarkers and sensitive outcome measures makes clinical research conduct challenging. The primary objective of this study was to identify clinically meaningful and statistically sensitive outcome measures enabling the evaluation of therapeutic interventions in late-stage clinical trials.

Halving premature death and improving quality of life at all ages: cross-country analyses of past trends and future directions.

Background: Although death in old age is unavoidable, premature death-defined here as death before age 70 years-is not. To assess whether halving premature mortality by 2050 is feasible, we examined the large variation in premature death rates before age 70 years and trends over the past 50 years (1970-2019), covering ten world regions and the 30 most-populous nations. This analysis was undertaken in conjunction with the third report of The Lancet Commission on Investing in Health: Global Health 2050: the path to halving premature death by mid-century.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Protocol for a randomised, double-blinded, controlled trial of youth with childhood-onset obesity treated with semaglutide 2.4 mg/week: the RESETTLE trial.

Introduction: Childhood-onset obesity poses significant health risks, including early-onset type 2 diabetes, cardiovascular disease, and reduced quality of life. Hospital-based non-pharmacological obesity care can reduce childhood obesity, but 25% of children do not respond. Therefore, this study investigates the effect of the glucagon-like peptide-1 receptor agonist, semaglutide, as an add-on to hospital-based obesity care in youth who still have obesity following hospital-based obesity care as children.

Epigenomic biomarkers of cardiometabolic disease: How far are we from daily practice?

Determining whether someone has cardiometabolic disease (CMD), especially in the early stages, can be complicated. Risk stratification ordinarily depends on an extended process relying on medical history that typically considers blood pressure, cholesterol, smoking and diabetes status. Physicians have long relied on these key patient characteristics to assess CMD risk.