Evaluating the impact of stratification on the power and cross-arm balance of randomized phase 2 clinical trials.

Background/aims: Randomized clinical trials often use stratification to ensure balance between arms. Analysis of primary endpoints of these trials typically uses a "stratified analysis," in which analyses are performed separately in each subgroup defined by the stratification factors, and those separate analyses are weighted and combined. In the phase 3 setting, stratified analyses based on a small number of stratification factors can provide a small increase in power.

Cholangioblastic Cholangiocarcinoma (NIPBL::NACC1 cholangiocarcinoma): Expanded Morphologic Spectrum and Further Genetic Characterization.

The cholangioblastic variant of intrahepatic cholangiocarcinoma is a distinctive neoplasm that typically affects young women without underlying liver disease. Morphologically, it demonstrates solid, trabecular, and tubulocystic architecture, biphasic small cell-large cell cytology, and immunoreactivity for inhibin, neuroendocrine markers, and biliary but not hepatocellular markers. In 2021, our group identified a characteristic NIPBL::NACC1 gene fusion in cholangioblastic cholangiocarcinoma, and since then ~20 genetically confirmed cases have been reported in the literature.

Differential effect of nonpharmacological interventions according to prediabetes phenotype: Systematic review and meta-analysis of randomized clinical trials.

Background And Aims: Impaired glucose intolerance (IGT) and impaired fasting glucose (IFG) are totally different. Lifestyle modification is effective in moving from prediabetes to normoglycaemia. There is a lack of information showing the effect of lifestyle modification according to each prediabetes and assessing its effect on the degree of reversibility to normoglycaemia and on cardiometabolic markers.

Feasibility of home-based urine collection in children under 5 years in the ORIGINS birth cohort study: mixed method protocol and sample completion results.

Background: Urine is an attractive biospecimen for nutritional status and population health surveys. It is an excellent non-invasive alternative to blood for appropriate biomarkers in young children and is suitable for home-based collection, enabling representative collections across a population. However, the bulk of literature in this population is restricted to collection in primary care settings.

A rare haplotype of the GJD3 gene segregating in familial Meniere's disease interferes with connexin assembly.

Background: Familial Meniere's disease (FMD) is a rare polygenic disorder of the inner ear. Mutations in the connexin gene family, which encodes gap junction proteins, can also cause hearing loss, but their role in FMD is largely unknown.

Methods: We retrieved exome sequencing data from 94 individuals in 70 Meniere's disease (MD) families.

Derivation and validation of a clinical predictive model for longer duration diarrhea among pediatric patients in Kenya using machine learning algorithms.

Background: Despite the adverse health outcomes associated with longer duration diarrhea (LDD), there are currently no clinical decision tools for timely identification and better management of children with increased risk. This study utilizes machine learning (ML) to derive and validate a predictive model for LDD among children presenting with diarrhea to health facilities.

Methods: LDD was defined as a diarrhea episode lasting ≥ 7 days.

Clinical outcome changes in sarcopenic obesity: a meta-analysis of exercise training methods.

Aim: Assessing the effect of various forms of exercise training on patients with sarcopenic obesity.

Methods: Two independent reviewers systematically searched English and Chinese databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI) for randomized controlled trials on various exercise training effects in sarcopenic obesity patients until October 2023. Reference materials and grey literature were also included.

MRI-based analysis of the microstructure of the thalamus and hypothalamus and functional connectivity between cortical networks in episodic cluster headache.

Background: Neuroimaging studies have shown that hypothalamic/thalamic nuclei and other distant brain regions belonging to complex cerebral networks are involved in cluster headache (CH). However, the exact relationship between these areas, which may be dependent or independent, remains to be understood. We investigated differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the hypothalamus and thalamus in patients with episodic CH outside attacks and healthy controls (HCs).

Predicting the risk of hematoma expansion in acute intracerebral hemorrhage: the GIVE score.

Background: Numerous noncontrast computed tomography (NCCT) markers have been reported and validated as effective predictors of hematoma expansion (HE). Our objective was to develop and validate a score based on NCCT markers and clinical characteristics to predict risk of HE in acute intracerebral hemorrhage (ICH) patients.

Methods: We prospectively collected spontaneous ICH patients at the First Affiliated Hospital of Chongqing Medical University to form the development cohort (n = 395) and at the Third Affiliated Hospital of Chongqing Medical University to establish the validation cohort (n = 139).

Super-photostable organic dye for long-term live-cell single-protein imaging.

Organic dyes play a crucial role in live-cell imaging because of their advantageous properties, such as photostability and high brightness. Here we introduce a super-photostable and bright organic dye, Phoenix Fluor 555 (PF555), which exhibits an order-of-magnitude longer photobleaching lifetime than conventional organic dyes without the requirement of any anti-photobleaching additives. PF555 is an asymmetric cyanine structure in which, on one side, the indole in the conventional Cyanine-3 is substituted with 3-oxo-quinoline.

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

Patients with DCIS Seen at a Specialized High-Risk Breast Clinic Run by Surgical Advanced Practice Providers Have High Rates of Preventive Medication Uptake.

Background: Preventative medication (PM) uptake is low among patients at an elevated risk of breast cancer, largely due to fears of intolerance. This study aimed to investigate whether a new, surgical advanced practice provider (APP)-run clinic was effectively prescribing PM. We hypothesized equivalent rates of PM uptake compared to consultation with medical oncologists (MD).

The Landmark Series: The Future of Pancreatic Cancer Clinical Trials.

Pancreatic cancer has a poor prognosis despite ongoing advances in systemic and multimodal therapies. This review analyzes recent progress and future directions in pancreatic cancer clinical trials, emphasizing the evolution from traditional approaches to a more personalized and biologically-driven treatment paradigm. While improvements in overall survival have been achieved through perioperative therapies, gaps remain in our understanding of optimal treatment strategies.

Spatiotemporal imaging of nonlinear optics in van der Waals waveguides.

Van der Waals (vdW) semiconductors have emerged as promising platforms for efficient nonlinear optical conversion, including harmonic and entangled photon generation. Although major efforts are devoted to integrating vdW materials in nanoscale waveguides for miniaturization, the realization of efficient, phase-matched conversion in these platforms remains challenging. Here, to address this challenge, we report a far-field ultrafast imaging method to track the propagation of both fundamental and harmonic waves within vdW waveguides with femtosecond and sub-50 nanometre spatiotemporal precision.

Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.

Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.

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.

Incidence and management of internal hernia after laparoscopic Roux-en-Y gastric bypass without preventive closure of mesenteric defects: a single-center retrospective study.

The rising prevalence of obesity has led to an increase in bariatric procedures, with laparoscopic Roux-en-Y gastric bypass (LRYGB) being one of the most commonly performed surgeries due to its efficacy and safety. However, internal hernia (IH) remains a significant complication post-LRYGB. The debate over preventive closure of mesenteric defects (MD) during LRYGB continues, with no consensus on the optimal technique.

GestaltGAN: synthetic photorealistic portraits of individuals with rare genetic disorders.

The facial gestalt (overall facial morphology) is a characteristic clinical feature in many genetic disorders that is often essential for suspecting and establishing a specific diagnosis. Therefore, publishing images of individuals affected by pathogenic variants in disease-associated genes has been an important part of scientific communication. Furthermore, medical imaging data is also crucial for teaching and training deep-learning models such as GestaltMatcher.

Use of data mining algorithms in prediction of eggshell thickness from egg quality traits of Potchefstroom Koekoek layers.

Egg quality is affected by lot of factors. Study was conducted to compare performance of data mining algorithms; Classification and regression tree (CART), Chi-square automatic interaction detection (CHAID), Exhaustive chi-square automatic interaction detection (Ex-CHAID) and Multivariate adaptive regression spline (MARS) in prediction of Potchefstroom Koekoek's eggshell thickness from egg quality traits. 350 eggs were collected at 31st to 39th week to examine the egg quality traits.

Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.

Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.

Airborne observations reveal the fate of the methane from the Nord Stream pipelines.

The Nord Stream pipeline leaks on 26 September 2022 released 465 ± 20 kt of methane into the atmosphere, which is the largest recorded transient anthropogenic methane emission event. While most of the gas escaped directly to the atmosphere, a fraction dissolved in the water. So far, studies on the fate of this dissolved methane rely on pipeline volumetric estimates or spatially sparse concentration measurements and ocean models.

Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice.

Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain.

Photoreceptor metabolic window unveils eye-body interactions.

Photoreceptors are specialized neurons at the core of the retina's functionality, with optical accessibility and exceptional sensitivity to systemic metabolic stresses. Here we show the ability of risk-free, in vivo photoreceptor assessment as a window into systemic health and identify shared metabolic underpinnings of photoreceptor degeneration and multisystem health outcomes. A thinner photoreceptor layer thickness is significantly associated with an increased risk of future mortality and 13 multisystem diseases, while systematic analyses of circulating metabolomics enable the identification of 109 photoreceptor-related metabolites, which in turn elevate or reduce the risk of these health outcomes.