The NeuroML ecosystem for standardized multi-scale modeling in neuroscience.

Data-driven models of neurons and circuits are important for understanding how the properties of membrane conductances, synapses, dendrites, and the anatomical connectivity between neurons generate the complex dynamical behaviors of brain circuits in health and disease. However, the inherent complexity of these biological processes makes the construction and reuse of biologically detailed models challenging. A wide range of tools have been developed to aid their construction and simulation, but differences in design and internal representation act as technical barriers to those who wish to use data-driven models in their research workflows.

Slower swimming promotes chemotactic encounters between bacteria and small phytoplankton.

Chemotaxis enables marine bacteria to increase encounters with phytoplankton cells by reducing their search times, provided that bacteria detect noisy chemical gradients around phytoplankton. Gradient detection depends on bacterial phenotypes and phytoplankton size: large phytoplankton produce spatially extended but shallow gradients, whereas small phytoplankton produce steeper but spatially more confined gradients. To date, it has remained unclear how phytoplankton size and bacterial swimming speed affect bacteria's gradient detection ability and search times for phytoplankton.

Mapping patterns of thought onto brain activity during movie-watching.

Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the 'here and now' depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching.

CD3+ Tumor-Infiltrating Lymphocytes in Breast Carcinoma: Their Prognostic Role and Association With Clinical Parameters.

Background Breast carcinoma cases are rising steadily and represent a major cause of mortality and morbidity in India. In response to breast carcinoma, the immune system is activated, resulting in lymphocyte infiltration in and around the tumor nests. This interaction between the tumor and immune system is the basis for studying tumor-infiltrating lymphocytes (TILs).

Explainable unsupervised anomaly detection for healthcare insurance data.

Background: Waste and fraud are important problems for health insurers to deal with. With the advent of big data, these insurers are looking more and more towards data mining and machine learning methods to help in detecting waste and fraud. However, labeled data is costly and difficult to acquire as it requires expert investigators and known care providers with atypical behavior.

Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells.

Background: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors.

CRISPR-Enabled Autonomous Transposable Element (CREATE) for RNA-based gene editing and delivery.

To address a wide range of genetic diseases, genome editing tools that can achieve targeted delivery of large genes without causing double-strand breaks (DSBs) or requiring DNA templates are necessary. Here, we introduce CRISPR-Enabled Autonomous Transposable Element (CREATE), a genome editing system that combines the programmability and precision of CRISPR/Cas9 with the RNA-mediated gene insertion capabilities of the human LINE-1 (L1) element. CREATE employs a modified L1 mRNA to carry a payload gene, and a Cas9 nickase to facilitate targeted editing by L1-mediated reverse transcription and integration without relying on DSBs or DNA templates.

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.

Vitamin D as an add-on therapy to phosphodiesterase-5 inhibitor in experimental pulmonary arterial hypertension.

Severe vitamin D (vitD) deficiency is a very common condition in patients with pulmonary arterial hypertension (PAH) and it is predictor of poor prognosis. There is emerging evidence suggesting a connection between the insufficient response to phosphodiesterase-5 inhibitors (PDE5i) and vitD deficiency in patients with PAH. In the present translational study, vitD deficiency was induced in Wistar rats by exposure to vitD free diet for 5 weeks and followed by Su5416 administration and hypoxia (10%) for 3 weeks, a standard experimental model of PAH.

A high-throughput platform for single-molecule tracking identifies drug interaction and cellular mechanisms.

The regulation of cell physiology depends largely upon interactions of functionally distinct proteins and cellular components. These interactions may be transient or long-lived, but often affect protein motion. Measurement of protein dynamics within a cellular environment, particularly while perturbing protein function with small molecules, may enable dissection of key interactions and facilitate drug discovery; however, current approaches are limited by throughput with respect to data acquisition and analysis.

Percutaneous transhepatic arterial access for coil embolization of hepatic artery infusion pump-associated bleeding.

Background: Hepatic artery infusion pump (HAIP) chemotherapy is a locoregional treatment for intrahepatic malignancies. HAIPs are surgically implanted, and the catheter tip is typically inserted into a ligated gastroduodenal artery stump. Potential complications at the catheter insertion site include dehiscence, pseudoaneurysm or extravasation, and adjacent hepatic arterial stenosis and thrombosis.

Novel insights into the role of gut microbiota and its metabolites in diabetic chronic wounds.

Wounds in patients with diabetes present significant physical and economic challenges due to impaired healing and prolonged inflammation, exacerbated by complex interactions between microbes. Especially, the development and healing of diabetic foot ulcers (DFUs) remain an urgent clinical problem. The human gut harbors a vast microbial ecosystem comprising intestinal flora and their metabolic products.

Clinical and immunological outcomes after randomized trial of baked milk oral immunotherapy for milk allergy.

BACKGROUNDCow's milk (CM) allergy is the most common food allergy in young children. Treatment with oral immunotherapy (OIT) has shown efficacy, but high rates of adverse reactions. The aim of this study was to determine whether baked milk OIT (BMOIT) could reduce adverse reactions while still inducing desensitization, and to identify immunological correlates of successful BMOIT.

Benzimidazole Derivatives in Breast Cancer: Target-Specific Therapeutic Breakthroughs.

Despite ongoing advancements in drug design and developments, breast cancer remains a serious and devastating disease and is ranked as the second most common illness in women. Breast cancer rates have increased significantly during the last 40 years. This necessitates the development of novel treatment techniques.

Is mesh related morbidity the real thread in ventral rectopexy? Results of a retrospective international multicentre comparative analysis of biologic versus synthetic mesh.

Aim: Ventral mesh rectopexy (VMR) is an established surgical treatment for rectal prolapse and outlet obstruction. In contrast to continental Europe, in the UK and US the use of synthetic mesh has been abandoned in favour of biologic mesh, due to concerns regarding mesh related morbidity. The current study investigated if either material is superior, in terms of clinical recurrence and mesh related complications.

Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS.

Background: The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established.

Fertility journey of a patient with McCune-Albright syndrome associated with bilateral ovarian involvement.

Objective: To report a patient with McCune-Albright syndrome (MAS) with bilateral ovarian involvement who had achieved a pregnancy through in vitro fertilization (IVF).

Design: Case report.

Setting: Academic fertility center.

Arthroscopic-Assisted Lower Trapezius Tendon Transfer With Fascia Lata Autograft for Irreparable Posterior-Superior Rotator Cuff Tears.

Lower trapezius tendon transfer is a surgical procedure that has become increasingly popular in recent years. The biggest advantage of this method is that the pulling direction of the lower trapezius is the same as that of the infraspinatus. Thus, the transferred lower trapezius tendon can biomechanically mimic the functions of the posterior-superior rotator cuff.

Breaking boundaries: role of the brain barriers in metastatic process.

Brain metastases (BMs) are the most common intracranial tumors in adults and occur 3-10 times more frequently than primary brain tumors. Despite intensive multimodal therapies, including resection, radiotherapy, and chemotherapy, BMs are associated with poor prognosis and remain challenging to treat. BMs predominantly originate from primary lung (20-56%), breast (5-20%), and melanoma (7-16%) tumors, although they can arise from other cancer types less frequently.

The q-RASPR approach for predicting the property and fate of persistent organic pollutants.

This study presents a quantitative read-across structure-property relationship (q-RASPR) approach that integrates the chemical similarity information used in read-across with traditional quantitative structure-property relationship (QSPR) models. This novel framework is applied to predict the physicochemical properties and environmental behaviors of persistent organic pollutants, specifically polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). By utilizing a curated dataset and incorporating similarity-based descriptors, the q-RASPR approach improves the accuracy of predictions, particularly for compounds with limited experimental data.

Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals.

The analysis of circulating tumour DNA (ctDNA) through minimally invasive liquid biopsies is promising for early multi-cancer detection and monitoring minimal residual disease. Most existing methods focus on targeted deep sequencing, but few integrate multiple data modalities. Here, we develop a methodology for ctDNA detection using deep (80x) whole-genome TET-Assisted Pyridine Borane Sequencing (TAPS), a less destructive approach than bisulphite sequencing, which permits the simultaneous analysis of genomic and methylomic data.

Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study.

Introduction: The prognostic value of PAM50 intrinsic subtypes (IS), cell cycle, and immune-related gene expression in HR+ /HER2- advanced breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) in a first-line metastatic setting is unclear. This study evaluates these biomarkers in metastatic biopsies from patients diagnosed with HR+ /HER2- advanced BC.

Methods: CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals.

The Taiwan-ADNI workflow toward integrating plasma p-tau217 into prediction models for the risk of Alzheimer's disease and tau burden.

Introduction: We integrated plasma biomarkers from the Taiwan Alzheimer's Disease Neuroimaging Initiative and propose a workflow to identify individuals showing amyloid-positive positron emission tomography (PET) with low/intermediate tau burden based on [18F]Florzolotau PET-based quantification.

Methods: We assessed 361 participants across the Alzheimer's disease (AD) and non-AD continuum and measured plasma phosphorylated tau (p-tau)217, p-tau181, amyloid beta (Aβ)42/40 ratio, neurofilament light chain, and glial fibrillary acidic protein levels at two medical centers. We evaluated the diagnostic potential of these biomarkers.

Breaking the Bone Marrow Barrier: Peripheral Blood as a Gateway to Measurable Residual Disease Detection in Acute Myelogenous Leukemia.

Acute myeloid leukemia (AML) is a genetically heterogeneous disease with high rates of relapse after initial treatment. Identifying measurable residual disease (MRD) following initial therapy is essential to assess response, predict patient outcomes, and identify those in need of additional intervention. Currently, MRD analysis relies on invasive, serial bone marrow (BM) biopsies, which complicate sample availability and processing time and negatively impact patient experience.

Longitudinal association between nailfold capillaroscopy and incident interstitial lung disease: A EUSTAR database analysis.

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease.

Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e.