Safety of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer: A meta-analysis based expert panel discussion.

Importance: Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain.

Predictive model of intrahepatic collateral vessels among hepatic veins in patients with liver tumors involving the caval confluence.

Background: Communicating vessels among hepatic veins in patients with tumors invading/compressing hepatic veins at their caval confluence facilitate new surgical solutions. Although their recognition by intraoperative ultrasound has been described, the possibility of preoperative detection still remains uncertain. We aimed to develop a model to predict their presence before surgery.

Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis.

In the primary analysis of the open-label phase III PRECIOUS study, pertuzumab retreatment combined with trastuzumab plus chemotherapy of physician's choice (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with trastuzumab plus physician's choice chemotherapy (TC) in patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced/metastatic breast cancer (LA/mBC). Here, we report final overall survival (OS) at the median follow-up of 25.8 months.

Prevalence of FGFR2b Protein Overexpression in Advanced Gastric Cancers During Prescreening for the Phase III FORTITUDE-101 Trial.

Purpose: Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC.

Methods: As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.

Virtual patients using large language models: Scalable, contextualized simulation of clinician-patient dialog with feedback.

Background: Virtual patients (VPs) are computer screen-based simulations of patient-clinician encounters. VP use is limited by cost and low scalability.

Objective: Show proof-of-concept that VPs powered by large language models (LLMs) generate authentic dialogs, accurate representations of patient preferences, and personalized feedback on clinical performance; and explore LLMs for rating dialog and feedback quality.

Magnetic resonance angiography in diagnostic long-term follow-up of primary patency of the MOTIV drug-eluting bioresorbable vascular scaffold in the region below the knee: 5 years of experience.

Purpose: Treatment of peripheral artery disease (PAD) in the region below the knee (BTK) is dissatisfying as failure of treated target lesions (TLF) is frequent and diagnostic imaging is often challenging. In the BTK-region metallic drug-eluting stents (mDES) yielded best results concerning primary patency (PP), but also annihilate signal in magnetic resonance angiography (MR-A). A recently introduced non-metallic drug eluting bioresorbable Tyrocore® vascular scaffold (deBVS), that offers an option for re-treatment of lesions due to its full degradation within 3-4 years after placement, was investigated with respect to its compatibility with MR-A to unimpededly depict previously treated target lesions.

Investigating the functional and structural effect of non-synonymous single nucleotide polymorphisms in the cytotoxic T-lymphocyte antigen-4 gene: An in-silico study.

The cytotoxic T-lymphocyte antigen-4 (CTLA4) is essential in controlling T cell activity within the immune system. Thus, uncovering the molecular dynamics of single nucleotide polymorphisms (SNPs) within the CTLA4 gene is critical. We identified the non-synonymous SNPs (nsSNPs), examined their impact on protein stability, and identified the protein sequences associated with them in the human CTLA4 gene.

Analysis of seroprevalence and risk factors for syphilis and HIV among female sex workers and transgender individuals in different cities of Sindh, Pakistan.

Introduction: Co-infections of syphilis and HIV have been found to exacerbate the impact on sexual and reproductive health, especially among key population groups such as Female Sex Workers (FSWs) and Transgender Individuals (TGs). The data on the prevalence and determinants of syphilis and HIV in Pakistan, particularly in Sindh province, is limited. This prospective cross-sectional study aimed to determine the seroprevalence and risk factors for HIV and syphilis infections among FSWs and TGs in different cities of Sindh, Pakistan.

Impacts of continuing education on Primary Health Care professionals-A scoping review protocol.

Introduction: Continuing Health Education is a strategy that integrates learning into the work process to transform health practices. Primary health care has proved to be a powerful space for consolidating continuing education, as it promotes reflection and learning based on the local singularities of the territory. Continuing health education is an important strategy for transforming the reality of Primary health care, reinventing work, and consequently changing practices.

Insulin therapy adherence and its associated factors among diabetic patients in a Ghanaian primary care hospital.

Background: Diabetes mellitus (DM) is a global health problem. Adherence to intensive insulin therapy is necessary to achieve better glycemic control in types 1 and 2 DM. This study aimed to evaluate the extent of adherence to insulin therapy, its predictors and to identify barriers to its adherence.

The type of diet consumed during prepuberty modulates plasma cholesterol, hepatic LXRα expression, and DNA methylation and hydroxymethylation during adulthood in male rats.

Childhood obesity increases the risk of developing metabolic diseases in adulthood, since environmental stimuli during critical windows of development can impact on adult metabolic health. Studies demonstrating the effect of prepubertal diet on adult metabolic disease risk are still limited. We hypothesized that a prepubertal control diet (CD) protects the adult metabolic phenotype from diet-induced obesity (DIO), while a high-fat diet (HFD) would predispose to adult metabolic alterations.

Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy.

Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.

The X chromosome's influences on the human brain.

Genes on the X chromosome are extensively expressed in the human brain. However, little is known for the X chromosome's impact on the brain anatomy, microstructure, and functional networks. We examined 1045 complex brain imaging traits from 38,529 participants in the UK Biobank.

Mature chromatin packing domains persist after RAD21 depletion in 3D.

Understanding chromatin organization requires integrating measurements of genome connectivity and physical structure. It is well established that cohesin is essential for TAD and loop connectivity features in Hi-C, but the corresponding change in physical structure has not been studied using electron microscopy. Pairing chromatin scanning transmission electron tomography with multiomic analysis and single-molecule localization microscopy, we study the role of cohesin in regulating the conformationally defined chromatin nanoscopic packing domains.

Bioprinted optoelectronically active cardiac tissues.

Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation-induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light.

Evidence of a persistent altered neural state in people with fibromyalgia syndrome during functional MRI studies and its relationship with pain and anxiety.

Altered neural signaling in fibromyalgia syndrome (FM) was investigated with functional magnetic resonance imaging (fMRI). We employed a novel fMRI network analysis method, Structural and Physiological Modeling (SAPM), which provides more detailed information than previous methods. The study involved brain fMRI data from participants with FM (N = 22) and a control group (HC, N = 18), acquired during a noxious stimulation paradigm.

Realist evaluation of the AKU-SONAM mentorship program.

Background & Objectives: The context, mechanism, and outcome (CMO) framework is meant to identify specific contextual factors (C) related to organizational and program structure that trigger certain mechanisms (M) involving the unique characteristics of a program, leading to specific outcomes (O). The purpose of this study was to explore the contextual underpinnings, operational processes, and resultant effects of the faculty mentorship program at AKU-SONAM. This exploration involved the context in terms of organizational culture, mechanisms examining processes such as communication between mentors and mentees, quality of relationships, the challenges encountered, and the program's adaptability to cope up while, outcomes encompassed improvements in interpersonal relationships, career advancement, and skill development.

Weight trajectories in aging humanized APOE mice with translational validity to human Alzheimer's risk population: A retrospective analysis.

Translational validity of mouse models of Alzheimer's disease (AD) is variable. Because change in weight is a well-documented precursor of AD, we investigated whether diversity of human AD risk weight phenotypes was evident in a longitudinally characterized cohort of 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months of age which is equivalent to 81 human years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, and APOE genotype was employed to identify emergent weight trajectories and phenotypes.

Exploiting the similarity of dissimilarities for biomedical applications and enhanced machine learning.

The "similarity of dissimilarities" is an emerging paradigm in biomedical science with significant implications for protein function prediction, machine learning (ML), and personalized medicine. In protein function prediction, recognizing dissimilarities alongside similarities provides a more detailed understanding of evolutionary processes, allowing for a deeper exploration of regions that influence biological functionality. For ML models, incorporating dissimilarity measures helps avoid misleading results caused by highly correlated or similar data, addressing confounding issues like the Doppelgänger Effect.

Physical activity and metabolic syndrome in primary care patients in Spain.

Purpose: To determine the relationship between self-reported physical activity and the components of premorbid metabolic syndrome in patients treated in primary care according to sex.

Methods: Cross-sectional descriptive study conducted on a sample of 2,359 patients without cardiovascular disease or diabetes, included in the cohort of the IBERICAN study. Using ANOVA models and adjusting for age, economic status, employment situation, level of education, adherence to a Mediterranean diet, tobacco use and alcohol consumption, we estimated the association of the variables blood pressure, triglycerides, HDL cholesterol, blood glucose and waist circumference with the self-reported level of physical activity (sedentary, moderate, high, very high).

Detection and analysis of Serpin and RP26 specific antibodies for monitoring Schistosoma haematobium transmission.

Background: Schistosoma haematobium is the causative pathogen for urogenital schistosomiasis. To achieve progress towards schistosomiasis elimination, there is a critical need for developing highly sensitive and specific tools to monitor transmission in near-elimination settings. Although antibody detection is a promising approach, it is usually unable to discriminate active infections from past ones.

Transcranial Doppler sonography follow-up study in mild vascular cognitive impairment.

Background: To date, few data to transcranial Doppler sonography (TCD) are available in patients with mild vascular cognitive impairment (VCI) at risk for vascular or mixed dementia. In a previous study in patients with mild VCI and cerebral small vessels disease, a hemodynamic pattern of cerebral hypoperfusion and enhanced vascular resistance were observed; however, longitudinal data are currently lacking. Here, we perform a clinical, psychopathological, and neurosonological follow-up of patients with VCI in order to monitor any progression and to identify TCD measures to detect it.

Assessment of temporospatial and kinematic gait parameters using human pose estimation in patients with Parkinson's disease: A comparison between near-frontal and lateral views.

Gait disturbance is one of the most common symptoms in patients with Parkinson's disease (PD) that is closely associated with poor clinical outcomes. Recently, video-based human pose estimation (HPE) technology has attracted attention as a cheaper and simpler method for performing gait analysis than marker-based 3D motion capture systems. However, it remains unclear whether video-based HPE is a feasible method for measuring temporospatial and kinematic gait parameters in patients with PD and how this function varies with camera position.

Reference Values for Water-Specific T1, Intermuscular and Intramuscular Fat Content in Skeletal Muscle at 2.89 T.

Background: MRI offers quantification of proton density fat fraction (PDFF) and tissue characteristics with T1 mapping. The influence of age, sex, and the potential confounding effects of fat on T1 values in skeletal muscle in healthy adults are insufficiently known.

Purpose: To determine the accuracy and repeatability of a saturation-recovery chemical-shift encoded multiparametric approach (SR-CSE) for quantification of T1 and muscle fat content, and establish normative values (age, sex) from a healthy cohort.

Semi-Synthesis of Dimeric Cannabidiol Derivatives and Evaluation of their Affinity at Neurological Targets.

Cannabidiol (CBD) is a natural product associated with a wide range of biological and therapeutic activities. Despite the widespread cultural acceptance of CBD as a medicinal agent, much remains to be determined regarding its precise mechanism(s) of action in treating multiple conditions. CBD has been shown to promiscuously interact with several neurological targets with varying affinities.