Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Patterns of neuronal synchrony in higher-order networks.

Synchrony in neuronal networks is crucial for cognitive functions, motor coordination, and various neurological disorders. While traditional research has focused on pairwise interactions between neurons, recent studies highlight the importance of higher-order interactions involving multiple neurons. Both types of interactions lead to complex synchronous spatiotemporal patterns, including the fascinating phenomenon of chimera states, where synchronized and desynchronized neuronal activity coexist.

Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Purpose: ATM germline pathogenic variants (GPVs) are associated with a moderately increased risk of female breast cancer, pancreatic cancer, and prostate cancer. Resources for managing ATM heterozygotes in clinical practice are limited.

Methods: An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion.

The incidence of pancreatic cancer in women with a BRCA1 or BRCA2 mutation.

Background: The lifetime risk of pancreatic cancer in women with a germline mutation in BRCA1 and BRCA2 is not well established. In an international prospective cohort of female carriers of BRCA1 and BRCA2 mutations, the cumulative incidence of pancreatic cancer from age 40 until 80 years was estimated.

Methods: A total of 8295 women with a BRCA1 or BRCA2 mutation were followed for new cases of pancreatic cancer.

The Impact of Heart Failure Chronic Treatment Prior to Cardiac Transplantation on Early Outcomes.

: Cardiac transplantation represents the option for patients with end-stage heart failure (HF), providing the best survival rate. However, the postoperative complications of transplant patients remain a challenge for clinicians. The objective of our study was to evaluate the effect of preoperative chronic HF treatment on the occurrence of in-hospital complications.

Hormonal Actions in the Medial Preoptic Area Governing Parental Behavior: Novel Insights From New Tools.

The importance of hormones in mediating a behavioral transition in mammals from a virgin or nonparenting state to parental state was established around 50 years ago. Extensive research has since revealed a highly conserved neural circuit that underlies parental behavior both between sexes and between mammalian species. Within this circuit, hormonal action in the medial preoptic area of the hypothalamus (MPOA) has been shown to be key in timing the onset of parental behavior with the birth of offspring.

Imaging Findings and Management Strategy in Type II Popliteal Artery Entrapment Syndrome: A Tale of Two Cases.

Popliteal artery entrapment syndrome (PAES) is a frequently underdiagnosed condition that should be investigated in adults who experience exertional intermittent claudication in the lower limbs. If detected early, it is a surgically treatable cause of leg claudication in young individuals. PAES can be inherited or acquired through muscular hypertrophy, and the literature classifies it into six categories (I-VI) based on anatomical type.

Palatable solution overconsumption in the Cntnap2-/- murine model of autism: a link with oxytocin.

Dysregulated appetite is common in autism spectrum disorder (ASD) and it includes excessive interest in tasty foods. Overconsumption of palatable fluids has been found in the valproic acid-induced ASD rat. Though ASD has a strong genetic component, the link between ASD-related genes and appetite for palatable foods remains elusive.

MoS-CdS composite for photocatalytic reduction of hexavalent chromium and thin film optoelectronic device applications.

We introduce an enhanced light-harvesting MoS-based nanocomposite exhibiting improved solar light induced photocurrent generation, both in solution and solid phases. The MoS-CdS composite was synthesized via easy to achieve, cost effective, two-step solution process for the photocatalytic potassium dichromate [Cr(VI)] reduction and photocurrent generation in thin-film optoelectronic devices. Incorporating 10 wt% MoS into the composite increased the degradation efficiency of CdS from 43.

Differential Effects of Sequence-Local versus Nonlocal Charge Patterns on Phase Separation and Conformational Dimensions of Polyampholytes as Model Intrinsically Disordered Proteins.

Conformational properties of intrinsically disordered proteins (IDPs) are governed by a sequence-ensemble relationship. To differentiate the impact of sequence-local versus sequence-nonlocal features of an IDP's charge pattern on its conformational dimensions and its phase-separation propensity, the charge "blockiness" κ and the nonlocality-weighted sequence charge decoration (SCD) parameters are compared for their correlations with isolated-chain radii of gyration (s) and upper critical solution temperatures (UCSTs) of polyampholytes modeled by random phase approximation, field-theoretic simulation, and coarse-grained molecular dynamics. SCD is superior to κ in predicting because SCD accounts for effects of contact order, i.

From Data to Decisions: Leveraging Artificial Intelligence and Machine Learning in Combating Antimicrobial Resistance - a Comprehensive Review.

The emergence of drug-resistant bacteria poses a significant challenge to modern medicine. In response, Artificial Intelligence (AI) and Machine Learning (ML) algorithms have emerged as powerful tools for combating antimicrobial resistance (AMR). This review aims to explore the role of AI/ML in AMR management, with a focus on identifying pathogens, understanding resistance patterns, predicting treatment outcomes, and discovering new antibiotic agents.

Synthesis, quantum chemical calculations, in silico and in vitro bioactivity of a sulfonamide-Schiff base derivative.

The sulfonamide Schiff base compound (E)-4-((4-(dimethylamino)benzylidene)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide was successfully prepared and fully characterized. The foremost objective of this study was to explore the molecular geometry of the aforementioned compound and determine its drug likeness characteristics, docking ability as an insulysin inhibitor, anticancer and antioxidant activities. The molecular structure of this compound was optimized using the B3LYP/6-311G+(d,p) level of theory.

The Risk of Atrial Fibrillation and Previous Ischemic Stroke in Cognitive Decline.

: Our study investigated the inverse relationship between cognitive decline (CD) and the presence of documented atrial fibrillation (AFib), ischemic stroke, heart failure, lower extremity peripheral artery disease, and diabetes mellitus. : We conducted a retrospective cross-sectional study between December 2016 and November 2019. A total of 469 patients were enrolled who underwent cognitive evaluation with three cognitive tests (Montreal Cognitive Assessment-MOCA, Mini-Mental State Examination-MMSE, and General Practitioner Assessment of Cognition-GPCOG).

Comparing Cancer Risk Management between Females with Truncating 1100delC versus Missense I157T Variants.

Breast cancer (BC) risks imparted by c.1100delC ("1100delC") germline pathogenic/likely pathogenic variant (GPV) are 20-30%, compared to c.470T>C ("I157T") GPV with <20%, leading to different breast screening recommendations through MRI.

The Development and Evaluation of Novel Patient Educational Material for a Variant of Uncertain Significance (VUS) Result in Hereditary Cancer Genes.

A Variant of Uncertain Significance (VUS) is a difference in the DNA sequence with uncertain consequences for gene function. A VUS in a hereditary cancer gene should not change medical care, yet some patients undergo medical procedures based on their VUS result, highlighting the unmet educational needs among patients and healthcare providers. To address this need, we developed, evaluated, and refined novel educational materials to explain that while VUS results do not change medical care, it remains important to share any personal or family history of cancer with family members given that their personal and family medical history can guide their cancer risk management.

Tandem dehydrogenation-olefination-decarboxylation of cycloalkyl carboxylic acids via multifold C-H activation.

Dehydrogenation chemistry has long been established as a fundamental aspect of organic synthesis, commonly encountered in carbonyl compounds. Transition metal catalysis revolutionized it, with strategies like transfer-dehydrogenation, single electron transfer and C-H activation. These approaches, extended to multiple dehydrogenations, can lead to aromatization.