Quantifying liver-toxic responses from dose-dependent chemical exposures using a rat genome-scale metabolic model.

Because the liver plays a vital role in the clearance of exogenous chemical compounds, it is susceptible to chemical-induced toxicity. Animal-based testing is routinely used to assess the hepatotoxic potential of chemicals. While large-scale high-throughput sequencing data can indicate the genes affected by chemical exposures, we need system-level approaches to interpret these changes.

Geny: a genotyping tool for allelic decomposition of killer cell immunoglobulin-like receptor genes.

Introduction: Accurate genotyping of Killer cell Immunoglobulin-like Receptor (KIR) genes plays a pivotal role in enhancing our understanding of innate immune responses, disease correlations, and the advancement of personalized medicine. However, due to the high variability of the KIR region and high level of sequence similarity among different KIR genes, the generic genotyping workflows are unable to accurately infer copy numbers and complete genotypes of individual KIR genes from next-generation sequencing data. Thus, specialized genotyping tools are needed to genotype this complex region.

Impact of exposure to extreme heat events during pregnancy on the incidence of congenital heart disease in offspring: a meta-analysis.

Background: The aetiology of congenital heart disease (CHD) is multifactorial. Environmental risk factors have emerged as an important modifiable determinant of several congenital cardiac conditions. Previous studies have shown a strong relationship between CHD and air pollution.

Dehydrated amniotic membrane patch for the treatment of an ocular event secondary to mirvetuximab soravtansine-gynx (MIRV) therapy.

•Mirvetuximab soravtansine (MIRV) is used in the treatment of FRα positive, platinum-resistant epithelial ovarian cancer.•MIRV is associated with ocular events, leading to dose delays, dose reductions, and discontinuations of chemotherapy.•Mitigation strategies to prevent treatment disruption have historically relied on corticosteroid and lubricating drops.

Balancing Surface Chemistry and Flake Size of MXene-Based Electrodes for Bioelectrochemical Reactors.

MXenes have excellent properties as electrode materials in energy storage devices or fuel cells. In bioelectrochemical systems (for wastewater treatment and energy harvesting), MXenes can have antimicrobial characteristics in some conditions. Here, different intercalation and delamination approaches to obtain TiCT MXene flakes with different terminal groups and lateral dimensions are comprehensively investigated.

Biologically-informed killer cell immunoglobulin-like receptor gene annotation tool.

Summary: Natural killer (NK) cells are essential components of the innate immune system, with their activity significantly regulated by Killer cell Immunoglobulin-like Receptors (KIRs). The diversity and structural complexity of KIR genes present significant challenges for accurate genotyping, essential for understanding NK cell functions and their implications in health and disease. Traditional genotyping methods struggle with the variable nature of KIR genes, leading to inaccuracies that can impede immunogenetic research.

Biologically-informed Killer cell immunoglobulin-like receptor (KIR) gene annotation tool.

Natural killer (NK) cells are essential components of the innate immune system, with their activity significantly regulated by Killer cell Immunoglobulin-like Receptors (KIRs). The diversity and structural complexity of KIR genes present significant challenges for accurate genotyping, essential for understanding NK cell functions and their implications in health and disease. Traditional genotyping methods struggle with the variable nature of KIR genes, leading to inaccuracies that can impede immunogenetic research.

Metabolomic Fingerprints of Medical Therapy Versus Bariatric Surgery in Patients With Obesity and Type 2 Diabetes: The STAMPEDE Trial.

Objective: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective procedures to treat and manage type 2 diabetes (T2D). However, the underlying metabolic adaptations that mediate improvements in glucose homeostasis remain largely elusive. The purpose of this study was to identify metabolic signatures associated with biochemical resolution of T2D after medical therapy (MT) or bariatric surgery.

Discrepancy in PD-L1 expression between primary and metastatic tumors in two patients with recurrent cervical cancer.

Introduction: Pembrolizumab is an immunotherapy approved for use in patients with a combined positive score (CPS) greater than one with recurrent cervical cancer. In clinical practice, the CPS score is not typically analyzed in both primary and metastatic specimens.

Case Descriptions: Case 1A 42-year-old woman with history of an abnormal pap smears who presented with a large pelvic mass with initial biopsy of cervix demonstrating squamous cell carcinoma with negative PDL1 expression and a CPS score of 0.

Intricate Evaporation Dynamics in Different Multidroplet Configurations.

We experimentally investigate the evaporation dynamics of an array of sessile droplets arranged in different configurations. Utilizing a customized goniometer, we capture side and top view profiles to monitor the evolution of height, spread, contact angle, and volume of the droplets. Our results reveal that the lifetime of a droplet array surpasses that of an isolated droplet, attributed to the shielding effect induced by neighboring droplets, which elevates the local vapor concentration, thereby reducing the evaporation rate.

Phenotypic expression, genotypic profiling and clinical outcomes of infantile hypertrophic cardiomyopathy: a retrospective study.

Background: Infantile hypertrophic cardiomyopathy (HCM) is a heterogeneous disorder. Apart from registries in high-income nations, there is a shortage of data on the aetiological basis of infantile HCM in low- and middle-income nations. This study attempts to characterise the phenotypic expression, genetic architecture and short-term clinical outcomes of infantile HCM from a South Asian tertiary referral centre.

Exposure to PFAS chemicals induces sex-dependent alterations in key rate-limiting steps of lipid metabolism in liver steatosis.

Toxicants with the potential to bioaccumulate in humans and animals have long been a cause for concern, particularly due to their association with multiple diseases and organ injuries. Per- and polyfluoro alkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAH) are two such classes of chemicals that bioaccumulate and have been associated with steatosis in the liver. Although PFAS and PAH are classified as chemicals of concern, their molecular mechanisms of toxicity remain to be explored in detail.

B1-B2 transition in shock-compressed MgO.

Magnesium oxide (MgO) is a major component of the Earth's mantle and is expected to play a similar role in the mantles of large rocky exoplanets. At extreme pressures, MgO transitions from the NaCl 1 crystal structure to a CsCl 2 structure, which may have implications for exoplanetary deep mantle dynamics. In this study, we constrain the phase diagram of MgO with laser-compression along the shock Hugoniot, with simultaneous measurements of crystal structure, density, pressure, and temperature.

Choice of baseline hazards in joint modeling of longitudinal and time-to-event cancer survival data.

Longitudinal time-to-event analysis is a statistical method to analyze data where covariates are measured repeatedly. In survival studies, the risk for an event is estimated using Cox-proportional hazard model or extended Cox-model for exogenous time-dependent covariates. However, these models are inappropriate for endogenous time-dependent covariates like longitudinally measured biomarkers, Carcinoembryonic Antigen (CEA).

Geny: A Genotyping Tool for Allelic Decomposition of Killer Cell Immunoglobulin-Like Receptor Genes.

Accurate genotyping of Killer cell Immunoglobulin-like Receptor (KIR) genes plays a pivotal role in enhancing our understanding of innate immune responses, disease correlations, and the advancement of personalized medicine. However, due to the high variability of the KIR region and high level of sequence similarity among different KIR genes, the currently available genotyping methods are unable to accurately infer copy numbers, genotypes and haplotypes of individual KIR genes from next-generation sequencing data. Here we introduce Geny, a new computational tool for precise genotyping of KIR genes.

Common operational issues and possible solutions for sustainable biosurfactant production from lignocellulosic feedstock.

Surfactants are compounds with high surface activity and emulsifying property. These compounds find application in food, medical, pharmaceutical, and petroleum industries, as well as in agriculture, bioremediation, cleaning, cosmetics, and personal care product formulations. Due to their widespread use and environmental persistence, ensuring biodegradability and sustainability is necessary so as not to harm the environment.

Medicolegal, infrastructural, and financial aspects in gynecologic cancer surgery and their implications in decision making processes: Quo Vadis?

Surgical decision making is complex and involves a combination of analytic, intuitive, and cognitive processes. Medicolegal, infrastructural, and financial factors may influence these processes depending on the context and setting, but to what extent can they influence surgical decision making in gynecologic oncology? This scoping review evaluates existing literature related to medicolegal, infrastructural, and financial aspects of gynecologic cancer surgery and their implications in surgical decision making. Our objective was to summarize the findings and limitations of published research, identify gaps in the literature, and make recommendations for future research to inform policy.

Chemical composition, antioxidant properties, and antifungal activity of wild extracts against .

Introduction: , the causative agent of late blight disease, has gained notoriety for its destructive potential, leading to substantial losses in potato yields. Although conventional systemic fungicides have been shown to be effective in controlling plant pathogens, growing environmental concerns have prompted the need for more integrated disease management approaches. Hence, in this study, the effectiveness of wild extracts as biopesticides was explored in controlling and potentially mitigating its devastating impact .

Possible use of 2D shear wave liver elastography in new-onset ascites evaluation.

Background: No data on the use of 2D shear wave elastography exists regarding the evaluation of the new-onset ascites causality.

Aims: To determine whether 2D shear wave elastography can help in the non-invasive assessment of the new-onset ascites cause. To assess the applicability of liver stiffness measured by 2D shear wave elastography using Esaote MyLab Nine apparatus in patients with ascites.

: merging, comparing, and translating genome-scale metabolic models using universal identifiers.

Numerous methods exist to produce and refine genome-scale metabolic models. However, due to the use of incompatible identifier systems for metabolites and reactions, computing and visualizing the metabolic differences and similarities of such models is a current challenge. Furthermore, there is a lack of automated tools that can combine the strengths of multiple reconstruction pipelines into a curated single comprehensive model by merging different drafts, which possibly use incompatible namespaces.

Short-term survival analysis of a risk-adjusted model for ovarian cancer care.

Objective: To quantify the impact on short-term ovarian cancer survival associated with treatment at high-performing hospitals using the observed-to-expected ratio (O/E) for adherence to ovarian cancer treatment guidelines as a risk-adjusted measure of hospital quality care.

Methods: This was a retrospective population-based study of stage I-IV invasive epithelial ovarian cancer reported to California Cancer Registry 1996-2017. A fit logistic regression model, risk-adjusted for patient and disease characteristics, was used to calculate O/E for each hospital stratified by hospital annual case volume.

An Insight Into the Role of Alpha-Fetoprotein (AFP) in the Development and Progression of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the primary malignancy of hepatocytes and the second most common cause of cancer-related mortality across the globe. Despite significant advancements in screening, diagnosis, and treatment modalities for HCC, the mortality-to-incidence ratio remain unacceptably high. A recent study indicates that a minor population of HCCs are AFP negative or express the normal range of AFP levels.

A new method for the calculation of functional and path integrals.

This paper addresses a disconnect between the pivotal role of functional (path) integrals in modern theories, such as quantum mechanics and statistical thermodynamics, and the currently limited ability to perform the actual calculation. We present a new method for calculating functional integrals, based on a finite-element formulation, which solves all limitations of existing methods. This approach is far more robust, versatile, and powerful than the prevailing methods, thus allowing for more sophisticated computations and the study of problems that could not previously be tackled.

Opportunities and Cracks in Canada's Two-Step Migration Model During the Pandemic: Lessons from Chinese Migrant Experiences.

Canada's migration management has been evolving into a two-step model since the 1990s, creating pathways for temporary residents to apply for permanent status through federal and provincial programs. The COVID-19 pandemic brought with it unprecedented challenges but also holds the potential to be a key policy moment to re-imagine Canada's migration future. In this paper, we draw on semi-structured, in-depth interviews with 16 Chinese temporary residents, to reveal some of the successes, opportunities, as well as challenges, limitations, and conspicuous cracks in these new policies intended to maintain high levels of immigration during the pandemic and through Canada's post-pandemic recovery.