Antimicrobial Resistance in Curable Sexually Transmitted Infections.

Purpose Of Review: Antimicrobial resistance in sexually transmitted infections (STIs) has become an urgent global public health threat, raising the specter of untreatable infections. This review summarizes the determinants of resistance among the five most common curable STIs Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Treponema pallidum, and Trichomonas vaginalis, as well as strategies to mitigate the spread of resistance.

Recent Findings: Genetic mutations are key drivers of resistance for N.

Impact assessment of planned and unplanned urbanization on land surface temperature in Afghanistan using machine learning algorithms: a path toward sustainability.

The increasing trend in land surface temperature (LST) and the formation of urban heat islands (UHIs) has emerged as a persistent challenge for urban planners and decision-makers. The current research was carried out to study the land use and land cover (LULC) changes and associated LST patterns in the planned city (Kabul) and the unplanned city (Jalalabad), Afghanistan, using Support Vector Machine (SVM) and Landsat data from 1998 to 2018. Future changes in LULC and LST were predicted for 2028 and 2038 using Cellular Automata-Markov (CA-Markov) and Artificial Neural Network (ANN) models.

The Ca-actin-cytoskeleton axis in podocytes is an important, non-immunologic target of immunosuppressive therapy in proteinuric kidney diseases.

The integrity of the filtration barrier of the kidney relies on the proper composition of podocyte interdigitating foot processes. Their architecture is supported by a complex actin-cytoskeleton. Following podocyte stress or injury, podocytes encounter structural changes, including rearrangement of the actin network and subsequent effacement of the foot processes.

Prenatal depression and child developmental vulnerability.

Background: Prenatal depression is a potentially important fetal exposure as it may alter fetal development and have lasting effects.

Methods: We examined all live births from 2001 to 2012 in British Columbia with follow-up data on the Early Development Instrument (EDI) in Kindergarten. The odds of developmental vulnerability on EDI domains among those with and without depression during pregnancy were estimated.

A multidimensional fecal microbial and inflammatory biomarker profiling in preterm and full-term neonates.

Background: Preterm birth affects approximately one in every ten neonates. The clinical outcomes depend on care and management factors, including the birth delivery method and the use of antibiotics.

Methods: This observational cohort study determined antimicrobial peptides, proteases, metabolomic, and microbiome profiles in fecal samples collected from 20 preterm and nine full-term neonates 48 h after birth.

Pediatric COVID-19 severity by SARS-CoV-2 lineage and vaccine status in Canada: an IMPACT study.

Background: Interpretations of pediatric COVID-19 severity are complicated by novel lineages and COVID-19 vaccine introduction. We estimated the risk of severe COVID-19 by SARS-CoV-2 lineage and vaccination status among hospitalized Canadian children.

Methods: Data were collected through the Canadian Paediatric Surveillance Program (April 2020-May 2021) and Canadian Immunization Monitoring Program, ACTive (June 2021-December 2022).

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Impact of frequent ARID1A mutations on protein stability provides insights into cancer pathogenesis.

The ARID1A gene, frequently mutated in cancer, encodes the AT-rich interactive domain-containing protein 1 A, a key component of the chromatin remodeling SWI/SNF complex. The ARID1A protein features a conserved DNA-binding domain (ARID domain) of approximately 100 residues crucial for its function. Despite the frequency of mutations, the impact on ARID1A's stability and contribution to cancer progression remains unclear.

Dual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma.

We report the basal cell cancer (BCC) cohort of the SWOG/NCI 1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART), a phase II prospective, multicenter basket trial of nivolumab and ipilimumab. The primary endpoint was objective response rate (ORR) (RECIST v1.1).

Methylene blue at recommended concentrations alters metabolism in early zebrafish development.

Methylene blue (MB) is an antifungal agent widely used during critical stages of zebrafish development. Most guidelines recommend 0.00005% or 0.

Morphological diversity variation of seed traits among 587 germplasm resources of Medicago Genus and 32 germplasm resources of Trigonella Genus.

Germplasm resources within the Medicago genus are highly regarded for their value as forage crops and their critical roles in nitrogen cycling, ecosystem restoration, and soil structure improvement. Therefore, understanding the diversity of seed morphology in this genus is essential for advancing its development and utilization. This study analyzed seed samples from 587 germplasm accessions representing 77 species within Medicago genus, as well as 32 accessions from 21 species within the closely related genus Trigonella.

A phylogenetic epidemiology approach to predicting the establishment of multi-host plant pests.

Forecasting emergent pest spread is paramount to mitigating their impacts. For host-specialized pests, epidemiological models of spread through a single host population are well developed. However, most pests attack multiple host species; the challenge is predicting which communities are most vulnerable to infestation.

Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events.

Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis screen for the efficient identification of genes that are resistant to BRAF inhibition in melanoma.

Multi-assay assessment of cytotoxicity reveals multiple mechanisms of action in 3D microtissues.

Cell viability assays are an integral component of toxicology and high-throughput drug screening studies; however, many assays rely on a single biomarker of cell death which provides an incomplete assessment of cell viability. Here, we introduce an innovative approach that combines data from multiple assays using a linear mixed effects regression model and principal component analysis. We explored the cytotoxic response of various assay-treatment combinations using four assays with distinct mechanisms of action and seven different treatments across three types of microtissue cultures.

A paper-based HPV E7 oncoprotein assay for cervical precancer detection at the point of care.

Cervical cancer, while preventable through screening and treatment of cervical precancer, remains a global challenge with a disproportionately high burden of disease in resource-limited settings, especially in low- and middle-income countries (LMICs). Lack of affordable, easy-to-use screening and diagnostic tests contributes to this disparity. Most commercially available tests are not appropriate for use in LMICs due to resource constraints.

V3+ extends the V3 framework to ensure user-centricity and scalability of sensor-based digital health technologies.

We propose the addition of usability validation to the extended V3 framework, now "V3+", and describe a pragmatic approach to ensuring that sensor-based digital health technologies can be used optimally at scale by diverse users. Alongside the original V3 components (verification; analytical validation; clinical validation), usability validation will ensure user-centricity of digital measurement tools, paving the way for more inclusive, reliable, and trustworthy digital measures within clinical research and clinical care.

Immune infiltrate populations within distinct tumor immune microenvironments predictive of immune checkpoint treatment outcome.

Understanding the dynamic tumor immune microenvironment (TIME) is important in guiding immunotherapy. We have previously validated signatures predictive of checkpoint inhibitor efficacy which distinguish immunomodulatory, mesenchymal stem-like, and mesenchymal phenotypes. Here we use twenty tumor types (7162 samples) to identify potentially conserved immune biology within these TIME spaces, genes co-expressed across distinct cell types involved these immune processes, and the association of these signatures with ICI response.

Life cycle comparison of industrial-scale lithium-ion battery recycling and mining supply chains.

Recycling lithium-ion batteries (LIBs) can supplement critical materials and improve the environmental sustainability of LIB supply chains. In this work, environmental impacts (greenhouse gas emissions, water consumption, energy consumption) of industrial-scale production of battery-grade cathode materials from end-of-life LIBs are compared to those of conventional mining supply chains. Converting mixed-stream LIBs into battery-grade materials reduces environmental impacts by at least 58%.

Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice.

The gut microbiome modulates the anti-seizure effects of the ketogenic diet, but how specific dietary formulations differentially modify the gut microbiome in ways that impact seizure outcome is poorly understood. We find that medical ketogenic infant formulas vary in macronutrient ratio, fat source, and fiber content and differentially promote resistance to 6-Hz seizures in mice. Dietary fiber, rather than fat ratio or source, drives substantial metagenomic shifts in a model human infant microbial community.

Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal Fe through TRPML1 channel.

Lysosomes are best known for their roles in inflammatory responses by engaging in autophagy to remove inflammasomes. Here, we describe an unrecognized role for the lysosome, showing that it finely controls macrophage inflammatory function by manipulating the lysosomal Fe-prolyl hydroxylase domain enzymes (PHDs)-NF-κB-interleukin 1 beta (IL1B) transcription pathway that directly links lysosomes with inflammatory responses. TRPML1, a lysosomal cationic channel, is activated secondarily to ROS elevation upon inflammatory stimuli, which in turn suppresses IL1B transcription, thus limiting the excessive production of IL-1β in macrophages.

Diet-derived urolithin A is produced by a dehydroxylase encoded by human gut Enterocloster species.

Urolithin A (uroA) is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota. Once absorbed, uroA can trigger mitophagy and aryl hydrocarbon receptor signaling pathways, altering host immune function, mitochondrial health, and intestinal barrier integrity. Most individuals harbor a microbiota capable of uroA production; however, the mechanisms underlying the dehydroxylation of its catechol-containing precursor (uroC) are unknown.