ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.

Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.

Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER.

Catheter-Based Aspiration of A Large Superior Vena Cava Mass In A Patient With Endocarditis.

Infective endocarditis carries a high risk of morbidity and mortality with recurrent infections and non-compliance. In the case of right-sided endocarditis, the indications for intervention are less clear. The Angiovac procedure provides a treatment for right-sided endocarditis that is a less-invasive and ideal for a complicated patient population.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

β-barrel proteins dictate the effect of core oligosaccharide composition on outer membrane mechanics.

The outer membrane is the defining structure of Gram-negative bacteria. We previously demonstrated that it is a major load-bearing component of the cell envelope and is therefore critical to the mechanical robustness of the bacterial cell. Here, to determine the key molecules and moieties within the outer membrane that underlie its contribution to cell envelope mechanics, we measured cell-envelope stiffness across several sets of mutants with altered outer-membrane sugar content, protein content, and electric charge.

Diverging evolutionary trajectories for palm seed sizes in mainland Africa and Madagascar.

Seed size is a trait which determines survival rates for individual plants and can vary as a result of numerous trade-offs. In the palm family (Arecaceae) today, there is great variation in seed sizes. Past studies attempting to establish drivers for palm seed evolution have sometimes yielded contradictory findings in part because modern seed size variations are complicated by long-term legacies, including biogeographic differences across lineages.

Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.

One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.

Amelioration of premature aging in Werner syndrome stem cells by targeting SHIP/AKT pathway.

Background: Pathogenic or null mutations in WRN helicase is a cause of premature aging disease Werner syndrome (WS). WRN is known to protect somatic cells including adult stem cells from premature senescence. Loss of WRN in mesenchymal stem cells (MSCs) not only drives the cells to premature senescence but also significantly impairs the function of the stem cells in tissue repair or regeneration.

Evaluating programmatic reactive focal drug administration impact on malaria incidence in northern Senegal: an interrupted time series analysis.

Background: The World Health Organization conditionally recommends reactive drug administration to reduce malaria transmission in settings approaching elimination. However, few studies have evaluated the impact of reactive focal drug administration (rFDA) in sub-Saharan Africa, and none have evaluated it under programmatic conditions. In 2016, Senegal's national malaria control programme introduced rFDA, the presumptive treatment of compound members of a person with confirmed malaria, and reactive mass focal drug administration (rMFDA), an expanded effort including neighbouring compounds during an outbreak, in 10 low transmission districts in the north of the country.

Lay views in Southern France of the acceptability of refusing to provide treatment because of alleged futility.

Aim: To carry out a detailed study of existing positions in the French public of the acceptability of refusing treatment because of alleged futility, and to try to link these to people's age, gender, and religious practice.

Method: 248 lay participants living in southern France were presented with 16 brief vignettes depicting a cancer patient at the end of life who asks his doctor to administer a new cancer treatment he has heard about. Considering that this treatment is futile in the patient's case, the doctor refuses to prescribe it.

Diagnosis of lung cancer using salivary miRNAs expression and clinical characteristics.

Objective: Lung cancer (LC), the primary cause for cancer-related death globally is a diverse illness with various characteristics. Saliva is a readily available biofluid and a rich source of miRNA. It can be collected non-invasively as well as transported and stored easily.

Fluoride-induced testicular and ovarian toxicity: evidence from animal studies.

Fluoride (F), as a natural element found in a wide range of sources such as water and certain foods, has been proven to be beneficial in preventing dental caries, but concerns have been raised regarding its potential deleterious effects on overall health. Sodium fluoride (NaF), another form of F, has the ability to accumulate in reproductive organs and interfere with hormonal regulation and oxidative stress pathways, contributing to reproductive toxicity. While the exact mechanisms of F-induced reproductive toxicity are not fully understood, this review aims to elucidate the mechanisms involved in testicular and ovarian injury.

Semaglutide and laparoscopic sleeve gastrectomy in an adolescent with congenital adrenal hyperplasia due to 21-hydroxylase: a case report.

Background: Classic congenital adrenal hyperplasia, primarily due to 21-hydroxylase deficiency, leads to impaired cortisol and aldosterone production and excess adrenal androgens. Lifelong glucocorticoid therapy is required, often necessitating supraphysiological doses in youth to manage androgen excess and growth acceleration. These patients experience higher obesity rates, hypertension, and glucose metabolism issues, complicating long-term health management.

A meta-analysis of sex differences in neonatal rodent ultrasonic vocalizations and the implication for the preclinical maternal immune activation model.

As the earliest measure of social communication in rodents, ultrasonic vocalizations (USVs) in response to maternal separation are critical in preclinical research on neurodevelopmental disorders (NDDs). While sex differences in both USV production and behavioral outcomes are reported, many studies overlook sex as a biological variable in preclinical NDD models. We aimed to evaluate sex differences in USV call parameters and determine if USVs are differently impacted based on sex in the preclinical maternal immune activation (MIA) model.

Blood-based epigenome-wide association study and prediction of alcohol consumption.

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait.

Depression symptom severity and behavioral impairment in school-going adolescents in Uganda.

Background: During adolescence, a critical developmental phase, cognitive, psychological, and social states interact with the environment to influence behaviors like decision-making and social interactions. Depressive symptoms are more prevalent in adolescents than in other age groups which may affect socio-emotional and behavioral development including academic achievement. Here, we determined the association between depression symptom severity and behavioral impairment among adolescents enrolled in secondary schools of Eastern and Central Uganda.

Predicting bullying victimization among adolescents using the risk and protective factor framework: a large-scale machine learning approach.

Background: Bullying, encompassing physical, psychological, social, or educational harm, affects approximately 1 in 20 United States teens aged 12-18. The prevalence and impact of bullying, including online bullying, necessitate a deeper understanding of risk and protective factors to enhance prevention efforts. This study investigated the key risk and protective factors most highly associated with adolescent bullying victimization.

Predicting land use and land cover changes for sustainable land management using CA-Markov modelling and GIS techniques.

This study addresses the significant issue of rapid land use and land cover (LULC) changes in Lahore District, which is critical for supporting ecological management and sustainable land-use planning. Understanding these changes is crucial for mitigating adverse environmental impacts and promoting sustainable development. The main goal is to evaluate historical LULC changes from 1994 to 2024 and forecast future trends for 2034 and 2044 utilizing the CA-Markov hybrid model combined with GIS methodologies.

Bibliometric analysis of global research trends in vestibular neuritis (1980-2024).

Purpose: Vestibular neuritis (VN) is a common cause of vertigo with significant impact on patients' quality of life. This study aimed to analyze global research trends in VN using bibliometric methods to identify key themes, influential authors, institutions, and countries contributing to the field.

Methods: We conducted a comprehensive search of the Web of Science Core Collection database for publications related to VN from 1980 to 2024.

Mechanical Wear of Degraded Articular Cartilage.

Purpose: To evaluate the mechanical wear of cartilage with different types of degradation.

Methods: Bovine osteochondral explants were treated with interleukin-1β (IL-1β) to mimic inflammatory conditions, with chondroitinase ABC (ChABC) to specifically remove glycosaminoglycans (GAGs), or with collagenase to degrade the collagen network during 5 days of culture. Viscoelastic properties of cartilage were characterized via indentation.

Measurement and Assessment of Head-to-Helmet Contact Forces.

Purpose: To evaluate the population variation in head-to-helmet contact forces in helmet users.

Methods: Four different size Kevlar composite helmets were instrumented with contact pressure sensors and chinstrap tension meters. A total number of 89 volunteers (25 female and 64 male volunteers) participated in the study.