Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells.

The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia.

Following plasmid propagation in complex bacterial communities.

In this issue of Cell Reports, Ma et al. identify causative regulatory links between self-organization in surface-attached bacterial colonies and the rate of horizontal gene transfers (conjugations) and subsequent selection of the newly arising population of recipient bacteria (transconjugants).

The NLRP3 inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice.

The role of the inflammasomes in aging and progeroid syndromes remain understudied. Recently, MCC950, a NLRP3 inhibitor, was used in Zmpste24 mice to ameliorate the phenotypes. However, the safety of MCC950 was questioned due to liver toxicity observed in humans.

Recovering the activity parameters of an active fluid confined in a sphere.

The properties of an active fluid, for example, a bacterial bath or a collection of microtubules and molecular motors, can be accessed through the dynamics of passive particle probes. Here, in the perspective of analyzing experimental situations of confinement in droplets, we consider the kinematics of a negatively buoyant probe particle in an active fluid, both confined within a spherical domain. The active bath generates a fluctuating flow that pushes the particle with a velocity that is modeled as a colored stochastic noise, characterized by two parameters, the intensity and memory time of the active flow.

Accumulation and depletion of E. coli in surfaces mediated by curvature.

Can topography be used to control bacteria accumulation? We address this question in the model system of smooth-swimming and run-and-tumble Escherichia coli swimming near a sinusoidal surface, and show that the accumulation of bacteria is determined by the characteristic curvature of the surface. For low curvatures, cells swim along the surface due to steric alignment and are ejected from the surface when they reach the peak of the sinusoid. Increasing curvature enhances this effect and reduces the density of bacteria in the curved surface.

NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype.

Background: Senescence is a cellular aging-related process triggered by different stresses and characterized by the secretion of various inflammatory factors referred to as senescence-associated secretory phenotype (SASP), some of which are produced by the NLRP3 inflammasome. Here, we present evidence that the NLRP1 inflammasome is a DNA damage sensor and a key mediator of senescence.

Methods: Senescence was induced in fibroblasts in vitro and in mice.

The effects of person-centred active rehabilitation on symptoms of suspected Chronic Traumatic Encephalopathy: A mixed-methods single case design.

Objective: The objective was to investigate the effectiveness of a person-centred active rehabilitation programme on symptoms associated with suspected Chronic Traumatic Encephalopathy (CTE). This was accomplished by (1) assessing the effect that a person-centred active rehabilitation programme had on participant symptoms, and (2) exploring how temporal contextual factors affected the participants' experience with, and perceived effectiveness of, the active rehabilitation programme.

Methods: A twelve-month mixed-methods single case experimental research design was used with six cases (participants).

An Age-Progression Intervention for Smoking Cessation: A Pilot Study Investigating the Influence of Two Sets of Instructions on Intervention Efficacy.

Background: Research on age-progression facial morphing interventions for smoking cessation has not investigated the effect of different instructions for intervention delivery. The objective of this pilot study was to investigate the influence of two instruction types used to deliver the intervention on efficacy of the intervention.

Method: Women were recruited and randomly allocated to an age-progression intervention session with (i) neutral instructions; (ii) instructions designed to reassure; or (iii) a condition that controlled for participant engagement ("control").

A Modern Approach to Stability Studies via Bayesian Linear Mixed Models Incorporating Auxiliary Effects.

In preparation to the launch of a pharmaceutical product, an estimate of its shelf life via stability testing is required by regulatory agencies. The ICH-Q1E guidance has been the worldwide reference to reach this objective, but in recent years several authors have criticized many of its aspects. To that end we discuss a complete Bayesian transcript of the ICH-Q1E, treating all the apparent shortcomings, while also addressing the presence of multiple batches using a linear mixed model (LMM) for proper shelf life prediction by explicitly modelling the batch-to-batch variability.

Does Donor Age Have Effects on Senescence Biomarkers in Kidney-Transplanted Patients?

Renal transplantation is an effective treatment for severe chronic kidney diseases. However, young patients often face a scarcity of kidneys from donors of similar age, resulting in the transplantation of older organs, which increase the risk of graft rejection and several complications compared with older individuals who receive kidneys from donors of similar age or younger. This article focuses on studying different senescence biomarkers in donors and patients who received kidneys from various age ranges complying with the STROBE requirements.

Synthesis and Properties of 5,7-Diazaullazines.

Hitherto unknown 5,8-substituted-pyrimido[4,5,6-]pyrrolo[2,1,5-]quinolizines (5,7-diazaullazines) were prepared by a three-step synthesis via Clauson-Kaas, Sonogashira, and cycloisomerization reactions with diverse functionalization. The properties, including cyclovoltammetry and UV-vis and fluorescence spectroscopy, as well as solvatochromism, were studied for selected derivatives and supported by density functional theory calculations. Results were compared in detail with previously reported 5- and 6-azaullazines, and the impact of introduced nitrogen atoms was analyzed.

A comprehensive analysis of mRNA expression profiles of Esophageal Squamous Cell Carcinoma reveals downregulation of Desmoglein 1 and crucial genomic targets.

Aim: Esophageal Squamous Cell Carcinoma (ESCC) is a histological subtype of esophageal cancer that begins in the squamous cells in the esophagus. In only 19% of the ESCC-diagnosed patients, a five-year survival rate has been seen. This necessitates the identification of high-confidence biomarkers for early diagnosis, prognosis, and potential therapeutic targets for the mitigation of ESCC.

Geraniol reverses obesity by improving conversion of WAT to BAT in high fat diet induced obese rats by inhibiting HMGCoA reductase.

Objectives: Present report evaluates the protective effect of geraniol on high fat diet (HFD) induced obesity in rats and also determines the molecular mechanism of it.

Methods: Rats were induced with obesity with administration of HFD for four weeks and geraniol 200 and 400 mg/kg p.o.

Biological Characterization of L.f. Extracts for Phytochemical, Antimicrobial, and Hepatoprotective Activities in Wister Albino Rats.

The present study aims to explore the phytochemical constitution and biological activities of L.f. (Cleomaceae).

Silencing Glypican-1 enhances the antitumor effects of Pictilisib via downregulating PI3K/Akt/ERK signaling in chemo-resistant esophageal adenocarcinoma.

Poorly differentiated esophageal adenocarcinoma (PDEAC) has a dismal prognosis. Glypican-1(GPC-1) is known to be upregulated in several cancer types in contrast to healthy tissues, rendering it as a biomarker. Nevertheless, the potential therapeutic targeting of GPC-1 has not been explored in PDEAC.

Types of Psychiatric Beds and Mental Health Services in 16 Latin American Countries, 1990-2020.

Objective: Latin America has undergone major changes in psychiatric services over the past three decades. The authors aimed to assess the availability of service data and changes in psychiatric services in this region during the 1990-2020 period.

Methods: The authors formed a research network to collect data on psychiatric service indicators gathered between 1990 and 2020 from national registries in Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Panama, Paraguay, Peru, and Uruguay.

Global comparative transcriptomes uncover novel and population-specific gene expression in esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and is one of the deadliest gastrointestinal malignancies. Despite numerous transcriptomics studies to understand its molecular basis, the impact of population-specific differences on this disease remains unexplored.

Aims: This study aimed to investigate the population-specific differences in gene expression patterns among ESCC samples obtained from six distinct global populations, identify differentially expressed genes (DEGs) and their associated pathways, and identify potential biomarkers for ESCC diagnosis and prognosis.

Motility mediates satellite formation in confined biofilms.

Bacteria have spectacular survival capabilities and can spread in many, vastly different environments. For instance, when pathogenic bacteria infect a host, they expand by proliferation and squeezing through narrow pores and elastic matrices. However, the exact role of surface structures-important for biofilm formation and motility-and matrix density in colony expansion and morphogenesis is still largely unknown.

Between the personal and the political: life experiences during the covid-19 pandemic in Tucumán, Argentina, 2020-2022.

This article analyzes feelings, experiences, practices, and actions that underlie the meanings attributed to the covid-19 pandemic. Based on a case study located in the province of Tucumán (Argentina), a mixed-methods investigation was developed, interested in capturing life experiences. Discourse analysis show the resignification of life itself, the valorization of close ties, community social capital, the State and politics.

Self-expandable metallic stent-induced esophagorespiratory fistulas in patients with advanced esophageal cancer.

Background/aims: Self-expandable metallic stents (SEMSs) are widely adopted for the palliation of dysphagia in patients with malignant esophageal strictures. An important adverse event is the development of SEMS-induced esophagorespiratory fistulas (SEMS-ERFs). This study aimed to assess the risk factors related to the development of SEMS-ERF after SEMS placement in patients with esophageal cancer.

Analysis of female pre-clinical students' readiness, academic performance and satisfaction in online learning: an assessment of quality for curriculum revision and future implementation.

Background: The acceptance of online courses by medical and dental students, especially during the coronavirus disease 2019 crisis, is substantial, as reported in various studies. However, the unfavourable online learning experiences of the students during the pandemic were also highlighted. As the teaching-learning process is returning to the "new normal," it is necessary to identify online learning domains implemented during the pandemic crisis that may be applied in pre-clinical courses in the future.

Defining Physician-Nurse Efforts toward Collaboration as Perceived by Medical Students.

Collaboration between physicians and nurses is essential to healthcare delivery and is associated with high-quality patient care, greater patient satisfaction, and better health outcomes. Hence, it is imperative that doctors and nurses have a particular set of interprofessional collaboration skills. This descriptive cross-sectional study assessed how medical students in the pre-clinical and clinical years perceived attitudes toward collaboration between physicians and nurses in a hospital setting.