Impact of Vein-to-vein Time in Patients With R/R LBCL Treated With Axicabtagene Ciloleucel.

Chimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory large B-cell lymphoma (R/R LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel.

A Model of Zymogen Factor XII: Insights into Protease Activation.

In plasma, the zymogens factor XII (FXII) and prekallikrein reciprocally convert each other to the proteases FXIIa and plasma kallikrein (PKa). PKa cleaves high-molecular-weight kininogen (HK) to release bradykinin, which contributes to regulation of blood vessel tone and permeability. Plasma FXII is normally in a "closed" conformation that limits activation by PKa.

Migration of Health Workers and Its Impacts on the Nigerian Health Care Sector: Protocol for a Scoping Review.

Background: Health worker migration from Nigeria poses significant challenges to the Nigerian health care sector and has far-reaching implications for health care systems globally. Understanding the factors driving migration, its effects on health care delivery, and potential policy interventions is critical for addressing this complex issue.

Objective: This study aims to comprehensively examine the factors encouraging the emigration of Nigerian health workers, map out the effects of health worker migration on the Nigerian health system, document the loss of investment in health training and education resulting from migration, identify relevant policy initiatives addressing migration, determine the effects of Nigerian health worker migration on destination countries, and identify the benefits and demerits to Nigeria of health worker migration.

Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS: Nine-Year Data From the OPERA Studies Open-Label Extension.

Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).

Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.

Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey.

Background And Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023.

Current and Future Role of Circulating DNA in the Diagnosis and Management of Urothelial Carcinoma.

The growing sophistication of tumor molecular profiling has helped to slowly transition oncologic care toward a more personalized approach in different tumor types, including in bladder cancer. The National Comprehensive Cancer Network recommends that all patients with stage IVA and stage IVB urothelial carcinoma have molecular analysis that integrates at least testing to help facilitate the selection of future therapeutic options. Sequencing of tumor-derived tissue is the mainstay to obtain this genomic testing, but as in other cancers, there has been extensive research into the integration of liquid biopsies in longitudinal management.

Longer recreational screen time contributes to the risk of age-related macular degeneration: a UK Biobank cohort study and two-sample Mendelian randomisation.

Background: Recreational screen time (RST) has been found to be associated with cognitive decline and neurodegenerative diseases. However, the association between RST and age-related macular degeneration (AMD), an ocular neurodegenerative disease, is still unclear. We aimed to elucidate the association between RST and AMD.

Discovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models.

METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.

Plastic responses to past environments shape adaptation to novel selection pressures.

Phenotypic plasticity may pave the way for rapid adaptation to newly encountered environments. Although it is often contested, there is growing evidence that initial plastic responses of ancestral populations to new environmental cues may promote subsequent adaptation. However, we do not know whether plasticity to cues present in the ancestral habitat (past-cue plasticity) can facilitate adaptation to novel cues.

Extracorporeal Life Support Organization 2024 Guideline for Early Rehabilitation or Mobilization of Adult Patients on Extracorporeal Membrane Oxygenation.

This Extracorporeal Life Support Organization guideline describes early rehabilitation or mobilization of patients on extracorporeal membrane oxygenation (ECMO). The guideline describes useful and safe practices put together by an international interprofessional team with extensive experience in the field of ECMO and ECMO rehabilitation or mobilization. The guideline is not intended to define the delivery of care or substitute sound clinical judgment.

A framework for managing infectious diseases in rural areas in low- and middle-income countries in the face of climate change-East Africa as a case study.

Climate change is having unprecedented impacts on human health, including increasing infectious disease risk. Despite this, health systems across the world are currently not prepared for novel disease scenarios anticipated with climate change. While the need for health systems to develop climate change adaptation strategies has been stressed in the past, there is no clear consensus on how this can be achieved, especially in rural areas in low- and middle-income countries that experience high disease burdens and climate change impacts simultaneously.

Coevolutionary dynamics in the grass-livestock social-ecological system of China's alpine pastoral areas: A case study of the Qilian Mountains region in China.

Evaluating the dynamic co-evolution and feedback mechanisms within socio-ecological systems is crucial for determining the resilience and sustainability of environmental governance strategies. The grass-livestock system, as a complex entity encompassing livestock nutrition, foraging behavior, vegetation ecology, pastoralists' economic income, and policy interventions, indicates that any change in a single element may trigger a chain reaction within the system. This paper uses a system dynamics approach to construct a simulation model of the grass-livestock system in alpine pastoral areas, simulating the long-term dynamic co-evolution of the socio-ecological system in the Qilian Mountains region of China.

The involvement of non-governmental organisations in achieving health system goals based on the WHO six building blocks: A scoping review on global evidence.

Background: Non-governmental organisations (NGOs) have the potential to make a significant contribution to improving health system goals through the provision of resources, health services and community participation. Therefore, this paper examines the role of NGOs in achieving health system goals, based on the six building blocks of a health system framework, and identifies strategies to enhance NGO involvement in achieving health system goals.

Methods: A scoping systematic review methodology was used to map and synthesise the existing literature on the topic, following the latest JBI six-stage framework.

PRC2 promotes canalisation during endodermal differentiation.

The genetic circuitry that encodes the developmental programme of mammals is regulated by transcription factors and chromatin modifiers. During early gestation, the three embryonic germ layers are established in a process termed gastrulation. The impact of deleterious mutations in chromatin modifiers such as the polycomb proteins manifests during gastrulation, leading to early developmental failure and lethality in mouse models.

Developing and validating a HEalthCare NAvigation Competency (HECNAC) Scale for refugees in the United States.

The complex healthcare system in the United States (US) poses significant challenges for people, particularly minorities such as refugees. Refugees often encounter additional layers of challenges to healthcare navigation due to unfamiliarity with the system, limited health literacy, and language barriers. Despite their challenges, it is difficult to identify the gaps as few tools exist to measure navigation competency among this population and many conventional tools assume English proficiency, making them inadequate for refugees and other immigrants.

Extended receptor repertoire of an adenovirus associated with human obesity.

Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about its receptor profile. We investigated the receptor portfolio of HAdV-D36 using a combined structural biology and virology approach.

Incorporating preference uncertainty in best worst scaling.

In this paper, we enhance the Best-Worst Scaling (BWS) method by incorporating participants' preference uncertainty into the conventional BWS, known as case 1. In this context, respondents are tasked with making trade-offs among a set of items of interest. Applying this novel extended BWS method to a sample of Argentinian wine consumers (n = 342), we aim to a) provide a more informative elicitation of consumers' relative preferences for 16 wine attributes; b) identify the level of uncertainty with each of the attributes, exploring differences between the most and least important wine attributes influencing purchasing wine; and c) compare the results of the extended BWS with the standard BWS.

Investigating the miRNA-mRNA interactome of human trabecular meshwork cells treated with TGF-β1 provides insights into the pathogenesis of pseudoexfoliation glaucoma.

Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome.

A cross-sectional study on the assessment of adherence to cardiovascular medications in Sudan heart center.

Background: Non-adherence to cardiovascular medications is a global problem with clinical, economic, and humanistic consequences. Investigation of this problem may open the road for proper management of cardiovascular diseases.

Objective: Our objectives were to assess the level of adherence to, and to examine factors influencing adherence to, cardiovascular medications in subjects visiting a heart center in Sudan.

New information on Bonapartenykus (Alvarezsauridae: Theropoda) from the Allen Formation (middle Campanian-lower Maastrichtian) of Río Negro Province, Patagonia, Argentina clarifies the Patagonykinae body plan.

Alvarezsauria is a group of morphologically distinctive, medium- to small-sized later-diverging coelurosaurian theropod dinosaurs, whose record ranges from the Late Jurassic to the Late Cretaceous. This clade had a widespread distribution in Laurasia in what is now Europe, Asia, and North America, although there are also several Cretaceous taxa from Gondwana in what is now Argentina that all belong to the family Alvarezsauridae. Although alvarezsaurid taxonomic diversity and anatomical knowledge has expanded over the last decade, alvarezsaurid internal phylogenetic relationships remain highly debated.

The changes in health-related quality of life after attending cardiac rehabilitation: A qualitative systematic review of the perspective of patients living with heart disease.

Background: Although the benefits of engaging in cardiac rehabilitation are well established, patient perceptions of the changes in their health-related quality of life are poorly documented. This systematic review synthesized qualitative studies on patients' perspectives of change in their health-related quality of life after attending cardiac rehabilitation.

Objective: To identify and synthesize the best available evidence on the perspective of patients living with heart disease about the changes in their health-related quality of life after attending cardiac rehabilitation.

Examining the mediating role of motivation in the relationships between teacher-created motivational climates and quality of engagement in secondary school physical education.

Grounded in Duda's integrated model of the motivational climate, the current study examined the hypothesized mediating role of motivation quality in the relationships between empowering and disempowering teacher-created motivational climates and indicators of quality engagement in secondary school physical education (PE). The hypothesised model was tested cross-sectionally and longitudinally in two separate samples of students. Data were collected via questionnaires measuring the motivational climate, autonomous and controlled motivation and indicators of engagement (enjoyment, concentration and boredom).

Genetic diversity, population structure in a historical panel of Brazilian soybean cultivars.

Soybean [Glycine max (L.) Merrill] is one of the most widely grown legumes in the world, with Brazil being its largest producer and exporter. Breeding programs in Brazil have resulted from multiple cycles of selection and recombination starting from a small number of USA cultivar ancestors in the 1950s and 1960s years.

Limited research investigating the value of MRI in predicting future cognitive morbidity in survivors of paediatric brain tumours: A systematic-review and call to action for clinical neuroimaging researchers.

Survivors of pediatric brain tumours are at a high risk of cognitive morbidity. Reliable individual-level predictions regarding the likelihood, degree, and affected domains of cognitive impairment would be clinically beneficial. While established risk factors exist, quantitative MRI analysis may enhance predictive value, above and beyond current clinical risk models.