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.

Geosocial Media's Early Warning Capabilities Across US County-Level Political Clusters: Observational Study.

Background: The novel coronavirus disease (COVID-19) sparked significant health concerns worldwide, prompting policy makers and health care experts to implement nonpharmaceutical public health interventions, such as stay-at-home orders and mask mandates, to slow the spread of the virus. While these interventions proved essential in controlling transmission, they also caused substantial economic and societal costs and should therefore be used strategically, particularly when disease activity is on the rise. In this context, geosocial media posts (posts with an explicit georeference) have been shown to provide a promising tool for anticipating moments of potential health care crises.

High Areal Loading Silicon Nanoparticle-Based Lithium-Ion Batteries.

Interfacial mechanical stability between silicon (Si) and the current collector is crucial when high areal-loading of Si is demanded as intense stress develops at the interface due to its extreme volume alteration during the lithiation-delithiation process. Therefore, we propose using a thin, rough, porous, and highly conductive carbon nanotube network (CNT-N) as a buffer layer between the Si and current collector that provides abundant anchor sites for Si nanoparticles. The strong and elastic CNT-N, which is not involved directly in the lithiation process, reduces stress at interfaces between the Si and CNT-N and the CNT-N and current collector.

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.

Forecasting Asparaginase Need and Cost for Childhood Cancer Using ACCESS FORxECAST.

Purpose: Asparaginase (ASN) is a critical component of pediatric ALL protocols. Until recently, ASN was available in three formulations: native Escherichia coli, PEGylated E. coli (PEG), and Erwinase, with native E.

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.

Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma.

Purpose: We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities.

Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer.

Purpose: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

Methods: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

Atomic-Level Tin Regulation for High-Performance Zinc-Air Batteries.

The trade-off between the performances of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) presents a challenge in designing high-performance aqueous rechargeable zinc-air batteries (a-r-ZABs) due to sluggish kinetics and differing reaction requirements. Accurate control of the atomic and electronic structures is crucial for the rational design of efficient bifunctional oxygen electrocatalysts. Herein, we designed a Sn-Co/RuO trimetallic oxide utilizing dual-active sites and tin (Sn) regulation strategy by dispersing Co (for ORR) and auxiliary Sn into the near-surface and surface of RuO (for OER) to enhance both ORR and OER performances.

Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug.

Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named (), harboring a mutation in the - () gene. Loss of leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos, such as cellular senescence, genomic instability, and epigenetic alteration.

Optimal strategies for correcting merotelic chromosome attachments in anaphase.

Accurate chromosome segregation in mitosis depends on proper connections of sister chromatids, through microtubules, to the opposite poles of the early mitotic spindle. Transiently, many inaccurate connections are formed and rapidly corrected throughout the mitotic stages, but a small number of merotelic connections, in which a chromatid is connected to both spindle poles, remain lagging at the spindle's equator in anaphase. Most of the lagging chromatids are eventually moved to one or the other pole, likely by a combination of microtubules' turnover and the brute force of pulling by the microtubules' majority from the one pole against the microtubules' minority from the other pole.

Errors are robustly tamed in cumulative knowledge processes.

As knowledge accumulates in science and society in a distributed fashion, erroneous derivations can be introduced into the corpus of knowledge. Such derivations can compromise the validity of any units of knowledge that rely on them in the future. Can societal knowledge maintain some level of integrity given simple distributed error-checking mechanisms? In this paper, we investigate the following formulation of the question: assuming that a constant fraction of the new derivations is wrong, is it possible for simple error-checking mechanisms that apply when a new unit of knowledge is derived to maintain the integrity of the corpus of knowledge? This question was introduced by Ben-Eliezer et al.

Suppressed Degradation Process of PBDB-TF-T1:BTP-4F-12-Based Organic Solar Cells with Solid Additive Atums Green.

Solid additives have garnered significant attention due to their numerous advantages over liquid additives. This study explores the potential of the green-fluorescent conjugated polymer denoted Atums Green as a solid additive in green-solvent-based PBDB-TF-T1:BTP-4F-12 solar cells. Even tiny amounts of Atums Green doping significantly improve the device performance.

Global natural history infrastructure requires international solidarity, support, and investment in local capacity.

Amid global challenges like climate change, extinctions, and disease epidemics, science and society require nuanced, international solutions that are grounded in robust, interdisciplinary perspectives and datasets that span deep time. Natural history collections, from modern biological specimens to the archaeological and fossil records, are crucial tools for understanding cultural and biological processes that shape our modern world. At the same time, natural history collections in low and middle-income countries are at-risk and underresourced, imperiling efforts to build the infrastructure and scientific capacity necessary to tackle critical challenges.

Arthroscopic-assisted uniportal spinal surgery for treatment of lumbar burst fractures complicated with neurological symptoms: a case report.

Lumbar burst fractures account for 21% to 58% of all thoracolumbar fractures. L5 lumbar burst fractures are rare, comprising 1.2% of spinal burst fractures.

Randomizing the human genome by engineering recombination between repeat elements.

We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into repetitive sequences, up to 1697 per cell line, which enables generating large-scale deletions, inversions, translocations, and circular DNA. Recombinase induction produced more than 100 stochastic megabase-sized rearrangements in each cell.

Penehyclidine for postoperative nausea and vomiting in patients receiving general anesthesia: A systematic review and meta-analysis protocol.

Background: Postoperative nausea and vomiting (PONV) is a common complication of general anesthesia. This affects 30-80% of patients, and leads to discomfort and extended hospital stays. The effectiveness of penehyclidine for preventing PONV remains a subject of debate in the literature.

Genome-wide DNA methylation and transcriptome sequencing analyses of lens tissue in an age-related mouse cataract model.

DNA methylation is known to be associated with cataracts. In this study, we used a mouse model and performed DNA methylation and transcriptome sequencing analyses to find epigenetic indicators for age-related cataracts (ARC). Anterior lens capsule membrane tissues from young and aged mice were analyzed by MethylRAD-seq to detect the genome-wide methylation of extracted DNA.

The effects of integrated traditional Chinese and western medicine rehabilitation programs on post-acute ankle sprain: A randomized controlled trial study protocol.

Background: Ankle sprain is a common clinical disease, which has the highest incidence rate among joint and ligament injuries. And acute ankle sprains can easily develop into chronic ankle instability, thereby increasing the difficulty of treatment. The current clinical guidelines for post-acute ankle sprains are still controversial.

Abnormalities in male gametophytes development responsible for low seed set of Peudosasa subsolida.

Pseudosasa subsolida belongs to the Pseudosasa genus within the Poaceae family. Due to its unique flowering cycle and the physiological traits associated with asexual reproduction, acquiring floral material from P. subsolida is particularly challenging.

IL-34 aggravates myocardial ischemia-reperfusion injury by upregulating the HMGB1-IL-17A-IL-6 axis through the JAK signaling pathway.

Interleukin-34 (IL-34) was recently reported to be a new biomarker for atherosclerosis diseases, such as coronary artery disease and vascular dementia. IL-34 regulates the expression of proinflammatory cytokines (IL-17A, IL-1 and IL-6), which are classical cytokines involved in myocardial ischemia‒reperfusion (MI/R) injury. However, the exact role of IL-34 in MI/R remains unknown.

Multi-session tDCS over the posterior parietal cortex and associative memory.

Associative memory (AM) plays a crucial role in our ability to link disparate elements of our experiences, yet it is especially vulnerable to age-related decline and pathological conditions. Non-invasive brain stimulation (NIBS), particularly transcranial direct current stimulation (tDCS), has been investigated as a potential intervention to enhance cognitive functions, including AM. Previous tDCS studies yielded inconsistent results, often due to variations in stimulation sites and protocols.

Boosting Electrode Performance and Bubble Management via Direct Laser Interference Patterning.

Laser-structuring techniques like Direct Laser Interference Patterning show great potential for optimizing electrodes for water electrolysis. Therefore, a systematic experimental study is performed to analyze the influence of the spatial period and the aspect ratio between spatial period and structure depth on the electrode performance for pure Ni electrodes. Using a statistical design of experiments approach, it is found that the spatial distance between the laser-structures is the decisive processing parameter for the improvement of the electrode performance.