Persistence

Research opportunities for undergraduate students are strongly advantageous, but implementation at a large scale presents numerous challenges. The enormous diversity of the bacteriophage population and a supportive programmatic structure provide opportunities to engage early-career undergraduates in phage discovery, genomics, and genetics. The Science Education Alliance (SEA) is an inclusive Research-Education Community (iREC) providing centralized programmatic support for students and faculty without prior experience in virology at institutions from community colleges to research-active universities to participate in two course-based projects, SEA-PHAGES (SEA Phage Hunters Advancing Genomic and Evolutionary Science) and SEA-GENES (SEA Gene-function Exploration by a Network of Emerging Scientists)...

Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of early molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification toward definitive neural crest. Here, we combine ultradense single-cell transcriptomes with machine-learning and large-scale transcriptomic and epigenomic experimental validation of selected trajectories, to provide the general principles and highlight specific features of the GRN underlying neural crest fate diversification from induction to early migration stages using Xenopus frog embryos as a model...

Determining the pathogenicity of hypertrophic cardiomyopathy-associated mutations in the β-myosin heavy chain ( MYH7 ) can be challenging due to its variable penetrance and clinical severity. This study investigates the early pathogenic effects of the incomplete-penetrant MYH7 G256E mutation on myosin function that may trigger pathogenic adaptations and hypertrophy. We hypothesized that the G256E mutation would alter myosin biomechanical function, leading to changes in cellular functions. We developed a collaborative pipeline to characterize myosin function across protein, myofibril, cell, and tissue levels to determine the multiscale effects on structure-function of the contractile apparatus and its implications for gene regulation and metabolic state...

Proteins that are kinetically stable are thought to be less prone to both aggregation and proteolysis. We demonstrate that the classical lac system of Escherichia coli can be leveraged as a model system to study this relation. β-galactosidase (LacZ) plays a critical role in lactose metabolism and is an extremely stable protein that can persist in growing cells for multiple generations after expression has stopped. By attaching degradation tags to the LacZ protein, we find that LacZ can be transiently degraded during lac operon expression but once expression has stopped functional LacZ is protected from degradation...

Relapse is the leading cause of death after allogeneic hematopoietic stem cell transplantation (HCT) for leukemia. T cells engineered by gene transfer to express T cell receptors (TCR; TCR-T) specific for hematopoietic-restricted minor histocompatibility (H) antigens may provide a potent selective anti-leukemic effect post-HCT. We conducted a phase I clinical trial employing a novel TCR-T product targeting the minor H antigen HA-1 to treat or consolidate treatment of persistent or recurrent leukemia and myeloid neoplasms...

Epstein-Barr virus (EBV) persistently infects 95% of adults worldwide and is associated with multiple human lymphomas that express characteristic EBV latency programs used by the virus to navigate the B-cell compartment. Upon primary infection, the EBV latency III program, comprised of six Epstein-Barr Nuclear Antigens (EBNA) and two Latent Membrane Protein (LMP) antigens, drives infected B-cells into germinal center (GC). By incompletely understood mechanisms, GC microenvironmental cues trigger the EBV genome to switch to the latency II program, comprised of EBNA1, LMP1 and LMP2A and observed in GC-derived Hodgkin lymphoma...

Reactively canceling movements is a vital feature of the motor system to ensure safety. This behavior can be studied in the laboratory using the stop-signal task. There remains ambiguity about whether a "point-of-no-return" exists, after which a response cannot be aborted. A separate question concerns whether motor system inhibition associated with attempted stopping persists when stopping is unsuccessful. We address these two questions using electromyography (EMG) in two stop-signal task experiments. Experiment 1 (n = 24) involved simple right and left index finger responses in separate task blocks...

The fund investment industry heavily relies on the expertise of fund managers, who bear the responsibility of managing portfolios on behalf of clients. With their investment knowledge and professional skills, fund managers gain a competitive advantage over the average investor in the market. Consequently, investors prefer entrusting their investments to fund managers rather than directly investing in funds. For these investors, the primary concern is selecting a suitable fund manager. While previous studies have employed quantitative or qualitative methods to analyze various aspects of fund managers, such as performance metrics, personal characteristics, and performance persistence, they often face challenges when dealing with a large candidate space...

Humans can extract statistical regularities of the environment to predict upcoming events. Previous research recognized that implicitly acquired statistical knowledge remained persistent and continued to influence behavior even when the regularities were no longer present in the environment. Here, in an fMRI experiment, we investigated how the persistence of statistical knowledge is represented in the brain. Participants (n = 32) completed a visual, four-choice, RT task consisting of statistical regularities...

IMPORTANCE: Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases. OBJECTIVE: To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems...

Although the association between persistent hypertension and the compromise of both micro- and macro-circulatory functions is well recognized, a significant gap in quantitative investigations exploring the interplay between microvascular and macrovascular injuries still exists. In this study, the authors looked into the relationship between brachial-ankle pulse wave velocity (baPWV) and hypertensive retinopathy in treated hypertensive adults. The authors conducted a cross-sectional study of treated hypertensive patients with the last follow-up data from the China Stoke Primary Prevention Trial (CSPPT) in 2013...

Zwitterionic coatings are an efficient strategy for preventing biomolecule adsorption and enhancing nanoparticle stability in solution. The properties of zwitterions and other antifouling materials, including suppression of nonspecific adsorption and improved colloidal stability of nanoparticles, are believed to derive from their electroneutral and highly hydrophilic nature. Among different zwitterions, short sulfobetaines have been demonstrated to be effective in preventing protein adsorption onto several nanoparticles and providing enhanced colloidal stability...

BACKGROUND AIMS: Hepatocellular carcinoma (HCC), particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed...

Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as serum calcium and PTH levels, is complex in pregnant women. The aim of this report is to present a case of PHTP in a pregnant adolescent, with a special emphasis on an uncommon complication, as well as diagnostic and treatment strategies. A 17-year-old pregnant female presented with hyperemesis gravidarum and neurological symptoms, leading to the diagnosis of cerebral venous thrombosis...

BACKGROUND: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer. OBJECTIVE: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible...

The flood of Damodar river is a well-known fact which is used to the whole riverine society of the basin as well as to the eastern India. The study aims to estimate the spatio-temporal probability of floods and identify susceptible zones in the Lower Damodar Basin (LDB). A flood frequency analysis around 90 years hydrological series is performed using the Log-Pearson Type III model. The frequency ratio model has also been applied to determine the spatial context of flood. This reveals the extent to which the LDB could be inundated in response to peak discharge conditions, especially during the monsoon season...

INTRODUCTION: Non-responsive disease (NRCD), where symptoms and enteropathy persist despite a prolonged gluten-free diet (GFD), is common. Refractory coeliac disease (RCD), characterised by malabsorption and extensive enteropathy, is rare but serious. In both, treatment options are limited. Topical budesonide may help and an open capsule format promoting proximal small intestinal delivery may be advantageous. AIM: To describe the effect of budesonide and its presentation on mucosal healing, symptoms, and tolerability in NRCD and RCD...

PURPOSE: This study aimed to evaluate the clinical efficacy and safety of argon plasma coagulation (APC) therapy and interferon therapy in patients with grade I and II vaginal intraepithelial neoplasia (VaIN). METHODS: A total of 112 patients with VaIN were diagnosed via colposcopy-induced biopsy and classified into the APC group (n = 77) and interferon group (n = 35). Clinical data including age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, cytology, human papillomavirus (HPV) subtype, treatment modalities, and clinical outcomes were analyzed, retrospectively...

OBJECTIVES: Acute postsurgical pain (APSP) may persist over time and become chronic. Research on predictors for APSP and chronic postsurgical pain (CPSP) has produced inconsistent results. This observational study aimed to analyze psychological and psychophysical variables associated with APSP and CPSP after total knee or hip arthroplasty, and to explore the role of sex. METHODS: Assessments were conducted before surgery, 48 h, and 3 months postsurgery, including questionnaires (sociodemographic, pain related, and psychological) and quantitative sensory testing (QST)...

OBJECTIVE: To present the baseline clinical and demographic characteristics of CRSwNP patients over the age of 18 enrolled in a Patient Support Program (PSP) prior to biologic treatment. METHODS: Descriptive, cross-sectional study performed in a Colombian CRSwNP asthma PSP sponsored by Sanofi from Aug-2021 to Jul-2022. Data was collected from CRSwNP patients, prior to the start of Dupilumab treatment, who consented to the use of their data. The following information was reported: Age, reporting city, treating medical specialty, comorbidities, and persistence of treatment...