Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study.

Background: Effective treatment options are scarce for relapsed or refractory T-cell lymphoma. This study assesses the safety and activity of CTX130 (volamcabtagene durzigedleucel), a CD70-directed, allogeneic chimeric antigen receptor (CAR) immunotherapy manufactured from healthy donor T cells, in patients with relapsed or refractory T-cell lymphoma.

Methods: This single-arm, open-label, phase 1 study was done at ten medical centres across the USA, Australia, and Canada in patients (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma or cutaneous T-cell lymphoma, who had received at least one or at least two previous systemic therapy lines, respectively, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Manganese uptake by MtsABC contributes to the pathogenesis of human pathogen group A streptococcus by resisting host nutritional immune defenses.

The interplay between host nutritional immune mechanisms and bacterial nutrient uptake systems has a major impact on the disease outcome. The host immune factor calprotectin (CP) limits the availability of essential transition metals, such as manganese (Mn) and zinc (Zn), to control the growth of invading pathogens. We previously demonstrated that the competition between CP and the human pathogen group A streptococcus (GAS) for Zn impacts GAS pathogenesis.

Navigating the landscape of epitranscriptomics and host immunity.

RNA modifications, also termed epitranscriptomic marks, encompass chemical alterations to individual nucleotides, including processes such as methylation and editing. These marks contribute to a wide range of biological processes, many of which are related to host immune system defense. The functions of immune-related RNA modifications can be categorized into three main groups: regulation of immunogenic RNAs, control of genes involved in innate immune response, and facilitation of adaptive immunity.

Brain computed tomography reading of stroke patients by resident doctors from different medical specialities: An eye-tracking study.

Background: Using the eye-tracking technique, our work aimed to examine whether difference in clinical background may affect the training outcome of resident doctors' interpretation skills and reading behaviour related to brain computed tomography (CT).

Methods: Twelve resident doctors in the neurology, radiology, and emergency departments were recruited. Each participant had to read CT images of the brain for two cases.

The leaderless communication peptide (LCP) class of quorum-sensing peptides is broadly distributed among Firmicutes.

The human pathogen Streptococcus pyogenes secretes a short peptide (leaderless communication peptide, LCP) that mediates intercellular communication and controls bacterial virulence through interaction with its receptor, RopB. Here, we show that LCP and RopB homologues are present in other Firmicutes. We experimentally validate that LCPs with distinct peptide communication codes act as bacterial intercellular signals and regulate gene expression in Streptococcus salivarius, Streptococcus porcinus, Enterococcus malodoratus and Limosilactobacillus reuteri.

Concordance of the ACR TI-RADS Classification With Bethesda Scoring and Histopathology Risk Stratification of Thyroid Nodules.

Importance: Although most thyroid nodules are benign, 10% to 15% of them harbor cancer. Thyroid ultrasonography is useful for risk stratification of nodules, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) classification provides recommendations for fine-needle aspiration cytology (FNAC) based on objective ultrasonographic features of these nodules.

Objective: To validate the concordance of ACR TI-RADS classification with Bethesda classification and histopathology.

L-GIREMI uncovers RNA editing sites in long-read RNA-seq.

Although long-read RNA-seq is increasingly applied to characterize full-length transcripts it can also enable detection of nucleotide variants, such as genetic mutations or RNA editing sites, which is significantly under-explored. Here, we present an in-depth study to detect and analyze RNA editing sites in long-read RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors and read biases.

Sacubitril/valsartan: An antiarrhythmic drug?

Introduction: Heart failure (HF) is a major cause of morbidity and mortality, with nearly half of all HF-related deaths resulting from sudden cardiac death (SCD), most often from an arrhythmic event. The pathophysiologic changes that occur in response to the hemodynamic stress of HF may lead to increased arrhythmogenesis. Theoretically, medications that block these arrhythmogenic substrates would decrease the risk of SCD.

The screening for anticoagulant rodenticide gene VKORC1 polymorphism in the rat Rattus norvegicus, Rattus tanezumi and Rattus losea in Hong Kong.

Anticoagulants are a major component of rodenticides used worldwide, which function by effectively blocking the vitamin K cycle in rodents. The rat Vitamin K epoxide Reductase Complex (VKORC) subunit 1 is the enzyme responsible for recycling vitamin K, and five substitution mutations (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln and Leu120Gln) located in the VKORC1 could result in resistance to anticoagulant rodenticides. This study carried out a VKORC1-based survey to estimate the anticoagulant rodenticide resistance in three Rattus species (R.

Exogenous oxidative stressors elicit differing age and sex effects in Tigriopus californicus.

As organisms age, cellular function declines in a time-dependent manner. Oxidative stress induced by reactive oxygen species damages cellular machinery and contributes to senescence which narrows the homeostatic window needed to maintain function and survive stress. Sex differences in longevity are apparent in many species and may be related to sex-specific homeostatic responses.

Genetics of white color and iridophoroma in "Lemon Frost" leopard geckos.

The squamates (lizards and snakes) are close relatives of birds and mammals, with more than 10,000 described species that display extensive variation in a number of important biological traits, including coloration, venom production, and regeneration. Due to a lack of genomic tools, few genetic studies in squamates have been carried out. The leopard gecko, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns.

Hybrid Ubiquitous Coaching With a Novel Combination of Mobile and Holographic Conversational Agents Targeting Adherence to Home Exercises: Four Design and Evaluation Studies.

Background: Effective treatments for various conditions such as obesity, cardiac heart diseases, or low back pain require not only personal on-site coaching sessions by health care experts but also a significant amount of home exercises. However, nonadherence to home exercises is still a serious problem as it leads to increased costs due to prolonged treatments.

Objective: To improve adherence to home exercises, we propose, implement, and assess the novel coaching concept of hybrid ubiquitous coaching (HUC).

Evaluation of Homology-Independent CRISPR-Cas9 Off-Target Assessment Methods.

The ability to alter genomes specifically by CRISPR-Cas gene editing has revolutionized biological research, biotechnology, and medicine. Broad therapeutic application of this technology, however, will require thorough preclinical assessment of off-target editing by homology-based prediction coupled with reliable methods for detecting off-target editing. Several off-target site nomination assays exist, but careful comparison is needed to ascertain their relative strengths and weaknesses.

Sex differences in early transcriptomic responses to oxidative stress in the copepod Tigriopus californicus.

Background: Patterns of gene expression can be dramatically different between males and females of the same species, in part due to genes on sex chromosomes. Here we test for sex differences in early transcriptomic response to oxidative stress in a species which lacks heteromorphic sex chromosomes, the copepod Tigriopus californicus.

Results: Male and female individuals were separately exposed to control conditions and pro-oxidant conditions (hydrogen peroxide and paraquat) for periods of 3 hours and 6 hours.

Infection patterns of dengue, Zika and endosymbiont Wolbachia in the mosquito Aedes albopictus in Hong Kong.

Background: The mosquito Aedes albopictus is a vector of dengue and Zika viruses. Insecticide-resistant mosquito populations have evolved in recent decades, suggesting that new control strategies are needed. Hong Kong has a monsoon-influenced humid subtropical climate, which favours the spread of mosquitoes.

Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma.

Background: Cancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments.

Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination.

Caring for trafficked and unidentified patients in the EHR shadows: Shining a light by sharing the data.

Objective: Healthcare providers have key roles in the prevention of, detection of, and interventions for human trafficking. Yet caring for trafficked persons is particularly challenging: patients whose identities are unknown, unreliable, or false could receive subpar care from providers delivering care in a vacuum of relevant information. The application of precision medicine principles and integration of biometric data (including genetic information) could facilitate patient identification, enable longitudinal medical records, and improve continuity and quality of care for this vulnerable patient population.

S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood-Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder.

Background: Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV.

Methods: Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD.

Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels.

Maternal depressive symptoms during pregnancy are associated with risk for offspring emotional and behavioral problems, but the mechanisms by which this association occurs are not known. Infant elevated negative affect (increased crying, irritability, fearfulness, etc.) is a key risk factor for future psychopathology, so understanding its determinants has prevention and early intervention potential.

Core neurological examination items for neurology clerks: A modified Delphi study with a grass-roots approach.

Background: With the evolution of treatments for neurological diseases, the contents of core neurological examinations (NEs) for medical students may need to be modified. We aimed to establish a consensus on the core NE items for neurology clerks and compare viewpoints between different groups of panelists.

Methods: First, a pilot group proposed the core contents of NEs for neurology clerks.

Analysis of near crashes among teen, young adult, and experienced adult drivers using the SHRP2 naturalistic driving study.

Objective: Motor vehicle crashes are the leading cause of death among young drivers. Though previous research has focused on crash events, near crashes offer additional data to help identify driver errors that could potentially lead to crashes as well as evasive maneuvers used to avoid them. The Strategic Highway Research Program 2 (SHRP2) Naturalistic Driving Study (NDS) contains extensive data on real-world driving and offers a reliable methodology to quantify and study near crashes.

Parallel Effects of Methamphetamine on Anxiety and CCL3 in Humans and a Genetic Mouse Model of High Methamphetamine Intake.

Background: Methamphetamine (MA) abuse causes immune dysfunction and neuropsychiatric impairment. The mechanisms underlying these deficits remain unidentified.

Methods: The effects of MA on anxiety-like behavior and immune function were investigated in mice selectively bred to voluntarily consume high amounts of MA [i.