Determination of the Zebrafish Embryo Developmental Toxicity Assessment (ZEDTA) as an Alternative Non-Mammalian Approach for the Safety Assessment of Agrochemicals.

With the US Environment Protection Agency reducing requests for (and funding of) mammalian studies alongside the proposed elimination of requests by 2035, there is an urgent need for fully validated New Approach Methods (NAMs) to fill the resultant gap for safety assessment of agrochemicals. One promising NAM for assessing the potential for human prenatal developmental toxicity potential is the Zebrafish Embryo Developmental Toxicity Assessment, a bioassay that has been used by the pharmaceutical industry for more than a decade in early-stage drug safety assessment. Despite its promise, little data has been generated to assess the validity of ZEDTA for assessing Developmental and Reproductive Toxicity of new agrochemical products.

Prolonged neurologic symptoms following immune effector cell-associated neurotoxicity syndrome in patients with large B cell lymphoma treated with chimeric antigen receptor-modified T cell therapy.

Background: While immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-defined adverse effect associated with chimeric antigen receptor-modified T cell (CAR-T) therapy, some patients develop prolonged neurologic symptoms. Few studies have examined characteristics and outcomes of patients who develop such symptoms.

Objective: To provide an analysis of patients who developed ICANS in a single-center cohort of patients with large B-cell lymphoma (LBCL) who received commercial CAR-T and compare characteristics and outcomes between patients with vs.

Knowledge and Awareness of Medical and Dental Students About Oral Cancer Risk Factors: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis aims to assess the knowledge and awareness of oral cancer risk factors among medical and dental students.

Methods: This study followed the PRISMA guidelines and was registered in INPLASY (ID: 2024110035). Four databases were consulted (PubMed, Science Direct, Scopus, and Web of Science) from February 20th, 2005, to May 10th, 2024.

Hyperplex PCR enables highly multiplexed analysis of point mutations in wastewater: Long-term SARS-CoV-2 variant surveillance in Sweden as a case study.

Wastewater-based surveillance (WBS) allows the analysis of pathogens, chemicals or other biomarkers in wastewater to derive unbiased epidemiological information at population scale. After re-gaining attention during the SARS-CoV-2 pandemic, the field holds promise as a surveillance and early warning system by tracking emerging pathogens with pandemic potential. Expanding the current toolbox of analytical techniques for wastewater analysis, we explored the use of Hyperplex PCR (hpPCR) to analyse SARS-CoV-2 mutations in wastewater samples collected weekly in up to 22 sites across Sweden between October 2022 and December 2023.

Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer's Dementia.

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.

Methods: Participants were drawn from the population-based HELIAD cohort.

Unraveling the neuroprotective effect of perampanel and lacosamide combination in the corneal kindling model for epilepsy in mice.

Background: Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking. In this study, the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice, which is a cost-effective mechanism for screening of antiseizure drugs.

Methods: The impact of lacosamide (5 mg/kg) and perampanel (0.

Dynamic Outlier Slicing Allows Broader Exploration of Adaptive Divergence: A Comparison of Individual Genome and Pool-Seq Data Linked to Humic Adaptation in Perch.

How genetic variation contributes to adaptation at different environments is a central focus in evolutionary biology. However, most free-living species still lack a comprehensive understanding of the primary molecular mechanisms of adaptation. Here, we characterised the targets of selection associated with drastically different aquatic environments-humic and clear water-in the common freshwater fish, Eurasian perch (Perca fluviatilis).

Bioinformatic approach to explain how Mg from seawater may be incorporated into coral skeletons.

Corals have been used as geochemical proxies since the 1970s, playing a prominent role in paleoceanography. However, it has not been well elucidated how aqueous ions sourced from seawater are transported and precipitated in coral skeletons. There are limited foundational methods to differentiate and quantify biogenic and abiogenic effects during skeletal formation.

Small intestinal bacterial overgrowth in chronic liver disease: an updated systematic review and meta-analysis of case-control studies.

Background: Small Intestinal Bacterial Overgrowth (SIBO) has been implicated in the pathophysiology of chronic liver disease (CLD). We conducted a systematic review and meta-analysis to assess and compare the prevalence of SIBO among CLD patients (with and without with complications of end stage liver disease) and healthy controls.

Methods: Electronic databases were searched from inception up to July-2024 for case-control studies reporting SIBO in CLD.

Homology modeling and thermostability enhancement of PETase via hydrophobic interactions.

The quest for sustainable solutions to plastic pollution has driven research into plastic-degrading enzymes, offering promising avenues for polymer recycling applications. However, enzymes derived from natural sources often exhibit suboptimal thermostability, hindering their industrial viability. Protein engineering techniques have emerged as a powerful approach to enhance the desired properties of these biocatalysts.

Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae.

Background: Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture.

Identification of promising SARS-CoV-2 main protease inhibitor through molecular docking, dynamics simulation, and ADMET analysis.

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a major challenge to global health. Targeting the main protease of the virus (Mpro), which is essential for viral replication and transcription, offers a promising approach for therapeutic intervention. In this study, advanced computational techniques such as molecular docking and molecular dynamics simulations were used to screen a series of antiviral compounds for their potential inhibitory effect on the SARS-CoV-2 Mpro.

Going to extremes: progress in exploring new environments for novel antibiotics.

The discoveries of penicillin and streptomycin were pivotal for infection control with the knowledge subsequently being used to enable the discovery of many other antibiotics currently used in clinical practice. These valuable compounds are generally derived from mesophilic soil microorganisms, predominantly Streptomyces species. Unfortunately, problems with the replication of results suggested that this discovery strategy was no longer viable, motivating a switch to combinatorial chemistry in conjunction with existing screening programmes to derive new antimicrobials.

Toll/interleukin-1 receptor-only genes contribute to immune responses in maize.

Proteins with Toll/interleukin-1 receptor (TIR) domains are widely distributed in both prokaryotes and eukaryotes, serving as essential components of immune signaling. Although monocots lack the major TIR-nucleotide-binding (NB)-leucine-rich repeat (LRR)-type (TNL) immune receptors, they possess a small number of TIR-only proteins, the function of which remains largely unknown. In the monocot maize (Zea mays), there are three conserved TIR-only genes in the reference genome, namely ZmTIR1 to ZmTIR3.

The critical role of the variable domain in driving proteotoxicity and aggregation in full-length light chains.

Light chain (AL) amyloidosis is the most common systemic amyloid disease characterized by abnormal accumulation of amyloid fibrils derived from immunoglobulin light chains (LCs). Both full-length (FL) LCs and their isolated variable (VL) and constant (CL) domains contribute to amyloid deposits in multiple organs, with the VL domain predominantly forming the fibril core. However, the role and interplay of these domains in amyloid aggregation and toxicity are poorly understood.

Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).

Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.

Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.

Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria.

Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

Cell-Based Meat Safety and Regulatory Approaches: A Comprehensive Review.

Cell-based meat (CBM) technology is a highly promising alternative to traditional animal agriculture, with considerable advantages in terms of sustainability, animal welfare, and food security. Nonetheless, CBM's successful commercialization is dependent on efficiently dealing with several critical concerns, including ensuring biological, chemical, and nutritional safety as well as navigating the global regulatory framework. To ensure CBM's biological safety, detecting and mitigating any potential hazards introduced during the manufacturing process is crucial.

Swatting Flies: Biting Insects as Non-Invasive Samplers for Mammalian Population Genomics.

Advances in next-generation sequencing have allowed the use of DNA obtained from unusual sources for wildlife studies. However, these samples have been used predominantly to sequence mitochondrial DNA for species identification while population genetics analyses have been rare. Since next-generation sequencing allows indiscriminate detection of all DNA fragments in a sample, technically it should be possible to sequence whole genomes of animals from environmental samples.

Systematic Review of Vaccine Strategies Against Tritrichomonas foetus Infection in Cattle: Insights, Challenges, and Prospects.

Tritrichomonas foetus is a protozoan parasite that causes bovine trichomonosis (also referred to as trichomoniasis) resulting in substantial economic loss in extensive grazing systems. The parasite colonises the reproductive tracts of both male and female cattle, being asymptomatic in males but causing early reproductive failure in infected females. This systematic review aimed to examine research manuscripts describing the development of T.

Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

Identifying impairments and compensatory strategies for temporal gait asymmetry in post-stroke persons.

In post-stroke persons, temporal gait asymmetry (TGA) during comfortable gait involves a combination of pure impairments and compensatory strategies. In this study, we aimed to differentiate between pure impairments and compensatory strategies underlying TGA in post-stroke individuals and identify associated clinical factors. We examined 39 post-stroke individuals who participated in comfortable walking speed (CWS) and rhythmic auditory cueing (RAC).

NuFold: end-to-end approach for RNA tertiary structure prediction with flexible nucleobase center representation.

RNA plays a crucial role not only in information transfer as messenger RNA during gene expression but also in various biological functions as non-coding RNAs. Understanding mechanical mechanisms of function needs tertiary structure information; however, experimental determination of three-dimensional RNA structures is costly and time-consuming, leading to a substantial gap between RNA sequence and structural data. To address this challenge, we developed NuFold, a novel computational approach that leverages state-of-the-art deep learning architecture to accurately predict RNA tertiary structures.