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Neglected tropical diseases: the need for an integrated approach to achieve the 2030 roadmap

Riprap mitigation of downstream scour at grade-control structures considering tailwater depth and layer thickness

Spinal cord perfusion pressure protocol for acute spinal cord injury: Pragmatic implementation and early results at two sites

Study design Retrospective chart review. Objective Describe safety/feasibility of implementing a novel clinical protocol for acute spinal cord injury (SCI) management. Summary of background data Spinal cord perfusion pressure (SCPP) has emerged as a promising target for the medical management of SCI patients. We report our early experience implementing a pragmatic SCPP-driven clinical protocol to supplant conventional mean arterial pressure (MAP) monitoring in the setting of acute SCI. Methods We retrospectively reviewed charts of all SCI patients managed by our SCPP protocol since its adoption at two clinical sites as of 2/1/2023. The SCPP protocol was applied for all adult SCI patients of any injury grade, at any injury level with cord tissue involvement. Intrathecal pressure (ITP) was transduced by lumbar drain (LD). MAP was determined from invasive blood pressure recordings. SCPP was calculated as the difference between MAP and ITP, with an SCPP goal of >65mmHg. Results Eighteen patients have been treated since our SCPP protocol was adopted. Patients were predominately male (77.8%); the average age was 52.0 ± 16.2 years. Most injuries involved the cervical segment (72.2%), all of which were manifest clinically as central cord syndrome. The most common presenting injury severity was ASIA Impairment Scale D (44.4%). All patients underwent surgical intervention. There were no complications related to surgery, LD placement, or LD maintenance/ITP transduction during hospitalization. The SCPP protocol was continued for an average 5.2 ± 1.8 days. Eight patients required vasopressor support (44.4%) during that period, for an average 3.1 ± 2.1 days. Five patients underwent therapeutic CSF drainage to augment SCPP (27.8%). All patients maintained an average SCPP above goal for the duration of monitoring. Conclusions This study further establishes the safety and feasibility of monitoring SCPP via LD measurement of ITP in acute SCI patients treated by clinical protocol at two clinical sites. There were no complications related to LD placement/maintenance or SCPP monitoring.

Briefing Chat: What Brazilian centenarians could reveal about the science of ageing

Association-induced folding governs surrogate light chain and pre-B cell receptor core assembly

Abstract Binding of the surrogate light chain (SLC) to the heavy chain (HC) of the pre-B cell receptor (preBCR) is an important quality control checkpoint during B cell development as roughly 50% of the rearranged HCs are defective. Unlike the regular light chain (LC), the SLC is a hetero-dimer of VpreB and λ5, both containing unstructured extensions, the unique regions. The molecular mechanisms that underlie the complex assembly processes which give rise to the final pre-BCR is not fully understood. Here we show, via reconstitution of the pre-BCR in vitro and in cells that λ5 plays a key role in the pre-BCR assembly. During SLC assembly, a β-strand, located between the λ5 domain and the unique region, induces structure in the largely unfolded VpreB, creating a high affinity complex. In addition, association of λ5 with the unstructured HC C H 1 domain is required for its folding. This is essential for pre-BCR assembly and its release from the endoplasmic reticulum (ER). Finally, the unique region of λ5 plays a pivotal role in the antigen interaction of the SLC-HC complex. Together, our results reveal a multi-step mechanism for SLC and pre-BCR assembly, governed by association-induced folding reactions required for structural integrity and function.

Computational strategies for unraveling insights from known inhibitors for further lead optimization: A case study on Celecoxib analogues

Transcriptome profiling indicates varied gene responses to Pasteurella multocida mutant infections in cattle

Pasteurella multocida is a pathogen that causes bovine respiratory disease, and the development of an effective vaccine is important for improving animal health. Live-attenuated vaccines induce a long-lasting immune response with minimal side effects. The objective of this study was to evaluate potential live vaccine candidates from three P. multocida mutants produced by separately disrupting the genes of filamentous hemagglutinin 2 ( fhaB2 ) , hydrogenase-1 operon ( hyaE ) , and n-acylneuraminate-9-phosphatase ( nanP ) of a serogroup 3 strain (P1062, WT) by clinical testing and transcriptome analysis. Challenge with WT and the three mutants conferred protection against P. multocida , with less lung lesions (4.7–6.2%) compared to 22.4% in the sham group. Transcriptome analysis identified 807 differentially expressed protein-coding transcripts (DETs) in the blood and 6473 DETs in the liver compared to the sham, WT, and each of the mutants. In total, 15 and 64 differentially expressed microRNAs (DEmiRNAs) and 12 and 74 differentially expressed long non-coding RNAs (DElncRNAs) were identified in blood and liver, respectively. The DEmiRNAs were not significantly associated with the DETs within each comparison. DElncRNAs were associated with 12 and 170 DETs in blood and liver respectively. The greatest number of unique DETs were found between hyaE and sham groups in the liver, which agreed with the low colonization rate in the nares and palatine tonsils. For the DETs between sham and WT the under-enriched gene ontology terms in blood were all included in the liver for the DETs identified by WT vs. sham, nanP vs. sham, and hyaE vs. sham, and were related to the signaling pathway, stimulus, and sensory perceptions in biological processes with the molecular function of olfactory receptor activity. The number of identified DETs, decreased percentage of lung lesions, and colonization rates indicate that fhaB2 could be a promising vaccine candidate.

Dynamic stretching beyond electron transfer in a homointerpenetrated metal‒organic framework for enhanced Fenton-like reactions

Synthesis and characterization of activated carbon from acrylic acid-modified black liquor of sugarcane bagasse for enhanced cadmium removal

Streptococcus pneumoniae upregulates Toll2, Toll9, and defensin genes in Bombyx larvae infection model

Pneumococcal diseases caused by the human pathogenic bacterium Streptococcus pneumoniae are a major public health concern worldwide. In this study, we examined the pathogenicity of a clinical isolate of S. pneumoniae in the silk moth, Bombyx mori , larvae infection model. The whole genome sequencing of a clinical isolate of S. pneumoniae , Spn1 identified the presence of genes responsible for its virulence and antibiotic resistance. Spn1 infection of Bombyx larvae resulted in death within 24 h concomitant with an increase of phenoloxidase activity in the hemolymph. The bacterial load increased in the hemolymph within 9 h post-infection (p.i.) Ampicillin, ceftriaxone, tetracycline, imipenem, and erythromycin showed therapeutic effect in infected larvae, although the bacterial strain was resistant to erythromycin in vitro . The Bombyx homologs of mammalian TLR2 and TLR4 , known as BmToll2 and BmToll9 ( BmToll9−1 and BmToll9−2 isoforms), were upregulated in both the fat body and trachea. The antimicrobial peptide (AMP) genes, BmdefensinA and BmdefensinB , known to be regulated by the Toll signaling pathway, were significantly upregulated in both fat body and trachea after S. pneumoniae infection through hemolymph. Our data indicate that the Bombyx larvae can be a suitable infection model to study the pathogenicity of S. pneumoniae .

Engineered alcohol oxidases catalyse transesterification in aqueous media without competing hydrolysis

Abstract Transesterification reactions are fundamental transformations in organic chemistry, yet performing them in aqueous media is challenging because of the competing hydrolysis reaction. In this study, we describe a mutant of alcohol oxidase from Phanerochaete chrysosporium ( Pc AOx-VPN) that also exhibits transesterification activity. Moreover, Pc AOx-VPN displays no detectable hydrolytic activity, owing to its hydrophobic active site, which effectively excludes water. These characteristics make Pc AOx-VPN a promising catalyst for transesterification reactions in aqueous media, a context that is typically compromised by competing hydrolysis.

Spatiotemporal assessment of maize evapotranspiration and surface energy fluxes under varying irrigation regimes using UAV based METRIC

Communication and coordination as drivers of safety behaviours and outcomes in coal-fired power plants

Effective communication and coordination are vital for promoting safety in high-risk industries. While widely regarded as key drivers of safety behaviour, their direct and indirect effects on safety outcomes such as workplace accidents, near misses, fatalities, and lost-time injuries are not well understood, particularly in coal-fired power plants. The study investigates the influence of communication and coordination practices on safety behaviour and their subsequent impact on actual safety outcomes in Malaysian coal-fired power plants. 340 participants from five coal-fired power plants in Peninsular Malaysia participated in a quantitative cross-sectional survey. Stratified random sampling was employed to ensure balanced managerial and non-managerial staff representation. A systematic questionnaire with 60 items was used to gather data. It was divided into four sections: safety outcomes (accidents, near misses, fatalities, and lost-time injuries), safety behaviour dimensions (compliance, involvement, motivation, and knowledge), and demographic data. Five-point Likert scales modified from previously approved instruments were used to measure each issue. Partial Least Squares Structural Equation Modelling (PLS-SEM) in SmartPLS version 3.3.3 was used to analyse the data. The model was evaluated using a two-stage approach to assess formative and reflective constructs. The analysis showed that communication and coordination practices significantly enhanced safety compliance and participation. Among these, safety compliance had a statistically significant negative relationship with adverse safety outcomes. Mediation analysis confirmed that safety compliance played a key role in linking communication and coordination to safety outcomes, indicating that improvements in communication and coordination reduce incidents primarily by fostering better adherence to safety procedures. The results highlight the importance of collaboration and communication as proactive strategies for influencing employee behaviour and lowering unfavourable safety outcomes. One important mediating component surfaced was safety compliance, confirming that management’s coordination and communication efforts work best when they promote constant adherence to safety regulations. In order to foster a culture of safety and operational excellence, organisations in high-risk industries should prioritise establishing transparent, organised communication channels and methodical coordination efforts. These strategies can reduce accidents, injuries, and lost-time incidents while producing quantifiable increases in participation and compliance.

This robot hand detaches and walks by itself

Diversity and ecological roles of hidden viral players in groundwater microbiomes

Abstract Groundwater ecosystems harbor diverse microbial communities adapted to energy-limited, light-deprived conditions, yet the role of viruses in these environments remains poorly understood. Here, we analyzed 1.24 terabases of metagenomic and metatranscriptomic data from seven wells in the Hainich Critical Zone Exploratory (CZE) to characterize groundwater viromes. We identified 257,252 viral operational taxonomic units (vOTUs) (≥ 5 kb), with 99% novel at order, family and genus levels against global ocean, freshwater and/or other publicly available datasets. In silico host predictions suggest that vOTUs primarily targeted Proteobacteria, Candidate Phyla Radiation (CPR) bacteria, and DPANN archaea, which reflects abundant and active groundwater microbial members. Patterns of virus-host abundance ratios, CRISPR-spacers, and prophage screening suggest the potential for multi-layer interactions involving CPR/DPANN lineages, their hosts, and viruses. Additionally, we identified 289 KEGG metabolic modules, 31.1% of which were targeted by 3378 vOTUs encoded auxiliary metabolic genes (AMGs) linked to carbon, nitrogen, and sulfur cycling. These findings provide a baseline for exploring how viruses influence microbial community dynamics, metabolic reprogramming and nutrient cycling in groundwater.

Dual-directional CIM-based non-volatile SRAM for instant-on/off energy-constrained edge AI devices

Infection prevention practices and associated factors among healthcare professionals in West Gojjam Zone public Hospitals Northwest Ethiopia, 2023

Background Inadequate adherence to infection prevention and control standards places millions of patients and healthcare workers at risk of infectious diseases worldwide, including healthcare acquired infections. Effective infection prevention and control measures and interventions have been done after the occurrence of the COVID-19 pandemic; however, there is no data that shows infection prevention and control practice of healthcare professionals in West Gojjam zone hospitals. Objective To assess infection prevention practice and associated factors among healthcare professionals in West Gojjam Zone public hospitals. Methods A mixed institutional-based cross-sectional study was conducted among healthcare professionals in West Gojjam Zone public hospitals from March 10 to April 10, 2023. A simple random sampling technique was used to select 454 participants. A structured self-administered questionnaire, key informant interview guide, and observational checklist were used to gather the information. The collected data was entered into Epi-data 4.6 and exported into SPSS version 27 for analysis. For quantitative data, bivariate and multivariate generalized estimating equation analysis was computed, considering p < 0.05 to be statistically significant at the final model. The qualitative data was transcribed, translated, coded, and analyzed thematically. Finally, the qualitative data triangulated with quantitative data. Result Four hundred thirty-four (95.6%) healthcare professionals participated in the study. The overall infection prevention practice of healthcare professionals in West Gojjam zone hospitals was 32.7% (95% CI: 28.29%−37.15%). Knowledge of participants (1.95, 95% CI: 1.19–3.19), attitude (AOR = 1.96, 95%CI: 1.24–3.12), profession of midwives (AOR = 0.467, 95%CI: 0.24–0.92), and working in Adet, Dembecha, Durbete, Feresbet, Finote Selam, and Liben hospitals, respectively, were the significant factors of infection prevention practice and training. Infrastructure, budget, supplies, and attitude were the challenges of infection prevention supplemented by the qualitative data. Conclusion The study revealed that overall infection prevention practice was poor. Participant’s knowledge, participant’s attitude, and participant’s profession were significant factors for infection prevention practice, and there was variation in infection prevention practice between hospitals. The identified modifiable factors are the area of intervention to improve infection prevention practices.

Author Correction: Ocean fronts and eddies force atmospheric rivers and heavy precipitation in western North America

An exploratory investigation into the microbial and cyanobacterial presence on skin epibiotia and orofacial lesions in estuarine common bottlenose dolphins (Tursiops truncatus) through metabarcoding

Synthesis of new benzothiazole derivatives with in-depth In-vitro, In-vivo anti-oxidant, anti-inflammatory and anti-ulcer activities

Benzothiazoles (BTZ) possess various medicinal benefits and in this study, we have synthesized benzothiazole derivatives by substituting its side chains, and analyzed its spectral analysis along with its antioxidant and anti-inflammatory activity. In-vitro antioxidant activity of the benzothiazole derivatives indicated strong antioxidant potential of 3b , 3d and 3e which were then evaluated for their anti-inflammatory potential in mice’s paw edema and ethanol-induced gastric ulcer (GU). The compounds demonstrated strong anti-inflammatory ability in paw edema as well as ethanol-induced gastric ulcer. This was further confirmed by H&E staining and suppressed inflammatory mediators as tumor necrotic factor (TNF-α), nuclear factor B (p-NFkB), and cyclooxygenase-2 (COX-2). The antioxidant ability was assessed by measuring catalase (CAT), glutathione-S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels in both edema and ulcer models. Additionally, gastric lesions were detected in the ulcer and low Ulcer index confirmed anti-ulcer ability. These results suggest new benzothiazoles which can be further analyzed through clinical studies.