bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid identification of bacterial select agents using loop-mediated isothermal amplification
Authors: Egbo Timothy E. , Blancett Candace D. , Payne Jackie M. , Stefan Christopher P. , Minogue Timothy D. , Sellers John H. , Koehler Jeffrey W. 
Published: January 2025

Abstract

Background
Point of need diagnostics provide efficient testing capability for remote or austere locations, decreasing the time to answer by minimizing travel or sample transport requirements. Loop-mediated isothermal amplification (LAMP) is an appealing technology for point-of-need diagnostics due to its rapid analysis time and minimal instrumentation requirements.

Methods
Here, we designed and optimized nine LAMP assays that are sensitive and specific to targeted bacterial select agents including Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella spp. Evaluation of each assay determined preliminary limit of detection (LOD) with LOD confirmed across 60 replicates (≥ 95% positivity rate). Testing across a robust set of strains of the target agent, common DNA agents, and near-neighbors documented sensitivity and specificity for independent assays.

Results
Specifically, all assays were 100% specific and sensitive except for Y. pestis Caf1 (90% inclusive across Y. pestis strains).

Conclusion
Here, we optimized assay turn-around-time, decreasing a standard 60 min traditional polymerase chain reaction (PCR) to 30 min using LAMP with positive results in as little as 5–10 min. Incorporating point of need sample processing and evaluating the potential inhibitory impact of sample matrices such as whole blood and soil would be needed to enable this test system for use on field-forward clinical and environmental sample testing.
Kidney REPLACEment therapies in patients with acute kidney injury and RHABDOmyolysis (ReplaceRhabdo): a pilot trial
Authors: Weidhase Lorenz , Borrmann Antonia , Willenberg Anja , Mende Meinhard , Scharf-Janßen Christina , Petros Sirak , de Fallois Jonathan 
Published: January 2025

Abstract

Background
Rhabdomyolysis is frequently associated with acute kidney injury (AKI). Due to the nephrotoxic properties of myoglobin, its rapid removal is relevant. If kidney replacement therapy (KRT) is necessary for AKI, a procedure with effective myoglobin elimination should be preferred. This pilot trial was designed to compare different KRT modes that enable myoglobin elimination.

Methods
In this prospective randomized single-center study, 15 patients with rhabdomyolysis and severe AKI requiring KRT were randomized 1:1:1 into three groups: continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVHD) using a high cut-off dialyzer (CVVHD-HCO), or CVVHD using a high-flux dialyzer in combination with the adsorber CytoSorb (CVVHD-CS). Concentrations of serum myoglobin, urea, creatinine, β2-microglobulin, interleukin-6, and albumin were measured before and after the dialyzer 1, 6, 12, and 24 h after initiating KRT.

Results
There was no significant difference in the median myoglobin clearance between the KRT modes during the 24-h study period. Nevertheless, the CVVHD-CS group showed a significantly higher myoglobin elimination compared to the other modes in the first hours of treatment. However, as a greater decline in clearance performance was observed over time, no better performance was detected over the whole study period. Simulation of different device combinations showed the highest myoglobin clearance for CVVHD-HCO combined with CS with a 12-hourly adsorber exchange interval.

Conclusions
All tested modes showed an effective myoglobin elimination capacity. The time-dependent elimination performance could be further increased by combining KRT with more frequent adsorber exchange.

Trial registration
German Clinical Trials Registry (DRKS00023998); date of registration 03/03/2021.
Improving care experiences for premenstrual symptoms and disorders in the United Kingdom (UK): a mixed-methods approach
Authors: Funnell E. L. , Martin-Key N. A. , Bahn S. 
Published: January 2025

Abstract

Background
Poor care experiences are reported for premenstrual disorders, which may result in negative outcomes such as distress, reduced healthcare engagement, and delays to diagnosis. This research aimed to explore healthcare experiences for premenstrual symptoms in the United Kingdom and identify areas for potential improvements based on participant responses.

Method
An online survey was delivered, with participants recruited via social media. Experiences of care were explored using quantitative and qualitative questions. Quantitative data were explored using descriptive statistics, with group differences investigated using Mann–Whitney U tests and chi-square tests as appropriate. Qualitative data regarding care improvements was explored using inductive thematic analysis.

Results
The sample included 339 participants who completed at least 97% of the survey, reported premenstrual symptoms in consecutive cycles, and had sought formal help for these symptoms. Mean age was 34.66 (SD = 5.88), with the majority identifying as women (n = 332, 97.94%) and white/Caucasian (n = 311, 91.74%). 75.22% (n = 255) felt that care was poor. 44.25% (n = 150) felt their symptoms were not taken seriously. 37.76% perceived a lack of healthcare professional knowledge (n = 128). The majority did not receive recommendations of non-formal sources of help (i.e., websites, support groups; 84.96%, n = 288) or lifestyle changes (74.63%, n = 253). Better care experiences were associated with healthcare professionals taking symptoms seriously (U = 1383.00, p < .001), higher perceived healthcare professional knowledge (U = 1370.50, p < .001), and receiving recommendations of non-formal sources of help (X2 = 48.251, df = 1, p < .001, Φc = .382) or lifestyle changes (X2 = 7.849, df = 1, p = .005, Φc = .152). Thematic analysis revealed 8 aspects of care improvement: Empathetic care provision; Healthcare professional education, understanding, and research; Comprehensive symptom assessment and investigations; Diagnosis; Professional support and treatment provision; Signposting or referral to additional resources or sources of help; Wider healthcare system improvements; and Patient role/voice and preferences.

Conclusions
Poor care experiences for premenstrual symptoms in the UK are characterised by dismissive attitudes and perceived lack of knowledge. Improved training provision for healthcare professionals is required to address this and other aspects of care identified by qualitative analysis. However, research is needed to identify appropriate methods to deliver training. Utilisation of standardised screening tools and patient-centred communication will likely ensure comprehensive assessments and reduce self-advocacy burdens.
Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons
Authors: Harvey Calum , Nowak Alicja , Zhang Sai , Moll Tobias , Weimer Annika K , Barcons Aina Mogas , Souza Cleide Dos Santos , Ferraiuolo Laura , Kenna Kevin , Zaitlen Noah , Caggiano Christa , Shaw Pamela J , Snyder Michael P , Mill Jonathan , Hannon Eilis , Cooper-Knock Johnathan 
Published: January 2025

Abstract
Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals. By comparing MN methylation with an atlas of tissue methylation we have derived a MN-specific signature of hypomethylated genomic regions, which accords with genes important for MN function. Through simulation we have optimised the selection of regions for biomarker detection in plasma and CSF cell-free DNA (cfDNA). However, we show that MN-derived DNA is not detectable via WGBS in plasma cfDNA. In support of our experimental finding, we show theoretically that the relative sparsity of lower MN sets a limit on the proportion of plasma cfDNA derived from MN which is below the threshold for detection via WGBS. Our findings are important for the ongoing development of ALS biomarkers. The MN-specific hypomethylated genomic regions we have derived could be usefully combined with more sensitive detection methods and perhaps with study of CSF instead of plasma. Indeed we demonstrate that neuronal-derived DNA is detectable in CSF. Our work is relevant for all diseases featuring death of rare cell-types.
Reflecting on the impact of the COVID pandemic on patient management and its subsequent influence on long-term outcomes: a case–control study in the field of esophago-gastric cancer
Authors: Alasmar Mohamed , Matias Nadia , Alhamed Norah Ali M. , Alwani Omneya , Rudge Brogan , Moti Terngu David , Abdelwahab Muhammad Ossama Yassin , Stockton Jennifer , Raslan Charef , Cairney-Hill Jess , Altarawni Mohammad , Alkhaffaf Bilal ,   on behalf Greater Manchester Oesophago-Gastric Service
Published: January 2025

Abstract

Background
The delivery of cancer services changed significantly during the COVID-19 pandemic. This study aimed to describe changes in presentations, assess the change in recommendations by the MDT during the pandemic, and describe the subsequent long-term impact of these changes on survival rates in patients with EG cancer.

Methods
A retrospective cohort study was designed comparing three patient groups of those referred to EG MDT in the same 6-month period pre-pandemic (PP;2019) during the initial phase of the pandemic (P1;2020) and the year after the initial phase (P2;2021). The primary aim of this study was to describe and compare deviations from the standard of care across these three timeframes. Secondary outcomes included differences in the number of new cases with early and advanced oesophageal and gastric lesions, a comparison of survival rates among the groups, and an analysis of postoperative histopathology to identify any shifts in the tumour stage across the studied periods.

Results
A consistent demographic profile across these periods was maintained, but with a significant decrease in patient referrals during P1 (35.25% reduction from PP to P1 and 9.5% reduction from PP to P2), quicker ‘time to treatment’ during P1 (130.8 days in P1 vs 162 in PP and 178.9 in P2), and notable changes in treatment modalities. Additionally, we found an increased deviation from initial curative to palliative intent in the P2 group (6.4% changed in P2 vs 2.2% in PP and 3.5% in P2) primarily driven by disease progression. A further significant observation was the emergence of more aggressive tumour characteristics, particularly in the P2 group, albeit without a statistically significant difference in two-year overall survival rates among the groups (p-value 0.31).

Conclusion
The COVID-19 pandemic significantly impacted oesophagogastric cancer care, with a reduction in patient referral rates during the initial pandemic phase and a subsequent increase in more advanced stage disease. Our findings from a major UK EG centre highlight accelerated treatment decision-making during the initial pandemic phase was possible and that standard of care was maintained. These insights provide valuable lessons for healthcare systems in managing cancer care during global health emergencies.
In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats
Authors: Costain Will J. , Haqqani Arsalan S. , Hussack Greg , van Faassen Henk , Lessard Etienne , Ling Binbing , Brunette Eric , Ly Dao , Fang Hung , Bultinck Jennyfer , Geysens Steven , Pynaert Gwenda , Piens Kathleen , Ryckaert Stefan , Fudalej Franck , Vervecken Wouter , Stanimirovic Danica 
Published: January 2025

Abstract

Background
Iduronate-2-sulfatase (IDS) deficiency (MPS II; Hunter syndrome) is a disorder that exhibits peripheral and CNS pathology. The blood brain barrier (BBB) prevents systemic enzyme replacement therapy (ERT) from alleviating CNS pathology. We aimed to enable brain delivery of systemic ERT by using molecular BBB-Trojans targeting endothelial transcytosis receptors. Methods: Single-domain antibody (sdAb)-enzyme fusion protein constructs were prepared in Yarrowia lipolytica. sdAb affinity and BBB permeability were characterized using SPR and an in vitro rodent BBB assay, respectively. In vivo pharmacokinetic (PK) analysis was performed in rats. Quantification of fusion protein amounts were performed using LC-MS.

Results
Fusion proteins consisting of IDS and BBB-transmigrating sdAbs, albumin binding sdAbs or human serum albumin (HSA) were evaluated for their in vitro BBB permeability. IGF1R3H5-IDS was selected for in vivo PK analysis in rats. IDS and IGF1R3H5-IDS exhibited very short (< 10 min) serum half-life (t1/2α), while constructs containing either HSA or anti-serum albumin sdAbs (R28 or M79) showed 8–11 fold increases in the area under the curve (AUC) in serum. CSF analysis indicated that IGF1R3H5 increased brain exposure by 9 fold (AUC) and constructs containing HSA or R28 exhibited 42–52 fold increases. Quantitation of brain levels confirmed the increased and sustained delivery of IDS to the brain of HSA- and R28-containing constructs. Lastly, analysis of brain fractions demonstrated that the increases in brain tissue were due to parenchymal delivery without fusion protein accumulation in brain vessels.

Conclusions
These results demonstrate the utility of IGF1R-targeting sdAbs to effect brain delivery of lysosomal enzymes, as well as the utility of serum albumin-targeting sdAbs in t1/2 extension, to increase brain delivery of rapidly cleared enzymes.
Pangenome mining of the Streptomyces genus redefines species’ biosynthetic potential
Authors: Mohite Omkar S. , Jørgensen Tue S. , Booth Thomas J. , Charusanti Pep , Phaneuf Patrick V. , Weber Tilmann , Palsson Bernhard O. 
Published: January 2025

Background

Streptomyces is a highly diverse genus known for the production of secondary or specialized metabolites with a wide range of applications in the medical and agricultural industries. Several thousand complete or nearly complete Streptomyces genome sequences are now available, affording the opportunity to deeply investigate the biosynthetic potential within these organisms and to advance natural product discovery initiatives.

Results
We perform pangenome analysis on 2371 Streptomyces genomes, including approximately 1200 complete assemblies. Employing a data-driven approach based on genome similarities, the Streptomyces genus was classified into 7 primary and 42 secondary Mash-clusters, forming the basis for comprehensive pangenome mining. A refined workflow for grouping biosynthetic gene clusters (BGCs) redefines their diversity across different Mash-clusters. This workflow also reassigns 2729 known BGC families to only 440 families, a reduction caused by inaccuracies in BGC boundary detections. When the genomic location of BGCs is included in the analysis, a conserved genomic structure, or synteny, among BGCs becomes apparent within species and Mash-clusters. This synteny suggests that vertical inheritance is a major factor in the diversification of BGCs.

Conclusions
Our analysis of a genomic dataset at a scale of thousands of genomes refines predictions of BGC diversity using Mash-clusters as a basis for pangenome analysis. The observed conservation in the order of BGCs’ genomic locations shows that the BGCs are vertically inherited. The presented workflow and the in-depth analysis pave the way for large-scale pangenome investigations and enhance our understanding of the biosynthetic potential of the Streptomyces genus.
Susceptibility to organophosphate insecticides in Aedes aegypti (Diptera: Culicidae) from northern Colombia and associated resistance mechanisms
Authors: Atencia-Pineda María Claudia , García-Leal Javier , Diaz-Ortiz Diana , Pareja-Loaiza Paula , Pacheco-Lugo Lisandro , Hoyos-López Richard , Calderón-Rangel Alfonso , Fragozo-Castilla Pedro , Gutiérrez-Rodríguez Selene M. , Flores Adriana E. , Maestre-Serrano Ronald 
Published: January 2025

Abstract

Background

Aedes aegypti is the primary vector of dengue, chikungunya, and Zika viruses in Colombia. Various insecticides, including pyrethroid, organophosphate, and carbamate insecticides; growth regulators; and biological insecticides, such as Bacillus thuringiensis var. israelensis, have been used to control Ae. aegypti populations. However, organophosphates such as malathion, pirimiphos-methyl, and temephos have been used over the last decade owing to the high resistance to pyrethroids.

Methods
This study assessed the susceptibility to organophosphates in 14 Ae. aegypti populations from the Córdoba department in northern Colombia. Moreover, possible resistance mechanisms were investigated by determining the activity levels of α-esterases, β-esterases, mixed function oxidases (MFOs), glutathione S-transferases (GSTs), and insensitive acetylcholinesterase (iAChE). Additionally, the Ace-1 gene was sequenced to identify mutations at the target site of action.

Results
The populations were susceptible to temephos and malathion but resistant to fenitrothion, and in three of them, to pirimiphos-methyl. Alterations in the enzyme activity levels of α-esterases and β-esterases, GST, and iAChE were observed among the populations, with high enzyme activity levels of α and β esterases associated with resistance to fenitrothion. No mutations were identified in the Ace-1 gene.

Conclusions
These findings are highly relevant for vector control programs in the region, as they allow for adjustments in resistance management strategies and improve the effectiveness of interventions against these arboviruses.

Graphical Abstract
Impact of driver licensing renewal policies on older driver crash involvement and injury rates in 13 states, 2000–2019
Authors: Hamann Cara J. , Davis Jonathan A. , Pae Gilsu , Zhu Motao , Shill Gregory H. , Tefft Brian , Cavanaugh Joseph E. 
Published: January 2025

Abstract

Background
Motor vehicle crashes are the second leading cause of injury death among adults aged 65 and older in the U.S., second only to falls. A common state-level approach to mitigating older adult crash risk is the implementation of driver license renewal policies which vary largely between states and data on their effectiveness in preventing crashes and injuries are limited. To fill this gap, the aim of this study is to examine the association between state driver license renewal policies and older driver crash and injury rates.

Methods
Historical crash data, license renewal policy data, and other relevant policy and demographic data were gathered from 13 U.S. states (CO, IL, IA, KS, MN, MO, NE, ND, OH, SD, UT, WI, WY) for years 2000 through 2019, inclusive. Main exposures included six license renewal policies: renewal period, in-person renewal frequency, vision testing, knowledge testing, on-road drive testing, and mandatory physician reporting. The primary outcomes were crash and injury rates per 100,000 population.

Results
The study population included 19,010,179 crash-involved drivers aged 40 and older. State policies became less restrictive in many states over the study period, even for drivers aged 75 and older, resulting in longer times between renewals and fewer in-person renewal requirements. Loosening of in-person renewal from every time to less than every time was associated with increased crash rates, among drivers aged 65 to 74 (RRcrash = 1.08, 95% CI: 1.01–1.16). A longer duration between in-person renewals was associated with increased injury rates among drivers 75 and older (RRinjury = 1.18, 95% CI: 1.00–1.39).

Conclusions
Generally, state policies became less restrictive and resulted in longer required intervals between license renewal. Loosening of driver license renewal policies was associated with increased crash and injury rates. However, safety benefits of restrictive older driver licensing policies should be carefully weighed against costs to older adult well-being and quality of life following licensure loss. Additional methods to assess fitness to drive are necessary to identify the mechanisms behind the increased rates.
Characteristics and long-term health outcomes of the first domestic COVID-19 outbreak cases in Da Nang, Vietnam: a longitudinal cohort study
Authors: Tsuruoka Miyuki , Huynh Mai Kim , Toizumi Michiko , Hoang Thanh Tien , Nguyen Trieu Bao , Dao Anh The , Nguyen Luong Dinh , Le Huy Xuan , Le Chung Thanh , Dang Anh Quang , Do Hung Thai , Yoshida Lay Myint 
Published: January 2025

Abstract

Background
Vietnam experienced the first COVID-19 domestic outbreak due to the Wuhan strain (B.1.1) in Da Nang from July 2020. COVID-19 can cause acute as well as long-term health problems. We aimed to characterise clinical features and risk factors related to severe illness of COVID-19 among Da Nang outbreak cases and to describe long-term health outcomes among survivors of this outbreak.

Methods
We conducted an ambidirectional cohort study. Study subjects were all hospitalised cases with positive real-time PCR test of SARS-CoV-2 in the three major hospitals in Da Nang from 25 July to 28 August 2020. Clinical and demographic information was retrospectively collected from medical charts. Then, the survivors were followed-up prospectively at 6 and 16 months after acute infection to assess their health status via standardized questionnaires, physical examinations, chest X-rays and pulmonary function tests.

Results
A total of 362 cases including 20 fatal cases were enrolled into the study retrospectively. The median age of the participants included in the medical chart review was 46.5 years and 60.8% were female. Overall, 7.8% of the participants required respiratory support during hospitalisation and 20 of them died. Compared to the survivors, the fatal cases were significantly older (median age of survivors 45.0 yr vs fatal cases 66.5 yr, P < 0.001) and more likely to have underlying conditions. The proportions of participants who had at least one long COVID symptom within the 7 days of each follow-up at 6 and 16 months were 72.0% (134/186) and 63.5% (47/74), respectively. We also found that females and adults reported symptoms more often in the follow-up surveys, 78.9% (90/114) [females] vs 61.1% (44/72) [males] at 6 months, P = 0.008; 68.7% (46/67) [

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20 years] vs 14.3% (1/7)

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<

20 years] at 16 months, P = 0.004.

Conclusions
In the first domestic COVID-19 outbreak in Vietnam, the mortality rate was approximately 6% and associated with underlying medical conditions. In the follow-up surveys, a substantial proportion of participants reported long COVID related health problems, although the prevalence declined over time. Females and adults reported symptoms more often, which might be due to the pathophysiological differences according to sex and age.