bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of workflow times on successful reperfusion after endovascular treatment in the late time window
Authors: Alhabli Ibrahim , Benali Faysal , Hill Michael D , Murphy Sean , Toni Danilo , Patrik Michel , Casetta Ilaria , Power Sarah , Saia Valentina , Pracucci Giovanni , Mangiafico Salvatore , Boyle Karl , Nannoni Stefania , Fainardi Enrico , Thornton John , Kim Beom Joon , Menon Bijoy K , Almekhlafi Mohammed A , Bala Fouzi
Published: January 2025

Background and Purpose

Successful and complete reperfusion should be the aim of every endovascular thrombectomy (EVT) procedure. However, the effect of time delays on successful reperfusion in late window stroke patients presenting 6-to-24 h from onset has not been investigated.

Materials and Methods

We pooled individual patient-level data from seven trials and registries for anterior circulation stroke patients treated with EVT between 6 and 24 h from onset. We explored the impact of delays across multiple interval times, including onset to hospital arrival; hospital arrival to arterial puncture; imaging to arterial puncture; and onset to arterial puncture. Our primary outcome was successful reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2b–3. Logistic regression analyses were performed to assess the association between each of the interval times and successful reperfusion.

Results

We included 608 patients. The median age was 70 years (IQR 58–79), and 307 (50.5%) were females. Successful reperfusion was achieved in 494 (81.2%) patients. Patients with successful reperfusion had lower NIHSS scores (median 15 [IQR11–19] vs 17 [11–21], p = .02) and significantly shorter hospital arrival to arterial puncture time (90 min [60–150] vs 110 min [84.5–150], p = .01) than unsuccessful reperfusion. The odds of successful reperfusion decreased by 15% for every one-hour delay in arrival-to-puncture time (adjusted odds ratio 0.85, 95% CI: 0.75–0.95). Other workflow times did not impact the rate of successful reperfusion.

Conclusion

Faster hospital arrival to arterial puncture time is associated with higher odds of successful reperfusion in late window stroke patients.
A case series on combining repetitive transcranial magnetic stimulation with conventional rehabilitation therapies for upper limb motor-function restoration
Authors: Pong Mei Yin , Mazlan Mazlina , Chung Tze Yang , Sabirin Sakinah , Chan Soo Chin
Published: January 2025

This case series reports the integration of repetitive transcranial magnetic stimulation (rTMS) with conventional rehabilitation therapies in three early subacute ischemic stroke patients with upper limb motor impairment. In Malaysia, data on the combination of rTMS with intensive rehabilitation for stroke patients remains limited. The three patients with completely paretic upper limb, began therapy on post-stroke day 20, 16, and 15, respectively. They received rTMS sessions with inhibitory protocols targeting the contralesional primary motor area (M1) at 1 Hz, 5 days per week for 2 weeks (10 sessions). Each session included 1800 pulses at 120% resting motor threshold for 40 minutes, followed by 60 minutes of upper limb motor-function training. Outpatient occupational therapy was then continued for 3 months. All patients showed neurological and functional recovery as measured by the Medical Research Council scale and Fugl-Meyer Assessment-Upper Extremity Motor. The gains were observed immediately after the 10 rTMS sessions and persisted at 3 months post-stroke. Furthermore, all patients also achieved total independence in daily activities, with Modified Barthel Index scores of 99-100. No serious adverse events were reported. This case series suggests that combining rTMS with conventional rehabilitation therapies during the early subacute phase may enhance upper limb motor function recovery in stroke patients.
The role of genetic sequencing in the diagnostic work-up for chronic immune thrombocytopenia
Authors: Joshi Nehal , Lango Allen Hana , Downes Kate , Simeoni Ilenia , Vladescu Camelia , Paul Deena , Hart Alice C.J. , Ademokun Christine , Cooper Nichola
Published: January 2025

Immune Thrombocytopenia (ITP) is a heterogenous autoimmune disorder diagnosed by excluding other conditions. Misdiagnosis of primary ITP occurs in patients with inherited thrombocytopenia and primary immunodeficiency syndromes. This study investigates whether genetic testing for inherited thrombocytopenia or primary immunodeficiency can enhance diagnostic accuracy in ITP, and guide treatment strategies. We performed whole genome sequencing or targeted panel sequencing on peripheral blood samples in a cohort of 80 participants with chronic ITP, utilising the ThromboGenomics (TG) Panel (n=72) and the Genomics of Rare Immune Disorders (GRID) panel (n=50) consisting of genes known to cause bleeding and platelet disorders (BPDG) or primary immunodeficiency syndromes (PIDG) respectively. A replication cohort of 73 patients underwent clinical genomics testing with either the R90 (BPDG, n=35) or R15 (PIDG, n=50) NHS Genomics panels. Known pathogenic or likely pathogenic, disease-causing, variants were identified in 9 patients in the first cohort (11% CI:5-20); 7 patients (10% CI:4-19) in BPDG and 2 patients (4% CI:1-14) in PIDG. Additionally, 26 patients (32.5%) carried variants of uncertain significance (VUS). In the replication cohort, 8% (CI:2-20) and 9% (CI:2- 23) of patients had a pathogenic variant identified on the R15 (PIDG) or R90 panel (BPDG) respectively. The findings impacted clinical management such as avoidance of immunosuppression (ANKRD26, GP1BB, ETV6, TUBB1, ITGB3) and eligibility for allogeneic stem cell transplantation (UNC13D). Our findings demonstrate that genomic sequencing identifies diagnostically relevant variants in patients with chronic ITP. Identification of these variants can guide treatment decisions and improve patient outcome.
Slight thermal stress exerts genetic diversity selection at coral (Acropora digitifera) larval stages
Authors: Manullang Cristiana , Hanahara Nozomi , Tarigan Ariyo Imanuel , Abe Yuko , Furukawa Mao , Morita Masaya
Published: January 2025

Background

Rising seawater temperatures increasingly threaten coral reefs. The ability of coral larvae to withstand heat is crucial for maintaining reef ecosystems. Although several studies have investigated coral larvae’s genetic responses to thermal stress, most relied on pooled sample sequencing, which provides population-level insights but may mask individual genotype variability. This study uses individual larval sequencing to investigate genotype-specific responses to heat stress and the selective pressures shaping their genomes, offering finer resolution and deeper insights.

Results

This study investigates the larval response to heat stress before acquiring symbiotic algae, aiming to elucidate the relationship between coral genetic diversity and heat stress. Larvae sourced from eight Acropora digitifera colonies were subjected to ambient temperature (28 °C) and heat conditions (31 °C). The impact of heat stress on larval genetic diversity was assessed through sequencing. While overall genetic diversity, represented by π, did not significantly differ between the control and heat-exposed groups, Tajima’s D differed, indicating different selective pressures in each group. The genomic regions under higher and lower Tajima’s D were not broadly shared among control and head conditions, implying that selective pressures operated in distinctive manners. Many larval protein-coding sequences were identified in this genomic region, and the codon evolution of many of these genes showed signs of positive selection. These results highlight the complex selective pressures on coral larvae under different temperatures. The genes showing signs of positive selection in response to heat stress may have also been influenced by historical temperature fluctuations, as suggested by their association with loci identified during Acroporid speciation. These loci under codon-level positive selection during speciation highlight the potential role of genetic diversity in shaping adaptation to environmental changes over evolutionary timescales.

Conclusion

These findings underscore the significance of genetic diversity in coral reproduction for maintaining reef ecosystems. They also indicate that even minor heat stress can exert significant selective pressure, potentially leading to profound implications for coral reef ecosystems. This research is crucial for understanding the impact of rising seawater temperatures on coral reefs.
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

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

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

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

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

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

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

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

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

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.
Patient-reported outcomes of zirconia dental implants: a systematic review and future directions
Authors: Arefnia Behrouz , Fakheran Omid , Jakse Norbert , Payer Michael
Published: January 2025

Purpose

Zirconia dental implants show excellent biocompatibility and tissue integration, low affinity for plaque, and favorable biomechanical properties. However, these objective measures do not adequately replicate the patient’s perception. This systematic review evaluated the evidence on patient-reported outcome (PROs) in zirconia dental implant treatment.

Methods

A systematic literature review was conducted following the PRISMA guidelines, utilizing six electronic databases, and supplemented by a manual search of relevant journals and websites to ensure a thorough and comprehensive screening process. The identified studies were subjected to preidentified inclusion criteria. Only controlled clinical trials published in English were considered without limitations on the year of publication. Data on the study characteristics (follow-up, survival rate (%), implant system, number of implants, and type of treatment), PROMs, level of evidence, and Methodological Index for Nonrandomized Studies (MINORS) Bias Score were extracted.

Results

The initial database and hand search yielded 596 articles; 189 were included in the title and abstract screening after excluding the duplicates. Eighteen articles were selected based on the inclusion criteria, among which six were excluded because they did not match the research question. Thus, the final selection comprised 12 articles. Most PROMs (aesthetics, speaking, comfort, chewing ability, and general satisfaction) at prosthetic delivery revealed significantly improved average scores than those at pretreatment.

Conclusions

Despite the respective limitations of the articles included in this systematic review, patients revealed high satisfaction levels with regard to zirconia dental implants. A high level of heterogeneity was observed among the instruments used for measuring the patient-reported outcomes in patients with zirconia implants, thus highlighting the need to develop specific PROMs in the future.
Breaking the silos: integrated approaches to foster sustainable development and climate action
Authors: Lah Oliver
Published: January 2025

A number of critical disconnects across sectors, actors continue to affect implementation action on sustainable development and climate action. Even when technical solutions, political commitments, and funding streams are avaiable, implementation often remains siloed and fragmented. This debate piece does not present definitive solutions or conclusive evidence; rather, it aims to foster critical reflection on how co-design, participatory approaches, Living Labs, and epistemically connected actor coalitions may help break down institutional and conceptual barriers. It proposes the SCALE framework [Shared epistemic foundations, Cross-sectoral integration, Adaptive co-design, Local enabling environments, and Evaluation & expansion) as way of operationalising the Safe Systems for Sustainable Development concept presented in Lah 2024, exploring how knowledge integration, iterative experimentation, and locally grounded solutuions can help creating implementation partnerships that last. This approach highlights questions concerning resource intensity, longevity, and scalability that must be addressed. By facilitating co-design, testing and validation of concrete solutions at the local level, the approach presented in this paper invites policymakers, researchers, practitioners, and civil society actors to engage in a more nuanced and constructive debate on whether, how, and under what conditions sustainable development solutions are considered to be viable and hence can endure even in politically volatile environments.
Effective community engagement in one health research in Sub-Saharan Africa: a systematic review
Authors: Sangong Sidney , Saah Farrukh Ishaque , Bain Luchuo Engelbert
Published: January 2025

Background

The one health (OH) approach, linking human, animal, and environmental health, relies on effective community engagement (CE), education, stewardship, and effective regional and global partnerships. For real impact, communities should be at the centre of research agenda setting and program implementation. This review aimed at synthesizing empirical evidence on how communities are involved in one health research. Specifically, the review aimed at documenting the extent of community involvement in one health research, as well as to identify the barriers and facilitators to effective community engagement in one health research in sub Saharan Africa.

Methods

The study was a systematic review conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Empirical peer-reviewed research articles on community engagement in one health research published from January 2000 to September 2023 in English or French were retrieved from seven databases: MEDLINE, EMBASE, CINAHL, Cochrane Library, WHO Afro Library, the National Institute for Health Research, and African Journals Online databases. The extracted data from the included studies were analysed using a thematic synthesis approach.

Results

The final review and synthesis included eight studies. The extent of CE in the one health research approach is quite limited. Two main best practices of CE in OH research were: 1) Awareness raising on OH research through social mobilization, rural outreach sensitization, and wide community assembly and 2) Building local capacity through community-based OH Training and Leadership workshops. The barriers to effective CE included: inadequate community research literacy levels, contextual disparities in CE, inadequate dissemination of research findings, language barriers and ineffective and uncoordinated stakeholder involvement.

Conclusion

The review underscores the importance of effective CE in one health research. The best practices for CE in one health research are raising awareness and co-creation which should guide future initiatives. There are cultural, geographical, linguistic, and educational constraints that pose barriers to CE, requiring a more integrated and community-centric approach to one health research in SSA. An effective CE in one health research through this approach will ultimately lead to more effective responses and control of zoonotic disease outbreaks.
Effects of antidepressants on body weight in patients treated in a naturalistic setting in Oman
Authors: AL-Jahwari Latifa , Qutishat Mohammed , Almaqbali Mandhar , Al Risi Khalid , AlBreiki Mohammed , Albalushi Mohammed , Al-Huseini Salim
Published: January 2025

Background

The rising use of antidepressants is critical for managing mental health disorders, but weight gain is a concerning side effect, particularly with certain classes like TCAs and SSRIs. This study aims to investigate weight changes in Omani patients prescribed paroxetine, fluoxetine, mirtazapine, or venlafaxine.

Method

A cross-sectional study conducted from January to June 2023 at Sultan Qaboos University Hospital recruited adults with mental disorders on these medications. Weight measurements were taken at baseline and follow-up, with clinically significant weight gain defined as a ≥ 7% increase.

Results

A total of 135 participants were analyzed, showing a mean weight gain of 5.54 kg, with 60.7% experiencing significant weight gain. Mirtazapine and paroxetine exhibited the highest average weight increases (7.51 kg and 8.05 kg, respectively) compared to fluoxetine (0.69 kg) and venlafaxine (4.32 kg). No significant demographic factors influenced weight changes (p = 0.213).

Conclusion

The study highlights significant weight gain among Omani patients on antidepressants, particularly mirtazapine and paroxetine. This underscores the importance of monitoring weight in clinical practice and necessitates further investigations into individualized treatment strategies to manage both mental health and weight-related concerns.
Disordered eating behaviors among a sample of final-year medical students at Cairo University and its relationship with alexithymia and social cognition
Authors: Elsherif Esraa S. , Al-Rakhawy Mona Y. , Fathy Heba , Adel Ashraf , Khalaf Ola O.
Published: January 2025

Background

This study aims to estimate the risk of eating disorders and their related factors among final-year medical students. Additionally, the present study is assessing the disordered eating behaviors relationship with alexithymia and social cognition.

Methods

An approved descriptive cross-sectional study was carried out at Cairo University’s Faculty of Medicine from August 2021 to December 2022. The participants were categorized into two distinct groups: Group A (students at risk for eating disorders) and Group B (students not at risk for eating disorders). All participants were evaluated using the Eating Attitude Test-26 (EAT-26), the Eating Disorder Examination Questionnaire (EDE-Q), the Toronto Alexithymia Scale (TAS-20), the Emotion Identification Test from the Ekman Program, and Reading the Mind in the Eyes Test-revised version (RMET).

Results

A total of 370 final-year students, both male and female, participated in the study. Group A included 136 students (37%), while Group B consisted of 234 students (63%). Female students exhibited a greater risk for developing an eating disorder (p =  < 0.001). Students classified as at risk for eating disorders displayed significantly elevated alexithymia scores and diminished social cognition scores when compared to their counterparts without risk (p =  < 0.001).

Conclusion

Medical students are more susceptible to eating-related problems. Deficits in alexithymia and social cognition potentiate the risk of eating disorders.
Noninvasive in vivo assessment of placental insufficiency using pCASL: a prospective case–control study
Authors: Awad Ghada , Reda Alaa Mohamed , Younis Rasha Lotfy , Hassan Manal Mostafa , Ali Rania Essam Eldin Mohamed
Published: January 2025

Background

Arterial spin labeling is a noninvasive imaging modality that does not use contrast for evaluation of placental perfusion in the placental pathological conditions. Our study enrolled 30 pregnant females with different risk factors for developing IUGR and other 30 females with the same age group having normal pregnancy. The two groups were evaluated by free breathing arterial spin labeling magnetic resonance imaging. Image findings of pseudo-continuous arterial spin labeling were compared to color duplex Doppler ultrasound of umbilical and middle cerebral arteries.

Aim

The aim of the present study was to evaluate the role of pseudo-continuous arterial spin labeling in measurement of placental perfusion with quantitative analysis of regional placental blood flow.

Methods

This prospective case–control study enrolled 30 pregnant females who had different causes of placental insufficiency, and another healthy group of matched ages, all were evaluated by 2D and color duplex Doppler ultrasound, conventional non-contrast magnetic resonance imaging and MRI perfusion using arterial spin labeling technique. The study was carried out from October 2021 to October 2023.

Results

Significant relation was found between placental perfusion values and umbilical and middle cerebral artery resistive indices as indicator for placental insufficiency with sensitivity and specificity 77.8%, 80%, respectively, for umbilical artery resistive index and 90%, 83.3%, respectively, for middle cerebral artery resistive index. While the diagnostic value of ASL perfusion was as follows, it had sensitivity = 90%, specificity = 83.3%, PPV = 84.4%, NPV = 89.3% and accuracy = 86.7%.

Conclusions

ASL-MRI is an excellent noninvasive in vivo MRI technique for evaluation of placental perfusion and quantitative analysis of regional placental blood flow in cases of placental insufficiency. This study supported the value of the new noninvasive MRI techniques in the elaboration of placental pathology.
Sonographic assessment of post-intubation laryngeal obstruction as predictor of weaning outcome
Authors: Anwar Mohamed Taher , Esmat Amro Ahmed , Elfeqy Mohamed Elsaid Ali Hassan
Published: January 2025

Background

Post-extubation stridor indicates the presence of laryngeal edema. The documented occurrence of post-extubation airway blockage ranges from 4 to 37%.

Aim

To evaluate the effectiveness of sonar assessment of laryngeal air column width difference to predict post-extubation upper airway obstruction and its relation to cuff leak volume.

Patients and methods

This was an observational, descriptive cross-sectional study, conducted on 48 mechanically ventilated patients fulfilling weaning criteria at the ICU of Chest Department, Faculty of Medicine, Zagazig University, from July 2022 to March 2023.

Results

A statistically insignificant variance was observed among COPD, ILD, overlap (OSA-COPD), pneumonia, aspiration pneumonia, and PE regarding laryngeal air column width difference (LACWD), while a statistically significant variance was observed among COPD, ILD, overlap (OSA-COPD), pneumonia, aspiration pneumonia, and PE regarding CLV; there was no correlation among cuff leak volume and LACWD, and there were 40 patients (83.3%) who had no post-intubation upper air way obstruction and 8 patients (16.7%) had post-intubation upper airway obstruction: 4 of them (8.3%) had success weaning, and 4 (8.3%) had failed weaning; and at cutoff value 140 ml, cuff leak volume had sensitivity of 100% and specificity of 97.5% with significance for prediction of stridor, and at cutoff value 1.15 mm, LACWD had sensitivity of 87.5% and specificity of 67.5% with significance for prediction of stridor.

Conclusion

Cuff leak volume and ultrasound-guided LACWD effectively predict post-extubation upper airway obstruction, suggesting their integration into institutional extubation protocols.
Are Department Heads Ready for Change? Leveraging a Leadership Action Team to Advance Teaching Evaluation Practices
Authors: Ericson Hannah C. , Lemons Paula P. , Dolan Erin L. , Brickman Peggy , Krishnan Sandhya , Andrews Tessa C.
Published: January 2025

We relied on change theory to design a 3-year intervention with STEM department heads to provide space for busy heads to focus on research-based change in teaching evaluation practices. The impact on departmental practices was variable and department head readiness for change mattered.
Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials
Authors: Liu Jia , Farrow Max , Seymour Lesley , Desai Jayesh , Loong Herbert H. , Ivy Percy , Koyoma Takafumi , Cook Natalie , Blagden Sarah , Garralda Elena , Massard Christophe , Tolcher Anthony W. , Adashek Jacob J. , Zhang Li , Zhao Shen , Shen Lin , Kurzrock Razelle , El-Deiry Wafik S. , Subbiah Vivek , Joshua Anthony M.
Published: January 2025

PURPOSE

Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner. Networks and consortia may overcome some of these challenges of enrolling suitable patients and streamlining start-up, particularly when distance and disease trajectory come into play.

DESIGN

In this article, we provide an overview of EPCT consortia in adult oncology across different continents assembled through systematic review of the literature and snowball sampling methodology. We illustrate their scope, structure, funding, and achievements.

RESULTS

Fifteen EPCT consortia were identified including two in the United States, three in Europe, five in Asia-Pacific, two intercontinental consortia, and three within private oncology networks. These consortia vary in their scope, funding, and structure from government-funded models such as the National Cancer Institute Experimental Therapeutics Clinical Trials Networks through charitably funded and private research organizations. EPCT consortia play a role in collaborative research, molecular tumor boards to provide patient-centric biomarker-matched treatments, and streamlining trial conduct to improve timelines and cost efficiency.

CONCLUSION

The growth in EPCT activity and complexity has resulted in expansion in the number of EPCT consortia globally. By actively engaging with regulatory bodies and pharmaceutical and contract research organization industries, consortia have an opportunity to address the evolving challenges faced in this field and to accelerate the translation of scientific discoveries into clinical practice.