bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Electroporation Timing and Cumulus Cell Attachment on In Vitro Development and Genome Editing of Porcine Embryos
Authors: Torigoe Nanaka , Lin Qingyi , Liu Bin , Nakayama Yuichiro , Nakai Aya , Nagahara Megumi , Tanihara Fuminori , Hirata Maki , Otoi Takeshige 
Published: February 2025

ABSTRACTPig genome editing using the oviductal nucleic acid delivery (GONAD) method with electroporation would allow the efficient obtention of genetically modified pigs. However, oocytes and zygotes at various stages after ovulation must be targeted, and cumulus cell attachment and mosaic mutations are major obstacles. Therefore, we investigated whether two parameters (electroporation timing and the cumulus cell attachment) influence the effectiveness of multiplex genome editing by electroporation in porcine oocytes or zygotes. Three gRNAs targeting either GGTA1, CMAH or B4GALNT2 were introduced individually into oocytes and zygotes with and without cumulus cells at three different time points, 0 h before in vitro fertilisation (IVF) and 5 h and 10 h after IVF initiation. The introduction of gRNAs into oocytes and zygotes did not significantly affect the rates of blastocyst formation and total mutation of the resulting blastocysts irrespective of cumulus cell attachment and electroporation timing. In conclusion, the electroporation timing and the cumulus cell attachment did not interfere with the efficient delivery of the CRISPR/Cas9 system to the oocytes/zygotes, indicating that porcine genome editing in the oviduct using GONAD method may be possible.
Microplastic accumulation in soils around open dumping and scrapyard sites in Türkiye
Authors: Akca Muhittin Onur 
Published: February 2025

AbstractMicroplastic (MP) pollution is widespread and has become a significant global environmental concern. This study represents the first attempt to investigate the abundance of MPs in open dumping and scrapyard sites in Türkiye. Microplastics were identified in soils surrounding these areas, spanning eight provinces. The samples were analysed for MP distribution characteristics, including abundance, shape, size, colour and type. MPs were extracted using density separation with saturated K2CO3, followed by treatment with 30% H2O2. Chemical identification was conducted using ATR‐FTIR and μ‐FTIR. Various types of MPs were detected in the soil samples, with averages of 311.6 ± 113.9 particles kg−1 in open dumping areas and 463.3 ± 83.9 particles kg−1 in scrapyard areas. In open dumping areas, MPs were predominantly blue (35.3%), fragment‐shaped (36.6%), smaller than 500 μm (44.7%) and primarily polyethylene (81.5%). Similarly, in scrapyard areas, MPs were blue (33.1%), fragment‐shaped (63.4%), smaller than 500 μm (55.3%) and mostly polyethylene (70.1%). Principal Component Analysis (PCA) indicated that soil properties, such as pH, electrical conductivity, organic matter, aggregate stability, bulk density, average weight diameter, sand, clay and silt, significantly influenced the abundance and size of MPs in the soil. This study highlights potential concerns regarding soil contamination in three industrially developed regions of Türkiye because of the uncontrolled dumping of plastic waste in open dumping and scrapyard areas.
Development and Validation of the Well-Being in Sport Questionnaire and Sport Well-Being Enhancement Profile: Two Instruments to Measure and Promote Sport-Specific Well-Being
Authors: Rose Seth , Burton Damon , Stafford-Son Julie , Grindley Emma , Richardson Clarissa , Hammermeister Jon , Pickering Michael 
Published: February 2025

Athletes’ overall well-being (WB) often intertwines with their sport WB and vice versa. While holistic WB measures have been explored in nonsport contexts, researchers aim to understand competitive athletes’ WB using psychometrically rigorous assessments. Consequently, two interrelated studies were conducted to develop and validate companion instruments: (a) the Well-Being in Sport Questionnaire to gauge outcome-related sport WB and (b) the Sport Well-Being Enhancement Profile to identify strategies for enhancing sport WB. Following contemporary instrument development recommendations, including item development, content, and factor validity, the instruments underwent exploratory factor analysis, exploratory structural covariance modeling, confirmatory factor analysis, and measurement invariance. By utilizing the Well-Being in Sport Questionnaire and Sport Well-Being Enhancement Profile, coaches, athletes, and practitioners can comprehensively understand athletes’ WB, facilitating strategies for daily enhancement alongside peak sport performance.
Zinc-limited
Mycobacterium tuberculosis
stimulate distinct responses in macrophages compared with standard zinc-replete bacteria
Authors: Marcantonio Endrei , Burger Allexa D. , Chang Kelly H. , Hoffmann Fukun W. , Fu Yuanyuan , Khadka Vedbar S. , Smagghe Benoit J. , Deng Youping , Hoffmann Peter R. , Prisic Sladjana 
Published: February 2025

ABSTRACT

Tuberculosis (TB) is notoriously difficult to treat, likely due to the complex host-pathogen interactions driven by pathogen heterogeneity. An understudied area of TB pathogenesis is host responses to
Mycobacterium tuberculosis
bacteria (Mtb) that are limited in zinc ions. This distinct population resides in necrotic granulomas and sputum and could be the key player in tuberculosis pathogenicity. In this study, we tested the hypothesis that macrophages differentiate between Mtb grown under zinc limitation or in the standard zinc-replete medium. Using several macrophage infection models, such as murine RAW 264.7 and murine bone marrow-derived macrophages (BMDMs), as well as human THP-1-derived macrophages, we show that macrophages infected with zinc-limited Mtb have increased bacterial burden compared with macrophages infected with zinc-replete Mtb. We further demonstrate that macrophage infection with zinc-limited Mtb trigger higher production of reactive oxygen species (ROS) and cause more macrophage death. Furthermore, the increased ROS production is linked to the increased phagocytosis of zinc-limited Mtb, whereas cell death is not. Finally, transcriptional analysis of RAW 264.7 macrophages demonstrates that macrophages have more robust pro-inflammatory responses when infected with zinc-limited Mtb than zinc-replete Mtb. Together, our findings suggest that Mtb’s access to zinc affects their interaction with macrophages and that zinc-limited Mtb may be influencing TB progression. Therefore, zinc availability in bacterial growth medium should be considered in TB drug and vaccine developments.
Implementation of the children and young people’s health partnership model of paediatric integrated care: a mixed-methods process evaluation
Authors: Satherley Rose-Marie , Newham James , Cecil Elizabeth , Forman Julia , Kelly Clare , Wolfe Ingrid , Lingam Raghu 
Published: February 2025

ObjectiveA process evaluation of the Children and Young People’s Health Partnership (CYPHP) model of integrated care for the interpretation of trial findings and building evidence on the implementation of integrated care for children.DesignA mixed-methods process evaluation.SettingCYPHP was implemented at scale across two inner-city London boroughs in South London, England, as a pragmatic cluster-randomised controlled trial involving nearly 98 000 children, with a nested process evaluation.ParticipantsLinked data were available from 73 000 participants. Qualitative data collection was through 102 interviews (group and 1:1) and observations.InterventionsLocal child health clinics delivered by paediatricians and general practitioners and a nurse-led early intervention service for children with tracer conditions (asthma, eczema and constipation), decision support, a primary care hotline, self-management support and health promotion.Main outcome measuresFive domains of the RE-AIM implementation framework: Reach, Effectiveness, Adoption, Implementation and Maintenance.ResultsImplementation varied depending on resource availability, competing priorities and natural changes over time. Successful implementation drivers included cohesive interprofessional and partnership collaboration.ConclusionsIntegrated care for children can be implemented at scale, but variability, particularly low reach, may limit measurable impact at the population level. Significant health system strengthening, implementation plasticity and contextual tailoring are crucial for ensuring the efficacy and sustainability of impactful integrated care for children.Trial registration numberNCT03461848.
Co-occurrence of depression, anxiety and increased alcohol use during the late stage of the COVID-19 pandemic in Saskatchewan, Canada: a cross-sectional survey
Authors: Muhajarine Nazeem , Dixon James , Ahmed Md Sabbir , Bukhari Ali , Clifford Jim , Adeyinka Daniel A , Novotna Gabriela , Dyck Erika 
Published: February 2025

BackgroundImpact of the COVID-19 pandemic on mental health and substance use is well recognised. COVID-19 impacted Saskatchewan particularly hard as it has a higher prevalence of alcohol consumption than the national average. Our study investigated the prevalence and associated factors of co-occurrence of poor mental health and alcohol consumption (also referred to as dual experience) among Saskatchewan adults.MethodCross-sectional data of 1034 eligible adults collected between July and November 2022, were analysed. Dual experience was defined as mild to severe symptoms of depression (Patient Health Questionaire-9) and/or anxiety (Generalised Anxiety Disorder-7) AND increased alcohol consumption during the later stage of COVID-19 pandemic. Multivariable binary logistic regression models were fitted to identify the factors that are associated with dual experience.ResultsThe prevalence of different forms of dual experience was 7.32% for depression and alcohol use, 6.09% for anxiety and alcohol use and 5.44% for co-occurrence of depression, anxiety and alcohol use. Dual experiences were less likely among participants from racialised groups, and more likely among those with household food insecurity, as well as concerns over alcohol consumption.ConclusionOur analysis suggests that Saskatchewan adults are still experiencing poor mental health due to the impact of the COVID-19 pandemic, and a large proportion of people continue to consume alcohol at a higher rate than before the pandemic. Data driven interventions, for example, improving mental health and substance use treatment and counselling services, harm reduction strategies, especially targeting people living in food insecure households, are needed.
Demographic variation and socioeconomic inequalities in all forms of malnutrition among children aged 6 months to 9 years: findings from the Vietnamese General Nutrition Survey 2020
Authors: Tan Pui Yee , Som Somphos Vicheth , Nguyen Son Duy , Tan Xiaomian , Tran Do Tranh , Tran Nga Thuy , Tran Van Khanh , Dye Louise , Moore J Bernadette , Caton Samantha , Ensaff Hannah , Lin Xiaodong , Smith Geoffry , Gong Yun Yun 
Published: February 2025

IntroductionThe double burden of malnutrition (DBM) is a global public health challenge. This study examined the prevalence of population-level DBM, its demographic and socioeconomic determinants as well as the associations between anthropometric indicators of undernutrition and overnutrition, and micronutrient deficiencies (MNDs), among Vietnamese children, using the data from the nationally representative General Nutrition Survey 2020.MethodsData on anthropometric parameters, micronutrient biomarkers, demographic and socioeconomic indicators for 7289 children aged 6 months to 9 years were analysed. Determinants of malnutrition were assessed using logistic regressions, reported as OR with 95% CIs.ResultsAt national level, 12.7%, 10.5% and 4.7% of children were stunted, underweight and wasted/thin, while 7.3% and 7.1% were overweight and obese, respectively. Low serum zinc, anaemia and iron deficiency were the common MNDs observed, affecting 53.1%, 15.2% and 13.9% of the study participants. Older children aged 2–4 years (OR (95% CI) 1.43 (1.20, 1.72)), ethnic minorities (5.94 (3.78, 9.36)) and those living in mountainous areas (5.06 (1.18, 14.42)) had increased odds of stunting, whereas reduced odds were found in children from the richest quintile (0.13 (0.05, 0.32)). Similar determinants were associated with underweight and MNDs. Males (1.43 (1.16, 1.76)), children aged 5–9 years (10.02 (6.71, 14.97) and children from the richest quintile (2.91 (1.20, 7.05)) had increased odds of overweight. Children with anaemia, low serum retinol and low serum zinc had increased odds of stunting and underweight than non-micronutrient-deficient children (adjusted OR=1.43–1.71). Compared with children without MNDs, those with ≥3 MNDs had almost double the odds of stunting and underweight, whereas those with ≤3 MNDs had reduced odds of overweight (adjusted OR=0.38–0.60).ConclusionsSignificant demographic variation and socioeconomic inequalities in child malnutrition were identified. National policies and programmes in Vietnam should address age-specific, sex-specific, geographical and socioeconomic disparities to accelerate progress in reducing child malnutrition.
Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma
Authors: Eigentler Thomas , Thomas Ioannis , Samoylenko Igor , Erdmann Michael , Heinzerling Lucie , Ochsenreither Sebastian , Krauss Jürgen , Oberoi Arjun , Robert Caroline , Lebbe Celeste , Martin-Liberal Juan , Koch Lukas , Richtig Erika , Terheyden Patrick , Weishaupt Carsten , Mohr Peter , Semiletova Yulia , Perez Casilda Llacer , Brossart Peter , Bauernfeind Franz Georg , Fluck Michael , Poltoratskiy Artem , Sekacheva Marina , Soria Ainara , Schmitt-Bormann Beate , Gonzalez Marina , Heß Jana , Wengenmayer Peter , Seibel Tobias , Koch Sven D , Quintini Gianluca , Codó Paula , Falk Martin , Schönborn-Kellenberger Oliver , Gnad-Vogt Ulrike 
Published: February 2025

BackgroundCV8102, a toll-like receptor 7/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death protein-1 (PD-1) therapy-naïve or anti-PD-1 therapy-refractory cutaneous melanoma (cMEL) and in patients with advanced cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma and adenoid cystic carcinoma.MethodsThis open-label, cohort-based, phase I dose escalation study aimed to establish the maximum tolerated dose (MTD), recommended dose (RD), safety and preliminary efficacy of CV8102 as monotherapy or in combination with a PD-1 inhibitor. The preliminary efficacy of the RD was assessed in patients with cMEL in the expansion cohorts.ResultsBetween September 2017 and October 2022, 98 patients were enrolled in monotherapy and combination therapy dose escalation and dose expansion cohorts. Two patients in the CV8102 monotherapy dose escalation cohort experienced relevant toxicities at the 900 µg dose level. One patient had Grade 3 aspartate transaminase/alanine aminotransferase elevation which met dose-limiting toxicity (DLT) criteria. Another patient experienced Grade 3 immune-mediated pneumonitis. No DLTs occurred in the combination therapy dose escalation cohort. The MTD was not formally reached and the RD for expansion was 600 µg. Common treatment-emergent adverse events were fever (57%), chills (37%) and fatigue (25%). In the dose escalation part, objective responses occurred in 3/33 patients treated with CV8102 as monotherapy and in 2/25 patients treated with CV8102 plus a PD-1 inhibitor. In the expansion cohorts in patients with anti-PD-1 therapy-refractory melanoma, 0/10 patients treated with CV8102 as monotherapy and 5/30 patients (17%) treated in combination with a PD-1 inhibitor experienced objective responses.ConclusionsIT CV8102 was generally well tolerated with preliminary signs of efficacy as monotherapy and in combination with a PD-1 inhibitor.Trial registration numberNCT03291002.
Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis
Authors: Wood Cameron , Lyniv Liliana , Isaacs James M , Kaufman Jacob M , Oduah Eziafa I , Clarke Jeff , Crawford Jeffrey , Stinchcombe Thomas , Tong Betty C , Wang Xiaofei , Gu Lin , Wigle Dennis , Dragnev Konstantin H , Antonia Scott J , Weinhold Kent , Ready Neal 
Published: February 2025

BackgroundOur study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC.MethodsThis is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers.Results30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively.ConclusionsPerioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.
Factors affecting visual outcomes after dural venous sinus stenting in idiopathic intracranial hypertension
Authors: Wang Shuran , Raynald  , Zhang Runhua , Yang Hongchao , Tong Xu , Song Shuang , Liang Xiaofang , Wang Yilong , Miao Zhongrong , Mo Dapeng 
Published: February 2025

ObjectivesThis study aimed to identify factors at baseline associated with visual outcomes of patients with idiopathic intracranial hypertension (IIH) with venous sinus stenosis who underwent venous sinus stenting.MethodsThe study eyes were divided into two groups according to mean deviation (MD) at 6-month post-stenting follow-up: MD better than −2.0 dB (the favorable visual outcome group) and equal to −2.0 or worse (the poorer visual outcome group). Variables at baseline between the two groups were compared. A multivariable logistic regression model was performed to identify the factors at baseline associated with poorer MD outcomes at 6 months.ResultsThe poorer recovery group had a lower incidence of tinnitus (5.9% vs 27.5%, P=0.015), worse initial best corrected visual acuity (0.22 vs 0, in logMAR, P=0.000), worse preoperative MD (−8.64 vs −3.05, P=0.000) and higher trans-stenotic gradient pressure (19.5 vs 16, P=0.002) and total cranial gradient pressure (TCGP) (25.75 vs 18, P=0.000), lower ganglion cell complex (GCC) thickness (90.5 vs 99, P=0.005), higher focal loss volume percentage (2.35 vs 0.84, P=0.002) and global loss volume percentage (4.87 vs 1.8, P=0.012) of GCC. Multivariate analysis showed that worse preoperative MD and higher TCGP (OR 45.61, 95% CI 5.21 to 399.48; P=0.001 and OR 8.45, 95% CI 1.60 to 44.67; P=0.012, respectively) were associated with an increased risk of poorer MD outcomes at the 6-month follow-up.ConclusionThis study found that worse preoperative MD and higher TCGP at baseline may be associated with poorer visual outcomes after stenting treatment.
Qualitative assessment of combat-related injury patterns and injury prevention in Ukraine since the Russian invasion
Authors: Lawry Lynn Lieberman , Mani V , Hamm TE , Janvrin M , Juman L , Korona-Bailey J , Maddox J , Berezyuk O , Schoenfeld AJ , Koehlmoos TP 
Published: February 2025

IntroductionThe ongoing invasion of Ukraine by the Russian Federation represents one of the largest ongoing conventional military engagements in the last 20 years. Since the start of the war, an estimated 210 000 Ukrainian soldiers have been injured or killed as a result of combat. This experience could help prognosticate the nature of large-scale combat operations for modern militaries. The aim of this study was to assess current patterns of injuries among military combatants in Ukraine and identify prevention and mitigation methods.MethodsWe conducted a series of key informant interviews during the ongoing conflict using an expanded version of the global trauma system evaluation tool. We focused the analysis on injury patterns and prevention of combat-related injuries.ResultsWe interviewed 36 participants from June 2023 to February 2024. Respondents described complex polytrauma as representing the injury norm, with prominent battle injuries, including blast wounds to the extremities, traumatic brain injuries and spinal cord trauma. The primary source of injury prevention on the battlefield remains combat body armour. Military commanders and the Ministry of Defence were identified as principal bodies for the authorising equipment and tactical changes. Most respondents stated there was no formal process for using data to inform injury prevention initiatives.ConclusionThe current conflict in Ukraine is characterised by a high prevalence of devastating combat-related injury, with limited measures for battlefield injury prevention. We believe that the provision of additional protective gear could mitigate the severity of some combat-related injuries, while the creation of a trauma registry would provide greater insight into prevention, wounding patterns, treatment and outcomes.
Cardiac events and procedures following COVID-19 compared with other pneumonias: a national register study
Authors: Øvrebotten Tarjei , Tholin Birgitte , Berge Kristian , Myhre Peder Langeland , Stavem Knut 
Published: February 2025

BackgroundStudies have shown an increased risk of cardiac disease following COVID-19, but how it compares to pneumonia of other etiologies is unclear.AimsTo determine the incidence and HRs of cardiac disease in patients hospitalised with COVID-19 compared with other viral or bacterial pneumonias.MethodsUsing nationwide registry data, we estimated the incidence of cardiac events after hospitalisation with COVID-19 (n=2082) in February to November 2020 vs hospitalisation with viral (n=9018) or bacterial (n=29 339) pneumonia in 2018–2019. We defined outcomes using ICD-10 codes for incident myocarditis, acute myocardial infarction, atrial fibrillation/flutter, heart failure, ischaemic heart disease, other cardiac disease and total cardiac disease (any heart condition). We used Cox regression and logistic regression for analysis.ResultsPatients with COVID-19 had a mean (SD) age of 60 (18) years, compared with 69 (19) years for viral and 72 (17) years for bacterial pneumonia. Those with COVID-19 were more often male and had fewer comorbidities and fewer prior hospitalisations. Patients with COVID-19 had a lower hazard of new-onset cardiac disease compared with viral (HR 0.79 [95%CI 0.66 to 0.93]) and bacterial pneumonia (HR 0.66 [95%CI 0.57 to 0.78]), adjusted for age, sex, comorbidity, hospital admission prior year and respiratory support. Results were similar when including recurrent events.ConclusionPatients hospitalised with COVID-19 had a lower hazard of new-onset cardiac disease during the first 9 months after hospitalisation compared with patients with other viral or bacterial pneumonias after adjusting for multiple possible confounders. However, there may still be residual confounding from other or unknown factors.