bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of direct oral anticoagulation in patients with and without radiofrequency ablation of non-valvular atrial fibrillation: a multicenter retrospective cohort study
Authors: Wu Shuyi , Guan Chengfu , Xu Wenlin , Zhang Feilong , Huang Nianxu , Chen Xia , Zhang Wang , Hu Wei , Su Jun , Dai Hengfen , Gu Ping , Huang Xiaohong , Du Xiaoming , Li Ruijuan , Zheng Qiaowei , Lin Xiangsheng , Zhang Yanxia , Zou Lang , Liu Yuxin , Zhang Min , Liu Xiumei , Zhu Zhu , Sun Jianjun , Hong Shanshan , She Weibin , Zhang Jinhua 
Published: April 2023

Abstract
Background
Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs.

Methods
This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death.

Results
After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P<0.001], thrombosis [OR 0.535 (95% CI, 0.316-0.908), P=0.020] and the composite endpoint [ OR 0.835 (95% CI, 0.710-0.982), P=0.029]. In the RFA PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. In the no RFA PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 ( 95% CI, 0.535-0.811), P<0.001].

Conclusion
Among patients with NVAF treated with DOACs, RFA was a negative correlate of major bleeding, thrombosis, and composite endpoints but was not associated with total bleeding or all-cause mortality.
Immediate improvements in post-stroke gait biomechanics are induced with both real-time limb position and propulsive force biofeedback
Authors: Santucci Vincent , Alam Zahin , Liu Justin , Spencer Jacob , Faust Alec , Cobb Aijalon , Konantz Joshua , Eicholtz Steven , Wolf Steven , Kesar Trisha M. 
Published: April 2023

Abstract
Background
Paretic propulsion [measured as anteriorly-directed ground reaction forces (AGRF)] and trailing limb angle (TLA) show robust inter-relationships, and represent two key modifiable post-stroke gait variables that have biomechanical and clinical relevance. Our recent work demonstrated that real-time biofeedback is a feasible paradigm for modulating AGRF and TLA in able-bodied participants. However, the effects of TLA biofeedback on gait biomechanics of post-stroke individuals are poorly understood. Thus, our objective was to investigate the effects of unilateral, real-time, audiovisual TLA versus AGRF biofeedback on gait biomechanics in post-stroke individuals.

Methods
Nine post-stroke individuals (6 males, age 63 ± 9.8 years, 44.9 months post-stroke) participated in a single session of gait analysis comprised of three types of walking trials: no biofeedback, AGRF biofeedback, and TLA biofeedback. Biofeedback unilaterally targeted deficits on the paretic limb. Dependent variables included peak AGRF, TLA, and ankle plantarflexor moment. One-way repeated measures ANOVA with Bonferroni-corrected post-hoc comparisons were conducted to detect the effect of biofeedback on gait biomechanics variables.

Results
Compared to no-biofeedback, both AGRF and TLA biofeedback induced unilateral increases in paretic AGRF. TLA biofeedback induced significantly larger increases in paretic TLA than AGRF biofeedback. AGRF biofeedback increased ankle moment, and both feedback conditions increased non-paretic step length. Both types of biofeedback specifically targeted the paretic limb without inducing changes in the non-paretic limb.

Conclusions
By showing comparable increases in paretic limb gait biomechanics in response to both TLA and AGRF biofeedback, our novel findings provide the rationale and feasibility of paretic TLA as a gait biofeedback target for post-stroke individuals. Additionally, our results provide preliminary insights into divergent biomechanical mechanisms underlying improvements in post-stroke gait induced by these two biofeedback targets. We lay the groundwork for future investigations incorporating greater dosages and longer-term therapeutic effects of TLA biofeedback as a stroke gait rehabilitation strategy.
Trial registrationNCT03466372
Biokinetics of subacutely co-inhaled same size gold and silver nanoparticles
Authors: Lee Philku , Kim Jin Kwon , Jo Mi Seong , Kim Hoi Pin , Ahn Kangho , Park Jung Duck , Gulumian Mary , Oberdörster Günter , Yu Il Je 
Published: April 2023

Abstract
Background
Toxicokinetics of nanomaterials, including studies on the absorption, distribution, metabolism, and elimination of nanomaterials, are essential in assessing their potential health effects. The fate of nanomaterials after inhalation exposure to multiple nanomaterials is not clearly understood.

Methods
Male Sprague–Dawley rats were exposed to similar sizes of silver nanoparticles (AgNPs, 10.86 nm) and gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for four weeks) either with separate NP inhalation exposures or with combined co-exposure in a nose-only inhalation system. Mass concentrations sampled from the breathing zone were AuNP 19.34 ± 2.55 μg/m3 and AgNP 17.38 ± 1.88 μg/m3 for separate exposure and AuNP 8.20 μg/m3 and AgNP 8.99 μg/m3 for co-exposure. Lung retention and clearance were previously determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). In addition, the fate of nanoparticles, including translocation and elimination from the lung to the major organs, were determined during the post-exposure observation period.

Results
AuNP was translocated to the extrapulmonary organs, including the liver, kidney, spleen, testis, epididymis, olfactory bulb, hilar and brachial lymph nodes, and brain after subacute inhalation and showed biopersistence regardless of AuNP single exposure or AuNP + AgNP co-exposure, showing similar elimination half-time. In contrast, Ag was translocated to the tissues and rapidly eliminated from the tissues regardless of AuNP co-exposure. Ag was continually accumulated in the olfactory bulb and brain and persistent until PEO-28.

Conclusion
Our co-exposure study of AuNP and AgNP indicated that soluble AgNP and insoluble AuNP translocated differently, showing soluble AgNP could be dissolved into Ag ion to translocate to the extrapulmonary organs and rapidly removed from most organs except the brain and olfactory bulb. Insoluble AuNPs were continually translocated to the extrapulmonary organs, and they were not eliminated rapidly.
Global health governance performance during Covid-19, what needs to be changed? a delphi survey study
Authors: Abu El Kheir-Mataria Wafa , El-Fawal Hassan , Chun Sungsoo 
Published: April 2023

Abstract
Background
Covid-19 is not the first pandemic to challenge GHG. Preceding outbreaks and epidemics were sources of continuous debate on GHG leadership and structure resulting in its current structure. However, Covid-19 proved the presence of many deficits in the current GHG. The response to the Covid-19 pandemic is a cumulative result of all policies and actions of different governments and agencies active in global health. Assessing how Covid-19 is being handled globally provides lessons for ensuring better performance in facing upcoming outbreaks. This study has three main objectives: first, to evaluate the performance of GHG during Covid-19 in general and in relation to Covid-19 vaccine equity in particular. Second, to identify the reasons behind this performance; and third, to propose prospective changes in GHG for better performance.

Methods
A cross-sectional research design using the Delphi method was applied. A panel of experts participated in the three-round Delphi surveys. Their scores were used to perform consensus, performance and correlation analysis.

Results
GHG performance limited the achievement of Covid-19 vaccines’ global equity. GHG performance is a product of the existing GHG system, its actors and legal framework. It is a collective result of individual GHG actors’ performance. The most influential actors in decision-making regarding Covid-19 vaccine are the vaccine manufacturers and governments. While the most invoked power to influence decision are economic and political powers. Covid-19 decisions underlying value, although had human right to health at the base, overlooked the concept of health as a global public good and was skewed towards market-oriented values. GHG mal-performance along with its underlying factors calls for four main changes in GHG structure: assigning a clear steward for GHG, enhanced accountability, centralized authority, more equitable representation of actors, and better legal framework.

Conclusion
GHG structure, actors’ representation, accountability system, and underlying priorities and value require future modification for GHG to achieve better future performance and higher health equity levels.
Newly developed 3D in vitro models to study tumor–immune interaction
Authors: Mu Peiyuan , Zhou Shujuan , Lv Tao , Xia Fan , Shen Lijun , Wan Juefeng , Wang Yaqi , Zhang Hui , Cai Sanjun , Peng Junjie , Hua Guoqiang , Zhang Zhen 
Published: April 2023

AbstractImmunotherapy as a rapidly developing therapeutic approach has revolutionized cancer treatment and revitalized the field of tumor immunology research. 3D in vitro models are emerging as powerful tools considering their feature to maintain tumor cells in a near-native state and have been widely applied in oncology research. The novel 3D culture methods including the co-culture of organoids and immune cells, ALI culture, 3D-microfluidic culture and 3D-bioprinting offer new approaches for tumor immunology study and can be applied in many fields such as personalized treatment, immunotherapy optimizing and adoptive cell therapy. In this review, we introduce commonly used 3D in vitro models and summarize their applications in different aspects of tumor immunology research. We also provide a preliminary analysis of the current shortcomings of these models and the outlook of future development.
Targeted next-generation sequencing of 21 candidate genes in hereditary ovarian cancer patients from the Republic of Bashkortostan
Authors: Prokofyeva D. S. , Mingazheva E. T. , Valova Ya. V. , Sakaeva D. D. , Faishanova R. R. , Nurgalieva A. Kh. , Valiev R. R. , Bogdanova N. , Dörk T. , Khusnutdinova E. K. 
Published: April 2023

AbstractAbout 5–10% of all ovarian cancer cases show familial clustering, and some 15–25% of familial ovarian cancer cases are mediated by high-penetrance mutations in the BRCA1 and BRCA2 genes. Only few other genes have been identified for familial ovarian cancer.We conducted targeted next-generation sequencing of the protein coding region of 21 candidate genes, including UTR regions, in genomic DNA samples of 48 patients with familial ovarian cancer from the Republic of Bashkortostan. We identified deleterious variants in BRCA1, BRCA2, CHEK2, MSH6 and NBN in a total of 16 patients (33%). The NBN truncating variant, p.W143X, had not previously been reported. Seven patients (15%) were carriers of the c.5266dupC variant in BRCA1, supporting a Russian origin of this founder allele. An additional 15 variants of uncertain clinical significance were observed. We conclude that our gene panel explains about one-third of familial ovarian cancer risk in the Republic of Bashkortostan.
Lifetime changes in body fatness and breast density in postmenopausal women: the FEDRA study
Authors: Masala Giovanna , Bendinelli Benedetta , Caini Saverio , Duroni Giacomo , Ermini Ilaria , Pastore Elisa , Fontana Miriam , Facchini Luigi , Querci Andrea , Gilio Maria Antonietta , Mazzalupo Vincenzo , Assedi Melania , Ambrogetti Daniela , Palli Domenico 
Published: April 2023

Abstract
Background
High mammographic breast density (MBD) is an established risk factor for breast cancer (BC). Body fatness conveys an increased BC risk in postmenopause but is associated with less dense breasts. Here, we studied the relationship between body fatness and breast composition within the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) longitudinal study.

Methods
Repeated anthropometric data and MBD parameters (obtained through an automated software on BC screening digital mammograms) were available for all participants, as well as information on other BC risk factors. Multivariate linear regression and functional data analysis were used to longitudinally evaluate the association of body fatness, and changes thereof over time, with dense (DV) and non-dense (NDV) breast volumes and volumetric percent density (VPD).

Results
A total of 5,262 women were included, with anthropometric data available at 20 and 40 years of age, at EPIC baseline (mean 49.0 years), and an average of 9.4 years thereafter. The mean number of mammograms per woman was 3.3 (SD 1.6). Body fatness (and increases thereof) at any age was positively associated with DV and NDV (the association being consistently stronger for the latter), and inversely associated with VPD. For instance, an increase by 1 kg/year between the age of 40 years and EPIC baseline was significantly associated with 1.97% higher DV, 8.85% higher NDV, and 5.82% lower VPD.

Conclusion
Body fatness and its increase from young adulthood until midlife are inversely associated with volumetric percent density, but positively associated with dense and non-dense breast volumes in postmenopausal women.
NSD2 E1099K drives relapse in pediatric acute lymphoblastic leukemia by disrupting 3D chromatin organization
Authors: Narang Sonali , Evensen Nikki A. , Saliba Jason , Pierro Joanna , Loh Mignon L. , Brown Patrick A. , Kolekar Pandurang , Mulder Heather , Shao Ying , Easton John , Ma Xiaotu , Tsirigos Aristotelis , Carroll William L. 
Published: April 2023

Abstract
Background
The NSD2 p.E1099K (EK) mutation is shown to be enriched in patients with relapsed acute lymphoblastic leukemia (ALL), indicating a role in clonal evolution and drug resistance.

Results
To uncover 3D chromatin architecture-related mechanisms underlying drug resistance, we perform Hi-C on three B-ALL cell lines heterozygous for NSD2 EK. The NSD2 mutation leads to widespread remodeling of the 3D genome, most dramatically in terms of compartment changes with a strong bias towards A compartment shifts. Systematic integration of the Hi-C data with previously published ATAC-seq, RNA-seq, and ChIP-seq data show an expansion in H3K36me2 and a shrinkage in H3K27me3 within A compartments as well as increased gene expression and chromatin accessibility. These results suggest that NSD2 EK plays a prominent role in chromatin decompaction through enrichment of H3K36me2. In contrast, we identify few changes in intra-topologically associating domain activity. While compartment changes vary across cell lines, a common core of decompacting loci are shared, driving the expression of genes/pathways previously implicated in drug resistance. We further perform RNA sequencing on a cohort of matched diagnosis/relapse ALL patients harboring the relapse-specific NSD2 EK mutation. Changes in patient gene expression upon relapse significantly correlate with core compartment changes, further implicating the role of NSD2 EK in genome decompaction.

Conclusions
In spite of cell-context-dependent changes mediated by EK, there appears to be a shared transcriptional program dependent on compartment shifts which could explain phenotypic differences across EK cell lines. This core program is an attractive target for therapeutic intervention.
Quantifying the impact of the COVID-19 pandemic on clinical trial screening rates over time in 37 countries
Authors: McDonald Kelsey , Seltzer Earl , Lu Mary , Gaisenband Stefan Diaz , Fletcher Cassandra , McLeroth Patrick , Saini Kamal S 
Published: April 2023

AbstractThe COVID-19 pandemic has had an unprecedented and disruptive impact on people’s health and lives worldwide. In addition to burdening people’s health in the short-term in the form of infection, illness, and mortality, there has been an enormous negative impact on clinical research. Clinical trials experienced challenges in ensuring patient safety and enrolling new patients throughout the pandemic. Here, we investigate and quantify the negative impact that the COVID-19 pandemic has industry-sponsored clinical trials, both in the USA and worldwide. We find a negative correlation between the severity of the COVID-19 pandemic and clinical trial screening rate, with the relationship being strongest during the first three months of the pandemic compared to the entire duration of the pandemic. This negative statistical relationship holds across therapeutic areas, across states in the USA despite the heterogeneity of responses at the state-level, and across countries. This work has significant implications for the management of clinical trials worldwide in response to the fluctuating severity of COVID-19 moving forward and for future pandemics.
Mechanical overloading-induced miR-325-3p reduction promoted chondrocyte senescence and exacerbated facet joint degeneration
Authors: Zhao Jinyun , Li Chengjun , Qin Tian , Jin Yuxin , He Rundong , Sun Yi , Liu Zhide , Wu Tianding , Duan Chunyue , Cao Yong , Hu Jianzhong 
Published: April 2023

Abstract
Objective
Lumbar facet joint (LFJ) degeneration is one of the main causes of low back pain (LBP). Mechanical stress leads to the exacerbation of LFJ degeneration, but the underlying mechanism remains unknown. This study was intended to investigate the mechanism of LFJ degeneration induced by mechanical stress.

Methods
Here, mice primary chondrocytes were used to screen for key microRNAs induced by mechanical overloading. SA-β-gal staining, qRT-PCR, western blot, and histochemical staining were applied to detect chondrocyte senescence in vitro and in vivo. We also used a dual-luciferase report assay to examine the targeting relationship of miRNA-325-3p (miR-325-3p) and Trp53. By using NSC-207895, a p53 activator, we investigated whether miR-325-3p down-regulated trp53 expression to reduce chondrocyte senescence. A mice bipedal standing model was performed to induce LFJ osteoarthritis. Adeno-associated virus (AAV) was intraarticularly injected to evaluate the effect of miR-325-3p on facet joint degeneration.

Results
We observed chondrocyte senescence both in human LFJ osteoarthritis tissues and mice LFJ after bipedally standing for 10 weeks. Mechanical overloading could promote chondrocyte senescence and senescence-associated secretory phenotype (SASP) expression. MicroRNA-array analysis identified that miR-325-3p was obviously decreased after mechanical overloading, which was further validated by fluorescence in situ hybridization (FISH) in vivo. Dual-luciferase report assay showed that miR-325-3p directly targeted Trp53 to down-regulated its expression. MiR-325-3p rescued chondrocyte senescence in vitro, however, NSC-207895 reduced this effect by activating the p53/p21 pathway. Intraarticular injection of AAV expressing miR-325-3p decreased chondrocyte senescence and alleviated LFJ degeneration in vivo.

Conclusion
Our findings suggested that mechanical overloading could reduce the expression of miR-325-3p, which in turn activated the p53/p21 pathway to promote chondrocyte senescence and deteriorated LFJ degeneration, which may provide a promising therapeutic strategy for LFJ degeneration.
Responsiveness of Persian 12-Item multiple sclerosis walking scale: a replication study
Authors: Naghdi Soofia , Ansari Noureddin Nakhostin , Haghparast Afarin , Nakhostin-Ansari Amin , Khalifeloo Maede , Biglar Mahmoud , Lotfi Roghie , Hasson Scott 
Published: April 2023

Abstract
Objective
To re-explore the responsiveness of the Persian version of Multiple Sclerosis Walking Scale-12 (MSWS-12p) to physiotherapy intervention and determine the minimally clinically important change (MCIC). This study followed a prospective cohort design. Patients with MS (PwMS) underwent physiotherapy treatment for 10 sessions. The outcome measures were the MSWS-12p and Timed 25-Foot Walk test (T25-FW). Data was collected before and after ten sessions of physiotherapy. The effect sizes and the area under receiver operating characteristics curve (AUC) and MCIC were calculated.

Results
Thirty PwMS (16 female, mean age 43.07 years) participated in the study. The effect sizes for MSWS-12p were moderate (0.52, 0.64). The change scores of MSWS-12p showed excellent correlation with the dichotomized smallest detectable change (SDC) criterion (Eta coefficient test = 0.84). There was no correlation between the MSWS-12p total change scores and the T25-FW (r = − 0.14, p = 0.45). The AUC was perfect and the MCIC for the MSWS-12p was calculated 10.0 points. The MSWS-12p is responsive and demonstrates changes after physiotherapy. Changes > 10.0 points on MSWS-12p total score should be considered as true improvement after physiotherapy.
Identification of EGFR mutation status in male patients with non-small-cell lung cancer: role of 18F-FDG PET/CT and serum tumor markers CYFRA21-1 and SCC-Ag
Authors: Jiang Maoqing , Chen Ping , Guo Xiuyu , Zhang Xiaohui , Gao Qiaoling , Zhang Jingfeng , Zhao Guofang , Zheng Jianjun 
Published: April 2023

Abstract
Background
The high incidence of epidermal growth factor receptor (EGFR) mutations is usually found in female patients with lung adenocarcinoma who have never-smoked. However, reports concerning male patients are scarce. Thus, this study aimed to explore a novel approach based on 18F-fluoro-2-deoxy-2-deoxyglucose (18F-FDG) PET/CT and serum tumor markers (STMs) to determine EGFR mutation status in male patients with non-small-cell lung cancer (NSCLC).

Methods
A total of 121 male patients with NSCLC were analyzed between October 2019 and March 2022. All patients underwent 18F-FDG PET/CT scan before treatment and monitored 8 STMs (cytokeratin 19 fragment [CYFRA21-1], squamous cell carcinoma-related antigen [SCC-Ag], carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], carbohydrate antigen [CA] 50, CA125, CA72-4, and ferritin). A comparison was done between EGFR mutant and wild-type patients in terms of the maximum standardized uptake value of primary tumors (pSUVmax) and 8 STMs. We performed receiver operating characteristic (ROC) curve and multiple logistic regression analyses to determine predictors for EGFR mutation status.

Results
EGFR mutations were detected in 39 patients (32.2%). Compared with patients with EGFR wild-type, EGFR-mutant patients had lower concentrations of serum CYRFA21-1 (2.65 vs. 4.01, P = 0.002) and SCC-Ag (0.67 vs. 1.05, P = 0.006). No significant differences of CEA, NSE, CA 50, CA125, CA72-4 and ferritin were found between the two groups. The presence of EGFR mutations was significantly associated with low pSUVmax (< 8.75), low serum SCC-Ag (< 0.79 ng/mL) and CYFRA21-1 (< 2.91 ng/mL) concentrations. The area under ROC curve values were 0.679, 0.655, 0.685 and 0.754, respectively, for low CYFRA21-1, SCC-Ag, pSUVmax and the combination of these three factors.

Conclusions
We demonstrated that low concentrations of CYFRA21-1 and SCC-Ag, as well as low pSUVmax, were associated with EGFR mutations, and that the combination of these factors resulted in a higher differentiation of EGFR mutation status in male patients with NSCLC.