bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fixed-effects model for robust analysis of stepped-wedge cluster trials with a small number of clusters and continuous outcomes: a simulation study
Authors: Lee Kenneth Menglin , Cheung Yin Bun 
Published: October 2024

Abstract
Background
Stepped-wedge cluster trials (SW-CTs) describe a cluster trial design where treatment rollout is staggered over the course of the trial. Clusters are commonly randomized to receive treatment beginning at different time points in this study design (commonly referred to as a Stepped-wedge cluster randomized trial; SW-CRT), but they can also be non-randomized. Trials with this design regularly have a low number of clusters and can be vulnerable to covariate imbalance. To address such covariate imbalance, previous work has examined covariate-constrained randomization and analysis adjustment for imbalanced covariates in mixed-effects models. These methods require the imbalanced covariate to always be known and measured. In contrast, the fixed-effects model automatically adjusts for all imbalanced time-invariant covariates, both measured and unmeasured, and has been implicated to have proper type I error control in SW-CTs with a small number of clusters and binary outcomes.

Methods
We present a simulation study comparing the performance of the fixed-effects model against the mixed-effects model in randomized and non-randomized SW-CTs with small numbers of clusters and continuous outcomes. Additionally, we compare these models in scenarios with cluster-level covariate imbalances or confounding.

Results
We found that the mixed-effects model can have low coverage probabilities and inflated type I error rates in SW-CTs with continuous outcomes, especially with a small number of clusters or when the ICC is low. Furthermore, mixed-effects models with a Satterthwaite or Kenward-Roger small sample correction can still result in inflated or overly conservative type I error rates, respectively. In contrast, the fixed-effects model consistently produced the target level of coverage probability and type I error rates without dramatically compromising power. Furthermore, the fixed-effects model was able to automatically account for all time-invariant cluster-level covariate imbalances and confounding to robustly yield unbiased estimates.

Conclusions
We recommend the fixed-effects model for robust analysis of SW-CTs with a small number of clusters and continuous outcomes, due to its proper type I error control and ability to automatically adjust for all potential imbalanced time-invariant cluster-level covariates and confounders.
A genome-based survey of invasive pneumococci in Norway over four decades reveals lineage-specific responses to vaccination
Authors: Eldholm Vegard , Osnes Magnus N. , Bjørnstad Martha L. , Straume Daniel , Gladstone Rebecca A. 
Published: October 2024

Abstract
Background
Streptococcus pneumoniae is a major cause of mortality globally. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced the incidence of the targeted serotypes significantly, but expansion of non-targeted serotypes, serotype replacement, and incomplete vaccine-targeting contribute to pneumococcal disease in the vaccine era. Here, we characterize the changing population genetic landscape of S. pneumoniae in Norway over a 41-year period (1982–2022).

Methods
Since 2018, all cases of invasive pneumococcal disease have undergone whole-genome sequencing (WGS) at the Norwegian Institute of Public Health. In order to characterize the changing population over time, historical isolates were re-cultured and sequenced, resulting in a historical WGS dataset. Isolates were assigned to global pneumococcal sequence clusters (GPSCs) using PathogenWatch and assigned to serotypes using in silico (SeroBA) and in vitro methods (Quellung reaction). Temporal phylogenetic analyses were performed on GPSCs of particular interest.

Results
The availability of WGS data allowed us to study capsular variation at the level of individual lineages. We detect highly divergent fates for different GPSCs following the introduction of PCVs. For two out of eight major GPSCs, we identified multiple instances of serotype switching from vaccine types to non-vaccine types. Dating analyses suggest that most instances of serotype switching predated the introduction of PCVs, but expansion occurred after their introduction. Furthermore, selection for penicillin non-susceptibility was not a driving force for the changing serotype distribution within the GPSCs over time.

Conclusions
PCVs have been major shapers of the Norwegian disease-causing pneumococcal population, both at the level of serotype distributions and the underlying lineage dynamics. Overall, the introduction of PCVs has reduced the incidence of invasive disease. However, some GPSCs initially dominated by vaccine types escaped the effect of vaccination through expansion of non-vaccine serotypes. Close monitoring of circulating lineages and serotypes will be key for ensuring optimal vaccination coverage going forward.
Intrauterine adhesions repair with menstrual blood-derived mesenchymal stem cells via CXCL13-CXCR5 signal axis and its mechanism
Authors: Luo Bing , Zeng Xun , Luo Li 
Published: October 2024

Abstract
Backgroud
Intrauterine Adhesions (IUA) is a common gynecological disease which is seriously endangers the reproductive function of women without any ideal treatment. Some researchers found Menstrual Blood-derived Mesenchymal Stem Cells (MenSCs) can repair of damaged endometrium, however, has not been fully clarified. This study aims to evaluate the therapeutic effects of MenSCs in IUA and the repair mechanism in vivo.

Methods
This study is Laboratory-based study. To evaluate the therapeutic effects of MenSCs in IUA, We cultivated MenSCs, established mouse endometrial injury model, observed the uterine morphology and degree of endometrial fibrosis and compared the expression of CXC chemokine ligand-13 (CXCL13)、CXC chemokine receptor-5 (CXCR5)、Plasmin Activating Inhibitor-1(Pai-1), Transforming Growth Faction-β1(TGF- β1) and Matrix Metalloproteinase-9 (Mmp-9) among each groups. GraphPad Prism 8.0 was used for statistical processing. Data were expressed as mean ± SD. Statistical comparisons among groups were performed with one-way ANOVA. P < 0.05 were considered statistically significant.

Results
We successfully cultured and identified MenSCs and established mice model of uterine adhesion. After treatment with MenSCs, endometrial morphology of mice was partially restored, endometrial thickness was increased, and glands were multipiled. The concentrations of CXCL13 and CXCR5 were significantly increased by immunofluorescence detection compared with the control group. The results of RT-qPCR showed that the expressions of Pai-1 and Mmp-9 were significantly lower than those of the control group.

Conclusions
MenSCs may reduce endometrial fibrosis and the down-regulating expression of Pai-1、Mmp-9 and CXCL13-CXCR5 axis were involved in the process of MenSCs repaired IUA.
Using EMS data to explore community-level factors associated with firearm violence in North Carolina
Authors: Tang Yuni , Taylor Nandi L. , Neuroth Lucas M. , Higgins Kathleen A. , Waller Anna E. , Marshall Stephen W. , Harmon Katherine J. 
Published: October 2024

Abstract
Background
Firearm violence is a significant public health issue. However, it is unclear if there is an association between the Social Vulnerability Index (SVI) and the intent of both fatal and nonfatal firearm injuries, and if these associations are modified by community race and ethnic composition. This study examines the association between community-level social vulnerability and firearm injury incidence in North Carolina (NC) using 2021–2022 emergency medical services (EMS) data. Additionally, it investigates how these associations vary by the intent of injury (assault, self-inflicted, and unintentional), and whether they are modified by community racial/ethnic composition.

Methods
This cross-sectional study utilized NC EMS data, capturing firearm incidents from January 1, 2021, to December 31, 2022. The SVI from the Centers for Disease Control and Prevention (CDC) was used to assess community-level vulnerability. The SVI’s racial/ethnic minority status component was removed for stratification analysis. Firearm injury rates were calculated per 100,000 population, and negative binomial regression models were used to estimate Incidence Rate Ratios (IRRs) for different SVI levels and intents of firearm injuries.

Results
During the study period, we identified 7,250 EMS encounters at non-healthcare locations related to firearm injuries, encompassing 2,648 NC census tracts. Assault was the leading cause of firearm injuries (n = 3,799), followed by self-inflicted (n = 1,498), and unintentional injuries (n = 722). High-SVI communities had significantly higher rates of firearm injuries compared to low-SVI communities, particularly for assault-related injuries. When the minority status component was excluded from SVI, racial/ethnic minority status emerged as a significant modifier, with higher rates of firearm injuries being observed in communities with larger racial/ethnic minority populations.

Conclusion
Community-level social vulnerability is significantly associated with firearm injury incidence, with the effect being more pronounced in racial/ethnic minority communities. These findings underscore the need for targeted public health interventions that address underlying social determinants of health (e.g., access to education) to reduce firearm violence. Future research should further explore the intersection of social vulnerability and racial/ethnic composition to develop effective prevention strategies.
Ultrasound-guided intra-tumoral administration of directly-injected therapies: a review of the technical and logistical considerations
Authors: Bitar George Gabriel , Persad Melissa , Dragan Alina , Alade Adebayo , Jiménez-Labaig Pablo , Johnston Edward , Withey Samuel J , Fotiadis Nicos , Harrington Kevin J. , ap Dafydd Derfel 
Published: October 2024

Abstract
Background
Directly-injected therapies (DIT) include a broad range of agents within a developing research field in cancer immunotherapy, with encouraging clinical trial results in various tumour subtypes. Currently, the majority of such therapies are only available within clinical trials; however, more recently, talimogene laherparepvec (T-VEC, Imlygic) has been approved as the first oncolytic virus therapy in the USA and Europe. Our institution contributes to multiple different trials exploring the efficacy of DIT, the majority of which are performed by oncologists in clinic. However, specific, challenging cases – mainly neck tumours – require image-guided administration.

Main body
This review article addresses the technical and logistical factors relevant to the incorporation of image-guided DIT into an established ultrasound service. Image-guidance (usually with ultrasound) is frequently needed for certain targets that cannot be palpated or are in high-risk locations, e.g. adjacent to blood vessels. A multi-disciplinary approach is essential to facilitate a safe and efficient service, including careful case-selection. Certain protocols and guidance need to be followed when incorporating such a service into an established ultrasound practice to enhance efficiency and optimise safety. Key learning points are drawn from the literature and from our early experience at a tertiary cancer centre following image guided DIT for an initial cohort of 22 patients (including 11 with a neck mass), addressing trial protocols, pre-procedure work-up, organisation, planning, consent, technical aspects, procedure tolerability, technical success, and post-procedure considerations.

Conclusion
With appropriate planning and coordination, and application of the learning points discussed herein, image-guided administration of DIT can be safely and efficiently incorporated into an established procedural ultrasound list. This has relevance to cancer centres, radiology departments, individual radiologists, and other team members with a future role in meeting the emerging need for these procedures. This paper provides advice on developing such an imaging service, and offers certain insights into the evolving remit of radiologists within cancer care in the near future.
Differentiation of pathological subtypes and Ki-67 and TTF-1 expression by dual-energy CT (DECT) volumetric quantitative analysis in non-small cell lung cancer
Authors: Wu Yuting , Li Jingxu , Ding Li , Huang Jianbin , Chen Mingwang , Li Xiaomei , Qin Xiang , Huang Lisheng , Chen Zhao , Xu Yikai , Yan Chenggong 
Published: October 2024

Abstract
Background
To explore the value of dual-energy computed tomography (DECT) in differentiating pathological subtypes and the expression of immunohistochemical markers Ki-67 and thyroid transcription factor 1 (TTF-1) in patients with non-small cell lung cancer (NSCLC).

Methods
Between July 2022 and May 2024, patients suspected of lung cancer who underwent two-phase contrast-enhanced DECT were prospectively recruited. Whole-tumor volumetric and conventional spectral analysis were utilized to measure DECT parameters in the arterial and venous phase. The DECT parameters model, clinical-CT radiological features model, and combined prediction model were developed to discriminate pathological subtypes and predict Ki-67 or TTF-1 expression. Multivariate logistic regression analysis was used to identify independent predictors. The diagnostic efficacy was assessed by the area under the receiver operating characteristic curve (AUC) and compared using DeLong’s test.

Results
This study included 119 patients (92 males and 27 females; mean age, 63.0 ± 9.4 years) who was diagnosed with NSCLC. When applying the DECT parameters model to differentiate between adenocarcinoma and squamous cell carcinoma, ROC curve analysis indicated superior diagnostic performance for conventional spectral analysis over volumetric spectral analysis (AUC, 0.801 vs. 0.709). Volumetric spectral analysis exhibited higher diagnostic efficacy in predicting immunohistochemical markers compared to conventional spectral analysis (both P < 0.05). For Ki-67 and TTF-1 expression, the combined prediction model demonstrated optimal diagnostic performance with AUC of 0.943 and 0.967, respectively.

Conclusions
The combined predictive model based on volumetric quantitative analysis in DECT offers valuable information to discriminate immunohistochemical expression status, facilitating clinical decision-making for patients with NSCLC.
Sarcopenia in the foot on magnetic resonance imaging in patients with diabetes mellitus – a systematic review
Authors: Ahmad Manal , Mohamed Abdulla , Amiras Dimitri , Siracusa Francesca , Shalhoub Joseph , Davies Alun Huw 
Published: October 2024

Abstract
Introduction
Sarcopenia is defined by low measures of muscle quantity, quality and reduced physical performance. It is associated with higher levels of frailty. Individuals with diabetes mellitus (DM) undergo sarcopenia at an accelerated rate resulting in structural changes potentially culminating in limb loss.

Aims
To review the evidence on methods of detecting and measuring sarcopenic changes on magnetic resonance imaging (MRI) in the foot in patients with diabetes.

Methods
A literature review was conducted in accordance with PRISMA guidelines. We searched Embase and Medline (via Ovid), CINAHL (via Ebsco Host), Web of Science and Scopus as well as the grey literature. The MeSH terms “sarcopenia” AND “diabetes mellitus” AND “magnetic resonance imaging” were employed in the primary search string.

Results
874 studies were identified. 404 articles were excluded in the title and abstract screening. 33 studies were assessed for eligibility after abstract and title screening was completed by two reviewers. 7 studies evaluating sarcopenia in the foot were included in the final review.

Conclusion
Sarcopenic changes are evident on MRI of the foot in patients with diabetes and is profound in patients with diabetic neuropathy. The general extent and severity of sarcopenia seems to correlate with clinical scores to assess neuropathy and is implicated in the development of diabetic foot disease.
“Catch me if you can” - locating the “Black Sheep” neurons after early-life seizures
Authors: Tang Yingying , Guo Xiongfeng , Yan Mengqi , Xu Cenglin 
Published: October 2024

AbstractUnprovoked seizures in early life are one of the most severe conditions in pediatric neurology, and are often associated with long-lasting cognitive and behavioral deficits, as well as pharmacoresistant epilepsy in adulthood in some conditions. Unillustrated mechanisms greatly restrict the development of preventive strategies for early-life seizures (ELSs) related neuronal impairments. The recent groundbreaking study published in The Journal of Clinical Investigation represents a giant leap forward in understanding the complex pathogenesis mechanism and developing targeted therapies for ELS related neuronal impairments. The authors conducted elegant experiments to locate the activated pyramidal neuron subpopulation in the hippocampus and demonstrated the altered functions of (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors (AMPARs). And we believe that the conclusions of this study may assist in further translational efforts to identify preventive targets for neurological disorders associated with early life seizures and propose new avenues for further exploration in this field.
VvD14c-VvMAX2-VvLOB/VvLBD19 module is involved in the strigolactone-mediated regulation of grapevine root architecture
Authors: Xu Yan , Lv Zhengxin , Manzoor Muhammad Aamir , Song Linhong , Wang Maosen , Wang Lei , Wang Shiping , Zhang Caixi , Jiu Songtao 
Published: October 2024

AbstractThe D14 protein, an alpha/beta hydrolase, is a key receptor in the strigolactone (SL) signaling pathway. However, the response of VvD14 to SL signals and its role in grapevine root architecture formation remain unclear. This study demonstrated that VvD14c was highly expressed in grapevine tissues and fruit stages than other VvD14 isoforms. Application of GR24, an SL analog, enhanced the elongation and diameter of adventitious roots but inhibited the elongation and density of lateral roots (LRs) and increased VvD14c expression. Additionally, GR24 is nested within the VvD14c pocket and strongly bound to the VvD14c protein, with an affinity of 5.65 × 10−9 M. Furthermore, VvD14c interacted with grapevine MORE AXILLARY GROWTH 2 (VvMAX2) in a GR24-dependent manner. Overexpression of VvD14c in the d14 mutant and VvMAX2 in the max2 Arabidopsis mutant reversed the increased LR number and density, as well as primary root elongation. Conversely, homologous overexpression of VvD14c and VvMAX2 resulted in reduced LR number and density in grapevines. VvMAX2 directly interacted with LATERAL ORGAN BOUNDARY (VvLOB) and VvLBD19, thereby positively regulating LR density. These findings highlight the role of SLs in regulating grapevine root architecture, potentially via the VvD14c-VvMAX2-VvLOB/VvLBD19 module, providing new insights into the regulation of root growth and development in grapevines.
Outcomes of ST-Segment Elevation Myocardial Infarction in Patients With Adrenal Insufficiency
Authors: Abdallah Nadhem , Mohamoud Abdilahi , Ismayl Mahmoud , Aronow Herbert D , Abdallah Meriam , Goldsweig Andrew M 
Published: October 2024

Abstract

Context
Patients with adrenal insufficiency (AI) have both increased risk of cardiovascular disease and adverse outcomes with many medical emergencies. However, limited data exist specifically regarding ST-segment elevation myocardial infarction (STEMI) in the context of AI.

Objective
To evaluate associations between AI and in-hospital outcomes of patients with STEMI.

Methods
Admissions for STEMI were identified in the 2016-2019 National Inpatient Sample. In-hospital outcomes were compared between patients with and without AI. The primary outcome was in-hospital mortality. Secondary outcomes included percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), intervention, acute kidney injury (AKI), vasopressor use, mechanical circulatory support (MCS), mechanical ventilation, ventricular tachycardia (VT), hospital length of stay (LOS), and total charges. Multivariable regression models were used to adjust for potential confounders.

Results
Among 690 430 STEMI hospitalizations, 1382 (0.2%) had a diagnosis of AI. AI was associated with higher odds of in-hospital mortality (adjusted OR [aOR] 1.51, 95% CI 1.03-2.2), lower odds of PCI (aOR 0.73, 95% CI 0.55-0.98), higher odds of CABG (aOR 2.8, 95% CI 1.89-4.2) and, AKI (aOR 2.38, 95% CI 1.72-3.3), VT (aOR 1.55, 95% CI 1.1-2.2), need for vasopressors (aOR 2.34, 95% CI 1.33-4.1), mechanical ventilation (aOR 2.11, 95% CI 1.54-2.89), and MCS (aOR 2.18, 95% CI 1.57-3.03). Patients with AI also had a longer LOS (10 days vs 4.2 days, P &lt; .001) and higher charges ($258 475 vs $115 505, P &lt; .001).

Conclusion
Patients with AI admitted for STEMI had higher in-hospital mortality, nonfatal adverse outcomes, and resource utilization than patients without AI.
On Discrete Subproblems in Integer Optimal Control with Total Variation Regularization in Two Dimensions
Authors: Manns Paul , Severitt Marvin 
Published: October 2024

We analyze integer linear programs that we obtain after discretizing two-dimensional subproblems arising from a trust-region algorithm for mixed integer optimal control problems with total variation regularization. We discuss NP-hardness of the discretized problems and the connection to graph-based problems. We show that the underlying polyhedron exhibits structural restrictions in its vertices with regard to which variables can attain fractional values at the same time. Based on this property, we derive cutting planes by employing a relation to shortest-path and minimum bisection problems. We propose a branching rule and a primal heuristic which improves previously found feasible points. We validate the proposed tools with a numerical benchmark in a standard integer programming solver. We observe a significant speedup for medium-sized problems. Our results give hints for scaling toward larger instances in the future. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms–Discrete. Funding: This work was supported by the Deutsche Forschungsgemeinschaft [Grant MA 10080/2-1]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2024.0680 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2024.0680 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .