bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of clinics offering non-traditional Lyme disease therapies in Lyme endemic states of the US
Authors: Sakizadeh Jason R , Rothenberger Meghan K , Alpern Jonathan D 
Published: January 2025

Abstract
In this cross-sectional analysis, we analyzed 117 US clinics in Lyme endemic states that provide non-traditional care for Lyme disease. We found that unproven therapies are routinely offered, and some therapies raise safety concerns. The cost of care can be high, which may lead to significant out-of-pocket expenditures for patients.
Strategic tips to successfully undertake research: a comprehensive roadmap for medical trainees
Authors: Akefe Isaac Oluwatobi , Adegoke Victoria Aderonke , Akefe Elijah 
Published: January 2025

Abstract
Engaging in research during medical training is crucial for fostering critical thinking, enhancing clinical skills, and deepening understanding of medical science. Despite its importance, the shortage of physician-scientists lingers with many trainees and junior doctors encountering challenges navigating the research process. Drawing on current literature, this article provides a comprehensive roadmap, categorising 12 actionable strategies into five themes, to help medical trainees overcome common obstacles and optimise their research experience. The strategies include early planning, research conduct and integrity, productivity and time management, collaboration and dissemination, and personal growth and development. By implementing these evidence-based recommendations, derived from current literature and expert insights, medical trainees can refine their research skills, produce high-quality outputs, and contribute meaningfully to the scientific community, ultimately enriching their medical training and future careers.
What Factors Inform Decisions about Where to Submit High-Quality Scholarship? A National Sample of Social Work Faculty Share Their Perspectives
Authors: Hodge David R , Yu Mansoo 
Published: January 2025

Abstract
Social work journals are essential repositories of the profession’s disciplinary knowledge, but some commentators suggest social work faculty may prioritize sending their best work to extradisciplinary journals. This mixed-methods study examined the propensity of faculty to submit their scholarship to disciplinary rather than extradisciplinary periodicals, and the factors or rationales that informed their respective decisions. To conduct this cross-sectional investigation, a national sample of tenure-track faculty (N = 270) affiliated with PhD conferring programs was employed. In addition to computing descriptive analyses, qualitative analysis was used to understand the factors that contribute to the selection of either disciplinary or extradisciplinary outlets. Among the 29% of faculty who prioritized sending their high-quality work to social work periodicals, the key themes that informed the selection process included goodness of fit with a journal’s aims and readership; a desire to support social work knowledge; and a journal’s impact factor, reputation, and overall publishing speed. For the 70% who prioritized extradisciplinary periodicals, the themes were goodness of fit with a journal’s aims and readership, impact factor, reputation, the quality of the reviews, increased rigor, and more extensive indexing. The findings raise important questions about the future of the profession’s knowledge base.
Prevalence of Pulmonary Embolism in COVID-19 Positive Critically Ill Children
Authors: Fonseca Yudy , Davies Alise , Jarrin Stephanie , Simon Liliana , Foster Cortney , Kai Sun , Bhutta Adnan 
Published: January 2025

OBJECTIVES:
To investigate the prevalence of pulmonary embolism (PE) in children admitted to critical care diagnosed with COVID-19 infection.

DESIGN:
Retrospective database study.

SETTING:
Data reported to the Virtual Pediatric Systems, 2018–2021.

PATIENTS:
Patients 28 days to younger than 18 years old, admitted to a PICU with either PE or COVID-19 diagnoses.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Among the PE-positive subgroups, from January 2020 to December 2021, 78 patients (14%) had an acute COVID-19 infection. The prevalence of PE pre-pandemic period (2018–2019) was 0.19% and for pandemic period (2020–2021) was 0.26% (p < 0.001). During the pandemic period, the prevalence of PE for COVID-negative patients was 0.21% and for COVID-positive patients was 1.01% (p < 0.001). The result shows that the chance to develop PE for COVID-positive patients is 4.8 times that for COVID-negative patients during the pandemic. In the subgroup of the PE-positive patients, 55.1% were Black or African American in the COVID-positive group and 19% in the COVID-negative group (p < 0.001). A multivariable logistic regression showed that race was an independent risk factor for COVID in PE-positive patients.

CONCLUSIONS:
Our study demonstrates a significant increase in the prevalence of PE among pediatric patients admitted to PICUs during the COVID-19 pandemic compared with pre-pandemic. Our study indicates that COVID-positive patients are 4.8 times more likely to develop PE than COVID-negative patients. Additionally, the study highlights substantial racial disparities in the prevalence of PE, with Black or African American patients being disproportionately affected.
Neuroprotective effects of hypidone hydrochloride (YL-0919) after traumatic brain injury in mice
Authors: Zhang Yue , Bai Yafan , Hou Xiaojuan , Yang Yixin , Ma Hui , Wang Guyan , Li Yunfeng 
Published: January 2025

Abstract

Background:
Neurological dysfunction is a common complication of traumatic brain injury (TBI), and early treatments are critical for the long-term prognosis. This study aimed to investigate whether hypidone hydrochloride (YL-0919) improves neurological function impairment in mice with TBI.

Methods:
TBI was induced in adult male C57BL/6J mice using the controlled cortical impact (CCI) method. First, the modified neurological severity score (mNSS), rotarod test, and Morris water maze (MWM) test were conducted to assess the impact of YL-0919 on neurological function in mice with TBI. Next, immunofluorescence and laser speckle contrast imaging were utilized to measure the number and activation of microglia and cerebral blood flow (CBF) after TBI. Enzyme-linked immunosorbent assays (ELISAs) were employed to assess the inflammatory factors. Finally, Western blotting was performed to measure the expression of proteins. Golgi–Cox staining was utilized to investigate the structure of pyramidal neurons.

Results:
YL-0919 significantly alleviated neurological dysfunction in TBI+YL-0919 mice compared with TBI+Vehicle mice, increased the time spent on the rotarod (F = 1.297, P <0.05), and partially relieved cognitive dysfunction in TBI mice (for mNSS, F = 5.540, P <0.01; for MWM test, F = 30.78, P <0.05). Additionally, YL-0919 effectively inhibited the proliferation and activation of microglia (both P <0.01), promoted the recovery of CBF around the brain injury site and inhibited the expression of tumor necrosis factor-α (F = 9.142, P <0.05) and IL-1β (F = 4.662, P <0.05), and increased the concentration of IL-4 (F = 5.172, P <0.05). Furthermore, continuous gavage of YL-0919 (2.5 mg/kg) for seven days effectively increased the protein expression of brain-derived neurotrophic factor (BDNF), promoted the phosphorylation of mammalian target of rapamycin (mTOR), increased postsynaptic density protein 95 (PSD95) and synapsin1 levels, and increased the neuronal dendritic complexity and the dendritic spine density around the brain injury site (all P <0.05).

Conclusions:
Our findings indicated that YL-0919 can ameliorate neurological dysfunction in mice after TBI through the suppression of inflammation and the stimulation of the BDNF-mTOR signaling pathway. These findings provide an insightful perspective on the potential pharmacological mechanism involved in the neuroprotective effect of YL-0919.
Unraveling the chains: Exploring the impact of ownership on administrator turnover in nursing homes
Authors: Pradhan Rohit , Ghiasi Akbar , Orewa Gregory , Gupta Shivani , Weech-Maldonado Robert 
Published: January 2025

Background
Leadership instability in nursing homes marked by high administrator turnover threatens the well-being of vulnerable residents. Although numerous factors have been implicated, the role of ownership remains unexplored.

Purposes
Based upon the tenets from institutional theory and strategic management theory, the primary goal of this study was to examine the impact of ownership on administrator turnover.

Methodology/Approach
Data were derived from different sources: LTCFocus.org, Nursing Home Five-Star Quality Rating System, and Area Health Resources Files (2021–2022). The dependent variable was administrator turnover categorized as follows: 0 = no administrators left, 1 = one administrator left, and 2 = two or more administrators left. The primary independent variable was ownership/chain affiliation categorized as four possible interactions of for-profit (FP) status and chain affiliation: not-for-profit (NFP) independent, FP independent, NFP chain, and FP chain. An ordinal logistic regression model was used, and predicted turnover probabilities were calculated across the four ownership categories.

Results
The primary hypothesis was supported and compared to NFP independent, FP chain, FP independent, and NFP chain nursing homes that exhibited approximately 2.3, 1.7, and 1.4 times higher odds of administrator turnover. Predicted probabilities confirmed these trends: FP chain nursing homes had the lowest retention, with a 42% probability of no turnover, 32% for one administrator leaving, and 26% for two or more leaving. In contrast, NFP independent facilities had the highest retention rates, with a 62% chance of no turnover, 25% for one leaving, and 13% for two or more. Differences between groups were statistically significant (p < .001).

Conclusion
FP chain ownership was associated with the highest administrator turnover rates, whereas NFP facilities experienced the lowest. FP independent and NFP chain homes had intermediate probabilities of administrator turnover.

Practice Implications
Tailoring management strategies to the specific ownership structure may reduce administrator turnover and ensure consistent resident care.
Multicentric Castleman’s Disease presenting with bilateral panuveitis
Authors: Murta Afonso , Mota Catarina , Cunha Bruna , Alves Nuno Rodrigues , Saunders Christopher , Pinheiro Sofia , Costa Lívio , Anjos Rita 
Published: January 2025

Purpose:
To report a rare case of Multicentric Castleman’s Disease presenting with bilateral panuveitis.

Methods:
Case report.

Results:
A 65-years-old caucasian man presented with progressive blurred vision in both eyes for two weeks, along with weight loss, polyarthralgias and reduced muscle strength persisting for about a year. Examination revealed bilateral panuveitis after intraocular lymphoma being initially considered. CT scans showed multiple lymph node enlargements suggestive of lymphoproliferative disorder. Excisional biopsy of an axillary lymph node confirmed the diagnosis of plasmacytic type Castleman’s disease. Treatment was started with topical dexamethasone and tropicamide for anterior chamber inflammation, followed by oral prednisolone. After definitive diagnosis, treatment with siltuximab was initiated, which led to significant improvement in panuveitis and systemic symptoms. The patient became off corticosteroids and continued on siltuximab with stable visual acuity and low-grade vitritis.

Conclusion:
To the best of our knowledge we described the first case in which the diagnosis of Multicentric Castleman’s Disease was established through the investigation of bilateral panuveitis, which was successfully managed with corticosteroids and siltuximab.
Outcomes and challenges in adolescents living with HIV in France: a nationwide cohort study over 35 years (1985-2020)
Authors: Dollfus Catherine , Chenadec Jérôme LE , Reliquet Véronique , Alby-Laurent Fanny , Brehin Camille , Caseris Marion , Runel-Belliard Camille , Blanche Stéphane , Warszawski Josiane , Faye Albert , Frange Pierre 
Published: January 2025

Objective:
Most data published on adolescents living with HIV (ALH) have been collected before the large diffusion of second-generation integrase strand transfer inhibitors (INSTI) among the pediatric population. We analyzed the nationwide ANRS-MIE CO10 Pediatric cohort to assess the changes over time in health and social outcomes of French ALH.

Design:
The cohort enrolled children born in France since 1985 and, from 2005, children diagnosed with HIV at ≤13 years, including those born abroad if antiretroviral-naive at first medical care in France.

Methods:
Adolescents aged ≥10 years at their last visit were included in this analysis. Their characteristics were compared between three periods of birth (1985-1993, 1994–1999, 2000–2010).

Results:
Overall, 529 ALH were included. Their median age at first HAART initiation decreased from 94 to 29 months (p < 0·0001). At the last evaluation, the proportions of ALH receiving HAART, receiving INSTI, having HIV-RNA < 50 copies/mL and having CD4 count ≥500/μL increased over time (p < 0.0001), reaching 98·7%, 53·3%, 81·3% and 85·0%, respectively, for those born in 2000–2010. The proportion of maternal and paternal orphans decreased until 14·4% and 11·0%, respectively, for ALH born recently. Compared to middle adolescents (15–17 years) born in 1994–1999, those born in 2000–2010 demonstrated higher academic success (69·2% versus 42·3%) and less frequent academic failure (4·6% versus 6·2%).

Conclusions:
Despite spectacular improvement in their health and immunovirological status, ALH remain vulnerable compared to other French adolescents, with a higher risk of being orphan and/or experiencing academic failure. Specific interventions are required to improve their global quality of life.
Three-dimensional Finite Element Analysis of Implant Prosthesis After Mandibular Reconstruction by Upper Distal Free Double-Barrel Fibula
Authors: Su Ming , Wu Shifeng , Sun Haibin , Yang Yang , Xu Ning , Han Zhengxue 
Published: January 2025

Objective:
This study aimed to compare the biomechanics of implant prostheses and peri-implant bone among 6 different mandibular reconstruction models based on patient data involving the use of an upper free-end double-barrel fibula.

Methods:
This study was an observational study. Five models were reconstructed using fibular-supported and implant-supported partial dentures. Two of these models were double-barrel fibula models with different gaps between the upper and lower segments. The other 2 were single-layered fibular models (the fibula was placed at the inferior or superior mandibular borders). The fifth model was a double-barrel fibula with a free distal end on the upper segment. In addition, a typical mandibular model was created for comparison. Two fixed partial-denture models were used in this study. The von Mises stress and strain of the models were analyzed.

Results:
The maximum stress decreased with increasing gap between the upper and lower fibula. The distal free-end double-barrel fibula showed a potential to reduce the maximum stress around the implant apex while increasing it around the implant neck compared with a fixed distal-end double-barrel fibula.

Conclusions:
Utilizing a free distal end on the upper fibula may be a viable option for mandibular reconstruction, especially when the fibula length is limited.
Single-cell transcriptomics-guided development of flow cytometric tests predicting chronic myeloid leukemia blast crisis transformation at chronic phase diagnosis
Authors: Yu Mengge , Krishnan Vaidehi , Shyamsundar Pavithra , Lee Kian Leong , Schmidt Florian , Ren Xi , Chuah Charles , Prabhakar Shyam , Saunders Verity , Yeung David , Shanmuganathan Naranie , Yong Agnes S.M. , Hughes Timothy P. , Ong S. Tiong 
Published: January 2025

AbstractClinical risk scores in chronic myeloid leukemia (CML) are inadequate for identifying chronic phase (CP) patients at high-risk of blast crisis (BC) progression. The lack of accurate predictive tests hamper timely interventions, including stem cell transplants, that are more effective in early disease. By interrogating a single cell atlas of primary imatinib resistance for a BC-like gene expression signature, we identify aberrant CD42A+megakaryocytic and CD10+CD19+lymphoid progenitor expansion, as well as STAT1- and IFNγ-related inflammatory programs, as consistent features in the bone marrow and peripheral blood of CP patients at high-risk of BC transformation. We develop multi-color flow cytometry-based tests (MFC) to detect these features in CP patients at the time of diagnosis. Validating our MFC panels on a combined Australia-Singapore cohort comprising 28 CP patients, including 14 who underwent transformation, we demonstrate their ability to detect 100% of CP patients who transform with no false positives. Our findings highlight small populations of inflamed hematopoietic stem and progenitor cells, present at CP diagnosis, as powerful harbingers of future BC transformation. The ability of MFC panels to detect these cells at diagnosis support their inclusion as accurate risk-assessment tools to improve management of high-risk patients.
Inhibition of EMT driver PTK6 enhances anti-tumor immune responses against triple-negative breast cancer
Authors: Harada Ibuki , Martinez Criseyda , Ito Koichi , Lee Eunjee , Zhu Jun , Irie Hanna Y 
Published: January 2025

ABSTRACTThe non-receptor tyrosine kinase PTK6 is expressed in 70% of triple negative breast cancers (TNBC) and is an oncogenic driver of epithelial-mesenchymal transition (EMT). EMT promotes metastasis and immune evasion of TNBC. Therefore, targeting EMT drivers could reverse these properties and lead to more favorable outcomes. Treatment of TNBC tumors with a small molecule inhibitor of PTK6 kinase (P21d) suppressed their growthin vivo. Tumor inhibition by P21d is dependent on an induced immune response because: 1) inhibition is observed in immunocompetent, but not immunodeficient, mice; 2) P21d increases tumor-infiltrating CD8+T and NK cells and decreases immunosuppressive myeloid-derived suppressor cells; and 3) tumor inhibition by P21d is abrogated by co-treatment with NK or CD8+T cell-depleting antibodies. These effects on tumor growth and cytotoxic TILs are phenocopied by the knockdown of tumoral PTK6 or SNAIL, which supports EMT inhibition as a mechanism for enhanced anti-tumor immune response. RNA sequencing (RNA-seq) profiling of P21d-treated tumors also revealed changes consistent with activation of the immune response and identified CXCL10 as a critical chemokine induced intratumorally by P21d that promotes recruitment of NK/CD8+ T cells to the tumor site, leading to tumor growth inhibition. Our study highlights the novel tumor immune microenvironmental functions of PTK6 with important consequences for tumor growth that could lead to new immunotherapeutic approaches for TNBC.
Simultaneous Targeting of KRAS and CDK4 Synergistically Suppresses Pancreatic Cancer Cells
Authors: Paulsohn Maj-Britt , Frahnert Klara Henrike , Fang Xin , Schneider Carolin , Tapia Contreras Constanza , Schneider Günter , Hessmann Elisabeth , Dobbelstein Matthias 
Published: January 2025

ABSTRACTMutant Ras oncoproteins, particularly KRAS, are among the most prevalent drivers of cancer. Small-molecule inhibitors of KRAS have been developed, bearing high potential for cancer therapy but considerable risk of resistance development. To avoid cancer cell adaptation, effective combinatorial partners for increasing immediate efficacy remain to be explored. Here, we demonstrate that combining the KRAS inhibitor Sotorasib with the CDK4/6 inhibitor Palbociclib synergistically eliminates pancreatic ductal adenocarcinoma (PDAC) cells and organoids harboring KRAS G12C mutations. This synergy was particularly pronounced after drug washout, indicating a durable impact. Similar effects were observed in non-small-cell lung cancer (NSCLC) cells. Additionally, MRTX1133, a KRAS G12D inhibitor, synergized with Palbociclib to suppress KRAS G12D-mutant PDAC-derived cells. Mechanistically, these combinations induced sustained cell cycle arrest through reduced RB phosphorylation, decreased E2F1 levels, and increased CDKN1B/p27 expression. Deletion of CDKN1B largely rescued tumor cell proliferation, underscoring its critical role in mediating the observed synergy. These findings support the therapeutic potential of combining KRAS and CDK4/6 inhibitors for treating PDAC and other Ras-driven cancers.
Liver Lymphatic Dysfunction as a Driver of Fibrosis and Cirrhosis Progression
Authors: Jeong Jain , Hsu Shao-Jung , Horikami Daiki , Utsumi Teruo , Yang Yilin , Arefyev Nikolai , Zhang Xuchen , Cai Shi-Ying , Boyer James L. , Garcia-Milan Rolando , Tanaka Masatake , McConnell Matthew J. , Huang Hui-Chun , Iwakiri Yasuko 
Published: January 2025

AbstractThe liver lymphatic system plays a critical role in maintaining interstitial fluid balance and immune regulation. Efficient lymphatic drainage is essential for liver homeostasis, but its role in liver disease progression remains poorly understood. In cirrhosis, lymphangiogenesis initially compensates for increased lymph production, but impaired lymphatic drainage in advanced stages may lead to complications such as ascites and portal hypertension. This study aimed to evaluate how liver lymphatic dysfunction affects disease progression and to assess therapeutic strategies. Using a surgical model to block liver lymphatic outflow, we found that impaired drainage accelerates liver injury, fibrosis, and immune cell infiltration, even in healthy livers. Mechanistically, enhanced TGF-β signaling in liver lymphatic endothelial cells (LyECs) contributed to reduced lymphatic vessel (LV) density and function in late-stage decompensated cirrhosis. This dysfunction was linked to the progression from compensated to decompensated cirrhosis, particularly in patients with primary sclerosing cholangitis (PSC). Conversely, liver-specific overexpression of VEGF-C via AAV8 improved lymphatic drainage, restored LV density, reduced fibrosis, mitigated liver injury, and alleviated portal hypertension in cirrhotic rats. These findings establish impaired liver lymphatic function as a pivotal driver of cirrhosis progression and identify VEGF-C as a promising therapeutic target to prevent decompensation.
Tissue-dependent mechanosensing by cells derived from human tumors
Authors: Parihar Kshitiz , Nukpezah Jonathan , Iwamoto Daniel V , Cruz Katrina , Byfield Fitzroy J , Chin LiKang , Murray Maria E , Mendez Melissa G , van Oosten Anne S , Herrmann Anne , Charrier Elisabeth E , Galie Peter A , Donlick Megan , Lee Tongkeun , Janmey Paul A , Radhakrishnan Ravi 
Published: January 2025

AbstractAlterations of the extracellular matrix (ECM), including both mechanical (such as stiffening of the ECM) and chemical (such as variation of adhesion proteins and deposition of hyaluronic acid (HA)) changes, in malignant tissues have been shown to mediate tumor progression. To survey how cells from different tissue types respond to various changes in ECM mechanics and composition, we measured physical characteristics (adherent area, shape, cell stiffness, and cell speed) of 25 cancer and 5 non-tumorigenic cell lines on 7 different substrate conditions. Our results indicate substantial heterogeneity in how cell mechanics changes within and across tissue types in response to mechanosensitive and chemosensitive changes in ECM. The analysis also underscores the role of HA in ECM with some cell lines showing changes in cell mechanics in response to presence of HA in soft substrate that are similar to those observed on stiff substrate. This pan-cancer investigation also highlights the importance of tissue-type and cell line specificity for inferences made based on comparison between physical properties of cancer and normal cells. Lastly, using unsupervised machine learning, we identify phenotypic classes that characterize the physical plasticity, i.e. the distribution of physical feature values attainable, of a particular cell type in response to different ECM-based conditions.