bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative chemo-CIRT in Re/BRe pancreatic cancer: Insights from a multicenter prospective phase II clinical study (NCT03822936)
Authors: Barcellini Amelia , Molinelli Silvia , Vanoli Alessandro , Vitolo Viviana , Fossati Piero , Vai Alessandro , Pagani Anna , Inzani Frediano , Pecorilla Mattia , Butturini Giovanni , Klersy Catherine , Preda Lorenzo , Facoetti Angelica , Valvo Francesca , Orlandi Ester 
Published: October 2024

Purpose: There is debate about the optimal management of borderline resectable (bRe) and resectable (Re) pancreatic ductal adenocarcinoma (PDAC). Both preclinical and clinical evidence showed that carbon ion radiotherapy (CIRT) produces superior control on radioresistant histologies compared to conventional photon beam radiotherapy (RT). However, so far there is a lack of data concerning the integration of CIRT in a multimodal approach with chemotherapy and surgery for bRe/Re. Methods: We recently presented the first analysis of a multicenter prospective phase II clinical study aimed at assessing the feasibility and effectiveness of a neoadjuvant chemotherapy + short course of CIRT followed by surgery and adjuvant chemotherapy in the management of bRe/Re PDAC. The study was terminated early due to low patient enrollment.Herein, we reported a post-hoc analysis focusing on toxicity, dosimetry and translational assessment. Results: In our experience, CIRT can be integrated into a multimodal treatment strategy for bRe/Re PDAC, alongside chemotherapy and surgery. A case of fatal liver failure occurring three months post-surgery has been documented, likely related to the combination approach. Although the treatment plans were satisfactory according to the Local Effect Model (LEM) model, recalculations using the modified Microdosimetric Kinetic Model (mMKM) revealed suboptimal target coverage. Additionally, we observed an increased expression of PD-L1 following CIRT. Conclusions: This multimodal approach was well tolerated; however, clinicians should carefully monitor for vascular disorders during follow-up and further investigate surgical techniques after CIRT. The increased PD-L1 expression supports the immunogenic effects of particle therapy and lays the groundwork for future studies. To enhance the therapeutic ratio of CIRT treatments, integrating LET-d based objectives into the plan optimization process should be considered. Trial Registration Number: ClinicalTrials.gov Identifier: NCT03822936
Clinical features of tularemia in cats: a retrospective study from 2000 to 2021
Authors: Nikpour Hoda , Hung Chien-Che , Lanka Saraswathi , Barger Anne M , Reinhart Jennifer M 
Published: October 2024

Objectives The objectives of this study were to describe the clinical features of cats diagnosed with tularemia, and to compare the clinical features of cats with and without tularemia and identify characteristics increasing the likelihood of a tularemia diagnosis. Methods Diagnostic laboratory data and medical records were retrospectively reviewed of cats tested for tularemia between 2000 and 2021. Clinical features including signalment, presenting complaint(s), physical examination findings and clinicopathologic data were described for cats with tularemia diagnosed by culture and/or PCR. Clinical features were also compared between PCR+ vs PCR− cats and logistic regression was used to identify features that predicted PCR+ status. Results A total of 18 cats were diagnosed with tularemia. The affected cats had a mean age of 5.8 ± 4.9 years, with a slight male predominance. Most were domestic shorthair cats and had outdoor access. Common presenting complaints included lethargy and anorexia, while physical examination findings frequently revealed fever, peripheral lymphadenomegaly and oral ulcers. Laboratory findings varied, with notable abnormalities including neutrophilic inflammation observed on cytology and widespread acute systemic pathologic changes in necropsy results. Leukopenia and neutropenia were more common in PCR+ vs PCR− cats, and these factors were 7.4 times (confidence interval [CI] 1.2–62.3) and 10.0 times (CI 1.4–83.2) more likely to occur in PCR+ vs PCR− cats, respectively. There were no significant differences between the groups in other parameters including anemia, thrombocytopenia, band neutrophilia and hyperbilirubinemia. Conclusions and relevance This study provides a more comprehensive description of tularemia in cats than has been available to date. In particular, leukopenia and neutropenia are significantly associated with tularemia-positive cats. These clinical features should be considered and raise suspicion for tularemia in cats. These findings may be valuable for the timely diagnosis, treatment and prevention of tularemia outbreaks in cats and humans.
A Review of the Effectiveness and Safety of Catheter-Directed Thrombolysis for Venous Thromboembolism
Authors: Xiang Sai , Wang Xiaodong 
Published: October 2024

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity, mortality, and elevated healthcare costs. Between 20% and 50% of patients with lower extremity deep vein thrombosis will develop an advanced complication called post-thrombotic syndrome (PTS) within 2 years. Early mortality rates for DVT and acute high-risk pulmonary embolism are 3.8% and 38.9%, respectively. Additionally, PE is the most common and preventable cause of in-hospital death. Early removal of thrombus and improvement of vascular function can reduce the incidence of serious complications and mortality. Catheter-directed thrombolysis (CDT) involves the placement of a thrombolytic catheter into a venous thrombus, allowing the thrombolytic drug to act directly on the thrombus. Compared to conventional anticoagulation, CDT removes thrombus more rapidly, thereby enhancing venous function in the lower extremities and reducing pulmonary artery pressure. Compared to systemic thrombolytic therapy, CDT is safer, and complications from the procedure are uncommon. However, the risk of bleeding is slightly higher with CDT than with anticoagulation alone. In this review, we will discuss the pathophysiology of VTE and the technical advancements in CDT. We will also examine a selection of notable studies on CDT for the treatment of DVT in the lower extremities and PE in recent years, with the aim of integrating the findings. Clinical Impact Catheter-directed thrombolysis reduces the thrombolytic time and dose of thrombolytic drugs without affecting the thrombolytic effect to ensure that bleeding does not occur. This helps clinicians choose safer CDT treatments for their patients. We combine the historical process of catheter-directed thrombolytic therapy for VTE and prospect the future development of CDT.
Clinical and Radiological Outcomes After Isolated Double-Bundle Medial Patellofemoral Ligament Reconstruction: A 5-Year Analysis
Authors: Hong Sung-Yup , Kim Seounghyeon , Lee Hyo-Beom , Song Won-Ho , Kim Jeehyoung , Seo Young-Jin , Song Si Young 
Published: October 2024

Background: There are few studies that have examined clinical and radiological outcomes at 5 years after isolated medial patellofemoral ligament (MPFL) reconstruction. To date, midterm outcomes after isolated double-bundle (DB) MPFL reconstruction are not well known. Hypothesis: Isolated DB MPFL reconstruction using a patellar suture anchor technique would lead to improved functional scores and radiological findings, and these improvements would remain stable over the 5-year postoperative period. Study Design: Case series; Level of evidence, 4. Methods: Isolated MPFL reconstruction was performed in patients with recurrent patellar instability between March 2013 and February 2017. Clinical and functional evaluations were performed via an interview using the Kujala, Lysholm, and Tegner scores preoperatively and at 6, 12, 24, and 60 months postoperatively. Radiographs were taken preoperatively, immediately postoperatively, and at 24 and 60 months after surgery. Radiographic assessments included measuring the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle. Results: A total of 31 patients (31 knees) underwent isolated MPFL reconstruction; 4 patients did not complete 5-year follow-up, and thus, 27 patients (27 knees) were enrolled in the study. The mean age at the time of surgery was 22.0 ± 6.4 years (range, 14-32 years). All clinical and functional scores significantly improved in the first 2 years ( P < .001), with the mean Kujala, Lysholm, and Tegner scores improving from 52.7 to 90.7, 49.6 to 92.7, and 2.9 to 5.1, respectively. There was no significant difference in scores between 2- and 5-year follow-up. All radiographic parameters significantly improved between preoperatively and immediately postoperatively ( P < .001), with mean values for the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle improving from 1.7° to 1.6°, 5.7° to −6.6°, and 3.0° to 5.9°, respectively. No significant differences were observed in radiographic measurements between the postoperative time points. No patients experienced a patellar redislocation or fracture. Conclusion: The prospective analysis of isolated DB MPFL reconstruction at 5-year follow-up showed that clinical and radiological outcomes significantly improved postoperatively and were maintained to 5 years. These midterm results suggest that isolated DB MPFL reconstruction is an effective treatment option for patients with patellar instability.
Family leadership and CSR decoupling: Founder–descendant differences in socioemotional wealth
Authors: Park Sang-Bum 
Published: October 2024

Founders of family firms differ from descendants, particularly in terms of affective attachment, cognitive identification, and social concern. This study examines how these generational differences between founder-led and descendant-led family firms affect corporate social responsibility (CSR) decoupling, which is the gap between stated CSR policies on paper and their actual implementation in practice. While decoupling may yield economic benefits by saving on implementation costs if concealed, it can damage socioemotional wealth if revealed. The findings, based on a sample of 3,576 firm-year observations from large firms in the United States, demonstrate that the relationship between family ownership and CSR decoupling is contingent upon family generation. Family ownership decreases CSR decoupling in founder family firms, while it increases CSR decoupling in descendant family firms. It indicates that family firms perceive the benefits and risks of CSR decoupling differently based on the generation of family leaders. JEL CLASSIFICATION: M14, G32, D22, L25
Incidental Gastrointestinal Stromal Tumors in Thoracic and Bariatric Surgery
Authors: Conrad Hope , June Ciara , Hamidi Mohammad , Rizvi Omar , Ghaderi Iman , Worrell Stephanie 
Published: October 2024

Background: Gastrointestinal stromal tumors (GISTs) are rare. This study aims to determine GIST rates in bariatric sleeve gastrectomy (SG) patients and esophageal cancer (EC) patients who receive esophagectomy. Methods: Retrospective review of an institution from 01/2022 to 03/2023 was performed. Incidental GIST rate was determined utilizing pathology reports. Results: One hundred thirteen patients were included (21% esophagectomy, 79% SG). Of EC patients, 21% had incidental GIST compared to 0 SG patients ( P < .01). All GIST patients had a secondary malignancy and 50% had a tertiary malignancy. Conclusions: Esophagectomy patients with EC had a significantly higher rate of incidental GIST compared to bariatric SG patients and general population.
Characteristics and Correlates of Health Information Literacy Among Patients With Type 2 Diabetes and Metabolic Syndrome: A Cross-Sectional Study
Authors: Wu Kailu , Wen Aichun , Jin Pina , Wang Xiaojing , Li Aihua , Dong Huan , Ji Meihua 
Published: October 2024

Purpose The purpose of the study was to examine the characteristics and the influential effect of individual and social contextual factors on health information literacy among Chinese patients with type 2 diabetes coexisting with metabolic syndrome. Methods Following convenience sampling, a total of 225 patients with type 2 diabetes coexisting with metabolic syndrome were recruited from a tertiary hospital in a suburban area of Beijing, China. Participants’ information was gathered through a set of self-reported questionnaires. Descriptive statistics, normality test, correlational analysis, univariate analysis, multiple linear regression, and logistic regression analysis were adopted to examine the potential factors of personal and social contextual resource related to health information literacy based on the health empowerment theory. Results The health information literacy in this current sample was limited, with a mean score of 16.83 ± 2.96. Correlational analysis showed that self-management knowledge, attitude, and practice for metabolic syndrome; self-efficacy; health problem-solving; resilience; and chronic illness resources were significantly and positively related to health information literacy. Logistic regression analysis showed that self-management knowledge, health problem-solving, and the chronic illness resources were significantly correlated with health information literacy after controlling covariates. Conclusions Overall, the health information literacy among Chinese patients with type 2 diabetes coexisting with metabolic syndrome is suboptimal. Study findings demonstrated that personal and social contextual resources factors are significantly related to health information literacy. Health care professionals should consider strategies to enhance people’s health information literacy level and promote individuals’ health problem-solving, enhance chronic illness resources, and improve self-management knowledge when developing tailored interventions.
Deciphering STAT3’s negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis
Authors: Chen Yurao , Zheng Zemao , Wang Luoshai , Chen Ronghuai , He Ming , Zhao Xiang , Jin Liyan , Yao Juan 
Published: October 2024

Abstract
Background
Esophageal Squamous Cell Carcinoma (ESCC) remains a predominant health concern in the world, characterized by high prevalence and mortality rates. Advances in single-cell transcriptomics have revolutionized cancer research by enabling a precise dissection of cellular and molecular diversity within tumors.

Objective
This study aims to elucidate the cellular dynamics and molecular mechanisms in ESCC, focusing on the transcriptional influence of STAT3 (Signal Transducer and Activator of Transcription 3) and its interaction with LHPP, thereby uncovering potential therapeutic targets.

Methods
Single-cell RNA sequencing was employed to analyze 44,206 cells from tumor and adjacent normal tissues of ESCC patients, identifying distinct cell types and their transcriptional shifts. We conducted differential gene expression analysis to assess changes within the tumor microenvironment (TME). Validation of key regulatory interactions was performed using qPCR in a cohort of 21 ESCC patients and further substantiated through experimental assays in ESCC cell lines.

Results
The study revealed critical alterations in cell composition and gene expression across identified cell populations, with a notable shift towards pro-tumorigenic states. A significant regulatory influence of STAT3 on LHPP was discovered, establishing a novel aspect of ESCC pathogenesis. Elevated levels of STAT3 and suppressed LHPP expression were validated in clinical samples. Functional assays confirmed that STAT3 directly represses LHPP at the promoter level, and disruption of this interaction by promoter mutations diminished STAT3's repressive effect.

Conclusion
This investigation underscores the central role of STAT3 as a regulator in ESCC, directly impacting LHPP expression and suggesting a regulatory loop crucial for tumor behavior. The insights gained from our comprehensive cellular and molecular analysis offer a deeper understanding of the dynamics within the ESCC microenvironment. These findings pave the way for targeted therapeutic interventions focusing on the STAT3-LHPP axis, providing a strategic approach to improve ESCC management and prognosis.
Academic orientation and alcohol-related harm among adolescents
Authors: Thor Siri , Landberg Jonas , Karlsson Patrik , Gripe Isabella 
Published: October 2024

Abstract
Background
This study aimed to examine the social gradient in self-reported alcohol-related harm (ARH) among young alcohol consumers by including a largely overlooked group of adolescents. We also explored the extent to which such a gradient could be attributed to differential exposure or differential vulnerability to risk factors.

Method
Cross-sectional survey of upper-secondary students (n = 2996) in Sweden. Negative binomial regressions estimated the relationship between academic orientation (higher education preparatory; HEP, vocational; VP and introductory; IP) and ARH. To assess the contribution of explanatory factors, we estimated models that included risk factors such as heavy episodic drinking (HED).

Results
A graded association was observed between academic orientation and ARH, with more ARH among students in IP (IRR = 1.79) and VP (IRR = 1.43) than in HEP. Adjustments for risk factors attenuated the estimates by approximately half, but there was still 14% more ARH in VP and 50% more in IP than in HEP. The additive interaction test indicated a positive and significant interaction for students in VP who engaged in HED, versus students in HEP, who did not.

Conclusion
The findings suggest a negative gradient in the association between academic orientation and ARH, where the students in IP experienced the highest levels of ARH. While differential exposure and vulnerability to HED account for a significant proportion of the excess risk among VP students, HED seems to be less important relative to other risk factors among IP students. More research is needed to identify the mechanisms underlying the elevated levels of ARH among the most disadvantaged group—students enrolled in IP.
Novel rapid molecular diagnosis methods for comprehensive genetic analysis of 21-hydroxylase deficiency
Authors: Xia Yanjie , Yu Feng , Bai Ying , Jiang Lili , Shi Panlai , Jiang Zhengwen , Kong Xiangdong 
Published: October 2024

Abstract
Background
Molecular analysis of the CYP21A2 gene is highly important for understanding the aetiology of 21-hydroxylase deficiency (21-OHD). The aim of this study was to use a novel approach named CNVplex, together with the SNaPshot assay and direct sequencing, to identify CYP21A2 mutations efficiently and comprehensively. Targeted CYP21A2 mutation analysis was performed in 113 patients and 226 parents. Large rearrangements of CYP21A2 were characterized by CNVplex; twenty prevalent mutations, including nine common micro-conversions and eleven high-frequency mutations reported in the literature, were detected by SNaPshot; and rare mutations were investigated by direct sequencing.

Results
Among the 113 21-OHD patients, 95.6% of the affected alleles were detected accurately by SNaPshot and CNVplex. Prevalent mutations were detected in 69.5% of the alleles; 62.4% of alleles contained pseudogene-derived micro-conversions, 1.8% contained nonpseudogene-derived mutations, and 5.3% contained complex variations resulting from multiple recombinations between CYP21A2 and CYP21A1P. Large rearrangements were identified in 27.0% of the alleles, including five types (CH-1, CH-3, CH-4, CH-5 and CH-8) of chimeric CYP21A1P/CYP21A2 genes. Two novel CYP21A2 haplotypes and four de novo CYP21A2 mutations were characterized. A rare haplotype with a c.955 C > T mutation in the duplicated CYP21A2 gene was found in 0.9% of the probands and 33.3% of the parents. In addition, four parents were also diagnosed with 21-OHD.

Conclusion
CNVplex and SNaPshot appear to be highly efficient and reliable techniques for use in a molecular diagnosis laboratory, and combined with direct sequencing based on locus-specific PCR, they might constitute a definitive way to detect almost all common and rare 21-OHD-related alleles.
First report of Angiostrongylus vasorum in an African golden wolf (Canis lupaster) in Algeria
Authors: Mechouck Noureddine , Deak Georgiana , Ionică Angela Monica , Toma Corina , Negoescu Andrada Gabriela , Taulescu Marian , Bouslama Zihad , Mihalca Andrei Daniel 
Published: October 2024

Abstract
Background
Angiostrongylus vasorum, commonly known as the “French heartworm,” is a nematode belonging to the Metastrongyloidea superfamily. This parasite was first identified in Toulouse, France in 1853 infecting the pulmonary arteries and the right side of the heart of a Pointer dog. Angiostrongylosis is an important infection due its severe clinical signs and potential for causing high morbidity and mortality in domestic dogs. This nematode has not been studied in Algeria. The aim of this study was investigate the presence of lungworms among different mammal species in a number of Algerian regions.

Methods
Between February 2022 and September 2023, 47 road-killed animals were collected from six administrative units (departments) in Algeria. All carcasses underwent a full parasitological necropsy, and lung tissues were preserved in 10% buffered formalin and concentrated ethanol for further study. All collected samples were subjected to histological and PCR (cytochrome c oxidase subunit 1 gene) analyses for lungworm identification.

Results
Histological examination revealed the presence of nematode eggs and larvae in the alveolar space and chronic obstructive vascular changes were detected in a single golden African wolf (Canis lupaster) collected from the department of Constantine. First-stage larvae were collected and morphologically identified as Angiostrongylus spp. The molecular identification confirmed the presence of A. vasorum. All other animals tested were negative for lungworms.

Conclusions
To the best of our knowledge, this is the first report of A. vasorum infection in an African golden wolf (Canis lupaster). We report a new host association, highlighting the importance of further studies to update the geographical distribution of A. vasorum and its epidemiology across Algeria.

Graphical Abstract
Developmental-status-aware transcriptional decomposition establishes a cell state panorama of human cancers
Authors: Luo Yikai , Liang Han 
Published: October 2024

Abstract

Background
Cancer cells evolve under unique functional adaptations that unlock transcriptional programs embedded in adult stem and progenitor-like cells for progression, metastasis, and therapeutic resistance. However, it remains challenging to quantify the stemness-aware cell state of a tumor based on its gene expression profile.

Methods
We develop a developmental-status-aware transcriptional decomposition strategy using single-cell RNA-sequencing-derived tissue-specific fetal and adult cell signatures as anchors. We apply our method to various biological contexts, including developing human organs, adult human tissues, experimentally induced differentiation cultures, and bulk human tumors, to benchmark its performance and to reveal novel biology of entangled developmental signaling in oncogenic processes.

Results
Our strategy successfully captures complex dynamics in developmental tissue bulks, reveals remarkable cellular heterogeneity in adult tissues, and resolves the ambiguity of cell identities in in vitro transformations. Applying it to large patient cohorts of bulk RNA-seq, we identify clinically relevant cell-of-origin patterns and observe that decomposed fetal cell signals significantly increase in tumors versus normal tissues and metastases versus primary tumors. Across cancer types, the inferred fetal-state strength outperforms published stemness indices in predicting patient survival and confers substantially improved predictive power for therapeutic responses.

Conclusions
Our study not only provides a general approach to quantifying developmental-status-aware cell states of bulk samples but also constructs an information-rich, biologically interpretable, cell-state panorama of human cancers, enabling diverse translational applications.