bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex, myelin, and clinical characteristics of Parkinson’s disease
Authors: Cai Jiayue , Kim Jowon L. , Wang Yuheng , Baumeister Tobias R. , Zhu Maria , Liu Aiping , Lee Soojin , McKeown Martin J. 
Published: September 2023

ObjectiveTo determine if there are sex differences in myelin in Parkinson’s disease, and whether these explain some of the previously-described sex differences in clinical presentation.MethodsThirty-three subjects (23 males, 10 females) with Parkinson’s disease underwent myelin water fraction (MWF) imaging, an MRI scanning technique of in vivo myelin content. MWF of 20 white matter regions of interest (ROIs) were assessed. Motor symptoms were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Principal component analysis, logistic and multiple linear regressions, and t-tests were used to determine which white matter ROIs differed between sexes, the clinical features associated with these myelin changes, and if overall MWF and MWF laterality differed between males and females.ResultsConsistent with prior reports, tremor and bradykinesia were more likely seen in females, whereas rigidity and axial symptoms were more likely seen in males in our cohort. MWF of the thalamic radiation, cingulum, cingulum hippocampus, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate were significant in predicting sex. Overall MWF and asymmetry of MWF was greater in males. MWF differences between sexes were associated with tremor symptomatology and asymmetry of motor performance.ConclusionSex differences in myelin are associated with tremor and asymmetry of motor presentation. While preliminary, our results suggest that further investigation of the role of biological sex in myelin pathology and clinical presentation in Parkinson’s disease is warranted.
High-dose liraglutide improves metabolic syndrome in poor responders to bariatric surgery
Authors: Vinciguerra Federica , Piazza Luigi , Di Stefano Carla , Degano Claudia , Pulvirenti Alfredo , Baratta Roberto , Frittitta Lucia 
Published: September 2023

BackgroundBariatric surgery (BS) represents the most effective therapy for obesity class III, or class II with at least one weight-related comorbidity. However, some patients have insufficient weight loss or clinically relevant weight regain after a successful primary procedure. This study aimed to assess the efficacy of liraglutide treatment on weight loss, body composition and improvement of metabolic syndrome (MS) in patients defined as poor responders after BS.MethodsThe study involved 59 non-diabetic adults with obesity (M/F: 17/42, age: 38.6 ± 11.8 years, BMI 38.3 ± 5.5 kg/m2) who had been treated with BS and experienced a poor response, categorized as either IWL (insufficient weight loss) or WR (weight regain). All patients were prescribed pharmacological therapy with liraglutide and attended nutritional counseling. Anthropometric and clinical measurements, body composition and the presence of MS defined according to the ATP-III classification were evaluated before starting liraglutide and after 24 weeks of treatment.ResultsAfter 24 weeks of treatment with liraglutide, the mean weight loss was 8.4% ± 3.6% with no difference between gender, bariatric procedure, or type of poor response (IWL or WR). A significant decrease in fat mass, free-fat mass and total body water was documented. After 24 weeks, patients presented significantly lowered fasting glucose, total cholesterol, triglycerides, AST and ALT. The prevalence of MS was reduced from 35% at baseline to 1.6% after 24 weeks. No patients discontinued the treatment during the study.ConclusionIn patients who experience poor response after BS, liraglutide is well tolerated and promotes significant weight loss, ameliorates cardiometabolic comorbidities, and reduces the prevalence of MS.
Whole-exome sequencing of calcitonin-producing pancreatic neuroendocrine neoplasms indicates a unique molecular signature
Authors: Döring Claudia , Peer Katharina , Bankov Katrin , Bollmann Carmen , Ramaswamy Annette , Di Fazio Pietro , Wild Peter Johannes , Bartsch Detlef Klaus 
Published: September 2023

IntroductionCalcitonin-producing pancreatic neuroendocrine neoplasms (CT-pNENs) are an extremely rare clinical entity, with approximately 60 cases reported worldwide. While CT-pNENs can mimic the clinical and diagnostic features of medullary thyroid carcinoma, their molecular profile is poorly understood.MethodsWhole-exome sequencing (WES) was performed on tumor and corresponding serum samples of five patients with increased calcitonin serum levels and histologically validated calcitonin-positive CT-pNENs. cBioPortal analysis and DAVID gene enrichment analysis were performed to identify dysregulated candidate genes compared to control databases. Immunohistochemistry was used to detect the protein expression of MUC4 and MUC16 in CT-pNEN specimens.ResultsMutated genes known in the literature in pNENs like MEN1 (35% of cases), ATRX (18-20% of cases) and PIK3CA (1.4% of cases) were identified in cases of CT-pNENs. New somatic SNVs in ATP4A, HES4, and CAV3 have not been described in CT- pNENs, yet. Pathogenic germline mutations in FGFR4 and DPYD were found in three of five cases. Mutations of CALCA (calcitonin) and the corresponding receptor CALCAR were found in all five tumor samples, but none of them resulted in protein sequelae or clinical relevance. All five tumor cases showed single nucleotide variations (SNVs) in MUC4, and four cases showed SNVs in MUC16, both of which were membrane-bound mucins. Immunohistochemistry showed protein expression of MUC4 in two cases and MUC16 in one case, and the liver metastasis of a third case was double positive for MUC4 and MUC16. The homologous recombination deficiency (HRD) score of all tumors was low.DiscussionCT-pNENs have a unique molecular signature compared to other pNEN subtypes, specifically involving the FGFR4, DPYD, MUC4, MUC16 and the KRT family genes. However, a major limitation of our study was the relative small number of only five cases. Therefore, our WES data should be interpreted with caution and the mutation landscape in CT-pNENs needs to be verified by a larger number of patients. Further research is needed to explain differences in pathogenesis compared with other pNENs. In particular, multi-omics data such as RNASeq, methylation and whole genome sequencing could be informative.
Anlotinib combined with whole-brain radiotherapy in non-small cell lung cancer with multiple brain metastases that progressed or developed after at least one lines of prior treatment
Authors: Kong Cheng , Yu Shaorong , Qian Pudong , Song Xue , Wen Jing , Jiang Ming , Zhu Jun , Xu Jianhua , Zhao Lijun , Guo Zhen , Wu Jianfeng , He Xia , Zhu Xiangzhi 
Published: September 2023

BackgroundIntracranial metastasis that failed standard systematic treatment is common in advanced non-small cell lung cancer (NSCLC), contributing significantly to morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of anlotinib combined with whole-brain radiotherapy (WBRT) for NSCLC with brain metastases (BMs) that progressed or developed after at least one line of prior treatment and compare the outcomes with that of the contemporary institutional control.MethodsNSCLC patients with multiple BMs that progressed or developed after at least one line of prior systematic treatment and treated with WBRT subsequently between 2019 and 2021 were selected retrospectively for analysis. Based on whether concurrent anlotinib had been used in combination with WBRT, the cases were divided into the anlotinib group and control group. The primary endpoints were intracranial progression-free survival (iPFS) and safety.ResultsA total of 76 patients met the inclusion criteria of the study. Of the 76 patients, 34 received concurrent WBRT and anlotinib followed by anlotinib maintenance and 42 were treated with WBRT alone or in combination with other systemic agents at the physicians’ discretion. The median follow-up for the entire cohort was 21 months. The median iPFS for the anlotinib and control group was 6.7 months (95% CI, 4.6–9.9) and 5.3 months (95% CI, 4.0–6.5), respectively (log-rank P = 0.04). There was no difference in overall survival between the two groups (log-rank P = 0.38). In the anlotinib group, treatment-related adverse events were reported in 15 patients (44.1%), with acute or late grade 3–5 adverse events identified in 14.7% of patients (n = 5).ConclusionsWBRT plus anlotinib, as a convenient chemo-free regimen, may represent an overall safe and effective procedure in advanced NSCLC with multiple BMs that progressed or developed after standard systematic treatment.
Head and neck cancers survival in Europe, Taiwan, and Japan: results from RARECAREnet Asia based on a privacy-preserving federated infrastructure
Authors: Botta Laura , Matsuda Tomohiro , Charvat Hadrien , Chiang Chun-ju , Lee Wen-Chung , van Gestel Anna Jacoba , Martin Frank , Geleijnse Gijs , Cellamare Matteo , Bonfarnuzzo Simone , Marcos-Gragera Rafael , Guevara Marcela , Mousavi Mohsen , Craig Stephanie , Rodrigues Jessica , Rubió-Casadevall Jordi , Licitra Lisa , Cavalieri Stefano , Resteghini Carlo , Gatta Gemma , Trama Annalisa ,   the RARECAREnet working group
Published: September 2023

BackgroundThe head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries.MethodsWe used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data.FindingsFive-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan.InterpretationSurvival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors.
Tumorigenic effects of human mesenchymal stromal cells and fibroblasts on bladder cancer cells
Authors: Frerichs Lucie M. , Frerichs Bastian , Petzsch Patrick , Köhrer Karl , Windolf Joachim , Bittersohl Bernd , Hoffmann Michèle J. , Grotheer Vera 
Published: September 2023

BackgroundPatients with muscle-invasive bladder cancer face a poor prognosis due to rapid disease progression and chemoresistance. Thus, there is an urgent need for a new therapeutic treatment. The tumor microenvironment (TME) has crucial roles in tumor development, growth, progression, and therapy resistance. TME cells may also survive standard treatment of care and fire up disease recurrence. However, whether specific TME components have tumor-promoting or tumor-inhibitory properties depends on cell type and cancer entity. Thus, a deeper understanding of the interaction mechanisms between the TME and cancer cells is needed to develop new cancer treatment approaches that overcome therapy resistance. Little is known about the function and interaction between mesenchymal stromal cells (MSC) or fibroblasts (FB) as TME components and bladder cancer cells.MethodsWe investigated the functional impact of conditioned media (CM) from primary cultures of different donors of MSC or FB on urothelial carcinoma cell lines (UCC) representing advanced disease stages, namely, BFTC-905, VMCUB-1, and UMUC-3. Underlying mechanisms were identified by RNA sequencing and protein analyses of cancer cells and of conditioned media by oncoarrays.ResultsBoth FB- and MSC-CM had tumor-promoting effects on UCC. In some experiments, the impact of MSC-CM was more pronounced. CM augmented the aggressive phenotype of UCC, particularly of those with epithelial phenotype. Proliferation and migratory and invasive capacity were significantly increased; cisplatin sensitivity was reduced. RNA sequencing identified underlying mechanisms and molecules contributing to the observed phenotype changes. NRF2 and NF-κB signaling was affected, contributing to improved cisplatin detoxification. Likewise, interferon type I signaling was downregulated and regulators of epithelial mesenchymal transition (EMT) were increased. Altered protein abundance of CXCR4, hyaluronan receptor CD44, or TGFβ-signaling was induced by CM in cancer cells and may contribute to phenotypical changes. CM contained high levels of CCL2/MCP-1, MMPs, and interleukins which are well known for their impact on other cancer entities.ConclusionsThe CM of two different TME components had overlapping tumor-promoting effects and increased chemoresistance. We identified underlying mechanisms and molecules contributing to the aggressiveness of bladder cancer cells. These need to be further investigated for targeting the TME to improve cancer therapy.
The association between plasma osmolality and in-hospital mortality in the first 24 h after neonatal intensive care unit admission
Authors: Liu Weiqin , Xiang Lingling , Zhao Zhiwei , Lin Lu , Wei Hong , Hua Ziyu 
Published: September 2023

BackgroundPerturbation of osmolality is associated with increased mortality in adults and children in critically ill conditions. However, it is still unclear whether osmolality imbalance impacts the prognosis of critically ill infants. This study aimed to investigate the relationship between plasma osmolality and prognosis in critically ill infants within 24 h of admission.MethodsThis retrospective study enrolled 1,042 infants who had plasma osmolality data from 2010 to 2018. The initial plasma osmolality (within 24 h after admission) was extracted from the pediatric intensive care database (PIC V1.1). The locally weighted scatter-plot smoothing (LOWESS) and restricted cubic splines (RCS) methods were used to explore the approximate relationship between plasma osmolality and in-hospital mortality. Univariate and multivariate logistic regression analyses were used to further analyse this relationship. Kaplan–Meier analysis was applied to estimate the probability of hospital mortality within 90 days of admission. Subgroup analysis was employed to assess the impact of potential confounders (including postnatal days, gender, and gestational age).ResultsAn approximately“U”-shaped relationship between plasma osmolality and mortality was detected. In the logistic regression model, plasma osmolality &lt;270 mmol/L (low osmolality group) was significantly associated with in-hospital mortality (P &lt; 0.05; OR 2.52; 95% CI, 1.15–5.06). Plasma osmolality &gt;300 mmol/L (high osmolality group) was also significantly associated with mortality (P &lt; 0.05; OR 3.52; 95% CI, 1.16–8.83). This association remained even after multivariable adjustments. The 90-day survival rate was lower in the abnormal plasma osmolality group (including high or low osmolality groups) than in the intermediate group (log-rank test, P &lt; 0.05). The abnormal plasma osmolality group had a significantly higher incidence of all-cause mortality in the 0–7 postnatal days subgroup (high osmolality group, P &lt; 0.05; OR 5.25; low osmolality group, P &lt; 0.05; OR 3.01). Infants with abnormal osmolality had a significantly higher mortality rate in the female group (P &lt; 0.05). High osmolality was associated with a higher mortality rate in the preterm group (P &lt; 0.05).ConclusionsBoth hypoosmolality and hyperosmolality were shown to be independently associated with increased risk of in-hospital infant mortality in NICUs.
Case report: Novel insights into hemorrhagic destruction of the brain, subependymal calcification, and cataracts disease
Authors: Abdallah Moady Tameemi , Odeh Marwan , Fedida Ayalla , Segal Zvi , Gruber Maayan , Goldfeld Moshe , Kalfon Limor , Falik-Zaccai Tzipora C. 
Published: September 2023

IntroductionPathogenic variants of the junctional adhesion molecule 3 (JAM3/JAM-C; OMIM#606871) is the cause of the rare recessive disorder called hemorrhagic destruction of the brain, subependymal calcification, and cataracts (HDBSCC, OMIM#613730) disease. A similar phenotype is universal, including congenital cataracts and brain hemorrhages with high mortality rate in the first few weeks of life and with a poor neurologic outcome in survivors. We aim to describe and enlighten novel phenotype and genotype of a new patient and review the literature regarding all reported patients worldwide.Case reportWe report the case of a prenatal and postnatal phenotype of a new patient with a novel pathogenic loss-of-function variant in JAM3, who presented prenatally with cataracts and brain anomalies and postnatally with brain hemorrhages, failure to thrive (FTT), progressive microcephaly, recurrent posterior capsule opacities, and auditory neuropathy.DiscussionThis study enlightens novel possible functions of JAM3 in the normal development of the brain, the ocular lenses, the auditory system, and possibly the gastrointestinal tract. This study is the first to report of cataracts evident in as early as 23 weeks of gestation and a rare phenomenon of recurrent posterior capsule opacities despite performing recurrent posterior capsulectomy and anterior vitrectomy. We suggest that auditory neuropathy, which is reported here for the first time, is part of the phenotype of HDBSCC, probably due to an endothelial microvasculature disruption of the peripheral eighth nerve or possibly due to impaired nerve conduction from the synapse to the brainstem.ConclusionsPrenatal cataracts, brain anomalies, FTT, and auditory neuropathy are part of the phenotype of the HDBSCC disease. We suggest including JAM3 in the gene list known to cause congenital cataracts, brain hemorrhages, and hearing loss. Further studies should address the auditory neuropathy and FTT phenomena in knockout mice models. We further suggest performing comprehensive ophthalmic, audiologic, and gastroenterologic evaluations for living patients worldwide to further confirm these novel phenomena in this rare entity.
Risk factors for death associated with severe influenza in children and the impact of the COVID-19 pandemic on clinical characteristics
Authors: Hu Qian , Liang Wen , Yi Qiuwei , Zheng Yuejie , Wang Wenjian , Wu Yuhui 
Published: September 2023

BackgroundTo summarize the clinical features of severe influenza in children and the high-risk factors for influenza-related deaths and to raise awareness among pediatricians.MethodsA retrospective study of clinical manifestations, laboratory tests, and diagnosis and treatment of 243 children with severe influenza admitted to Shenzhen Children's Hospital from January 2009 to December 2022 was conducted. Univariate logistic regression analysis and Boruta analysis were also performed to identify potentially critical clinical characteristics associated with death, and clinically significant were used in further multivariate logistic regression analysis. Subject receiver operating characteristic (ROC) curves were applied to assess the efficacy of death-related independent risk factors to predict death from severe influenza.ResultsThere were 169 male and 74 female patients with severe influenza, with a median age of 3 years and 2 months and 77.4% of patients under six. There were 46 cases (18.9%) in the death group. The most common pathogen was Influenza A virus (IAV) (81.5%). The most common complication in the death group was influenza-associated acute necrotizing encephalopathy (ANE [52.2%]). Severe influenza in children decreased significantly during the COVID-19 pandemic, with a median age of 5 years, a high predominance of neurological symptoms such as ANE (P = 0.001), and the most common pathogen being H3N2 (P &lt; 0.001). D-dimer, acute respiratory distress syndrome (ARDS), and acute necrotizing encephalopathy (ANE) were significant independent risk factors for severe influenza-associated death. Furthermore, the ROC curves showed that the combined diagnosis of independent risk factors had significant early diagnostic value for severe influenza-related deaths.ConclusionNeurological disorders such as ANE are more significant in children with severe influenza after the COVID-19 pandemic. Influenza virus infection can cause serious multisystem complications such as ARDS and ANE, and D-dimer has predictive value for early diagnosis and determination of the prognosis of children with severe influenza.
SGLT2 inhibitors for patients with heart failure with preserved ejection fraction in China: a cost-effectiveness study
Authors: Lu He , Shang Pingping , Zhou Dexing 
Published: September 2023

Background: The potential benefits of intervention with empagliflozin or dapagliflozin for patients with heart failure with preserved ejection fraction (HFpEF) were first demonstrated in the EMPEROR-Preserved and DELIVER studies. However, the cost-effectiveness of this intervention (empagliflozin or dapagliflozin) is yet to be established.Methods: In the context of Chinese healthcare, a Markov model was proposed, which incorporates clinical outcomes from the EMPEROR-Preserved and DELIVER studies, to predict the utility and costs over a lifetime. The time horizon was 20 years, and a 5% discount rate was applied to the costs and utilities. The incremental cost-effectiveness ratio (ICER) threshold against willingness to pay (WTP) was set as the primary outcome. The robustness of the decision was evaluated using sensitivity analyses.Results: After a simulated 20-year lifetime, a 72-year-old patient with HFpEF in the intervention group (empagliflozin) showed an increase of 0.44 quality-adjusted life years (QALYs) and $1,623.58 with an ICER of $3,691.56 per QALY, which was lower than the WTP threshold of $12,032.10 per QALY. A 72-year-old patient with HFpEF in the intervention group (dapagliflozin) showed an increase of 0.34 QALYs and $2,002.13 with an ICER of $5,907.79 per QALY, which was lower than the WTP threshold of $12,032.10 per QALY. One-way sensitivity analyses showed that cardiovascular (CV) mortality in the intervention and comparator groups was the most sensitive to the decision. Cost-effectiveness was demonstrated in the intervention group (empagliflozin or dapagliflozin) in 67.9% or 62.2% of 1000 Monte Carlo simulations, respectively.Conclusion: In Chinese healthcare, the interventions (empagliflozin or dapagliflozin) for HFpEF were more cost-effective than the comparators. Our study has provided a quantitative evaluation of the costs and benefits of such interventions for a lifetime using the model.