bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arecoline induces neurotoxicity in HT22 cells via the promotion of endoplasmic reticulum stress and downregulation of the Nrf2/HO‐1 pathway
Authors: Yan He , Ding Jiameng , Li Xiong , Li Shuyue , Zhang Dongxian 
Published: March 2024

AbstractArecoline, the predominant bioactive substance extracted from areca nut (AN), is the world's fourth most frequently used psychoactive material. Research has revealed that chewing AN can affect the central nervous system (CNS) and may lead to neurocognitive deficits that are possibly linked to the action of arecoline. However, the mechanism behind the neurotoxicity caused by arecoline remains unclear. This study aimed to investigate the neurotoxic effects of arecoline and its underlying mechanism. The results showed that arecoline caused cytotoxicity against HT22 cells in a dose‐dependent manner and induced apoptosis by upregulating the expression of pro‐apoptotic caspase and Bcl‐2 family proteins. Furthermore, arecoline escalated intracellular reactive oxygen species (ROS) levels and Ca2+ concentration with increasing doses, thereby motivating endoplasmic reticulum stress (ERS) and ERS‐associated apoptotic protein expression. Additionally, the study found that arecoline attenuates intracellular antioxidant defense by inhibiting the translocation of NF‐E2‐related factor‐2 (Nrf2) into the nucleus and decreasing downstream Heme oxygenase‐1 (HO‐1) levels. The specific inhibitor Sodium 4‐phenylbutyrate (4‐PBA) can dramatically attenuate arecoline‐mediated cell apoptosis and ERS‐associated apoptotic pathway expression by blocking ERS. The antioxidant N‐Acetylcysteine (NAC) also effectively reverses the arecoline‐mediated increase of ERS‐related apoptotic pathway protein levels by scavenging intracellular ROS accumulation. In conclusion, this study suggests that arecoline induces neurotoxicity in HT22 cells via ERS mediated by oxidative stress‐ and Ca2+ disturbance, as well as by downregulation of the Nrf2/HO‐1 pathway.
Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single‐cell RNA sequencing
Authors: Zhao Songyun , Xie Yi , Ding Xu , Zheng Chuanhua , Chen Jiaxing , Zhao Ning , Ji Yi , Wang Qi , Liu Yuankun , Cheng Chao 
Published: March 2024

AbstractRecent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome‐wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, β‐receptor blockers (BBs), and thiazide diuretics. Positive control studies were performed using GWAS data in chronic heart failure. The primary method for causality estimation was the inverse‐variance‐weighted method. Mendelian randomization analysis showed that BBs with the β1‐adrenergic receptor (ADRB1) as a therapeutic target could significantly reduce the risk of GBM by mediating DBP (OR = 0.431, 95% CI: 0.267–0.697, p < .001) and that they could also significantly reduce the risk of GBM by mediating SBP (OR = 0.595, 95% CI: 0.422–0.837, p = .003). Sensitivity analysis and colocalization analysis reinforced the robustness of these findings. Finally, the low expression of the ADRB1 gene in malignant gliomas was found by GBM data from TCGA and single‐cell RNA sequencing, which most likely contributed to the poor prognosis of GBM patients. In summary, our study provides preliminary evidence of some causal relationship between ADRB1‐targeted BBs and glioblastoma development. However, more studies are needed to validate these findings and further reveal the complex relationship between BP and GBM.
Association between sarcopenia‐related markers and cholelithiasis: A prospective and Mendelian randomization study
Authors: Ma Pengcheng , Li Ruining , Zeng Lin , Hong Chang , Li Yan , Liang Shengxing , Zhu Hongbo , Cui Hao , Wang Jiaren , He Jingzhe , Li Zeyang , Xu Jun , Liu Li , Xiao Lushan 
Published: March 2024

AbstractCholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia‐related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia‐related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two‐sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow‐up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.
Temporal progression of pancreatic cancer computed tomography findings until diagnosis: A large‐scale multicenter study
Authors: Gonda Masanori , Masuda Atsuhiro , Kobayashi Takashi , Iemoto Takao , Kakuyama Saori , Ezaki Takeshi , Ikegawa Takuya , Hirata Yuichi , Tsumura Hidetaka , Ogisu Kyohei , Nakano Ryota , Fujigaki Seiji , Nakagawa Takashi , Takagi Megumi , Yamanaka Kodai , Sato Yu , Fujita Koichi , Furumatsu Keisuke , Kato Takao , Sakai Arata , Shiomi Hideyuki , Sanuki Tsuyoshi , Arisaka Yoshifumi , Okabe Yoshihiro , Toyama Hirochika , Sofue Keitaro , Kodama Yuzo 
Published: March 2024

AbstractBackgroundFocal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers.ObjectiveTo ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them.MethodsA multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated.ResultsOut of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis.ConclusionThis large‐scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.
Intracranial invasion of a mast cell tumour in a dog: A case report and review of the literature
Authors: Kingsbury Edward , Odatzoglou Petros , Peschard A. L. , Wong Hannah , Elders Richard 
Published: March 2024

AbstractAn 11‐year‐old, female‐neutered beagle was presented with a growing soft tissue mass arising within the deep tissues of the left cranial cervical region. At presentation, facial asymmetry was evident along with palpable lymphadenomegaly. Magnetic resonance imaging demonstrated a locally invasive cervical mass with intracranial invasion through focal osteolysis of the occipital bone. After antihistamine administration, cytology confirmed mast cell tumour (MCT) with metastasis to local lymph nodes and liver. The owner chose to pursue lomustine and prednisolone, which were dispensed, but, before home administration, prolonged seizures/status epilepticus occurred prompting euthanasia. Postmortem examination confirmed a high‐grade MCT associated with, and infiltrating through, muscle, calvarium, dura mata, leptomeninges and the underlying brain. We present the clinical, imaging, and pathological findings of an unprecedented case of extracranial MCT tumour causing osteolysis of an imperforate flat bone (occipital bone) and intracranial invasion.
A combined score for predicting clinically relevant postoperative pancreatic fistula based on inflammatory parameters and drainage fluid culture results on postoperative day 3
Authors: Suto Hironobu , Matsukawa Hiroyuki , Ando Yasuhisa , Oshima Minoru , Fuke Takuro , Norikane Takashi , Sanomura Takayuki , Kamada Hideki , Kobara Hideki , Masaki Tsutomu , Kumamoto Kensuke , Okano Keiichi 
Published: March 2024

AbstractBackgroundClinically relevant postoperative pancreatic fistula (CR‐POPF) after pancreatic resection can lead to severe postoperative complications. POPF is defined based on postoperative day (POD) 3 drainage fluid amylase level. POPF correlates with inflammatory parameters as well as drainage fluid bacterial infection. However, a standardized model based on these factors for predicting CR‐POPF remains elusive. We aimed to identify inflammatory parameter‐ and drainage fluid culture‐related risk factors for CR‐POPF on POD 3 after pancreatoduodenectomy (PD) and distal pancreatectomy (DP).MethodsData from 351 patients who underwent PD or DP between 2013 and 2022 at a single institution were retrospectively analyzed. Risk factors for CR‐POPF were investigated using multivariate analyses, and a prediction model combining the risk factors for CR‐POPF was developed.ResultsOf the 351 patients, 254 and 97 underwent PD and DP, respectively. Multivariate analyses revealed that drainage fluid amylase level ≥722 IU/L, culture positivity, as well as neutrophil count ≥5473/mm3 on POD 3 were independent risk factors for CR‐POPF in PD group. Similarly, drainage fluid, amylase level ≥500 IU/L, and culture positivity on POD 3 as well as pancreatic thickness ≥11.1 mm were independent risk factors in the DP group. The model for predicting CR‐POPF achieved the maximum overall accuracy rate when the number of risk factors was ≥2 in both the PD and DP groups.ConclusionsInflammatory parameters on POD 3 significantly influence the risk of CR‐POPF onset after pancreatectomy. The combined models based on these values can accurately predict the risk of CR‐POPF after pancreatectomy.
Arztbegleitete Interhospitaltransporte – eine Analyse aus Schleswig-Holstein
Authors: Köser Andrea , Eimer Christine , Feth Maximilian , Lorenzen Ulf , Seewald Stephan , Lehn Henrik , Corzillius Michael , Schmalbach Bjarne , Reifferscheid Florian 
Published: March 2024

Zusammenfassung

Hintergrund
Durch Veränderungen in der Krankenhauslandschaft nehmen Interhospitaltransporte (IHT) einen immer höheren Stellenwert im Rettungsdienst ein. Durch die Spannbreite der Anforderungen hinsichtlich Personals und Rettungsmittel bedürfen diese Transporte einer sorgfältigen Einsatzplanung.

Zielsetzung
Um den Status quo zu untersuchen, führten wir eine Analyse im Versorgungsbereich der Integrierten Regionalleitstelle Mitte (IRLS-Mitte) in Schleswig-Holstein durch.

Material und Methoden
Im Zeitraum vom 01.10.2021 bis 30.09.2022 wurden arztbegleitete IHT analysiert.

Ergebnisse
Von insgesamt 158.823 dokumentierten Einsätzen der ILRS-Mitte konnten 2264 (1,4 %) Datensätze als arztbegleitete IHT identifiziert und eingeschlossen werden. Es erfolgten 1389 Transporte (61,4 %) durch spezialisierte Rettungsmittel, sowie 875 (38,6 %) durch Rettungsmittel der Primärversorgung. Der Einsatz von Primärrettungsmittel erfolgte schwerpunktmäßig bei zeitkritischen Verlegungen und außerhalb der Dienstzeiten des Intensivtransportwagens (ITW)/Verlegungseinsatzfahrzeugs (VEF), 21,2 % erfolgten luftgebunden. Bei 43,1 % aller Transporte handelte es sich um Aufwärtsverlegungen.

Diskussion
Arztbegleitete IHT nehmen einen relevanten Anteil am Einsatzspektrum des Rettungsdiensts ein und betreffen sowohl Rettungsmittel der Primärversorgung als auch spezialisierte Rettungsmittel. Außerhalb der Vorhaltezeiten von ITW/VEF übernehmen Notarzteinsatzfahrzeuge (NEF) und Rettungstransporthubschrauber (RTH) vorrangig die Transporte. Für die nächtlichen Notfalltransporte ist aufgrund des Zeitvorteils eine Ausweitung der luftgebundenen Verlegungskapazitäten zu erwägen. Für weniger dringliche Transporte könnte eine Anpassung der Kapazitäten spezialisierter bodengebundener Rettungsmittel in Schleswig-Holstein sinnvoll sein.
Staged trees and asymmetry-labeled DAGs
Authors: Varando Gherardo , Carli Federico , Leonelli Manuele 
Published: March 2024

AbstractBayesian networks are a widely-used class of probabilistic graphical models capable of representing symmetric conditional independence between variables of interest using the topology of the underlying graph. For categorical variables, they can be seen as a special case of the much more general class of models called staged trees, which can represent any non-symmetric conditional independence. Here we formalize the relationship between these two models and introduce a minimal Bayesian network representation of a staged tree, which can be used to read conditional independences intuitively. A new labeled graph termed asymmetry-labeled directed acyclic graph is defined, with edges labeled to denote the type of dependence between any two random variables. We also present a novel algorithm to learn staged trees which only enforces a specific subset of non-symmetric independences. Various datasets illustrate the methodology, highlighting the need to construct models that more flexibly encode and represent non-symmetric structures.
Clinical evidence for efficacy of pembrolizumab in MSI-H and TMB-H advanced solid tumor: results from three cancer centers in China
Authors: Yan Huan , Song Lianxi , Li Yizhi , Xu Qinqin , Guo Wenhuan , Lin Shaoding , Jiang Wenjuan , Wang Zhan , Deng Li , Huang Zhe , Qin Haoyue , Zhang Xing , Tong Fan , Zhang Ruiguang , Liu Zhaoyi , Zhang Lin , Yu Juan , Dong Xiaorong , Gong Qian , Deng Jun , Chen Xue , Wang Jing , Zhang Gao , Yang Nong , Zhang Yongchang , Zeng Liang 
Published: March 2024

Abstract
Background
Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H.

Methods
This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS).

Results
The top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H). The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6% (n = 10) of cases and partial responses (PR) in 43.9% (n = 51). Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6–21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9–7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events.

Conclusion
Our study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers.
Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes
Authors: Al Ghorani Hussam , Kulenthiran Saarraaken , Lauder Lucas , Recktenwald Michael Johannes Maria , Dederer Juliane , Kunz Michael , Götzinger Felix , Ewen Sebastian , Ukena Christian , Böhm Michael , Mahfoud Felix 
Published: March 2024

Abstract
Background
Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce.

Aims
This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension.

Methods
This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years.

Results
Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up.

Conclusion
Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension.

Graphical abstract
Left panel, Change in 24-h and office SBP. Right panel, eGFR over time. SBP, systolic blood pressure; eGFR, estimated glomerular filtration rate.
Evaluation of the effect of cervical and lumbar disc herniations on female sexual function: a comparative prospective study
Authors: GamalEl Din Sameh Fayek , Nabil Nashaat , Alaa Mohamed , Salam Mohamed Ahmed Abdel , Raef Ahmed , Elhalaly Rana Barakat , Abo Sief Ahmed 
Published: March 2024

Abstract
Purpose
We aimed to evaluate the effect of cervical disc herniation (CDH) and lumbar disc herniation (LDH) on female sexual functioning before and after surgical intervention.

Methods
The current study was conducted from February 2022 to February 2023. A total of 100 sexually active female patients in their reproductive phase who were diagnosed with CDH and LDH based on physical examination and previous magnetic resonance imaging (MRI) results, as well as 50 healthy females, were enrolled. The female subjects were evaluated using the validated Arabic version of the female sexual function index (ArFSFI), a 0 to 10 visual analogue scale (VAS), the Oswestry disability index (ODI) and Beck’s depression index (BDI).

Results
The baseline ArFSFI domains and total scores were greatest in the controls, followed by the CDH group. The ArFSFI domains and total scores were greatest in the control group, followed by the postoperative ArFSFI domains and total scores in the cervical group. The variations in satisfaction, pain, and overall ArFSFI ratings were significant across research groups. The difference in desire, arousal, lubrication, and orgasm was substantial in the lumbosacral group, but there were no significant changes between the cervical and control groups. Postoperatively, ArFSFI domains and overall scores improved in both of the cervical and lumbar groups. Both research groups’ ODI score and grade improved after surgery. Finally, both groups’ BDI score and grade improved after surgery.

Conclusion
Female sexual dysfunctions caused by CDH and LDH improved considerably after surgery.
Assessing adverse childhood experiences in young refugees: a systematic review of available questionnaires
Authors: Abdelhamid Shaymaa , Kraaijenvanger Eline , Fischer Joachim , Steinisch Maria 
Published: March 2024

AbstractToday, various questionnaires are available to assess Adverse Childhood Experiences (ACEs) in children; however, it is uncertain if these questionnaires are comprehensive in addressing adversities of vulnerable subgroups, specifically refugee children. This review’s objectives are to (1) identify current ACE questionnaires and determine if they are suitable in assessing refugee children’s adversities, and (2) identify those previously used within a refugee population. A systematic literature search was conducted across five databases for articles published since 2010, including studies using an ACE-questionnaire that recognized multiple adversities in healthy children and were published in English. A total of 103 ACE questionnaires were identified in 506 studies. Only 14 of the 103 questionnaires addressed a refugee-specific adversity. Their ability to capture refugee children’s experiences was limited: available questionnaires used a maximum of three items to assess refugee-specific adversities, covering only a fraction of forms of adversities relevant to refugee children. Psychometric characteristics were rarely reported. In addition, only two ACE questionnaires were used within a refugee population. With the tools currently available, it is not possible to comprehensively assess the exposure to and severity of the adversities faced by refugee children. The perpetuation of ongoing crises necessitates assessing refugee children’s adversities to understand how their wellbeing is affected and to identify children at risk.