bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Regulation of PMCA Activity by Defective CFTR Expression Promotes Epithelial Cell Damage in Alcoholic Pancreatitis and Hepatitis
Authors: Madacsy Tamara , Varga Árpád , Papp Noémi , Tél Bálint , Pallagi Petra , Szabó Viktória , Kiss Aletta , Fanczal Júlia , Rakonczay Zoltan , Tiszlavicz László , Rázga Zsolt , Hohwieler Meike , Kleger Alexander , Gray Mike , Hegyi Péter , Maléth József 
Published: January 2022

Abstract
Background and aims. Alcoholic pancreatitis and hepatitis are frequent, potentially lethal diseases with limited treatment options. Our previous study reported that the expression of CFTR Cl- channel is impaired by ethanol in pancreatic ductal cells leading to more severe alcohol-induced pancreatitis. In addition to determining epithelial ion secretion, CFTR has multiple interactions with other proteins, which may influence intracellular Ca2+ signaling. Thus, we aimed to investigate the impact of ethanol-mediated CFTR damage on intracellular Ca2+ homeostasis in pancreatic ductal epithelial cells and cholangiocytes.Methods. Human and mouse pancreas and liver samples and ex vivo organoids were used to study ion secretion, intracellular signaling and protein expression and interaction. The effect of PMCA4 inhibition was analysed in a mouse model of alcohol-induced pancreatitis.Results. The decreased CFTR expression impaired PMCA function and resulted in sustained intracellular Ca2+ elevation in ethanol-treated and mouse and human pancreatic organoids. Liver samples derived from alcoholic hepatitis patients and ethanol-treated mouse liver organoids showed decreased CFTR expression and function, and impaired PMCA4 activity. PMCA4 co-localizes and physically interacts with CFTR on the apical membrane of polarized epithelial cells, where CFTR-dependent calmodulin recruitment determines PMCA4 activity. The sustained intracellular Ca2+ elevation in the absence of CFTR inhibited mitochondrial function and was accompanied with increased apoptosis in pancreatic epithelial cells and PMCA4 inhibition increased the severity of alcohol-induced AP in mice.Conclusion. Our results suggest that improving Ca2+ extrusion in epithelial cells may be a potential novel therapeutic approach to protect the exocrine pancreatic function in alcoholic pancreatitis and prevent the development of cholestasis in alcoholic hepatitis.
Heterogeneity, Inherent and Acquired Drug Resistance in Patient-Derived Organoids Models of Primary Liver Cancer
Authors: Cao Guang-Wen , Xian Linfeng , Zhao Pei , Chen Xi , Wei Zhimin , Ji Hongxiang , Zhao Jun , Liu Donghong , Li Zishuai , Liu Wenbin , Han Xue , Qian Youwen , Dong Hui , Zhou Xiong , Fan Junyan , Zhu Xiaoqiong , Yin Jianhua , Tan Xiaojie , Jiang Dongming , Yu Hongping 
Published: January 2022

Abstract
To screen for sensitive drugs for recurrent primary liver cancer (PLC) and elucidate the mechanisms underlying inherent and acquired drug resistance, we established a platform of organoids, organoids-derived xenograft (ODX) mouse models, and patient-derived xenograft (PDX) mouse models of primary liver cancer (PLC). Fifty-two organoids were established from 153 PLC patients. Establishing organoids of hepatocellular carcinoma (HCC) displayed a trend toward a higher success rate than establishing PDX (29.0% vs. 23.7%) and took a shorter duration (13.0 ± 4.7 vs. 25.1 ± 5.4 days, P=2.28×10−13) than establishing PDX models. Larger tumor, vascular invasion, and advanced stage were significantly associated with successful establishment of organoids and PDX in HCC. Organoids and ODX recapitulated PLC histopathological features but enriched more aggressive cell types. PLC organoids were mostly resistant to lenvatinib in vitro but sensitive in ODX model, indicating innate immunity plays a role. Acquired sorafenib-resistant HCC organoids were generated via 3–5 months of induction. RNA-sequencing indicated that stemness– and epithelial–mesenchymal transition (EMT)–related gene sets were upregulated, whereas liver development– and liver specific molecule–related gene sets were downregulated, in acquired sorafenib-resistant organoids. Targeting mTOR signaling pathway was effective in treating acquired sorafenib-resistant HCC, possibly via inducing phosphorylated S6 kinase. Genes upregulated in acquired sorafenib-resistant HCC organoids were often associated with unfavorable prognosis. Conclusively, HCC organoids perform better than PDX for drug selection. Acquired sorafenib resistance in organoids promotes HCC aggressiveness via facilitating the stemness, retrodifferentiation, and EMT. Phosphorylated S6 kinase might be predictive for drug resistance in HCC.
Transformer for Sub-Seasonal Extreme High Temperature Probabilistic Forecasting Over Eastern China
Authors: Jin Wei , Zhang Wei , Hu Jie , Chen Jiazhen , Weng Bin , Gao Jianyun , Huang Tianqiang 
Published: January 2022

Abstract
Sub-seasonal high temperature forecasting is significant for early warning of extreme heat weather. Currently, deep learning methods, especially Transformer, have been successfully applied to the meteorological field. Relying on the excellent global feature extraction capability in natural language processing, Transformer may be useful to improve the ability in extended periods. To explore this, we introduce the Transformer and propose a Transformer-based model, called Transformer to High Temperature (T2T). In the details of the model, we successively discuss the use of the Transformer and the position encoding in T2T to continuously optimize the model structure in an experimental manner. In the dataset, the multi-version data fusion method is proposed to further improve the prediction of the model with reasonable expansion of the dataset. The performance of well-desinged model (T2T) is verified against the European Centre for Medium-Range Weather Forecasts (ECMWF) and Multi-Layer Perceptron (MLP) at each grid of the 100.5°E to 138°E, 21°N to 54°N domain for the April to October of 2016-2019. For case study initiated from 2 June 2018, the results indicated that T2T is significantly better than ECMWF and MLP, with smaller absolute error and more reliable probabilistic forecast for the extreme high event happened during the third week. Over all, the deterministic forecast of T2T is superior to MLP and ECMWF due to ability of utilize spatial information of grids. T2T also provided a better calibrated probability of high temperature and a sharper prediction probability density function than MLP and ECMWF. All in all, T2T can meet the operational requirements for extended period forecasting of extreme high temperature. Furthermore, our research can provide experience on the development of deep learning in this field and achieve the continuous progress of seamless forecasting systems.
Radiotherapy for Postsurgical Vaginal Recurrences of Cervical Squamous Cell Carcinoma: Analysis of Dosing and Prognosis
Authors: Yan Junfang , Zheng Ziye , Hu Ke , Hou Xiaorong , Yu Lihua , Zhang Fuquan 
Published: January 2022

Abstract
Background: This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of cervical squamous carcinoma in patients who previously underwent surgery and to explore prognostic factors (particularly dose-related) associated with survival post-recurrence.Methods: Ninety-seven patients with histologically proven squamous cell carcinoma-subtype cervical cancer who were treated for vaginal recurrence at Peking Union Medical College Hospital between July 2011 and November 2019 were identified. All patients had previously undergone surgery for the primary tumor and received salvage external beam radiotherapy, brachytherapy, or both. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated, as were adverse effects.Results: The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%, respectively. On multivariate analysis, a tumor size ≤4 cm and an endovaginal recurrence pattern were associated with longer PFS (both P < 0.05); however, only the latter was predictive of a longer LC (P < 0.05). In the 33 patients with recurrences that were paravaginal or invasive of surrounding organs, biologically equivalent doses in 2 Gy fractions of ≥70 Gy were independently predictive of longer LC (P < 0.05). Finally, 12.4% of the patients experienced grades ≥2 late complications; only 1 patient who received EBRT alone experienced grade 5 late complications.Conclusions: RT is an effective treatment for post-surgical vaginal recurrence in patients with cervical squamous cell carcinoma. For patients with extravaginal recurrence, a salvage dose of ≥70 Gy appears to be optimal.
Supervised Learning in image enhance from electron microscopy inversion results
Authors: Stagakis Georgios 
Published: January 2022

Abstract
In Nondestructive testing there is a variety of applications in Material Science, where the specimen is imaged by an Electron Microscope and then by image inversion, informationis extracted for the material interior. This type of information might contain noise either by the imaging procedure or by the numerical part of the inversion. We present a method that can improve the interior density results of an inversed material from a series of Scanning Electron Microscope (SEM) images. For this method, the material density can contain some discontinuity, such as regions where it is dense and regions where there are voids.The proposed method directly stands on the Bayesian learning framework, adopting Gaussian Stochastic Processes (GSPs). Two test sample cases that contain some discontinuities in the density are tested. We also provide a comparison between two different GSP modelling approaches; one is a typical GSP and the other accounts for discontinuity, by introducing hyperparameters. The GSP method gives reconstructed data in reasonable agreement with the known original density distribution, giving confidence that the method can be applied to experimentally obtained SEM images.
Optimization of Cooperative Offloading Model with Cost Consideration in Mobile Edge Computing
Authors: Xu Bin , Deng Tao , Liu Yichuan , Zhao Yunkai , Xu Zipeng , Qi Jin , Wang Sitao , Liu Dan 
Published: January 2022

Abstract
The combination of idle computing resources in mobile devices and the computing capacity of mobile edge servers enables all available devices in an edge network to complete all computing tasks in coordination to effectively improve the computing capacity of the edge network. This is a research hotspot for 5G technology applications. Previous research has focused on the minimum energy consumption and/or delay to determine the formulation of the computational offloading strategy but neglected the cost required for the computation of collaborative devices (mobile devices, mobile edge servers, etc.); therefore, we proposed a cost-based collaborative computation offloading model. In this model, when a task requests these devices' assistance in computing, it needs to pay the corresponding calculation cost; and on this basis, the task is offloaded and computed. In addition, for the model, we propose an adaptive neighborhood search based on simulated annealing algorithm (ANSSA) to jointly optimize the offloading decision and resource allocation with the goal of minimizing the sum of both the energy consumption and calculation cost. The adaptive mechanism enables different operators to update the probability of selection according to historical experience and environmental perception, which makes the individual evolution have certain autonomy. A large number of experiments conducted on different scales of mobile user instances show that the ANSSA can obtain satisfactory time performance with guaranteed solution quality. The experimental results demonstrate the superiority of the mobile edge computing (MEC) offloading system. It is of great significance to strike a balance between maintaining the life cycle of smart mobile devices and breaking the performance bottleneck of MEC servers.
Enabling global analysis of protein citrullination and homocitrullination via biotin thiol tag-assisted mass spectrometry
Authors: Li Lingjun , Shi Yatao , Li Zihui , Wang Bin , Shi Xudong , Ye Hui , Delafield Daniel , Lv Langlang , Ye Zhengqing , Chen Zhengwei , Ma Fengfei 
Published: January 2022

Abstract
Citrullination and homocitrullination are key post-translational modifications (PTMs) that affect protein structures and functions. Although they have been linked to various biological processes and disease pathogenesis, the underlying mechanism remains poorly understood due to a lack of effective tools to enrich, detect, and localize these PTMs. Herein, we report the design and development of a biotin thiol tag that enables derivatization, enrichment, and confident identification of these two PTMs simultaneously via mass spectrometry. We perform global mapping of the citrullination and homocitrullination proteomes of mouse tissues. In total, we identify 691 citrullination sites and 81 homocitrullination sites from 432 and 63 proteins, respectively, representing the largest datasets to date. We discover novel distribution and functions of these two PTMs. We also perform multiplexing quantitative analysis via isotopic labeling techniques. This study depicts a landscape of protein citrullination and homocitrullination and lays the foundation for further deciphering their physiological and pathological roles.
External Validation of Models to Predict Unsuccessful Endometrial Ablation: a Retrospective Study
Authors: Stevens Kelly , Houterman Saskia , Weyers Steven , Muller Iris , Schoot Benedictus C. 
Published: January 2022

Abstract
Study Objective: External validation of our previously presented and locally established prediction models to help counsel patients for failure of endometrial ablation (EA) or surgical re-intervention within 2 years after EA, called ‘Failure model’ and ‘Re-intervention model’ respectively. Design: Retrospective external validation study, minimal follow-up time of 2 years.Setting: Two non-academic teaching hospitals in the Netherlands.Patients: Pre-menopausal women (18+) who had undergone EA for abnormal uterine bleeding problems between January 2010 and November 2012. A total of 329 patients were eligible for analysis.Interventions: Interventions used for EA were Novasure (Hologic, Marlborough, Massachusetts, US) and ThermaChoice III (Ethicon, Sommerville, US). Measurements and Main Results: The Area Under the Receiver Operating characteristics Curve (AUROC) for the outcome parameter of failure within 2 years after EA was 0.59 (95% CI 0.53 – 0.65). Variables in this model were dysmenorrhea, age, parity ≥5 and preoperative menorrhagia. The Hosmer-Lemeshow test showed no significant difference between the observed and predicted outcome. (Chi-square: 4.62, P-value: .80) The AUROC for the outcome parameter surgical re-intervention within 2 years was 0.62 (95% CI 0.53 – 0.70) Variables in this model were dysmenorrhea, age, menstrual duration> 7 days, parity ≥5 and a previous caesarean section. The Hosmer-Lemeshow test showed no significant difference between the observed and predicted outcome (Chi-square 11.34, P-value .18).Conclusion: Both the failure model and the re-intervention model can be used to predict unsuccessful endometrial ablation in the general population within two years after the procedure. It can be used prior to surgery to facilitate tailor-made shared decision-making, and help counsel patients with regards to the potential outcome of their treatment with the use of a personally calculated percentage.
Rare Case of Gastric Schwannoma Simulating Gastrointestinal Stromal Tumour-A Case Report
Authors: Panduranga Shruthi , Kade Samson , Varwatte Pooja , V Harisha 
Published: January 2022

Abstract
Gastric schwannoma (GS) is a rare, benign, slow-growing neoplasm representing 0.2% of all gastric tumors. We report a rare case of Gastric schwannoma in a 56 year old woman who presented with abdominal discomfort and vomiting since few years. Contrast enhanced Computed Tomography showed a well-defined homogeneously attenuating lesion with homogenous enhancement. Wedge gastrectomy was done with a possible diagnosis of Gastrointestinal stromal tumor, but was confirmed to have Gastric schwannoma on histopathology showing spindle cells with peripheral cuff of lymphoid aggregates and S-100 protein positivity on immunohistochemistry. Gastric schwannoma should be included in the differential diagnosis of a gastric intramural or exophytic mass when Computed Tomography shows a well-defined homogeneously attenuating lesion with progressively increasing homogenous enhancement without hemorrhage, necrosis, and degeneration.
Evaluation of the Kano State Lassa Fever Surveillance System, 2015-2018 – Nigeria
Authors: Umar Usman yahya , Abubakar Mikha'il Abdu , Bello Imam Wada , Balogun Muhammad Shakir , Tahir Sadiq , Umeokonkwo Chukwuma David 
Published: January 2022

Abstract
BackgroundLassa fever (LF) is one of the priority diseases under surveillance through the integrated disease surveillance and response system (IDSR). We evaluated the LF surveillance system against its set objectives and assessed its attributes. MethodsWe used cross-sectional study design. Forty-seven stakeholders involved in the surveillance system were interviewed using the Centers for Disease Control and Prevention’s Updated Guidelines for Evaluating Public Health Surveillance Systems. The LF surveillance data from January 2015 to December 2018 were also analyzed. The attribute and objectives of the system were evaluated. ResultsOut of the 76 suspected cases recorded in kano state during the study period, only 54 samples were laboratory tested, 11 of them were confirmed positive with 9 deaths (case fatality rate of 82%). Confirmed cases were predominantly in Tudun Wada LGA (63.6%), while the age-group 20-39 years constituted 55% of the confirmed cases. There was male preponderance of cases (73%). The predictive value positive (PVP) was 14.5%. The surveillance system was however meeting its objectives of determining LF burden and detecting and characterizing cases and outbreak.ConclusionLF surveillance system in Kano was simple, flexible, stable, acceptable and timely. However, data was not representative. We recommended improved reporting from private and tertiary facilities and more personnel training and support to improve the system.
Wallop of Symptoms and Co-morbidities on COVID-19 Outcome
Authors: Abo ElNaga Heba H. , AbdelHalim Hesham A. , Abdellatif Mohamed , BG Haroun , Elnagdy Basem , Ashraf Taghreed , ElNaggar Bahaa , S. Eldin Passant , TA Ismail , Mosaad Beshoy , Ismail Tasbeeha , Boules Rasmy , Methuselah Shawky , Rafaat Paula 
Published: January 2022

Background:
Fever, cough, fatigue, and myalgia are usually the original clinical picture of the COVID-19 pandemic, which appears non-specific and not exclusive.

Objectives:
To illustrate the clinical picture pattern and assess the prevalence of underlying co-morbidities and their correlation with the severity of COVID-19 infected patients.

Methods:
A cross-sectional online survey included 580 participants who were either suspected or confirmed with COVID-19 infection.

Results:
The severity of the disease significantly correlates with both age (p=.01) and the time lag of the diagnosis of COVID-19 (p=.03). Hypertension (p=.015) and diabetes mellitus (p<.01) were significantly associated with the duration of symptoms. A wide range of ages (21-60 years) seemed to be the only risk factor for the severity. When symptoms were tested, dyspnea appeared to be the most prevalent symptom, predicting a more severe disease (OR= .066, 95% CI: .022- .200), followed by diarrhea (OR= .285, 95% CI: .122-.663), then fever (OR= .339, 95% CI: .139-.824). During the examination of co-morbidities influences on the severity, the only major co-morbidity that predicted a more severe disease was IHD (OR= .218, 95% CI: .073- .648), p= .006.

Conclusion:
Special consideration is required for patients with COVID-19 with an associated longer gap between symptoms and diagnosis and associated co-morbidities including hypertension, diabetes, and established chronic kidney disease (CKD), for which this study proved its profound influence on the severity of the illness and duration of symptoms.
DDH Diagnosis: What do we Know so Far?
Authors: Al-Naser Saeed , Altamimi Anas A.R. 
Published: January 2022

Background:
Developmental Dysplasia of the Hip (DDH) is a common disease worldwide. The success of treatment depends on making an early and accurate diagnosis using clinical examination and imaging. Diagnosis of DDH patients is challenging and controversial, and many cases still present late. There is still a lack of consensus among health care providers regarding the diagnostic methods in terms of interpretation, accuracy and appropriate timing. The clinical practice seems to widely vary between healthcare providers in different parts of the world.

Aims:
We aim to provide a clear pathway to help healthcare professionals from different disciplines in diagnosing DDH at the earliest age possible in order to start an effective treatment and avoid complex procedures and unnecessary complications. We also aim to provide an extensive review that will provide a standardized reference detailing the whole diagnostic process in order to improve the clinical outcome and save resources.

Methods:
We reviewed the relevant literature using Pubmed, Google Scholar, and the Cochrane library and looked into the references lists of all of these papers to gather all the available evidence. All papers were carefully critiqued to use the most rigorous in the conclusions of this review. We included articles discussing clinical examination and radiological diagnosis. Papers discussing the most used clinical examination tests and the timing of clinical evaluation were reviewed. Also, we looked into papers discussing radiological diagnosis using ultrasound scanning and standard radiographs in terms of sensitivity, specificity and reliability and their relation to patient’s age and other variables.

Results:
DDH diagnosis must start at a very young age by repeated examination using specific clinical tests looking mainly for signs of major instability. Ultrasound scanning is the investigation of choice in screening and early diagnosis, and the Graf method seems to be the most reliable method. X-rays are not reliable in early diagnosis, especially in the first four months of life, and can lead to over-diagnosis, particularly when using the Acetabular Index as the sole measurement tool.

Conclusion:
DDH diagnosis has many controversies, and the practice is still widely variable. This review provides an evidence-based, updated pathway for early DDH diagnosis in order to improve the clinical outcome, avoid complications, reduce the need for surgical treatment and save public resources. It highlights some malpractices that are still used in the diagnostic process. The review provides a standardized reference to doctors from different specialties and with different experience levels who are tasked with assessing children for DDH.