bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobility and freedom of movement: A novel out-of-hospital treatment for pediatric patients with terminal cardiac insufficiency and a ventricular assist device
Authors: Rottermann Kathrin , Dittrich Sven , Dewald Oliver , Teske Andreas , Kwapil Nicola , Bleck Steffen , Purbojo Ariawan , Münch Frank 
Published: November 2022

BackgroundDue to rapid medical and technological progress, more and more pediatric patients with terminal cardiac insufficiency are being implanted with a ventricular assist device as a bridge to transplant without legal approval for hospital discharge. EXCOR® Active is a recently developed mobile driving unit for the EXCOR® ventricular assist device (EXCOR® VAD) with a long-lasting battery life that can manage small blood pumps, offering improved mobility for pediatric patients. This study strives to elaborate the requirements necessary for a safe home healthcare environment (HHE) for pediatric patients on EXCOR® VAD powered by the EXCOR® Active driving unit.Materials and methodsPatient- and device-related preconditions (medical, ethical, psychological, technical, structural, organizational) were analyzed with regard to feasibility and safety in three individual patient cases. Included were pediatric patients with terminal cardiac insufficiency in a stable medical condition receiving in-hospital treatment with a univentricular or biventricular EXCOR® VAD powered by EXCOR® Active. Analysis was single-center, data was obtained 05/2020–02/2022.ResultsA total of three patients on EXCOR® VAD were identified for HHE treatment with the EXCOR® Active driving unit. Switch was performed safely and increased mobility led to improved psychomotor development and improved quality of life. No complications directly related to HHE-treatment occurred. One patient recently underwent an orthotopic heart transplant, one patient remains in HHE, and one patient died due to a complication not related to the HHE. Ethical approval for off-label use was obtained and patients and parents were given the required technical training and psychological support. Caregivers and medical professionals involved in the patients’ care at home were briefed intensely. Remote consultations were implemented and interdisciplinary in-hospital checks reduced to a long-term 4-week-scheme.ConclusionWhile it is challenging to discharge pediatric patients being treated with a paracorporeal ventricular assist device (EXCOR® VAD) from hospital, it is feasible and can be managed safely with the novel driving unit EXCOR® Active. A HHE may help to improve patients’ psychomotor development, offer normalized social contacts and strengthen both patients’ and parents’ physical and mental resources. Legal approval and another study with a larger sample size are warranted.
Case report: Cefoperazone-sulbactam induced Kounis syndrome and cardiogenic shock
Authors: Ding Peng , Zhou Yuan , Long Kun-lan , Zhang Li , Gao Pei-yang 
Published: November 2022

BackgroundKounis syndrome is a hypersensitive coronary artery disease caused by the body's exposure to allergens, which is induced by various drugs and environmental factors. This entity has been described primarily in isolated case reports and case series. We report a case of type III Kounis syndrome caused by cefoperazone-sulbactam.Case presentationA 79-year-old man who received an infusion of cefoperazone-sulbactam in Respiratory Department of our hospital for recurrent infections. 28 minutes later, he developed skin flushing of the trunk and extremities, soon followed by loss of consciousness and shock. With antianaphylaxis, pressor therapy, and fluid rehydration, the patient was admitted to the ICU for treatment. During which, he experienced recurrent ventricular fibrillation and a progressive increase in troponin I levels. The ECG of the patient showed that the ST segment elevation of lead II, III, avF, and V3R–V5R was 0.10–0.20 MV. An urgent coronary angiography showed an in-stent thrombosis in the middle part of the right coronary artery, occlusion of the distal flow with TIMI grade 0. The diagnosis was type III Kounis syndrome with cardiogenic shock. Despite aggressive treatment, the patient died on day 7 after ICU admission.ConclusionKunis syndrome is a life-threatening disease, and therefore allergic reactions in patients with a history of cephalosporin allergy and coronary stent implantation should be considered and treated promptly.
Protective effects of safranal on diabetic retinopathy in human microvascular endothelial cells and related pathways analyzed with transcriptome sequencing
Authors: Xiao Qin , Sun Yao-Yao , Lu Zhan-Jun , Li Shan-shan , Su Riguga , Chen Wen-Lin , Ran Lin-Lin , Zhang Surina , Deng Kaixin , Yu Wen-Zhen , Chen Wenqian 
Published: November 2022

AimTo determine the effect of safranal on diabetic retinopathy in vitro and its possible mechanisms.MethodsWe used human retinal microvascular endothelial cells (HRMECs) to test the influence of safranal in vitro. High glucose damage was established and an safranal was tested at various concentrations for its potential to reduce cell viability using the MTT assay. We also employed apoptosis detection, cell cycle detection, a transwell test, and a tube formation assay to look into safranal’s inhibitory effects on high glucose damage at various doses. Furthermore, mRNA transcriptome sequencing was performed. mRNA expression levels in a high glucose damage model, a high glucose damage model treated with safranal, and a blank control were compared to find the possible signaling pathway. Western blotting was used to confirm the expressions of several molecules and the levels of phosphorylation in each for the newly discovered pathway.ResultsCell proliferation was inhibited under a high glucose condition but could be protected by safranal at different concentrations (P&lt;0.001). Flow cytometry results suggested safranal also protected cells from apoptosis (P=0.006). A transwell test demonstrated reduced invasiveness of safranal-treated cells in a high glucose condition (P&lt;0.001). In a tube formation investigation, there were noticeably more new branches in the high gloucose group compared to a high glucose treated with safranal group (P&lt;0.001). In mRNA expression patterns on transcriptome sequencing, the MAPK signaling pathway showed an expression ratio. With western blotting, the phosphorylation level of p38-AKT was elevated under a high glucose condition but could be inhibited by safranal. The expression of molecules associated with cell adhesion, including E-cadherin, N-cadherin, Snail, Twist, and fibronectin also changed significantly after safranal treatment under a high glucose condition.ConclusionSafranal can protect diabetic retinopathy in vitro, and the p38-AKT signaling pathway was found to be involved in the pathogenesis of diabetic retinopathy and could be inhibited by safranal. This pathway may play a role by influencing cell migration and adhesion.
Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of gestational diabetes mellitus
Authors: Lu Ling , Li Chanyu , Deng Jie , Luo Jianbo , Huang Chaolin 
Published: November 2022

ObjectiveGestational diabetes mellitus (GDM) has adverse effects on the health of mothers and their offspring. Currently, no known biomarker has been proven to have sufficient validity for the prediction of GDM in the first trimester of pregnancy. The aim of this study was to investigate the potential relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) levels in the first trimester of pregnancy and later GDM risk and to evaluate the performance of serum NGAL as a biomarker for the prediction of GDM.MethodsThe study was conducted by recruiting participants at 8–13 weeks of gestation from The First Affiliated Hospital of Chengdu Medical College between January and June 2021; participants were followed up for oral glucose tolerance test (OGTT) screening at 24–28 gestational weeks. We examined the serum NGAL levels of all subjects in the first trimester who met the inclusion and exclusion criteria. Anthropometric, clinical, and laboratory parameters of the study subjects were obtained during the same study period. A logistic regression model was carried out to investigate the potential relationship between serum NGAL levels in the first trimester of pregnancy and later GDM risk. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the discrimination and calibration of serum NGAL as a biomarker for the prediction of GDM in the first trimester of pregnancy.ResultsSerum NGAL levels in the first trimester of pregnancy were significantly higher in women who later developed GDM than in those who did not develop GDM. Serum NGAL levels in the first trimester of pregnancy were positively associated with an increased risk of GDM after adjustment for potential confounding factors. The risk prediction model for GDM constructed by using serum NGAL levels in the first trimester of pregnancy achieved excellent performance.ConclusionsMaternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of GDM, which could help guide the clinical practice of antenatal care.
Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
Authors: Yu Yang , Huang Yuexi , Li Chen , Ou Santao , Xu Chaojie , Kang Zhengjun 
Published: November 2022

Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well.Methods: CIBERSOR algorithm was applied for identification tumor-infiltrating immune cells (TICs) subtypes of subjects from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. We identified potential modules of M1 macrophages by weighted gene co-expression network analysis (WGCNA). Nomogram was determined by one-way Cox regression and lasso regression analysis for M1 macrophage genes. The data from GEO are taken to verify the models externally. Kaplan-Meier and receiver operating characteristic (ROC) curves validated prognostic value of M1 macrophage genes. Finally, we divided patients into the low-risk group (LRG) and the high-risk group (HRG) based on the median risk score (RS), and the predictive value of RS in patients with BLCA immunotherapy and chemotherapy was investigated. Bladder cancer (T24, 5637, and BIU-87) and bladder uroepithelial cell line (SV-HUC-1) were used for in vitro validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to validate the associated genes mRNA level.Results: 111 macrophage M1-related genes were identified using WGCNA. RS model containing three prognostically significant M1 macrophage-associated genes (FBXO6, OAS1, and TMEM229B) was formed by multiple Cox analysis, and a polygenic risk model and a comprehensive prognostic line plot was developed. The calibration curve clarified RS was a good predictor of prognosis. Patients in the LRG were more suitable for programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associate protein-4 (CTLA4) combination immunotherapy. Finally, chemotherapeutic drug models showed patients in the LRG were more sensitive to gemcitabine and mitomycin. RT-qPCR result elucidated the upregulation of FBXO6, TMEM229B, and downregulation of OAS1 in BLCA cell lines.Conclusion: A predictive model based on M1 macrophage-related genes can help guide us in the treatment of BLCA.
Combined impact of the inter and intra-patient variability of tacrolimus blood level on allograft outcomes in kidney transplantation
Authors: Park Yohan , Lee Hanbi , Eum Sang Hun , Ko Eun Jeong , Min Ji Won , Yoon Se-Hee , Hwang Won-Min , Yun Sung-Ro , Yang Chul Woo , Shin Jieun , Chung Byung Ha 
Published: November 2022

IntroductionTacrolimus (TAC) has been widely used as an immunosuppressant after kidney transplantation (KT); however, the combined effects of intra-patient variability (IPV) and inter-patient variability of TAC-trough level (C0) in blood remain controversial. This study aimed to determine the combined impact of TAC-IPV and TAC inter-patient variability on allograft outcomes of KT.MethodsIn total, 1,080 immunologically low-risk patients who were not sensitized to donor human leukocyte antigen (HLA) were enrolled. TAC-IPV was calculated using the time-weighted coefficient variation (TWCV) of TAC-C0, and values &gt; 30% were classified as high IPV. Concentration-to-dose ratio (CDR) was used for calculating TAC inter-patient variability, and CDR &lt; 1.05 ng•mg/mL was classified as rapid metabolizers (RM). TWCV was calculated based on TAC-C0 up to 1 year after KT, and CDR was calculated based on TAC-C0 up to 3 months after KT. Patients were classified into four groups according to TWCV and CDR: low IPV/non-rapid metabolizer (NRM), high IPV/NRM, low IPV/RM, and high IPV/RM. Subgroup analysis was performed for pre-transplant panel reactive antibody (PRA)-positive and -negative patients (presence or absence of non-donor-specific HLA-antibodies). Allograft outcomes, including deathcensored graft loss (DCGL) and biopsy-proven allograft rejection (BPAR), were compared.ResultsThe incidences of DCGL, BPAR, and overall graft loss were the highest in the high-IPV/RM group. In addition, a high IPV/RM was identified as an independent risk factor for DCGL. The hazard ratio of high IPV/RM for DCGL and the incidence of active antibody-mediated rejection were considerably increased in the PRA-positive subgroup.DiscussionHigh IPV combined with RM (inter-patient variability) was closely related to adverse allograft outcomes, and hence, more attention must be given to pre-transplant PRA-positive patients.
PET image enhancement using artificial intelligence for better characterization of epilepsy lesions
Authors: Flaus Anthime , Deddah Tahya , Reilhac Anthonin , Leiris Nicolas De , Janier Marc , Merida Ines , Grenier Thomas , McGinnity Colm J. , Hammers Alexander , Lartizien Carole , Costes Nicolas 
Published: November 2022

Introduction[18F]fluorodeoxyglucose ([18F]FDG) brain PET is used clinically to detect small areas of decreased uptake associated with epileptogenic lesions, e.g., Focal Cortical Dysplasias (FCD) but its performance is limited due to spatial resolution and low contrast. We aimed to develop a deep learning-based PET image enhancement method using simulated PET to improve lesion visualization.MethodsWe created 210 numerical brain phantoms (MRI segmented into 9 regions) and assigned 10 different plausible activity values (e.g., GM/WM ratios) resulting in 2100 ground truth high quality (GT-HQ) PET phantoms. With a validated Monte-Carlo PET simulator, we then created 2100 simulated standard quality (S-SQ) [18F]FDG scans. We trained a ResNet on 80% of this dataset (10% used for validation) to learn the mapping between S-SQ and GT-HQ PET, outputting a predicted HQ (P-HQ) PET. For the remaining 10%, we assessed Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), and Root Mean Squared Error (RMSE) against GT-HQ PET. For GM and WM, we computed recovery coefficients (RC) and coefficient of variation (COV). We also created lesioned GT-HQ phantoms, S-SQ PET and P-HQ PET with simulated small hypometabolic lesions characteristic of FCDs. We evaluated lesion detectability on S-SQ and P-HQ PET both visually and measuring the Relative Lesion Activity (RLA, measured activity in the reduced-activity ROI over the standard-activity ROI). Lastly, we applied our previously trained ResNet on 10 clinical epilepsy PETs to predict the corresponding HQ-PET and assessed image quality and confidence metrics.ResultsCompared to S-SQ PET, P-HQ PET improved PNSR, SSIM and RMSE; significatively improved GM RCs (from 0.29 ± 0.03 to 0.79 ± 0.04) and WM RCs (from 0.49 ± 0.03 to 1 ± 0.05); mean COVs were not statistically different. Visual lesion detection improved from 38 to 75%, with average RLA decreasing from 0.83 ± 0.08 to 0.67 ± 0.14. Visual quality of P-HQ clinical PET improved as well as reader confidence.ConclusionP-HQ PET showed improved image quality compared to S-SQ PET across several objective quantitative metrics and increased detectability of simulated lesions. In addition, the model generalized to clinical data. Further evaluation is required to study generalization of our method and to assess clinical performance in larger cohorts.
Intention to give birth in the health institutions and associated factors among women who gave birth in the last 6 months in Debre Berhan town, North Showa zone, Ethiopia: A community-based cross-sectional study
Authors: Amare Nakachew Sewnet , Mekuriyaw Abebayehu Melesew , Tesema Getaye Worku , Ambaw Yeshinat Lakew 
Published: November 2022

BackgroundInstitutional delivery is a proxy for skilled birth attendance, which is an important intervention to reduce maternal and neonatal mortality. Even though institutional delivery has such importance, significant numbers of women in Ethiopia do not prefer to give birth in health institutions. This study aimed to assess women’s intention to give birth in health institutions and associated factors among women who gave birth in the last 6 months in Debre Berhan town, North Showa Zone, Ethiopia, 2020.Materials and methodsA community-based cross-sectional study was conducted among women who gave birth in the last 6 months in Debre Berhan town from October 30 to November 30, 2020. A cluster sampling technique was used to select study participants. Pretested semi-structured interviewer-administered questionnaires were administered. A logistic regression model was performed, and adjusted odds ratios with a 95% confidence interval based on p &lt; 0.05 were used to identify statistically significant variables.ResultThis study found that a total of 689 (88.8%) (95% CI: 86.6, 91%) respondents intended to deliver in the health facility. Being multiparous [AOR = 0.18 (95% CI: 0.08, 0.36)], having planned pregnancy [AOR = 3.1 (95% CI: 1.6, 5.9)], had no complications during previous delivery (AOR = 6.0 (95% CI: 3.5, 10.4)], and received respectful maternity care (RMC) during preceding delivery [AOD = 1.8 (95% CI: 1.05, 3.10)] are significantly associated with women’s intention to give birth in the health institution.ConclusionChildbirth is a special event that requires the safest place to save the lives of both the mother and newborn. In this study, the number of women who do not have the intention to give birth in the health institution is still high. Strategies to promote planned pregnancy, reduce complications during childbirth and provide RMC during childbirth should be designed and interventions should be implemented for all childbearing women.
The anorexic effect of DL-fenfluramine is dependent on animals' habituation to different food types
Authors: Yi Sun Shin , Choi SuJean 
Published: November 2022

BackgroundAs rates of obesity and diabetes have increased dramatically over the past few decades, the use of anti-obesity drugs has now become a routine therapeutic measure. However, the pharmacological effects of chronic use of these drugs in humans frequently lead to reduced efficacy in reducing appetite and body weight through as-yet-unidentified mechanisms. An example of this can be found in animal studies where the appetite suppressant DL-fenfluramine (FEN) is chronically administered and its tolerance develops in animals and humans. The appetite effects of FEN are typically measured in several animal studies by the feeding changes in a balanced standard diet. To determine whether FEN differentially altered appetite suppression in animals with long-term expression with different macronutrient diet compositions, its anorexic effects were measured specifically in male rats that had previously been chronically maintained on normal chow (NC) or a high-fat and high-carbohydrate western diet (WD).MethodsThree experiments were conducted by feeding the animals either NC or WD for 1 month to habituate them with their diet. Animals maintained on either NC or WD were subsequently offered both diet options ad libitum for a 2- or 7-day adaptation period while receiving daily systemic FEN treatment.ResultsThe results suggested that long-term habituated food affected the food preference of animals and their appetite even after chronic systemic FEN administration. Therefore, the effectiveness and success or failure of repeated use of chronic anti-obesity drugs may depend on habituated food type.ConclusionThe appetite suppressant effect was found to be determined by the palatability of a specific macronutrient and the habituated food rather than by a change in the concentration of the administered FEN. This results in a critical analysis of the rationale for taking medication considering the patient's past dietary habits to achieve successful weight loss.
PD-1 inhibitors plus nab-paclitaxel-containing chemotherapy for advanced gallbladder cancer in a second-line setting: A retrospective analysis of a case series
Authors: Tan Sirui , Yu Jing , Huang Qiyue , Zhou Nan , Gou Hongfeng 
Published: November 2022

BackgroundGallbladder cancer (GBC) is a fatal cancer, and the efficacy of the current standard second-line chemotherapy for GBC is limited. Novel therapies need to be explored. This retrospective analysis was aimed to investigate the outcomes of patients treated at West China Hospital with PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy (nab-paclitaxel monotherapy or nab-paclitaxel plus other cytotoxic agents) in a second-line setting.MethodsBetween April 2020 and May 2022, the patients with advanced GBC receiving PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy after resistance to first-line gemcitabine-based chemotherapy at West China Hospital were retrospectively screened.ResultsEleven patients were included, and all received gemcitabine-based chemotherapy as first-line therapy. Eight patients underwent next-generation sequencing (NGS), and all had microsatellite stability (MSS) and a low tumor mutation burden (TMB). Six patients were negative for PD-L1 expression and one patient was positive for PD-L1. Therapeutically relevant genetic alterations were not found. All patients received PD-1 inhibitors in combination with nab-paclitaxel-based chemotherapy as second-line therapy. Pembrolizumab was administered in 3 patients, and sintilimab was administered in eight patients. One patient had no measurable target lesion. Complete response (CR) was observed in one (10.0%) patient, partial response (PR) in four (40%) patients, and stable disease (SD) in four (40%) patients. The median progression-free survival (PFS) was 7.5 (95% CI: 2.5-12.5) months, and the median overall survival (OS) was 12.7 (95% CI: 5.5-19.9) months. The adverse events (AEs) were manageable.ConclusionOur results suggest that PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy as second-line therapy for advanced GBC might be a potential treatment and deserves further evaluation.