bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in advanced biliary tract cancer
Authors: Zhu Chengpei , Xue Jingnan , Wang Yunchao , Wang Shanshan , Zhang Nan , Wang Yanyu , Zhang Longhao , Yang Xu , Long Junyu , Yang Xiaobo , Sang Xinting , Zhao Haitao 
Published: January 2023

BackgroundLenvatinib combined with anti-PD-1 antibodies and systemic chemotherapy has demonstrated a relatively high antitumor activity for intrahepatic cholangiocarcinoma in phase 2 clinical trials. However, its efficacy and safety in advanced biliary tract cancer (BTC) has not been reported in a real-world study.MethodsPatients with advanced BTC who received lenvatinib combined with PD-1/PD-L1 inhibitors plus oxaliplatin and gemcitabine (Gemox) chemotherapy were retrospectively screened. The overall survival, progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety were evaluated.ResultsFifty-seven patients with advanced BTC were included in the study. The median follow-up time was 15.1 (95% CI: 13.6–19.7) months. The median overall survival and progression-free survival were 13.4 (95% CI: 10.0–NA), and 9.27 (95% CI: 7.1–11.6) months, respectively. The objective response rate, disease control rate and clinical benefit rate were 43.9% (95% CI: 31.8%–56.7%), 91.2% (95% CI: 81.1%–96.2%), and 73.7% (95% CI: 61.0%–83.4%), respectively. Subgroup analysis revealed that the first-line treatment group had a longer median progression-free survival (12.13 vs. 6.77 months, P&lt;0.01) and median overall survival (25.0 vs. 11.6 months, P=0.029) than the non-first-line treatment group. Moreover, three patients underwent conventional surgery after treatment. All patients (100%) experienced adverse events, and 45.6% (26/57) experienced grade 3 or 4 adverse events. The most commonly observed grade 3 or 4 adverse events was myelosuppression (7/57, 12.3%). No grade 5 adverse events were reported.ConclusionLenvatinib combined with PD-1/PD-L1 inhibitors and Gemox chemotherapy represents an effective and tolerable treatment option in patients with advanced BTC.
Seasonal variability in spatial patterns of sea surface cold- and warm fronts over the continental shelf of the northern South China Sea
Authors: Chen Jiayuan , Hu Zifeng 
Published: January 2023

Ubiquitous fronts are a key part of energy transfer from large scales to small scales and exert a great impact on material exchange and biogeochemical processes. The spatial pattern and seasonal variability of cold- and warm fronts over the wide shelf of the northern South China Sea (SCS) are investigated using a 20-year time series (2002−2021) of 1-km spatial resolution Group for High Resolution Sea Surface Temperature (GHRSST) images. Our analysis shows distinct spatial and temporal variability in the occurrence of the cold- and warm fronts. Over the inner shelf (depth &lt;50 m), the band-shaped cold fronts are predominately observed during spring through autumn from east of Hainan Island to Taiwan Shoal, with the presence of the maximum intensity and probability in winter. The frontal formations are possibly associated with the joint effect of the Guangdong Coastal Current (GCC) and the South China Sea Warm Current. During summer, the inshore fronts have relatively low probability and gradient magnitude. The warm fronts mainly occur off the western Guangdong coast possibly due to the southwestward-flowing GCC, whereas the cold fronts dominate off the eastern Guangdong coast and the eastern Hainan Island largely because of the coastal upwelling. Over the outer shelf (depth &gt;50 m), the finer-scale cold- and warm fronts are discretely observed, with relatively weaker intensity and lower probability. The frontal activities are very vigorous in winter but slightly quiescent in summer, apparently resulting from the influence of the rich submesoscale processes in the SCS. This study could help improve our understanding of the SCS oceanic multiscale dynamics.
Epidemiological and genomic characteristics of global mcr-positive Escherichia coli isolates
Authors: Shi Jiping , Zhu Hong , Liu Chang , Xie Hui , Li Chuchu , Cao Xiaoli , Shen Han 
Published: January 2023

ObjectiveThe worldwide dissemination of colistin-resistant Escherichia coli (E. coli) endangers public health. This study aimed to better understand the global genomic epidemiology of E. coli isolates carrying mobilized colistin resistance (mcr) genes, providing information to assist in infection and prevention.MethodsEscherichia coli genomes were downloaded from NCBI, and mcr was detected using BLASTP. Per software was used to extract information on hosts, resources, collection data, and countries of origin from GenBank. Sequence types (STs), prevalence of plasmids, antimicrobial resistance genes (ARG), and virulence factors (VF) in these genomes were analyzed. Statistical analyses were performed to assess the relationships between mcr, ARGs, plasmids, and STs.ResultsIn total, 778 mcr-positive isolates were identified. Four mcr variants were detected, with mcr-1 (86.1%) being the most widespread, followed by mcr-9 (5.7%), mcr-5 (4.4%), and mcr-3 (3.0%). Multiple ARGs were identified, with blaCTX–M (53.3%), fosA (28.8%), qnr (26.1%), blaNDM (19.8%), and aac (6’)-Ib-cr (14.5%) being the most common. Overall, 239 distinct STs were identified, of which ST10 (13.8%) was the most prevalent. A total of 113 different VFs were found, terC (99.9%) and gad (83.0%) were most frequently detected. Twenty types of plasmids were identified; IncFIB (64.1%), IncX (42.3%), and IncX (42.3%) were the most common replicons. IncI2 and IncX4 were frequently detected in mcr-1-positive isolates, whereas IncFII, IncI1-I, and IncHI2 were dominant plasmids in mcr-3, mcr-5, and mcr-9-positive isolates, respectively. A higher frequency of ARGs and VFs was observed among ST156 and ST131 isolates.ConclusionOur data indicated that more than half of the mcr-positive E. coli strains carried endemic ARGs and VFs. ST10 and ST156 isolates deserved further attention, given the rapid transmission of ST10 and the convergence of ARGs and VFs in ST156.
Pre- and in-hospital delays in the use of thrombolytic therapy for patients with acute ischemic stroke in rural and urban Egypt
Authors: Nasreldein Ahmed , Walter Silke , Mohamed Khaled O. , Shehata Ghaydaa Ahmed , Ghali Azza A. , Dahshan Ahmed , Faßbender Klaus , Abd-Allah Foad 
Published: January 2023

BackgroundReducing pre- and in-hospital delays plays an important role in increasing the rate of intravenous thrombolysis (IVT) in patients with acute ischemic stroke. In Egypt, the IVT rate has increased steadily but is still far away from an ideal rate.AimThe study aimed to investigate the factors associated with pre- and in-hospital delays of IVT among patients with acute ischemic stroke coming from urban and rural communities.MethodsThis prospective, multicenter, observational cohort study was conducted from January 2018 to January 2019. Patients with acute ischemic stroke, who did not receive IVT, were included in the study. Patients were recruited from three large university stroke centers in Egypt, Assiut (south of Egypt), Tanta (north of Egypt), both serving urban and rural patients, and the University Hospital in Cairo (capital city), only serving an urban community. All participants underwent the National Institutes of Health Stroke Scale and full neurological assessment, urgent laboratory investigations, and computed tomography or magnetic resonance imaging to confirm the stroke diagnosis. The patients were subjected to a structured questionnaire that was designed to determine the parameters and time metrics for the pre- and in-hospital delays among patients from rural and urban regions.ResultsA total of 618 patients were included in the study, of which 364 patients (58.9%) lived in rural regions and 254 (41.1%) in urban regions. General demographic characteristics were similar between both groups. Approximately 73.3% of patients who arrived within the therapeutic time window were urban patients. The time from symptom onset till hospital arrival (onset to door time, ODT) was significantly longer among rural patients (738 ± 690 min) than urban patients (360 ± 342 min). Delayed onset to alarm time (OAT), initial misdiagnosis, and presentation to non-stroke-ready hospitals were the most common causes of pre-hospital delay and were significantly higher in rural patients. For patients arriving within the time window, the most common causes of in-hospital delays were prolonged laboratory investigations and imaging duration.ConclusionThe limited availability of stroke-ready hospitals in rural Egypt leads to delays in stroke management, with subsequent treatment inequality of rural patients with acute stroke.
Application of TBSS-based machine learning models in the diagnosis of pediatric autism
Authors: He Xiongpeng , Zhao Xin , Sun Yongbing , Geng Pengfei , Zhang Xiaoan 
Published: January 2023

ObjectiveTo explore the microstructural changes of white matter in children with pediatric autism by using diffusion kurtosis imaging (DKI), and evaluate whether the combination of tract-based spatial statistics (TBSS) and back-propagation neural network (BPNN)/support vector machine (SVM)/logistic regression (LR) was feasible for the classification of pediatric autism.MethodsDKI data were retrospectively collected from 32 children with autism and 27 healthy controls (HCs). Kurtosis fractional anisotropy (FAK), mean kurtosis (MK), axial kurtosis (KA), radial kurtosis (RK), fractional anisotropy (FA), axial diffusivity (DA), mean diffusivity (MD) and Radial diffusivity (DR) were generated by iQuant workstation. TBSS was used to detect the regions of parameters values abnormalities and for the comparison between these two groups. In addition, we also introduced the lateralization indices (LI) to study brain lateralization in children with pediatric autism, using TBSS for additional analysis. The parameters values of the differentiated regions from TBSS were then calculated for each participant and used as the features in SVM/BPNN/LR. All models were trained and tested with leave-one-out cross validation (LOOCV).ResultsCompared to the HCs group, the FAK, DA, and KA values of multi-fibers [such as the bilateral superior longitudinal fasciculus (SLF), corticospinal tract (CST) and anterior thalamic radiation (ATR)] were lower in pediatric autism group (p &lt; 0.05, TFCE corrected). And we also found DA lateralization abnormality in Superior longitudinal fasciculus (SLF) (the LI in HCs group was higher than that in pediatric autism group). However, there were no significant differences in FA, MD, MK, DR, and KR values between HCs and pediatric autism group (P &gt; 0.05, TFCE corrected). After performing LOOCV to train and test three model (SVM/BPNN/LR), we found the accuracy of BPNN (accuracy = 86.44%) was higher than that of LR (accuracy = 76.27%), but no different from SVM (RBF, accuracy = 81.36%; linear, accuracy = 84.75%).ConclusionOur proposed method combining TBSS findings with machine learning (LR/SVM/BPNN), was applicable in the classification of pediatric autism with high accuracy. Furthermore, the FAK, DA, and KA values and Lateralization index (LI) value could be used as neuroimaging biomarkers to discriminate the children with pediatric autism or not.
Neural basis of dysphagia in stroke: A systematic review and meta-analysis
Authors: Qin Yin , Tang Yuting , Liu Xiaoying , Qiu Shuting 
Published: January 2023

ObjectivesDysphagia is a major cause of stroke infection and death, and identification of structural and functional brain area changes associated with post-stroke dysphagia (PSD) can help in early screening and clinical intervention. Studies on PSD have reported numerous structural lesions and functional abnormalities in brain regions, and a systematic review is lacking. We aimed to integrate several neuroimaging studies to summarize the empirical evidence of neurological changes leading to PSD.MethodsWe conducted a systematic review of studies that used structural neuroimaging and functional neuroimaging approaches to explore structural and functional brain regions associated with swallowing after stroke, with additional evidence using a live activation likelihood estimation (ALE) approach.ResultsA total of 35 studies were included, including 20 studies with structural neuroimaging analysis, 14 studies with functional neuroimaging analysis and one study reporting results for both. The overall results suggest that structural lesions and functional abnormalities in the sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections in individuals with stroke may contribute to dysphagia, and the ALE analysis provides additional evidence for structural lesions in the right lentiform nucleus and right thalamus and functional abnormalities in the left thalamus.ConclusionOur findings suggest that PSD is associated with neurological changes in brain regions such as sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections. Adequate understanding of the mechanisms of neural changes in the post-stroke swallowing network may assist in clinical diagnosis and provide ideas for the development of new interventions in clinical practice.
2.5D and 3D segmentation of brain metastases with deep learning on multinational MRI data
Authors: Ottesen Jon André , Yi Darvin , Tong Elizabeth , Iv Michael , Latysheva Anna , Saxhaug Cathrine , Jacobsen Kari Dolven , Helland Åslaug , Emblem Kyrre Eeg , Rubin Daniel L. , Bjørnerud Atle , Zaharchuk Greg , Grøvik Endre 
Published: January 2023

IntroductionManagement of patients with brain metastases is often based on manual lesion detection and segmentation by an expert reader. This is a time- and labor-intensive process, and to that end, this work proposes an end-to-end deep learning segmentation network for a varying number of available MRI available sequences.MethodsWe adapt and evaluate a 2.5D and a 3D convolution neural network trained and tested on a retrospective multinational study from two independent centers, in addition, nnU-Net was adapted as a comparative benchmark. Segmentation and detection performance was evaluated by: (1) the dice similarity coefficient, (2) a per-metastases and the average detection sensitivity, and (3) the number of false positives.ResultsThe 2.5D and 3D models achieved similar results, albeit the 2.5D model had better detection rate, whereas the 3D model had fewer false positive predictions, and nnU-Net had fewest false positives, but with the lowest detection rate. On MRI data from center 1, the 2.5D, 3D, and nnU-Net detected 79%, 71%, and 65% of all metastases; had an average per patient sensitivity of 0.88, 0.84, and 0.76; and had on average 6.2, 3.2, and 1.7 false positive predictions per patient, respectively. For center 2, the 2.5D, 3D, and nnU-Net detected 88%, 86%, and 78% of all metastases; had an average per patient sensitivity of 0.92, 0.91, and 0.85; and had on average 1.0, 0.4, and 0.1 false positive predictions per patient, respectively.Discussion/ConclusionOur results show that deep learning can yield highly accurate segmentations of brain metastases with few false positives in multinational data, but the accuracy degrades for metastases with an area smaller than 0.4 cm2.
The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial
Authors: Ujjan Ikram Din , Khan Saeed , Nigar Roohi , Ahmed Hammad , Ahmad Sagheer , Khan Amjad 
Published: January 2023

BackgroundCurcumin (CUR) and quercetin (QUE), two natural polyphenols, possess diverse biological activities including broad-spectrum antiviral, antioxidant, and immunomodulatory effects. Both CUR and QUE have shown inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in in vitro assays.ObjectiveIn the present study we aimed to assess the possible treatment benefits of a combined curcumin and quercetin (CUR-QUE) oral supplement, alongside standard of care (SOC), in the early-stage COVID-19 infection.MethodsThis was an exploratory, pragmatic, open-label, randomized controlled clinical trial, conducted at the Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro, PK. The study compared the treatment effect of an oral CUR-QUE supplement plus SOC vs. SOC alone, in the early-stage/mild to moderately symptomatic COVID-19 outpatients. Patients were randomized in a 1:1 ratio to CUR-QUE (n = 25) and control (n = 25) treatment groups. The CUR-QUE supplementation consisted of a daily intake of 168 mg curcumin and 260 mg quercetin, as two soft capsules, to be taken twice a day at home for 14 days.ResultsAfter one-week of treatment, most of the patients in the CUR-QUE group showed an expedited clearance of the viral infection i.e., 18 (72.0%) vs. 6 (24.0%) patients in the control group tested negative for SARS-CoV-2 in the nasal-oropharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) analysis (p = 0.0002). In addition, COVID-19-associated acute symptoms were also speedily resolved in the CUR-QUE treated patients, i.e., 10 (40.0%) vs. 4 (16.0%) patients in the control group (p = 0.061). The CUR-QUE supplementation therapy was well-tolerated by all 25 patients and no treatment-emergent effects or serious adverse events were reported.ConclusionThe results revealed in this exploratory study suggest a possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19. It is proposed that the two agents possibly acting in synergy, interfere the SARS-CoV-2 replication, and thus help a speedy recovery in the early-stage of COVID-19. Further research is highly encouraged.Clinical trial registrationClinicaltrials.gov, Identifier NCT04603690.
Association between healthy eating index-2015 and abdominal aortic calcification among US Adults
Authors: Jia Jundi , Zhang Jie , Ma Dan , Zhang Zihao , Zhao Lin , Wang Tongxin , Xu Hao 
Published: January 2023

AimsTo evaluate the relationship of the healthy eating index-2015 (HEI-2015) with abdominal aortic calcification (AAC) in US adults.MethodsWe conducted a cross-sectional study with data extracted from the National Health and Nutrition Examination Survey (NHANES). AAC score was measured using the scoring system of Kauppila (AAC-24) and Schousboe (AAC-8). HEI-2015, which was used for evaluating compliance with Dietary Guidelines for Americans (DGA), was calculated through two rounds of 24-h recall interviews. HEI-2015 was categorized as inadequate (&lt;50), average (50~70), and optimal (≥70) groups for analysis, while the AAC-24 score was grouped by whether the score was &gt;0. Weighted multiple regression analyses were conducted to estimate the association of HEI-2015 with AAC score and the presence of AAC. Moreover, smooth curve fittings, based on a generalized additive model (GAM), were applied to evaluate a possible non-linear relationship. Sensitivity analysis and subgroup analysis were performed to provide more supporting information.ResultsA total of 2,704 participants were included in the study (mean age, 57.61 ± 11.40 years; 51.78% were women). The mean score of HEI-2015 was 56.09 ± 13.40 (41.33 ± 6.28, 59.44 ± 5.54, and 76.90 ± 5.37 for inadequate, average, and optimal groups, respectively). After adjusting for covariates, higher HEI-2015 was associated with decreased AAC score (AAC-24: β = −0.121, 95% CI: −0.214, −0.028, P = 0.010; AAC-8: β= −0.054, 95% CI: −0.088, −0.019, P = 0.003) and lower risk of AAC (OR = 0.921, 95% CI: 0.855, 0.993, P = 0.031). Among the components of HEI-2015, a higher intake of fruits, greens, and beans was associated with a lower AAC score. Subgroup analysis showed that an inverse association of HEI-2015 with AAC score existed among different groups.ConclusionThe study presented that higher HEI-2015 was related to a lower AAC score and decreased risk of having AAC, indicating that greater compliance with 2015–2020 DGA, assessed by HEI-2015, might be beneficial for preventing vascular calcification and CVD among US adults.
The influence of the China GLIM standards on the diagnosis of malnutrition in patients with hematopoietic stem cell transplant
Authors: Guo Feng , Min Liu , Chengyuan Li , Hong Liu , Meng Wang , Chenyi Tang , Jinru Wu , Wei Wu , Hua Liu 
Published: January 2023

BackgroundThe muscle-related indicator is removed from Global Leadership Initiative on Malnutrition (GLIM) criteria implemented in China for many reasons. Patients with hematopoietic stem cell transplants are at nutrition risk and can enter into the second step of GLIM; thus, they are suitable for learning the diagnosing malnutrition significance between primary GLIM and GLIM-China criteria. This article aims to explore the role of muscle mass in the diagnostic criteria of malnutrition and the effects of GLIM-China for diagnosing malnutrition.MethodsA total of 98 inpatients with hematopoietic stem cell transplants (HSCT) were recruited. Nutrition risk was assessed by using the Nutritional Risk Screening 2002 (NRS-2002). Appendicular skeletal muscle mass (ASMI) and fat-free mass index (FFMI) were determined using the bioelectrical impedance analysis (BIA) method. Malnutrition is defined by GLIM-China, GLIM, and PG-SGA. We use erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess inflammation in GLIM and GLIM-China. The correlation or consistency among ASMI, FFMI, ESR, CRP, GLIM-China, GLIM, and PG-SGA was evaluated, respectively.ResultsOne hundred percent instead of the patients had nutritional risk. The magnitude of malnutrition using PG-SGA, GLIM, and GLIM-China was 75.5, 80.6, and 64.3%, respectively. GLIM-China and PG-SGA showed the same performance (p = 0.052 vs. 1.00) and agreement (kappa = 0.404 vs. 0.433, p &lt; 0.0001) with the FFMI. Consistency was noted between ASMI and PG-SGA in the assessment of malnutrition (p = 0.664) with a good agreement (kappa = 0.562, p = 0.084). ASMI and FFMI could determine muscle mass reduction, which could not be determined by BMI, albumin (ALB), and pre-albumin (pre-ALB); 34% of GLIM-China (–) patients were with low ASMI, and 40% with low FFMI; 30.0% of patients with PG-SGA (&lt;4) still have low ASMI, and 38.2% have low FFMI.ConclusionIf only the PG-SGA scale is used as a diagnostic criterion for evaluating malnutrition, a large proportion of patients with reduced muscle mass will be missed, but more patients with muscle loss will be missed via GLIM-China. Muscle-related indicators will help diagnose malnutrition.