bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival
Authors: Ottaiano Alessandro , Santorsola Mariachiara , Circelli Luisa , Perri Francesco , Cascella Marco , Sabbatino Francesco , Capuozzo Maurizio , Granata Vincenza , Zappavigna Silvia , Lombardi Angela , Scrima Marianna , Petrillo Nadia , Ianniello Monica , Casillo Marika , Gualillo Oreste , Nasti Guglielmo , Caraglia Michele , Savarese Giovanni 
Published: January 2023

IntroductionWe studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients.Patients and methodsT2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P &lt; 0.05 were considered statistically significant.ResultsTwo-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) (P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival (P &lt; 0.05). At multivariate analysis, age (≥65 vs. &lt;65 years), response to first-line chemotherapy (DC vs. no DC), and concomitant presence of T2D, BMI, and HT (HR: 4.56; 95% CI: 2.40–8.67; P = 0.0217) emerged as independent prognostic variables. P53 was mutated in 31/53 analyzed cases (60.4%). The most frequent gene variants were p.Arg175His and p.Cys135Tyr. High BMI (&gt;25 kg/m2) associated with occurrence of p53 mutations (P &lt; 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43–7.23; P = 0.0047).ConclusionDiabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence.
Rapid disease progression on immune checkpoint inhibitors in young patients with stage IV melanoma
Authors: Machiraju Devayani , Schäfer Sarah , Beckhove Philip , Roth Jasmin , Schulz Carsten , Hassel Jessica C. 
Published: January 2023

BackgroundImmune checkpoint inhibitors (ICIs) are the standard of care for metastatic cutaneous melanoma (mCM) patients, but their efficacy in young adults aged less than 40 years remains unclear.Materials and methodsWe retrospectively analyzed 303 stage IV melanoma patients of different ages treated with nivolumab, pembrolizumab, or ipilimumab plus nivolumab combination therapy. Clinical data and blood values such as LDH, CRP, and absolute immune cell counts were retrieved from the medical records. Pre-treatment serum concentrations of soluble immune checkpoint proteins were measured using ELISA. In addition, information on frequencies of various T cell subsets in the peripheral blood was collected from a previously reported study (ELEKTRA). Patient characteristics and clinical information was correlated with PFS and OS using univariate and multivariate cox regression analysis.ResultsOf 303 patients, 33 (11%) were ≤ 40 years old. The older patients had a median age of 64 (95% CI: 61–66). Concerning prognostic parameters, there was no difference between the age groups, e.g., in gender, LDH, or the existence of brain or liver metastases. Patients aged ≤ 40 years [p = 0.014; HR: 1.6 (95% CI: 1.1–2.4)], presence of liver metastases [p = 0.016; HR: 1.4 (95% CI: 1.0–1.9)], line of ICI treatment [p = 0.009; HR: 1.4 (1.0–1.9)], elevated LDH [p = 0.076; HR: 1.3 (95% CI: 0.97–1.8)], and brain metastasis [p = 0.080; HR: 1.3 (95% CI: 0.97–1.7)], were associated with shorter PFS in univariate analysis. Multivariate analysis revealed that the patient’s age (≤ 40 years) remains a high-risk factor upon adjusting for all potential confounders [p = 0.067; HR: 1.5 (95% CI: 0.97–2.3)]. Blood parameters revealed that patients ≤ 40 years have relatively higher frequencies of activated CD4 T cells (CD4 + Ki67 + CD4 + ICOS +) in the blood, and significantly lower number of basophils and CD45RA- memory T cells, compared to patients above 40 years (p &lt; 0.05). In addition, patients ≤ 40 years experiencing disease progression within 6 months of ICI treatment had increased concentrations of sPDL1 (p = 0.05) and sTIM3 (p = 0.054) at baseline.ConclusionYoung patients with stage IV melanoma may experience shorter progression-free survival upon ICI treatment compared to patients above 40 years and are characterized by fewer basophils and memory T cells in the blood.
Systems and processes for regulation of investigational medical devices in Uganda
Authors: Mpaata Charles Norman , Matovu Brian , Takuwa Mercy , Kiwanuka Noah , Lewis Steff , Norrie John , Ononge Sam , Tuck Sharon , Wolters Maria , Demulliez Marc , Ssekitoleko Robert T. 
Published: January 2023

BackgroundIn many parts of the world, medical devices and the processes of their development are tightly regulated. However, the current regulatory landscape in Uganda like other developing countries is weak and poorly defined, which creates significant barriers to innovation, clinical evaluation, and translation of medical devices.AimTo evaluate current knowledge, systems and infrastructure for medical devices regulation and innovation in Uganda.MethodsA mixed methods study design using the methods triangulation strategy was employed in this study. Data of equal weight were collected sequentially. First, a digital structured questionnaire was sent out to innovators to establish individual knowledge and experience with medical device innovation and regulation. Then, a single focus group discussion involving both medical device innovators and regulators to collect data about the current regulatory practices for medical devices in Uganda. Univariate and bivariate analysis was done for the quantitative data to summarize results in graphs and tables. Qualitative data was analyzed using thematic analysis. Ethical review and approval were obtained from the Makerere University School of Biomedical Sciences, Research and Ethics Committee, and the Uganda National Council for Science and Technology.ResultsA total of 47 innovators responded to the questionnaire. 14 respondents were excluded since they were not medical device innovators. Majority (76%) of individuals had been innovators for more than a year, held a bachelor's degree with a background in Engineering and applied sciences, and worked in an academic research institute. 22 of the 33 medical device innovators had stopped working on their innovations and had stalled at the proof-of-concept stage. Insufficient funding, inadequate technical expertise and confusing regulatory landscape were major challenges to innovation. The two themes that emerged from the discussion were “developing standards for medical devices regulation” and “implementation of regulations in practical processes”. Legal limitations, lengthy processes, and low demand were identified as challenges to developing medical device regulations.ConclusionsEfforts have been taken by government to create a pathway for medical device innovations to be translated to the market. More work needs to be done to coordinate efforts among stakeholders to build effective medical device regulations in Uganda.
Using machine learning to estimate the calendar age based on autonomic cardiovascular function
Authors: Schumann Andy , Gaser Christian , Sabeghi Rassoul , Schulze P. Christian , Festag Sven , Spreckelsen Cord , Bär Karl-Jürgen 
Published: January 2023

IntroductionAging is accompanied by physiological changes in cardiovascular regulation that can be evaluated using a variety of metrics. In this study, we employ machine learning on autonomic cardiovascular indices in order to estimate participants’ age.MethodsWe analyzed a database including resting state electrocardiogram and continuous blood pressure recordings of healthy volunteers. A total of 884 data sets met the inclusion criteria. Data of 72 other participants with an BMI indicating obesity (&gt;30 kg/m²) were withheld as an evaluation sample. For all participants, 29 different cardiovascular indices were calculated including heart rate variability, blood pressure variability, baroreflex function, pulse wave dynamics, and QT interval characteristics. Based on cardiovascular indices, sex and device, four different approaches were applied in order to estimate the calendar age of healthy subjects, i.e., relevance vector regression (RVR), Gaussian process regression (GPR), support vector regression (SVR), and linear regression (LR). To estimate age in the obese group, we drew normal-weight controls from the large sample to build a training set and a validation set that had an age distribution similar to the obesity test sample.ResultsIn a five-fold cross validation scheme, we found the GPR model to be suited best to estimate calendar age, with a correlation of r=0.81 and a mean absolute error of MAE=5.6 years. In men, the error (MAE=5.4 years) seemed to be lower than that in women (MAE=6.0 years). In comparison to normal-weight subjects, GPR and SVR significantly overestimated the age of obese participants compared with controls. The highest age gap indicated advanced cardiovascular aging by 5.7 years in obese participants.DiscussionIn conclusion, machine learning can be used to estimate age on cardiovascular function in a healthy population when considering previous models of biological aging. The estimated age might serve as a comprehensive and readily interpretable marker of cardiovascular function. Whether it is a useful risk predictor should be investigated in future studies.
Comparison of staged-stent and stent-assisted coiling technique for ruptured saccular wide-necked intracranial aneurysms: Safety and efficacy based on a propensity score-matched cohort study
Authors: Zhang Guanghao , Zhang Renkun , Wei Yanpeng , Chen Rundong , Zhang Xiaoxi , Xue Gaici , Lv Nan , Duan Guoli , Wang Chuanchuan , Yu Ying , Dai Dongwei , Zhao Rui , Li Qiang , Xu Yi , Huang Qinghai , Yang Pengfei , Zuo Qiao , Liu Jianmin 
Published: January 2023

BackgroundApplication of stent-assisted coiling and FD in acute phase of ruptured wide-necked aneurysms is relatively contraindicated due to the potential risk of ischemic and hemorrhagic complications. Scheduled stenting after initial coiling has emerged as an alternative paradigm for ruptured wide-necked aneurysms. The objective of this study is to evaluate the safety and efficacy of a strategy of staged stent-assisted coiling in acutely ruptured saccular wide-necked intracranial aneurysms compared with conventional early stent-assisted coiling strategy via propensity score matching in a high-volume center.MethodsA retrospective review of patients with acutely ruptured saccular wide-necked intracranial aneurysms who underwent staged stent-assisted coiling or conventional stent-assisted coiling from November 2014 to November 2019 was performed. Perioperative procedure-related complications and clinical and angiographic follow-up outcomes were compared.ResultsA total of 69 patients with staged stent-assisted coiling and 138 patients with conventional stent-assisted coiling were enrolled after 1:2 propensity score matching. The median interval time between previous coiling and later stenting was 4.0 weeks (range 3.5–7.5 weeks). No rebleeding occurred during the intervals. The rate of immediate complete occlusion was lower with initial coiling before scheduled stenting than with conventional stent-assisted coiling (21.7 vs. 60.9%), whereas comparable results were observed at follow-up (82.5 vs. 72.9%; p = 0.357). The clinical follow-up outcomes, overall procedure-related complications and procedure-related mortality between the two groups demonstrated no significant differences (P = 0.232, P = 0.089, P = 0.537, respectively). Multivariate analysis showed that modified Fisher grades (OR = 2.120, P = 0.041) were independent predictors for overall procedure-related complications and no significant predictors for hemorrhagic and ischemic complications.ConclusionsStaged stent-assisted coiling is a safe and effective treatment strategy for acutely ruptured saccular wide-necked intracranial aneurysms, with comparable complete occlusion rates, recurrence rates at follow-up and overall procedure-related complication rates compared with conventional stent-assisted coiling strategy. Staged stent-assisted coiling could be an alternative treatment option for selected ruptured intracranial aneurysms in the future.
Dietary patterns and risk for gastric cancer: A case-control study in residents of the Huaihe River Basin, China
Authors: Wu Xiaomin , Zhang Qian , Guo Hong , Wang Ning , Fan Xueqi , Zhang Bin , Zhang Wei , Wang Wanying , Fang Zhongze , Wu Jing 
Published: January 2023

AimEvidence linking dietary patterns and the risk of gastric cancer was limited, especially in Chinese populations. This study aimed to explore the association between dietary patterns and the risk of gastric cancer in residents of the Huaihe River Basin, China.MethodsThe association between dietary patterns and the risk of gastric cancer was investigated through a case-control study. Dietary patterns were identified with factor analysis based on responses to a food frequency questionnaire (FFQ). Gastric cancer was diagnosed according to the International Classification of Diseases, 10th Revision (ICD 10). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated across the tertiles of dietary pattern scores using unconditional logistic regression models.ResultsA total of 2,468 participants were included in this study. Six main dietary patterns were extracted, and those patterns explained 57.09% of the total variation in food intake. After adjusting for demographic characteristics, lifestyle factors, individual disease history, family history of cancer and Helicobacter. Pylori (H. pylori) infection, comparing the highest with the lowest tertiles of dietary pattern scores, the multivariable ORs (95% CIs) were 0.786 (0.488, 1.265; Ptrend &lt; 0.001) for the flavors, garlic and protein pattern, 2.133 (1.299, 3.502; Ptrend &lt; 0.001) for the fast food pattern, 1.050 (0.682, 1.617; Ptrend &lt; 0.001) for the vegetable and fruit pattern, 0.919 (0.659, 1.282; Ptrend &lt; 0.001) for the pickled food, processed meat products and soy products pattern, 1.149 (0.804, 1.642; Ptrend &lt; 0.001) for the non-staple food pattern and 0.690 (0.481, 0.989; Ptrend &lt; 0.001) for the coffee and dairy pattern.ConclusionsThe specific dietary patterns were associated with the risk of gastric cancer. This study has implications for the prevention of gastric cancer.
Pharmacokinetics and biosafety evaluation of a veterinary drug florfenicol in rainbow trout, Oncorhynchus mykiss (Walbaum 1792) as a model cultivable fish species in temperate water
Authors: Mallik Sumanta Kumar , Shahi Neetu , Pathak Richa , Kala Krishna , Patil Prasanna Kumar , Singh Bhupendra , Ravindran Rajisha , Krishna Nanitha , Pandey Pramod Kumar 
Published: January 2023

In two experimental trials; florfenicol pharmacokinetics following a single dose oral administration at 15 mg kg−1 fish body weight and biosafety through extended medicated feeding were studied in the rainbow trout, Oncorhynchus mykiss. The pharmacokinetic trial was conducted for 5 days, whereas the biosafety experiment lasted for a 30-day safety margin followed by a 20-day residual period analysis at 3, 5 and 10 times greater than the therapeutic dose 10 mg kg−1 biomass day−1. Cmax µg kg−1 calculated for florfenicol were found to be 5,360 in intestine, 2,890 in gill, 2,250 in kidney, 973 in liver and 273 in plasma, obtained at Tmax of 16 h. Intestine had utmost area under the concentration–time curve (tissue/plasma) of 13.83 h μg kg−1 and a prolonged half life (t1/2ß) of 28.62 h. The highest apparent metabolic rate value in the kidney (0.327) showed a high level of biotransformation of florfenicol to its metabolite florfenicol amine. The apparent distribution rate of florfenicol amine in muscle, in comparison to the parent drug florfenicol, indicated elimination of the medication mostly in the form of florfenicol amine with t1/2 of 16.75 h. The biosafety of florfenicol orally administered to rainbow trout recorded effective feed consumption, physiological responses, drug tolerance and significantly low drug concentrations in muscle of rainbow trout, thus its usage at 10 mg kg−1 fish body weight is recommended. In the study, the rapid absorption, greater bioavailability, enhanced dispersion, slower elimination and biosafety of the drug form a significant basis for the florfenicol and its metabolite florfenicol amine as a useful antibacterial agent in aquaculture.
Case Report: Clinical benefit from multi-target tyrosine kinase inhibitor and PARP inhibitor in a patient with cancer of unknown primary with BRCA1 large genomic rearrangement
Authors: Yu Ling , Lin Jietao , Li Hanhan , Sun Lingling , Wang Shubo , Chen Yaoxu , Chen Hanrui , Lin Lizhu 
Published: January 2023

Background: Cancer of unknown primary (CUP), which accounts for 3%–5% of new cancer cases every year, involves the presence of a type of histologically confirmed metastatic tumors whose primary site cannot be confirmed by conventional diagnostic methods. This difficulty in identifying the primary site means that CUP patients fail to receive precisely targeted therapy. Most patients are treated with empiric chemotherapy, with a median survival of 6 months and even poorer prognosis within an unfavorable subset of CUP.Case report: An 80-year-old woman presented with masses in the abdomen. Following comprehensive imagological and immunohistochemical examinations, she was diagnosed with CUP. She emphatically declined chemotherapy; thus, anlotinib has been administered with patient consent since 02/07/2019, and stable disease (SD) was observed for 2 years. During subsequent treatment, a large genomic rearrangement in BRCA1 was identified in the patient via NGS, and SD was observed for a further 6 months following olaparib treatment. The type of LGR identified in this patient was discovered to be BRCA1 exon 17-18 inversion (inv), which has never been previously reported.Conclusion: For CUP patients, a chemo-free regimen seems to be acceptable as a first-line treatment, and NGS-guided targeted treatment could improve patient outcomes.
The effect of educational computer games on the academic resilience, academic self-regulation, and academic achievement of EFL students
Authors: Deng Lin , Daverpanah Nikoo , Izadpanah Siros 
Published: January 2023

IntroductionIn recent years there has been an increasing interest in the field of educational computer games (ECGs). Although ECGs have been researched, more analyses still need to be performed on these variables to check their effects on language learning.MethodsTo this end, 74-third grade female state high school students from two schools in Zanjan were selected through a two-stage cluster random sampling method. The number of students in each class was 37. One of the classes (control group) was trained traditionally and the other was for one semester through the researchers-made ECGs. After completing the training, the research tools were performed as a post-test on the experimental and control groups. The data collection stage took place for about 6 months.ResultsBased on the results from the research questions, the use of training computers has been effective in increasing AR, ASR, and AA.DiscussionIt has significant implications for teachers and learners in the EFL context and opens interesting opportunities for administrators and curriculum developers to explore when planning EFL courses.
The impact of the digital economy on enterprise innovation behavior: Based on CiteSpace knowledge graph analysis
Authors: Yu Wenling , Zhang Lipai , Yang Chen 
Published: January 2023

IntroductionAs a new trend, the digital economy will promote “digital industrialization” in the process of promoting “industrial digitalization.” It can accelerate technological innovation by adjusting managerial behavior and strategic decisions, promoting and protecting technological research and development, and providing technological infrastructure. While technological innovation, which generally occurs in enterprises, will promote a new round of upgrading, optimization, and even reshaping of the whole industry. The two are highly synergistic. Therefore, it is of great practical significance to study the impact of the digital economy era on enterprise innovation behavior.MethodsWe analyzed the impact of the digital economy era on corporate innovation behavior in the Web of Science database from 2010 to 2020 through bibliometric and scientific knowledge mapping methods.Results and discussionOur study found that: the research on enterprise innovation behavior in the digital economy era has formed eight research directions, such as expertise, human capital FSA, integration in global value chains, financial innovation, fintech, people preference shift, internet of everything, and consumer co-creation. In addition, the research hotspots on enterprise innovation behavior in the digital economy era range from enterprises’ perception of digital economy contact, to enterprises’ familiarity with digital technology and its application, to enterprises’ attempted evolution of digital transformation, reflecting the potential of both theoretical and practical characteristics. Finally, we present an outlook on the future cross-sectional development of research on enterprise innovative behavior in the digital economy era and propose a research trend based on the Chinese context.
The association between gene polymorphisms in voltage-gated potassium channels Kv2.1 and Kv4.2 and susceptibility to autism spectrum disorder
Authors: Liu Zehui , Yang Xiaolei , Guo Peiwen , Wang Feng , Xia Wei , Chen Yuxin , Zou Mingyang , Sun Caihong 
Published: January 2023

BackgroundAutism spectrum disorder (ASD) is a heritable form of neurodevelopmental disorder that arises through synaptic dysfunction. Given the involvement of voltage-gated potassium (Kv) channels in the regulation of synaptic plasticity, we aimed to explore the relationship between the genetic variants in the KCNB1 and KCND2 genes (encoding Kv2.1 and Kv4.2, respectively) and the risk of developing ASD.MethodsA total of 243 patients with ASD and 243 healthy controls were included in the present study. Sixty single nucleotide polymorphisms (SNPs) (35 in KCNB1 and 25 in KCND2) were genotyped using the Sequenom Mass Array.ResultsThere were no significant differences in the distribution of allele frequencies and genotype frequencies in KCNB1 between cases and controls. However, the differences were significant in the allelic distribution of KCND2 rs1990429 (pBonferroni &lt; 0.005) and rs7793864 (pBonferroni &lt; 0.005) between the two groups. KCND2 rs7800545 (pFDR = 0.045) in the dominant model and rs1990429 (pFDR &lt; 0.001) and rs7793864 (pFDR &lt; 0.001) in the over-dominant model were associated with ASD risk. The G/A genotype of rs1990429 in the over-dominant model and the G/A–G/G genotype of rs7800545 in the dominant model were correlated with lower severity in the Autism Diagnostic Interview-Revised (ADI–R) restricted repetitive behavior (RRB) domain.ConclusionOur results provide evidence that KCND2 gene polymorphism is strongly associated with ASD susceptibility and the severity of RRB.