bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying immune cells-related phenotype to predict immunotherapy and clinical outcome in gastric cancer
Authors: Jiang Sutian , Ding Xuzhong , Wu Qianqian , Cheng Tong , Xu Manyu , Huang Jianfei 
Published: August 2022

BackgroundThe tumor microenvironment is mainly composed of tumor-infiltrating immune cells (TIICs), fibroblast, extracellular matrix, and secreted factors. TIICs are often associated with sensitivity to immunotherapy and the prognosis of multiple cancers, yet the predictive role of individual cells on tumor prognosis is limited.MethodsBased on single-sample gene set enrichment analysis, we combined three Gene Expression Omnibus (GEO) cohorts to build a TIIC model for risk stratification and prognosis prediction. The performance of the TIIC model was validated using our clinical cohort and the TCGA cohort. To assess the predictive power of the TIIC model for immunotherapy, we plotted the receiver operating characteristic curve with the IMvigor210 and GSE135222 cohorts.ResultsChemokines, tumor-infiltrating immune cells, and immunomodulators differed between the two TIIC groups. The TIIC model was vital for predicting the outcome of immunotherapy. In our clinical samples, we verified that the expression levels of PD-1 and PD-L1 were higher in the low TIIC score group than in the high TIIC score group, both in the tumor and stroma.ConclusionsCollectively, the TIIC model could provide a novel idea for immune cell targeting strategies in gastric cancer and predict the survival outcome of patients.
Nigella sativa supplementation improves cardiometabolic indicators in population with prediabetes and type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials
Authors: Saadati Saeede , Naseri Kaveh , Asbaghi Omid , Abhari Khadijeh , Zhang Pangzhen , Li Hua-Bin , Gan Ren-You 
Published: August 2022

ObjectiveNigella sativa (N. sativa) from the family Ranunculaceae has medicinal properties. Previous studies have reported promising findings showing that N. sativa may benefit cardiometabolic health; however, current evidence on its cardiometabolic effects on those with prediabetes and type 2 diabetes mellitus (T2DM) is still unclear. Hence, we conducted a systematic review and meta-analysis to assess the efficacy of N. sativa on cardiometabolic parameters in population with prediabetes and T2DM.MethodsPubMed/Medline, ISI Web of Science, Scopus, and Cochrane library were systematically searched up to June 20, 2022. Meta-analyses using random-effects models were used.ResultsEleven randomized controlled trials (RCTs) were included in the meta-analysis. N. sativa intervention resulted in significant changes in fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), c-reactive protein (CRP), and malondialdehyde (MDA), without overall changes in glucose levels after oral glucose tolerance test (OGTT), fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI) when compared with the control group. In subgroup analyses, N. sativa supplementation enhanced serum levels of HDL-C in subjects with baseline HDL-C lower than 40 mg/dL. Furthermore, HOMA-IR and BMI values decreased in the N. sativa-supplemented group compared with the control group, when the length of follow-up was more than 8 weeks and the dose was more than 1 g/day for N. sativa supplementation, respectively.ConclusionOur findings indicate that N. sativa supplementation may effectively improve cardiometabolic profiles in individuals with prediabetes and T2DM.
A new technique for performing interstitial implants for gynecologic malignancies using transvaginal ultrasound guidance
Authors: Yan Xiao-Jing , Yang Yi , Chen Xi , Wang Shi-Guang , Niu Shu-Huai , Niu Hui-Xian , Liu Hong 
Published: August 2022

ObjectivesThis study concerns a new technique that aims to achieve precise interstitial brachytherapy of pelvic recurrent tumors under transvaginal ultrasound (US) guidance, enhance the conformity index of the brachytherapy (BT), and improve the curative effect of radiotherapy for gynecological oncology patients with pelvic relapse.MethodsA real-time transvaginal US-guided interstitial implant device was developed to assist in implant BT. Prior to implant brachytherapy, the size and location of the tumor in the pelvis and the interrelationship with adjacent organs were first assessed with intracavitary ultrasound. The transvaginal US-guided interstitial implant device was then placed on the endoluminal ultrasound probe, the probe was oriented intravaginally to determine a safe needle path, the implant needle was placed into the needle passage of the device, and the implant needle was inserted into the tumor tissue in the direction guided by the ultrasound puncture guide line. After the implant needle was placed in place, the cover of the transvaginal US-guided interstitial implant device was opened perpendicular to the ultrasound probe, and the needle was separated from the ultrasound probe smoothly, and then the cover was re-covered for subsequent implantation.ResultsIn this study, 56 patients who underwent real-time transvaginal ultrasound-guided implantation for gynecologic oncology were enrolled, and insertion of 736 implant needles was completed. Among them, 13 patients had recurrent pelvic tumors after cervical cancer surgery and 6 patients had recurrent pelvic tumors after endometrial cancer surgery. Thirty-two patients who underwent radical radiation therapy for cervical cancer did not have adequate regression of parametrial invaded tissue after completion of standard EBRT treatment; and 5 patients had recurrent tumors in the radiation field after previous standard course of pelvic radiotherapy. The accuracy of the implant therapy was improved. The radiotherapy dose for recurrent pelvic masses was successfully increased, and the cumulative dose of external irradiation combined with BT was augmented to 80–100 Gy. The use of a new device for transvaginal implant for recurrent masses located in the lateral wall of the pelvic cavity was successful.ConclusionThis intravascular US-guided interstitial implant device can realize interstitial implant with the shortest path under transvaginal US guidance. With convenient operation, high precision, and good security, the device not only improves the accuracy of implant therapy, but it also reduces the risks of anesthesia and organ injury, so it is suitable for widespread promotion and use.
Development and validation of a deep learning model for breast lesion segmentation and characterization in multiparametric MRI
Authors: Zhu Jingjin , Geng Jiahui , Shan Wei , Zhang Boya , Shen Huaqing , Dong Xiaohan , Liu Mei , Li Xiru , Cheng Liuquan 
Published: August 2022

ImportanceThe utilization of artificial intelligence for the differentiation of benign and malignant breast lesions in multiparametric MRI (mpMRI) assists radiologists to improve diagnostic performance.ObjectivesTo develop an automated deep learning model for breast lesion segmentation and characterization and to evaluate the characterization performance of AI models and radiologists.Materials and methodsFor lesion segmentation, 2,823 patients were used for the training, validation, and testing of the VNet-based segmentation models, and the average Dice similarity coefficient (DSC) between the manual segmentation by radiologists and the mask generated by VNet was calculated. For lesion characterization, 3,303 female patients with 3,607 pathologically confirmed lesions (2,213 malignant and 1,394 benign lesions) were used for the three ResNet-based characterization models (two single-input and one multi-input models). Histopathology was used as the diagnostic criterion standard to assess the characterization performance of the AI models and the BI-RADS categorized by the radiologists, in terms of sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC). An additional 123 patients with 136 lesions (81 malignant and 55 benign lesions) from another institution were available for external testing.ResultsOf the 5,811 patients included in the study, the mean age was 46.14 (range 11–89) years. In the segmentation task, a DSC of 0.860 was obtained between the VNet-generated mask and manual segmentation by radiologists. In the characterization task, the AUCs of the multi-input and the other two single-input models were 0.927, 0.821, and 0.795, respectively. Compared to the single-input DWI or DCE model, the multi-input DCE and DWI model obtained a significant increase in sensitivity, specificity, and accuracy (0.831 vs. 0.772/0.776, 0.874 vs. 0.630/0.709, 0.846 vs. 0.721/0.752). Furthermore, the specificity of the multi-input model was higher than that of the radiologists, whether using BI-RADS category 3 or 4 as a cutoff point (0.874 vs. 0.404/0.841), and the accuracy was intermediate between the two assessment methods (0.846 vs. 0.773/0.882). For the external testing, the performance of the three models remained robust with AUCs of 0.812, 0.831, and 0.885, respectively.ConclusionsCombining DCE with DWI was superior to applying a single sequence for breast lesion characterization. The deep learning computer-aided diagnosis (CADx) model we developed significantly improved specificity and achieved comparable accuracy to the radiologists with promise for clinical application to provide preliminary diagnoses.
Identification of methylation signatures associated with CAR T cell in B-cell acute lymphoblastic leukemia and non-hodgkin’s lymphoma
Authors: Song Jiwei , Huang FeiMing , Chen Lei , Feng KaiYan , Jian Fangfang , Huang Tao , Cai Yu-Dong 
Published: August 2022

CD19-targeted CAR T cell immunotherapy has exceptional efficacy for the treatment of B-cell malignancies. B-cell acute lymphocytic leukemia and non-Hodgkin’s lymphoma are two common B-cell malignancies with high recurrence rate and are refractory to cure. Although CAR T-cell immunotherapy overcomes the limitations of conventional treatments for such malignancies, failure of treatment and tumor recurrence remain common. In this study, we searched for important methylation signatures to differentiate CAR-transduced and untransduced T cells from patients with acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. First, we used three feature ranking methods, namely, Monte Carlo feature selection, light gradient boosting machine, and least absolute shrinkage and selection operator, to rank all methylation features in order of their importance. Then, the incremental feature selection method was adopted to construct efficient classifiers and filter the optimal feature subsets. Some important methylated genes, namely, SERPINB6, ANK1, PDCD5, DAPK2, and DNAJB6, were identified. Furthermore, the classification rules for distinguishing different classes were established, which can precisely describe the role of methylation features in the classification. Overall, we applied advanced machine learning approaches to the high-throughput data, investigating the mechanism of CAR T cells to establish the theoretical foundation for modifying CAR T cells.
Case report: Congenital hyperinsulinemia with ABCC8 gene mutations
Authors: Zhang Jin , Wang Jiyang , Chen Hui 
Published: August 2022

BackgroundCongenital hyperinsulinemia (CHI) is an inherited disease of abnormal insulin secretion and is the main cause of persistent and intractable hypoglycemia in infants. The aim of this case report was to investigate the genetic mechanisms and treatment of CHI in an affected patient.Case summaryWe collected clinical data from, and performed gene capture, high-throughput gene sequencing analysis, and Sanger sequencing validation, in a child with CHI and his family to identify the causative gene mutations. Two heterozygous pathogenic mutations in the ATP-binding cassette subfamily C member 8 (ABCC8) gene were detected in the child: c.863G&gt;A (p.Trp288Ter) in exon 6 and c.2506C&gt;T (p.Arg836Ter) in exon 21. Sanger sequencing showed that c.863G&gt;A was inherited from heterozygous mutations in the paternal line and c.2506C&gt;T from heterozygous mutations in the maternal line.ConclusionThe child was a CHI with a biallelic recessive heterozygous mutations in ABCC8 resulting in impairment of its encoded ATP-sensitive potassium (KATP) channel, poor response to diazoxide treatment, and developed diabetes after subtotal pancreatectomy.
Outcomes and comparations of pediatric surgery about choledochal cyst with robot-assisted procedures, laparoscopic procedures, and open procedures: A meta-analysis
Authors: Xie Siqi , Huang Yanbing , He Yuanbin , Liu Mingkun , Wu Dianming , Fang Yifan 
Published: August 2022

BackgroundCholedochal cysts (CC) are rare disorders characterized by congenital biliary dilatation of the intrahepatic or extrahepatic bile ducts and always relate to pancreaticobiliary maljunction. Robot-assisted surgery has been able to complete almost all pediatric endoscopic surgery nowadays. But evidence of the post-operative outcomes of robotic-assisted operation is limited, comparing with the laparoscopic operation and traditional open operation. The aim of this meta-analysis was to identify the advantages and deficiencies about robotic-assisted operation for CC.MethodsA meta-analysis of retrospective studies published in PUBMED, MEDLINE, Web of Science and China National Knowledge Infrastructure (CNKI). No date limit was used, with the last search on April 30, 2022. No publication restrictions or study design filters were applied.ResultsNine retrospective cohort studies with 1,395 patients [366 in the robotic-assisted operation group (RG), 532 in the laparoscopic operation group (LG) and 497 in the open operation group (OG)] were enrolled in our study. Subgroup analysis demonstrated the RG had significant longer operative time [standardized mean difference (SMD) = 1.59, 95% CI = (0.02, 3.16), P &lt; 0.05], less blood loss [SMD = −1.52, 95% CI = (−2.71, −0.32), P &lt; 0.05], shorter enteral feeding time [SMD = −0.83, 95% CI = (−1.22, −0.44), P &lt; 0.001], shorter time to stay in the hospital [SMD = −0.81, 95% CI = (−1.23, −0.38), P &lt; 0.001], fewer post-operative complications [Relative risk (RR) =1.09, 95% CI = (1.04, 1.13), P &lt; 0.001] but higher expenses [SMD = 8.58, 95% CI = (5.27, 11.89), P &lt; 0.001] than LG. While a significant older age [SMD = 0.46, 95% CI = (0.26, 0.66), P &lt; 0.001], longer operative time [SMD = 3.96, 95% CI = (2.38, 5.55), P &lt; 0.001] and shorter time to stay in the hospital [SMD = −0.93, 95% CI = (−1.62, −0.25), P &lt; 0.05] than OG.ConclusionsLaparoscopic and robotic-assisted procedure are both safe and minimal invasive operational strategies. Robotic-assisted procedure may slowly surpass and has a trend to replace laparoscopy for its advantages. More experiences in robotic-assisted operation should be accumulated for the unexpected complexities, so as to be more stable in the younger age of children.
Endothelitis profile in acute heart failure and cardiogenic shock patients: Endocan as a potential novel biomarker and putative therapeutic target
Authors: Reina-Couto Marta , Silva-Pereira Carolina , Pereira-Terra Patrícia , Quelhas-Santos Janete , Bessa João , Serrão Paula , Afonso Joana , Martins Sandra , Dias Cláudia Camila , Morato Manuela , Guimarães João T , Roncon-Albuquerque Roberto , Paiva José-Artur , Albino-Teixeira António , Sousa Teresa 
Published: August 2022

Aims: Inflammation-driven endothelitis seems to be a hallmark of acute heart failure (AHF) and cardiogenic shock (CS). Endocan, a soluble proteoglycan secreted by the activated endothelium, contributes to inflammation and endothelial dysfunction, but has been scarcely explored in human AHF. We aimed to evaluate serum (S-Endocan) and urinary endocan (U-Endocan) profiles in AHF and CS patients and to correlate them with biomarkers/parameters of inflammation, endothelial activation, cardiovascular dysfunction and prognosis.Methods: Blood and spot urine were collected from patients with AHF (n = 23) or CS (n = 25) at days 1–2 (admission), 3-4 and 5-8 and from controls (blood donors, n = 22) at a single time point. S-Endocan, U-Endocan, serum IL-1β, IL-6, tumour necrosis factor-α (S-TNF-α), intercellular adhesion molecule-1 (S-ICAM-1), vascular cell adhesion molecule-1 (S-VCAM-1) and E-selectin were determined by ELISA or multiplex immunoassays. Serum C-reactive protein (S-CRP), plasma B-type natriuretic peptide (P-BNP) and high-sensitivity troponin I (P-hs-trop I), lactate, urea, creatinine and urinary proteins, as well as prognostic scores (APACHE II, SAPS II) and echocardiographic left ventricular ejection fraction (LVEF) were also evaluated.Results: Admission S-Endocan was higher in both patient groups, with CS presenting greater values than AHF (AHF and CS vs. Controls, p &lt; 0.001; CS vs. AHF, p &lt; 0.01). Admission U-Endocan was only higher in CS patients (p &lt; 0.01 vs. Controls). At admission, S-VCAM-1, S-IL-6 and S-TNF-α were also higher in both patient groups but there were no differences in S-E-selectin and S-IL-1β among the groups, nor in P-BNP, S-CRP or renal function between AHF and CS. Neither endocan nor other endothelial and inflammatory markers were reduced during hospitalization (p &gt; 0.05). S-Endocan positively correlated with S-VCAM-1, S-IL-6, S-CRP, APACHE II and SAPS II scores and was positively associated with P-BNP in multivariate analyses. Admission S-Endocan raised in line with LVEF impairment (p = 0.008 for linear trend).Conclusion: Admission endocan significantly increases across AHF spectrum. The lack of reduction in endothelial and inflammatory markers throughout hospitalization suggests a perpetuation of endothelial dysfunction and inflammation. S-Endocan appears to be a biomarker of endothelitis and a putative therapeutic target in AHF and CS, given its association with LVEF impairment and P-BNP and its positive correlation with prognostic scores.
The cost-effectiveness of digital health interventions: A systematic review of the literature
Authors: Gentili Andrea , Failla Giovanna , Melnyk Andriy , Puleo Valeria , Tanna Gian Luca Di , Ricciardi Walter , Cascini Fidelia 
Published: August 2022

BackgroundDigital health interventions have significant potential to improve safety, efficacy, and quality of care, reducing waste in healthcare costs. Despite these premises, the evidence regarding cost and effectiveness of digital tools in health is scarce and limited.ObjectivesThe aim of this systematic review is to summarize the evidence on the cost-effectiveness of digital health interventions and to assess whether the studies meet the established quality criteria.MethodsWe queried PubMed, Scopus and Web of Science databases for articles in English published from January 1, 2016 to December 31, 2020 that performed economic evaluations of digital health technologies. The methodological rigorousness of studies was assessed with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2009 checklist.ResultsSearch identified 1,476 results, 552 of which were selected for abstract and 35 were included in this review. The studies were heterogeneous by country (mostly conducted in upper and upper-middle income countries), type of eHealth intervention, method of implementation, and reporting perspectives. The qualitative analysis identified the economic and effectiveness evaluation of six different types of interventions: (1) seventeen studies on new video-monitoring service systems; (2) five studies on text messaging interventions; (3) five studies on web platforms and digital health portals; (4) two studies on telephone support; (5) three studies on new mobile phone-based systems and applications; and (6) three studies on digital technologies and innovations.ConclusionFindings on cost-effectiveness of digital interventions showed a growing body of evidence and suggested a generally favorable effect in terms of costs and health outcomes. However, due to the heterogeneity across study methods, the comparison between interventions still remains difficult. Further research based on a standardized approach is needed in order to methodically analyze incremental cost-effectiveness ratios, costs, and health benefits.
Pre-Pandemic Adversity Buffers the Role of Social Loneliness in Caregiver Mental Health During the COVID-19 Pandemic
Authors: Monahan Emma Kahle , McCrae Julie S. , Daferede Simeon 
Published: August 2022

Objectives: This study investigates how family profiles of risk and resilience established prior to COVID-19 are associated with changes in caregiver depression and stress 1 year after the pandemic onset, and how these associations are moderated by experiences of social loneliness.Methods: A sample of 243 caregivers in four risk and resilience profiles interviewed pre-COVID-19 were interviewed virtually in December 2020–February 2021 (during pandemic). Multi-level models were used to examine changes in mental health.Results: All caregivers reported increases in extreme stress during the pandemic. Caregivers with less relative adversity pre-pandemic showed significantly greater depression and loneliness in the pandemic compared to caregivers with higher pre-pandemic adversity. Social loneliness was a moderator of the association between pre-pandemic adversity and mental health.Conclusion: The study suggests families with more pre-pandemic adversity demonstrate coping that buffers the negative impact of social loneliness on mental health, emphasizing the strengths of these families that are assets to build upon in crisis. Families with more relative advantage pre-pandemic likely need assistance to reduce feelings of stress and depression in the face of increased social loneliness.
PENGEMBANGAN MODEL PERAN TRIPLE-HELIX TERHADAP PENGEMBANGAN ECOCANVAS CLEANTECH STARTUP BERBASIS GREEN INNOVATION & TECHNOLOGY ADOPTION
Authors: Ririh Kirana Rukmayuninda , Sundana Sambas , Kusumawati Amalia , Ningtyas Desinta Rahayu 
Published: August 2022

Startup memegang peranan penting dalam transformasi disruptif di beberapa sektor industri untuk menuju ekonomi sirkuler keberlanjutan. Cleantech Startup (CS) merupakan salah satu pemain bisnis utama dalam inovasi dan teknologi hijau, yang basisnya menghasilkan atau memanfaatkan energi bersih. Untuk mencapai kesukesan inovasi hijau yang keberlanjutan, kolaborasi antar aktor dalam sistem inovasi hijau seperti universitas-lembaga pemerintah-dan industri (termasuk CS) harus optimal. Ditambah dengan model bisnis CS perlu mengimplementasikan kanvas model bisnis hijau (EcoCanvas). Studi literatur ini akan mengulas tentang bagaimana kolaborasi Triple-Helix (TH) terhadap inovasi dan adopsi teknologi hijau yang dilakukan CS. Selain itu akan dirumuskan bagaimana EcoCanvas dari contoh kasus CS yang ada di Indonesia. Studi ini menggunakan desk review terhadap 51 artikel utama dari jurnal bereputasi. Dapat dilihat bahwa kolaborasi TH menitik beratkan pada : regulasi pemerintah, fokus pasar, partisipasi pemasok, koordinasi antar fungsi, dan pengembangan teknologi. Selain itu aliansi lisensi dan pengembangan teknologi akan mempengaruhi pola investasi finansial dan aktivitas paten. Model EcoCanvas pada CS juga menunjukkan bahwa isu lingkungan seperti sampah dan sumber daya berlimpah di Indonesia menjadi fokus utama dalam model bisnis berkelanjutan yang di adopsi oleh CS. Temuan dalam studi ini perlu dikaji lebih dalam dengan menggunakan bukti empiris lapangan dan data historis lain yang mendukung.