bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraperitoneal Chemotherapy Using Fluorouracil Implants Combined With Radical Resection and Postoperative Adjuvant Chemotherapy for Stage III Gastric Cancer: A Multi-Center, Randomized, Open-Label, Controlled Clinical Study
Authors: Xu Yan , Zhang Rupeng , Li Chunfeng , Sun Zhe , Deng Jingyu , Wang Xiaona , Ding Xuewei , Wang Baogui , Xue Qiang , Ke Bin , Zhan Hongjie , Liu Ning , Liu Yong , Wang Xuejun , Liang Han , Xue Yingwei , Xu Huimian 
Published: July 2021

BackgroundReducing peritoneal recurrence after radical surgery is an important choice to improve the prognosis of patients with advanced gastric cancer. Intraoperative intraperitoneal chemotherapy has the potential to be a promising treatment strategy. In the present study, we conducted a multi-center, randomized, controlled clinical study to evaluate the efficacy and safety of intraoperative intraperitoneal chemotherapy using sustained-release fluorouracil implants plus radical gastrectomy and adjuvant chemotherapy for cTNM stage III gastric cancer.MethodsThe patients were randomized into intraperitoneal chemotherapy group (sustained-release fluorouracil implants administration after standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy) and control group (standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy). A total of 122 patients from three centers were enrolled from September 2015 to February 2017.ResultsOne hundred and two eligible patients completed the treatment course. The median follow-up time was 41.7 months (36.1–52.9 months). The 3-year progression-free survival rate and overall survival of patients in the intraperitoneal chemotherapy group were 43.9% and 49.1%, respectively, which were significantly better than those of the control group, 31.0% and 38.4%. In the intraperitoneal chemotherapy group, the number of cases with peritoneal recurrence was significantly less than that of the control group, 9 cases (17.3%) vs. 19 cases (44.2%). There were neither significant differences between the groups in the incidence of hematogenous metastasis, lymph node metastasis, nor local metastasis.ConclusionFor cTNM stage III gastric cancer, intraoperative sustained-release fluorouracil implants after radical resection combined with postoperative adjuvant chemotherapy, could significantly reduce the risk of peritoneal recurrence and prolong PFS.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier (NCT02269904).
Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma
Authors: Fisch David , Bozorgmehr Farastuk , Kazdal Daniel , Kuon Jonas , Klotz Laura V. , Shah Rajiv , Eichhorn Florian , Kriegsmann Mark , Schneider Marc A. , Muley Thomas , Stenzinger Albrecht , Bischoff Helge , Christopoulos Petros 
Published: July 2021

BackgroundLarge-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options.MethodsWe retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010.Results191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years. The single most important factor associated with outcome was the type of systemic treatment, with a median overall survival (OS) of 26.4 months in case of immune checkpoint inhibitor administration (n=13), 9.0 months for other patients receiving first-line platinum doublets (n=129), and 4.0 months with non-platinum chemotherapies (n=17, p&lt;0.01). Other patient characteristics independently associated with longer OS were a lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008) and fewer initial metastatic sites (HR 0.52, p=0.006), while the platinum drug type (cisplatin vs. carboplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients’ smoking status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA) did not matter. 12% (23/191) of patients forewent systemic treatment, mainly due to tumor-related clinical deterioration (n=13), while patient refusal of therapy (n=5) and severe concomitant illness (n=5) were less frequent. The attrition between successive treatment lines was approximately 50% and similar for platinum-based vs. other therapies, but higher in case of a worse initial ECOG status or higher serum LDH (p&lt;0.05). 19% (36/191) of patients had secondary stage IV disease and showed fewer metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7 months, p=0.030). Among the 111 deceased patients with palliative systemic treatment and complete follow-up, after exclusion of oligometastatic cases (n=8), administration of local therapies (n=63 or 57%) was associated with a longer OS (HR 0.58, p=0.008), but this association did not persist with multivariable testing.ConclusionsHighly active systemic therapies, especially immunotherapy and platinum doublets, are essential for improved outcome in LCNEC and influence OS stronger than clinical disease parameters, laboratory results and other patient characteristics. The attrition between chemotherapy lines is approximately 50%, similar to other NSCLC. Patients with secondary metastatic disease have a more favorable clinical phenotype and longer survival.
The Ribosomal Protein L28 Gene Induces Sorafenib Resistance in Hepatocellular Carcinoma
Authors: Shi Yi , Wang Xiaojiang , Zhu Qiong , Chen Gang 
Published: July 2021

BackgroundSorafenib is the first molecular-targeted drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its treatment efficiency decreases after a short period of time because of the development of drug resistance. This study investigates the role of key genes in regulating sorafenib-resistance and elucidates the mechanism of drug resistance in hepatocellular carcinoma.MethodsThe HCC HepG2 cells were used to generate a sorafenib-resistant cell model by culturing the cells in gradually increasing concentration of sorafenib. RNA microarray was applied to profile gene expression and screen key genes associated with sorafenib resistance. Specific targets were knockdown in sorafenib-resistant HepG2 cells for functional studies. The HCC model was established in ACI rats using Morris hepatoma3924A cells to validate selected genes associated with sorafenib resistance in vivo.ResultsThe HepG2 sorafenib-resistant cell model was successfully established. The IC50 of sorafenib was 9.988μM in HepG2 sorafenib-resistant cells. A total of 35 up-regulated genes were detected by expression profile chip. High-content screening technology was used and a potential drug-resistance related gene RPL28 was filtered out. After knocking down RPL28 in HepG2 sorafenib-resistant cells, the results of cell proliferation and apoptosis illustrated that RPL28 is the key gene involving in drug resistance. Furthermore, it was found that both RNA and protein expression of RPL28 increased in HepG2 sorafenib-resistant specimens of Morris Hepatoma rats. In addition, the expression of proliferative protein Ki-67 increased in sorafenib-resistant cells.ConclusionOur study suggested that RPL28 is a key gene inducing sorafenib resistance in HCC and could be a potential target for the treatment of drug-resistant HCC.
Chronic Hepatitis Virus Infection Are Associated With High Risk of Gastric Cancer: A Systematic Review and Cumulative Analysis
Authors: Yang Yusha , Jiang Zufu , Wu Weizhou , Ruan Libin , Yu Chengyang , Xi Yuning , Wang Liling , Wang Kunpeng , Mo Jinggang , Zhao Shankun 
Published: July 2021

Mounting studies demonstrated both chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection might be associated not only with an increased risk of hepatocellular carcinoma but also extrahepatic malignancies, i.e., gastric cancer (GC). However, a quantitative result addressing the association between HBV/HCV infection and GC development is scarce. A systematic search to identify the eligible studies was performed in four databases, including MEDLINE, EMBASE, Cochrane Library, and the PsychINFO. The relationship between HBV/HCV infection and the risk of GC was quantified by calculating the hazard ratio (HR) with a 95% confidence interval (CI). More methodologies of this study were available in the PROSPERO (ID: CRD42021243719). Thirteen included studies involving 7,027,546 individuals (mean age, 42.6-71.9 years) were enrolled in the pooled analyses. Two articles provided the clinical data of both HBV and HCV infections. The proportion of high methodological quality studies was 76.9% (10/13). Synthetic results from 10 eligible studies of HBV showed that HBV infection was associated with a significantly higher risk of GC when compared with the healthy controls without HBV infection (pooled HR, 1.26; 95% CI, 1.08–1.47; P = 0.003; heterogeneity, I2 = 89.3%; P&lt; 0.001). In line with this finding, the combined effect derived from five included studies of HCV also supported a significant positive association between chronic HBV infection and GC development (pooled HR, 1.88; 95% CI, 1.28–2.76; P = 0.001; heterogeneity, I2 = 74.7%; P = 0.003). In conclusion, both chronic HBV and HCV infections were related to a high risk of GC. The plausible mechanisms underlying such association might be correlated to HBV/HCV infection-induced persistent inflammation, immune dysfunction, and cirrhosis.Systematic Review RegistrationPROSPERO (http://www.crd.york.ac.uk/PROSPERO), identifier (CRD42021243719).
Somatostatin Receptors and Chemokine Receptor CXCR4 in Lymphomas: A Histopathological Review of Six Lymphoma Subtypes
Authors: Juntikka Tiina , Vaittinen Samuli , Vahlberg Tero , Jyrkkiö Sirkku , Minn Heikki 
Published: July 2021

BackgroundSomatostatin receptors (SSTR) and chemokine receptor CXCR4 are expressed in lymphomas, while the abundance is known to be heterogeneous in different subtypes of lymphomas. Targeting tumor cells expressing these receptors might add to therapeutic opportunities while radiolabeled ligands for both imaging and therapy have been developed. The aim of this study was to establish SSTR subtype 2, 3 and 5 and also CXCR4 status immunohistochemically in six different lymphoma subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), mucosa-associated marginal B-cell lymphoma (MALT), Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL).Material and MethodsThis study included a total of 103 lymphoma patients (24 DLBCL, 22 FL, 18 HL, 9 MALT, 20 MCL and 10 PTCL) diagnosed in the Southwest hospital district of Finland during 2010-2019. SSTR 2, 3 and 5 and CXCR4 expression was analyzed immunohistochemically (IHC) in lymphoma samples obtained from local archival Biobank tissue repository. Immunopositivity of each receptor was scored on a four-point scale accounting for staining intensity and proportion of positively stained tumor cells.ResultsOf different SSTR subtypes SSTR2 immunopositivity was most common and seen predominantly at the cell membrane of the malignant cells in 46-56% of DLBCL, HL and FL. CXCR4 co-expression was frequently present in these cases. SSTR3 and SSTR5 IHC were negative in DLBCL and FL but in HL SSTR expression was more heterogenous and SSTR3 and SSTR5 positivity was found in cytoplasm in 35% and 25% of cases. 2/4 blastoid MCL variants and one pleomorphic MCL variant had positive CXCR4 IHC whilst all other MCL cases (85%) were negative for all receptors. 30% (n=3) of the PTCL patients had positive SSTR5 IHC and CXCR4. MALT lymphomas were negative for all receptors.ConclusionSSTR2 and CXCR4 are found in DLBCL, FL and HL and co-expression of these receptors is common. Although in general expression of SSTRs and CXCR4 is heterogenous and very low in some subtypes such as MCL and MALT there are also patients with abundant expression. The latter are candidates for trials studying SSTR2 and/or CXCR4 based treatments in the future.
To Combine or Not to Combine Physical Therapy With tDCS for Stroke With Shoulder Pain? Analysis From a Combination Randomized Clinical Trial for Rehabilitation of Painful Shoulder in Stroke
Authors: Andressa de Souza Janaina , Ferrari Corrêa João Carlos , Marduy Anna , Dall'Agnol Letizzia , Gomes de Sousa Maria Helena , Nunes da Silva Victor , Alves André Barreto , Silva Soraia Micaela , Fregni Felipe , Corrêa Fernanda Ishida 
Published: July 2021

Purpose: Transcranial Direct Current Stimulation (tDCS) is an intervention that seems to be an ideal tool to enhance the effects of rehabilitation therapies given it facilitates generation of plasticity in the stimulated brain area. In stroke this strategy has been highly utilized; however, the results have been mixed. In this trial we have evaluated the analgesic and functional effects of Transcranial Direct Current Stimulation (tDCS) combined with physiotherapy in stroke survivors with shoulder pain.Methods: Twenty-six stroke surviving adults with shoulder pain received 10 sessions of passive mobilization and performed upper limb exercises using a cycle ergometer, combined with active or sham tDCS. The intensity of pain in the hemiplegic shoulder was measured using the Visual Analog Scale (VAS); secondary outcomes were the level of motor impairment, handgrip strength, range of motion, motor function of the upper limbs, and quality of life (QOL) assessed before and after 10 sessions and 1 month after the end of the treatment.Results: A clinically important pain reduction (3 points) was found in both groups and was maintained at follow-up; there was no significant difference between groups (p = 0.3). Similarly, the shoulder range of motion improved, motor function and quality of life improved showed no significant differences between groups. One result that needs to be underscored is that both groups had a significant effect size toward improvement in all of these outcomes.Conclusions: We discuss in this study that tDCS is not a useful combination strategy when the physical therapy has a large effect by itself and we also review other negative trials of combined therapy under this framework of ceiling effect of the main physical therapy.Trial registry: Trial registration: Brazilian Registry of Clinical Trials, RBR-8F5MNY (http://www.ensaiosclinicos.gov.br/rg/RBR-8f5mny/). Registered on June 2, 2017.Beginning of the recruitment of the volunteers: august, 2017.
Case Report: Hodgkin Lymphoma and Refractory Systemic Lupus Erythematosus Unveil Activated Phosphoinositide 3-Kinase-δ Syndrome 2 in an Adult Patient
Authors: Conti Francesca , Catelli Arianna , Cifaldi Cristina , Leonardi Lucia , Mulè Rita , Fusconi Marco , Stefoni Vittorio , Chiriaco Maria , Rivalta Beatrice , Di Cesare Silvia , Schifino Gioacchino , Sbrega Fabiana , Di Matteo Gigliola , Ferrari Simona , Cancrini Caterina , Pession Andrea 
Published: July 2021

Introduction: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is a rare primary immune regulatory disorder caused by heterozygous gain of function mutation in the PIK3R1 gene encoding PI3Kδ regulatory p85α subunit and resulting in PI3Kδ hyperactivation. Clinical features range from recurrent infections to manifestations of immune dysregulation like autoimmunity, inflammation, systemic lymphoproliferation, and increased risk of cancer. We describe a new dominant PIK3R1 mutation causing APDS2 presenting with lymphoma and systemic refractory autoimmunity.Case Presentation: A 30-year-old woman was referred to the Immunology Unit of our hospital for uncontrolled systemic lupus erythematosus, including chilblains lesions, systemic lymphoproliferation and IgA deficiency. At 19 years of age, she was diagnosed with Hodgkin's lymphoma. Subsequently, she presented systemic lupus erythematosus onset, with episodes of severe exacerbation, including autoimmune hemolytic anemia and pleuro-pericarditis. Initial clinical response to conventional treatments was reported. Immunological investigations performed during our first observation showed severe lymphopenia, IgA deficiency, elevated IgM with reduced IgG2 levels, and low vaccination antibody titers. Quantitative real-time polymerase chain reaction (PCR) assay for Cytomegalovirus and Epstein-Barr virus showed low viral loads for both viruses in serum. An increase of serum inflammatory markers highlighted persistent systemic hyperinflammation. The next-generation sequencing (NGS)-based gene panel tests for primary immunodeficiency showed a heterozygous A&gt;G substitution in the splice acceptor site at c.1300-2 position of PIK3R1, leading to exon-skipping.Conclusion: This case emphasizes the importance of suspecting primary immune regulatory disorders in young adults, predominantly showing a severe, aggressive, and refractory to treatment immune dysregulation phenotype, even in the absence of major infectious diseases at the onset. Different treatments can be promptly started, and a delayed diagnosis can highly impact the outcome. Targeted therapy against PI3Kδ pathway defect effectively improves drug-resistant autoimmunity, lymphoproliferation, and risk of progression to malignancy; eligible patients could benefit from its use even as a bridge therapy to transplantation, currently the only definitive curative treatment. Therefore, identifying genetic mutation and prompt targeted treatment are essential to control disease manifestations, prevent long-term sequelae, and enable curative HSCT in APDS2 patients.
Heritability Estimation and Environmental Risk Assessment for Type 2 Diabetes Mellitus in a Rural Region in Henan, China: Family-Based and Case-Control Studies
Authors: Feng Yinhua , Li Xing , Mao Zhenxing , Huo Wenqian , Hou Jian , Wang Chongjian , Li Wenjie , Yu Songcheng 
Published: July 2021

Objective: The prevalence of type 2 diabetes mellitus (T2DM) varies greatly in different regions and populations. This study aims to assess the heritability and environmental risk factors of T2DM among rural Chinese adults.Methods: Thousand five hundred thirty three participants from 499 extended families, which included 24 nuclear families, were recruited in the family-based study to assess the heritable risk of T2DM. Heritability of T2DM was estimated by the Falconer method. Using conditional logistic regression model, couple case-control study involving 127 couples were applied to assess the environmental risk factors of T2DM.Results: Compared with the Henan Rural Cohort, T2DM was significantly clustered in the nuclear families (OR: 8.389, 95% CI: 5.537–12.711, P &lt; 0.001) and heritability was 0.74. No association between the heredity of T2DM and sex was observed between the extended families and the Henan Rural Cohort. Besides, results from the couple case-control study showed that physical activity (OR: 0.482, 95% CI: 0.261–0.893, P = 0.020) and fat intake (OR: 3.036, 95% CI: 1.070–8.610, P = 0.037) was associated with T2DM, and the proportion of offspring engaged in medium and high physical activity was higher than that of mothers in mother-offspring pairs.Conclusion: People with a family history of T2DM may have a higher risk of developing T2DM, however, there was no difference in genetic risk between males and females. Adherence to active physical activity and low fat intake can reduce the risk of T2DM.
Computer Vision Syndrome During SARS-CoV-2 Outbreak in University Students: A Comparison Between Online Courses and Classroom Lectures
Authors: Wang Lixiang , Wei Xin , Deng Yingping 
Published: July 2021

Purpose: To compare the prevalence of computer vision syndrome in university students of different teaching modes during the SARS-CoV-2 outbreak period.Methods: A cross-sectional survey study using the validated Computer Vision Syndrome Questionnaire in Chinese medical students of Sichuan University who took classroom lectures and the same-grade foreign students from a Bachelor of Medicine and Bachelor of Surgery (MBBS) program who took online lectures with similar schedules.Results: A total of 137 responses from 63 Chinese students and 74 MBBS students were obtained. The highest frequency of digital screen time was 7-9 h (43.24%, 32/74) for MBBS students and 2-4 h (46.03%, 29/63) for Chinese students. The prevalence of computer vision syndrome among Chinese students and MBBS students were 50.79% and 74.32%, respectively (P = 0.004). The average numbers of reported symptoms were 5.00 ± 2.17 in Chinese students and 5.91 ± 1.90 in MBBS students (P = 0.01). The three most highly reported symptoms were “heavy eyelids” (53.97%), “dryness” (50.79%), and “feeling of a foreign body” (46.03%) in Chinese students and “dryness” (72.97%), “feeling of a foreign body” (62.16%), and “heavy eyelids” (58.11%) in MBBS students. The sum grades of computer vision syndrome had a moderate positive correlation with screen time (Spearman's correlation coefficient = 0.386, P &lt; 0.001). The grades of symptoms of “feeling of a foreign body,” “heavy eyelids,” and “dryness” showed a weak positive correlation with screen time (Spearman's correlation coefficients were 0.220, 0.205, and 0.230, respectively).Conclusion: Online study may contribute to the prevalence of computer vision syndrome among university students.
Hurry Up, We Need to Find the Key! How Regulatory Focus Design Affects Children’s Trust in a Social Robot
Authors: Calvo-Barajas Natalia , Elgarf Maha , Perugia Giulia , Paiva Ana , Peters Christopher , Castellano Ginevra 
Published: July 2021

In educational scenarios involving social robots, understanding the way robot behaviors affect children’s motivation to achieve their learning goals is of vital importance. It is crucial for the formation of a trust relationship between the child and the robot so that the robot can effectively fulfill its role as a learning companion. In this study, we investigate the effect of a regulatory focus design scenario on the way children interact with a social robot. Regulatory focus theory is a type of self-regulation that involves specific strategies in pursuit of goals. It provides insights into how a person achieves a particular goal, either through a strategy focused on “promotion” that aims to achieve positive outcomes or through one focused on “prevention” that aims to avoid negative outcomes. In a user study, 69 children (7–9 years old) played a regulatory focus design goal-oriented collaborative game with the EMYS robot. We assessed children’s perception of likability and competence and their trust in the robot, as well as their willingness to follow the robot’s suggestions when pursuing a goal. Results showed that children perceived the prevention-focused robot as being more likable than the promotion-focused robot. We observed that a regulatory focus design did not directly affect trust. However, the perception of likability and competence was positively correlated with children’s trust but negatively correlated with children’s acceptance of the robot’s suggestions.
Case Report: A Rare Case of Fourth Ventricle to Spinal Subarachnoid Space Shunt Migration: Surgical Pearl and Literature Review
Authors: Serratrice Nicolas , Faddoul Joe , Tarabay Bilal , Taifour Sarkis , Abi Lahoud Georges Naïm 
Published: July 2021

Background: In the event of syringomyelia communicating with the fourth ventricle, a fourth ventricle to cervical subarachnoid space shunting could be proposed.Case Report: In this review article, we describe the case of a 40-year-old woman who had a previously implanted fourth ventricle to spinal subarachnoid space shunt for the treatment of syringomyelia in the context of Chiari syndrome. The catheter migrated intradurally to the lumbosacral space, but in the absence of neurological repercussions, we decided to leave it in place.Conclusions: To the best of our knowledge, this is the first case described in the literature review of a catheter migration in the subarachnoid space from occipitocervical to lumbosacral level.