bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anthocyanin-rich blue potato meals protect against polychlorinated biphenyl-mediated disruption of short-chain fatty acid production and gut microbiota profiles in a simulated human digestion model
Authors: Lu Fang , MacPherson Chad W. , Tremblay Julien , Iskandar Michèle M. , Kubow Stan 
Published: May 2023

BackgroundPolychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants associated with a wide variety of adverse human health outcomes. PCB 126 and PCB 153 are among the most prevalent congeners associated with human exposure. Emerging studies have suggested that PCB exposure leads to lower gut microbial diversity although their effects on microbial production of health promoting short-chain fatty acids (SCFAs) has been scarcely studied. Blue potatoes are rich in anthocyanins (ACNs), which is a class of polyphenols that promote the growth of beneficial intestinal bacteria such as Bifidobacterium and Lactobacillus and increase the generation of SCFAs. A batch-culture, pH-controlled, stirred system containing human fecal microbial communities was utilized to assess whether human gut microbiota composition and SCFA production are affected by: (a) PCB 126 and PCB 153 exposure; and (b) ACN-rich digests in the presence and absence of the PCB congeners.MethodsAnthocyanin-rich blue potato meals (11.03 g) were digested over 12 h with and without PCB 126 (0.5 mM) and PCB 153 (0.5 mM) using an in vitro simulated gut digestion model involving upper gastrointestinal digestion followed by metabolism by human fecal microbiota. Fecal digests were collected for analysis of gut microbial and SCFA profiles.ResultsPolychlorinated biphenyl-exposed fecal samples showed a significant (p &lt; 0.05) decrease in species richness and a significantly (p &lt; 0.05) different microbial community structure. PCB treatment was associated with an increased (p &lt; 0.05) relative abundance of Akkermansia, Eggerthella, and Bifidobacterium and a decreased (p &lt; 0.05) relative abundance of Veillonella, Streptococcus, and Holdemanella. ACN digests counteracted the altered abundances of Akkermansia and Bifidobacterium seen with the PCB treatment. PCB exposure was associated with a significant (p &lt; 0.05) decrease in total SCFA and acetate concentrations. ACN digests were associated with significantly (p &lt; 0.05) higher SCFA and acetate concentrations in the presence and absence of PCBs.ConclusionHuman fecal matter exposed to PCB 126 and PCB 153 led to decreased abundance and altered gut microbiota profiles as well as lowered SCFA and acetate levels. Importantly, this study showed that prebiotic ACN-rich potatoes counteract PCB-mediated disruptions in human gut microbiota profiles and SCFA production.
Optimizing patient selection for stereotactic ablative radiotherapy in patients with locally advanced pancreatic cancer after initial chemotherapy - a single center prospective cohort
Authors: Doppenberg D. , Lagerwaard F. J. , van Dieren S. , Meijerink M. R. , van der Vliet J. J. , Besselink M. G. , van Tienhoven G. , Versteijne E. , Slotman B. J. , Wilmink J. W. , Kazemier G. , Bruynzeel A. M. E. 
Published: May 2023

BackgroundThe role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking.MethodsA prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS.ResultsOverall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age &lt;70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%.ConclusionsSABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age &lt;70 years and absence of pain. Future randomized trials will have to confirm these findings.
Comprehensive analysis of the prognosis and immune effect of the oncogenic protein Four Jointed Box 1
Authors: Huang Mei , Guo Tian , Meng Yan , Zhou Ruling , Xiong Man , Ding Jian , Zhang Yali , Liu Side , Zhuang Kangmin 
Published: May 2023

BackgroundThe Four Jointed Box 1 (FJX1) gene has been implicated in the upregulation of various cancers, highlighting its crucial role in oncology and immunity. In order to better understand the biological function of FJX1 and identify new immunotherapy targets for cancer, we conducted a comprehensive analysis of this gene.MethodsWe analyzed the expression profiles and prognostic value of FJX1 using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Copy number alterations (CNAs), mutations, and DNA methylation were analyzed through cBioPortal. The Immune Cell Abundance Identifier (ImmuCellAI) was used to examine the correlation between FJX1 expression and immune cell infiltration. The relationship between FJX1 expression and immune-related genes and immunosuppressive pathway-related genes was analyzed using The Tumor Immune Estimation Resource version 2 (TIMER2). Tumor mutational burden (TMB) and microsatellite instability (MSI) were obtained from TCGA pan-cancer data. The effect of immunotherapy and the IC50 were assessed using IMvigor210CoreBiologies and Genomics For Drug Sensitivity in Cancer (GDSC). Finally, we evaluated the impact of FJX1 on colon cancer cell proliferation and migration through in vitro functional experiments.ResultsOur study indicated that FJX1 expression was high in most cancers and was significantly associated with poor prognosis. High FJX1 expression was also linked to significant alterations in CNA, DNA methylation, TMB, and MSI. Positive correlations were found between FJX1 expression and tumor-associated macrophages (TAMs) and with immune-related genes such as TGFB1 and IL-10 and immunosuppressive pathway-related genes such as TGFB1 and WNT1. On the other hand, FJX1 expression showed a negative relationship with CD8+ T cells. Furthermore, high FJX1 expression led to reduced effectiveness of immunotherapy and drug resistance. In colon cancer cells, FJX1 knockdown was found to decrease cell proliferation and migration.ConclusionOur research findings demonstrate that FJX1 is a new prognostic factor with a significant role in tumor immunity. Our results highlight the importance of further exploring the potential of targeting FJX1 as a therapeutic strategy in cancer.
Afatinib combined with anti-PD1 enhances immunotherapy of hepatocellular carcinoma via ERBB2/STAT3/PD-L1 signaling
Authors: Yu Chao , Zhang Xinyi , Wang Min , Xu Gaoxin , Zhao Siqi , Feng Yongheng , Pan Chao , Yang Weijun , Zhou Jin , Shang Longcheng , Ma Yong 
Published: May 2023

BackgroundAfatinib is mainly used to treat advanced non-small cell lung cancer, but its therapeutic effect on hepatocellular carcinoma is still unclear.MethodsOver 800 drugs were screened by CCK8 technology and afatinib was found to have a significant inhibitory effect on liver cancer cells. The expression of PDL1 in tumor cells treated with drugs were detected by qRT-PCR and Weston Blot experiments. The effects of afatinib on the growth, migration and invasion of HCC cells were evaluated using wound healing, Transwell, and cell cloning assays. The in vivo effects of afatinib in combination with anti-PD1 were evaluated in C57/BL6J mice with subcutaneous tumorigenesis. Bioinformatics analysis was performed to explore the specific mechanism of afatinib's inhibition of ERBB2 in improving the expression level of PD-L1, which was subsequently verified through experiments.ResultsAfatinib was found to have a significant inhibitory effect on liver cancer cells, as confirmed by in vitro experiments, which demonstrated that it could significantly suppress the growth, invasion and migration of HCC cells. qRT PCR and Weston Blot experiments also showed that Afatinib can enhance the expression of PD-L1 in tumor cells. In addition, in vitro experiments confirmed that afatinib can significantly enhance the immunotherapeutic effect of hepatocellular carcinoma. Afatinib’s ability to increase PD-L1 expression is mediated by STAT3 activation following its action on HCC cells.ConclusionAfatinib enhances PD-L1 expression in tumor cells through the STAT3/PD-L1 pathway. The combination of afatinib and anti-PD1 treatment significantly increases the immunotherapeutic effect of HCC.
Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis
Authors: Altaf Reem , Ilyas Umair , Ma Anmei , Shi Meiqi 
Published: May 2023

BackgroundDespite the high prevalence of lung cancer, with a five-year survival rate of only 23%, the underlying molecular mechanisms of non-small cell lung cancer (NSCLC) remain unknown. There is a great need to identify reliable candidate biomarker genes for early diagnosis and targeted therapeutic strategies to prevent cancer progression.MethodsIn this study, four datasets obtained from the Gene Expression Omnibus were evaluated for NSCLC- associated differentially expressed genes (DEGs) using bioinformatics analysis. About 10 common significant DEGs were shortlisted based on their p-value and FDR (DOCK4, ID2, SASH1, NPR1, GJA4, TBX2, CD24, HBEGF, GATA3, and DDR1). The expression of significant genes was validated using experimental data obtained from TCGA and the Human Protein Atlas database. The human proteomic data for post- translational modifications was used to interpret the mutations in these genes.ResultsValidation of DEGs revealed a significant difference in the expression of hub genes in normal and tumor tissues. Mutation analysis revealed 22.69%, 48.95%, and 47.21% sequence predicted disordered regions of DOCK4, GJA4, and HBEGF, respectively. The gene-gene and drug-gene network analysis revealed important interactions between genes and chemicals suggesting they could act as probable drug targets. The system-level network showed important interactions between these genes, and the drug interaction network showed that these genes are affected by several types of chemicals that could serve as potential drug targets.ConclusionsThe study demonstrates the importance of systemic genetics in identifying potential drug- targeted therapies for NSCLC. The integrative system- level approach should contribute to a better understanding of disease etiology and may accelerate drug discovery for many cancer types.
Surgical treatment of a distal radius and ipsilateral metacarpal hemophilic pseudotumor without recurrence or functional deficit: a case report
Authors: Wang Yingjie , Lv Zehui , Dong Xiying , Feng Bin , Weng Xisheng 
Published: May 2023

BackgroundDistal hemophilic pseudotumor (HP) occurring distal to the wrist appear to be secondary to intraosseous hemorrhage, which develops rapidly and should be treated primarily with long-term replacement therapy and cast immobilization. Surgical removal or even amputation is indicated when conservative management fails to prevent progression. Here, a practical strategy was described for those patients who cannot afford the cost of routine coagulation factor replacement therapy, namely immediate surgical curettage and bone grafting as well as continuous follow-up.Case descriptionA 7-year-old boy with a history of mild hemophilia A was admitted to our medical center because of a 2-year history of progressive swelling and pain around right forearm and hand. Coagulation factor VIII level was 11.1% of normal with no inhibitor. Radiographs revealed expansile swelling, bone destruction, and deformity of the distal right radius and the second metacarpal bone. He was diagnosed with distal HP. Surgical procedure of curettage and bone grafting was performed. The function and appearance of the right wrist were almost normal without discomfort at the 101-month follow-up. Significantly, the same patient was hospitalized again because of a year-long progressive swelling and pain around the left hand when he was 14 years old. X-ray showed multiple bone destruction of the left proximal phalanges of left thumb, middle finger and little finger with local pathological fractures. Surgical procedure of HPs including curettage and bone grafting was performed. Postoperative recovery was good, and the last clinical follow-up at 18 months after the operation displayed a satisfactory shape and functional outcomes.ConclusionsCurettage and bone grafting prove to be safe and feasible for patients with distal HP and continuous follow-up of patients with distal HP is very vital for timely finding and then treating successive HP in developing countries.
Outcomes after ABO incompatible pediatric liver transplantation are comparable to ABO identical/compatible transplant
Authors: Lemoine Caroline P. , Brandt Katherine A. , Keswani Mahima , Superina Riccardo 
Published: May 2023

BackgroundABO incompatible (ABOi) liver transplantation (LT) was initially associated with a higher incidence of vascular, biliary, and rejection complications and a lower survival than ABO compatible (ABOc) LT. Various protocols have been proposed to manage anti-isohemagglutinin antibodies and hyperacute rejection. We present our experience with a simplified protocol using only plasmapheresis.MethodsA retrospective review of all patients who received an ABOi LT at our institution was performed. Comparisons were made based on era (early: 1997–2008, modern: 2009–2020) and severity of disease (status 1 vs. exception PELD at transplant). A pair-matched comparison was done to patients who received an ABOc LT. p &lt; 0.05 was considered significant.Results17 patients received 18 ABOi LT (3 retransplants). Median age at transplant was 7.4 months (1.1–28.9). 66.7% patients were listed as status 1. Hepatic artery thrombosis (HAT) occurred in one patient (5.6%), there were 2 cases of portal vein thrombosis (PVT) (11.1%), and 2 biliary strictures (11.1%). Patient and graft survival improved in the ABOi modern era, although not significantly. In the pair-matched comparison, complications (HAT p = 0.29; PVT p = 0.37; biliary complications p = 0.15) and survival rates were similar. Patient and graft survivals were 100% in the non-status 1 ABOi patients compared to 67% (p = 0.11) and 58% (p = 0.081) respectively for patients who were transplanted as status 1.ConclusionABO incompatible liver transplants in infants with a high PELD score have excellent outcomes. Indications for ABO incompatible transplants should be liberalized to prevent deaths on the waiting list or deterioration of children with high PELD scores.
Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies
Authors: Theron A. , Ayadi S. , Boissier E. , Dautremay O. , Schved J.-F. , Sirvent N. , Diaz I. , Captier G. , Biron-Andreani C. , Jeziorski E. 
Published: May 2023

IntroductionIdiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication.MethodThis is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aβ2GP1).ResultsAmong the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aβ2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37–1.71], p = 1 and RR: 0.7 [95% CI: 0.33–1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.
Ginkgolide With Intravenous Alteplase Thrombolysis in Acute Ischemic Stroke Improving Neurological Function: A Multicenter, Cluster-Randomized Trial (GIANT)
Authors: Zhang Xuting , Zhong Wansi , Ma Xiaodong , Zhang Xiaoling , Chen Hongfang , Wang Zhimin , Lou Min , GIANT Investigators  
Published: May 2023

Background and Purpose: We aimed to investigate the effect of Ginkgolide® treatment on neurological function in patients receiving intravenous (IV) recombinant tissue plasminogen activator (rt-PA).Methods: This cluster randomized controlled trial included acute ischemic stroke patients in 24 centers randomized to intervention of intravenous Ginkgolide® or control group within the first 24 h after IV rt-PA therapy (IVT). Clinical outcome at 90 days was assessed with modified Rankin Scale (mRS) score and dichotomized into good outcome (0–2) and poor outcome (3–6). Hemorrhagic transformation represented the conversion of a bland infarction into an area of hemorrhage by computed tomography. Symptomatic intracerebral hemorrhage (sICH) was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 7-day or if the hemorrhage was likely to be the cause of the clinical deterioration. We performed logistic regression analysis and propensity score matching analysis to investigate the impact of Ginkgolide® treatment with IV rt-PA on good outcome, hemorrhagic transformation and sICH, respectively.Results: A total of 1113 patients were finally included and 513 (46.1%) were in the intervention group. Patients in the Ginkgolide® group were more likely to have good outcomes (78.6 vs. 66.7%, p &lt; 0.01) and lower rate of sICH (0 vs. 2.72%, p &lt; 0.01), compared with patients in the control group. The intra-cluster correlation coefficient (ICC) for good outcome at 90 days was 0.033. Binary logistic regression analysis revealed that treatment with Ginkgolide® was independently associated with 90-day mRS in patients with IV rt-PA therapy (OR 1.498; 95% CI 1.006–2.029, p = 0.009). After propensity score matching, conditional logistic regression showed intervention with Ginkgolide® was significantly associated with 90-day good outcome (OR 1.513; 95% CI 1.073–2.132, p = 0.018). No significant difference in hemorrhage transformation was seen between the 2 matched cohorts (OR 0.885; 95% CI 0.450–1.741, p = 0.724).Conclusion: Using Ginkgolide® within 24-hour after IV rt-PA is effective and safe and might be recommended in combination with rtPA therapy in acute ischemic stroke.Clinical Trial Registration:http://www.clinicaltrials.gov, identifier NCT03772847.
Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors
Authors: Fiedler Lukas , Motloch Lukas J. , Dieplinger Anna-Maria , Jirak Peter , Davtyan Paruir , Gareeva Diana , Badykova Elena , Badykov Marat , Lakman Irina , Agapitov Aleksandr , Sadikova Liana , Pavlov Valentin , Föttinger Fabian , Mirna Moritz , Kopp Kristen , Hoppe Uta C. , Pistulli Rudin , Cai Benzhi , Yang Baofeng , Zagidullin Naufal 
Published: May 2023

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date.Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days].Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p &lt; 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ2-statistics = 6.45, p = 0.013 and SCD: χ2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group.Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.