bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first‐line treatment of advanced esophageal squamous cell carcinoma
Authors: Zhang Bo , Qi Ling , Wang Xi , Xu Jianping , Liu Yun , Mu Lan , Wang Xingyuan , Bai Lidan , Huang Jing 
Published: December 2020

AbstractBackgroundEffective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma (ESCC). The incorporation of an immune checkpoint inhibitor and a molecular anti‐angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects. Therefore, we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first‐line treatment of advanced ESCC.MethodsIn this single‐arm prospective phase II trial, patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg, liposomal paclitaxel 150 mg/m2, and nedaplatin 50 mg/m2 on day 1, and apatinib 250 mg on days 1‐14. The treatments were repeated every 14 days for up to 9 cycles, followed by maintenance therapy with camrelizumab and apatinib. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Secondary endpoints included disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety.ResultsWe enrolled 30 patients between August 7, 2018 and February 23, 2019. The median follow‐up was 24.98 months (95% confidence interval [CI]: 23.05‐26.16 months). The centrally assessed ORR was 80.0% (95% CI: 61.4%‐92.3%), with a median duration of response of 9.77 months (range: 1.54 to 24.82+ months). The DCR reached 96.7% (95% CI: 82.8%‐99.9%). The median PFS was 6.85 months (95% CI: 4.46‐14.20 months), and the median OS was 19.43 months (95% CI: 9.93 months – not reached). The most common grade 3‐4 treatment‐related adverse events (AEs) were leukopenia (83.3%), neutropenia (60.0%), and increased aspartate aminotransferase level (26.7%). Treatment‐related serious AEs included febrile neutropenia, leukopenia, and anorexia in one patient (3.3%), and single cases of increased blood bilirubin level (3.3%) and toxic epidermal necrolysis (3.3%). No treatment‐related deaths occurred.ConclusionsCamrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first‐line treatment demonstrated feasible anti‐tumor activity and manageable safety in patients with advanced ESCC. Randomized trials to evaluate this new combination strategy are warranted.Trial registrationThis trial was registered on July 27, 2018, at ClinicalTrials.gov (identifier: NCT03603756).
Characteristics and mechanisms to control a COVID‐19 outbreak on a leukemia and stem cell transplantation unit
Authors: Greiner Jochen , Götz Marlies , Malner‐Wagner Waltraud , Wendt Constanze , Enders Martin , Durst Christine , Michel Detlef , von Harsdorf S , Jung Susanne 
Published: December 2020

AbstractImmunosuppressed patients like patients with leukemia or lymphoma, but also patients after autologous or allogeneic stem cell transplantation are at particular risk for an infection with COVID‐19. We describe a COVID‐19 outbreak on our leukemia and stem cell transplantation unit (LSCT‐Unit) originating from a patient with newly diagnosed acute myeloid leukemia. The patient was treated with intensive induction chemotherapy and we characterize the subsequent outbreak of COVID‐19 on a LSCT‐Unit. We describe the characteristics of the 36 contacts among the medical team, the results of their PCR and antibody tests and clinical aspects and features of infected employees. Of these 36 close contacts, 9 employees of the LSCT‐Unit were infected and were tested positive by PCR and/or antibody‐testing. 8/9 of them were symptomatic, 3/9 with severe, 5/9 with mild symptoms, and one person without symptoms. Due to stringent hygiene measures, the outbreak did not lead to infections of other patients despite ongoing clinical work. Moreover, we demonstrate that incubation period and clinical course of a COVID‐19 infection in an immunosuppressed patient could be unusual compared to that of immunocompetent patients. Consistent PCR and antibody testing are helpful to understand, control, and prevent outbreaks. For the safety of health‐care workers and patients alike, all employees wore FFP2 masks and were trained to adhere to several further safety guidelines. The implementation of rigorous hygiene measures is the key to controlling an outbreak and preventing infections of other patients.
Conditional survival in patients with esophageal or gastroesophageal junction cancer after receiving various treatment modalities
Authors: Deng Wei , Yang Zhao , Dong Xin , Yu Rong , Wang Weihu 
Published: December 2020

AbstractBackgroundTo estimate the adjusted conditional overall survival (COS) in patients with esophageal cancer after receiving various treatment modalities via a national population‐based database, and to investigate the possible time‐dependent effects.Materials and MethodsEligible patients diagnosed with esophageal cancer between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. The Kaplan‐Meier method was used to calculate conventional survival time. The inverse probability of treatment weighting method was used to estimate the adjusted COS in patients receiving different treatment modalities. Landmark analysis was employed to investigate the possible time‐dependent effects of different treatment modalities in patients who had survived a certain period of time.ResultsA total of 25,232 patients were included in the final analysis. The conventional 5‐year overall survival was 19.3%. The 5‐year adjusted COS increased most for the first 3 years, and increased slightly afterwards. In patients with regional esophageal or gastroesophageal junction cancer, stage‐specific analysis showed that surgery only and preoperative radiation therapy benefited most for patients with localized disease, preoperative radiation therapy plus surgery benefited regional, and preoperative radiation therapy plus surgery benefited distant disease, with the 5‐year adjusted COS given patients had survived 3 years being 67.0% (95% CI 65.2%–68.7%), 59.9% (95% CI 58.3%–61.5%), 58.4% (95% CI 56.3%–60.5%), and 61.8% (95% CI 59.5%–64.1%), respectively. In time‐dependent analysis, the benefits of surgery only in localized cases were prominent within 48 months after diagnosis. Preoperative radiation therapy showed long‐lasting benefits in patients with regional disease. In patients with distant disease, all treatment modalities showed similar and short‐term effects.ConclusionsThe adjusted COS in patients with esophageal cancer increased as time accrued after receiving various treatment modalities. The time‐dependent effects in specific tumor stage provided a dynamic view on optimization of treatment strategies.
Immune landscape and a promising immune prognostic model associated with TP53 in early‐stage lung adenocarcinoma
Authors: Wu Chengde , Rao Xiang , Lin Wei 
Published: December 2020

AbstractPurposeTP53 mutation, one of the most frequent mutations in early‐stage lung adenocarcinoma (LUAD), triggers a series of alterations in the immune landscape, progression, and clinical outcome of early‐stage LUAD. Our study was designed to unravel the effects of TP53 mutation on the immunophenotype of early‐stage LUAD and formulate a TP53‐associated immune prognostic model (IPM) that can estimate prognosis in early‐stage LUAD patients.Materials and methodsImmune‐associated differentially expressed genes (DEGs) between TP53 mutated (TP53MUT) and TP53 wild‐type (TP53WT) early‐stage LUAD were comprehensively analyzed. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis identified the prognostic immune‐associated DEGs. We constructed and validated an IPM based on the TCGA and a meta‐GEO composed of GSE72094, GSE42127, and GSE31210, respectively. The CIBERSORT algorithm was analyzed for assessing the percentage of immune cell types. A nomogram model was established for clinical application.ResultsTP53 mutation occurred in approximately 50.00% of LUAD patients, stimulating a weakened immune response in early‐stage LUAD. Sixty‐seven immune‐associated DEGs were determined between TP53WT and TP53MUT cohort. An IPM consisting of two prognostic immune‐associated DEGs (risk score = 0.098 * ENTPD2 expression + 0.168 * MIF expression) was developed through 397 cases in the TCGA and further validated based on 623 patients in a meta‐GEO. The IPM stratified patients into low or high risk of undesirable survival and was identified as an independent prognostic indicator in multivariate analysis (HR = 2.09, 95% CI: 1.43–3.06, p < 0.001). Increased expressions of PD‐L1, CTLA‐4, and TIGIT were revealed in the high‐risk group. Prognostic nomogram incorporating the IPM and other clinicopathological parameters (TNM stage and age) achieved optimal predictive accuracy and clinical utility.ConclusionThe IPM based on TP53 status is a reliable and robust immune signature to identify early‐stage LUAD patients with high risk of unfavorable survival.
Assessment of Thiosemicarbazone‐Containing Compounds as Potential Antileukemia Agents against P‐gp Overexpressing Drug Resistant K562/A02 Cells
Authors: Gu Xiaoke , Guan Mingyu , Jiang Chunyu , Song Qinghua , Li Xin , Sun Nan , Chen Jing , Qiu Jingying 
Published: December 2020

AbstractP‐Glycoprotein (P‐gp) overexpression is considered to be the leading cause of multidrug resistance (MDR) and failure of chemotherapy for leukemia. In this study, seventeen thiosemicarbazone‐containing compounds were prepared and evaluated as potential antileukemia agents against drug resistant K562/A02 cell overexpressing P‐gp. Among them, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide could significantly inhibit K562/A02 cells proliferation with an IC50 value of 0.96 μM. Interestingly, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide could dose‐dependently increase ROS levels of drug resistant K562/A02 cells, thus displaying a potential collateral sensitivity (CS)‐inducing effect and selectively killing K562/A02 cells. Furthermore, N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide possessed potent inhibitory effect on HDAC1 and HDAC6, and could promote K562/A02 cells apoptosis via dose‐dependently increasing Bax expression, reducing Bcl‐2 protein level, and inducing the cleavage of PARP and caspase3. These present findings suggest that N‐hydroxy‐6‐({(2E)‐2‐[(3‐nitrophenyl)methylidene]hydrazinecarbothioyl}amino)hexanamide might be a promising lead to discover novel antileukemia agents against P‐gp overexpressing leukemic cells.
Comparison of ultrasound‐guided versus angiography‐guided endovascular treatment for femoropopliteal artery occlusive disease
Authors: Tokuda Takahiro , Mori Shinsuke , Oba Yasuhiro , Koshida Ryoji , Kagase Ai , Matsuda Hiroaki , Suzuki Yoriyasu , Murata Akira , Ito Tatsuya , Hirano Keisuke 
Published: December 2020

AbstractPurposeThis study aimed to compare the efficacy of ultrasound‐guided and angiography‐guided intraluminal approach for femoropopliteal (FP) artery occlusive disease.MethodsA retrospective analysis was performed using the data collected regarding patients that underwent endovascular treatment (EVT) for FP artery occlusive disease between January 2010 and April 2018 at two centers. A total of 221 consecutive de novo lesions were analyzed according to the method of recanalization. Propensity score‐matched analysis was performed to compare the clinical outcomes of recanalization methods for FP occlusive lesions. The prognostic value was analyzed based on the number of guidewires, wire cross time, distal puncture rate, radiation exposure, the amount of contrast media, primary patency, and clinically driven‐target lesion revascularization (CD‐TLR) at 1 year.ResultsA total of 44 matched pairs of patients were analyzed after propensity score‐matched analysis. The number of guidewires, distal puncture rate, wire passage time, radiation exposure, and the amount of contrast media were significantly lower in the ultrasound‐guide group, with 3.4 vs. 4.7, 9.1% vs. 54.5%, 47 min vs. 83 min, 207 mGy vs. 821 mGy, 66 ml vs. 109 ml, respectively (p < .01), but there were no significant differences between the two groups in terms of primary patency and CD‐TLR.ConclusionsThe ultrasound‐guided EVT for FP occlusive disease significantly reduced the number of guidewires, wire cross time, the rate of distal puncture, radiation exposure, and the amount of contrast media used.
Encountering the accessory polar renal artery during retroperitoneal lymphadenectomy
Authors: Karadağ Ceyda , Birge Ozer , Bakir Mehmet Sait , Doğan Selen , Tuncer Hasan Aykut , Şimşek Tayup 
Published: December 2020

AbstractBecause of the accessory polar renal artery (APRA) is functional, it is extremely important to be careful with vascular injuries, to prevent ischemic damage and not to cause kidney failure complications.
Listeria monocytogenes infectious abdominal aortic aneurysm: Case report and review of the literature
Authors: Järve Heli , Kals Jaak 
Published: December 2020

AbstractListeria monocytogenes‐caused primary infected abdominal aortic aneurysm is a very rare disease. Aortic wall tissue sampling is essential for confirmation of diagnosis. Surgical repair and long‐term antibacterial treatment are crucial for management.
Type of atrial fibrillation and outcomes in patients without oral anticoagulants
Authors: Ren Jiameng , Yang Yanmin , Zhu Jun , Wu Shuang , Wang Juan , Zhang Han , Shao Xinghui , Lyu Siqi 
Published: December 2020

AbstractBackgroundThe effect of type of atrial fibrillation (AF) on adverse outcomes in Chinese patients without oral anticoagulants (OAC) was controversial.HypothesisThe type of AF associated with adverse outcomes in Chinese patients without OAC.MethodsA total of 1358 AF patients without OAC from a multicenter, prospective, observational study was included for analysis. Univariable and multivariable Cox regression models were utilized. Net reclassification improvement analysis was performed for the assessment of risk prediction models.ResultsThere were 896(66%) patients enrolled with non‐paroxysmal AF (NPAF) and 462(34%) with paroxysmal AF (PAF). The median age was 70.9 ± 12.6 years, and 682 patients (50.2%) were female. During 1 year of follow‐up, 215(16.4%) patients died, and 107 (8.1%) patients experienced thromboembolic events. Compared with the PAF group, NPAF group had a notably higher incidence of all‐cause mortality (20.2% vs. 9.4%, p < .001), thromboembolism (10.5% vs. 3.8%, p < .001). After multivariable adjustment, NPAF was a strong predictor of thromboembolism (HR 2.594, 95%CI 1.534–4.386; p < .001), all‐cause death (HR 1.648, 95%CI 1.153–2.355; p = .006). Net reclassification improvement analysis indicated that the addition of NPAF to the CHA2DS2‐VASc score allowed an improvement of 0.37 in risk prediction for thromboembolic events (95% CI 0.21–0.53; p < .001).ConclusionsIn Chinese AF patients who were not on OAC, NPAF was an independent predictor of thromboembolism and mortality. The addition of NPAF to the CHA2DS2‐VASc score allowed an improvement in the accuracy of the prediction of thromboembolic events.
TowardsoperandoIR‐ and UV‐vis‐Spectro‐Electrochemistry: A Comprehensive Matrix Factorisation Study on Sensitive and Transient Molybdenum and Tungsten Mono‐Dithiolene Complexes**
Authors: Elvers Benedict J. , Sawall Mathias , Oberem Elisabeth , Heckenberger Kilian , Ludwig Ralf , Neymeyr Klaus , Schulzke Carola , Krewald Vera , Fischer Christian 
Published: December 2020

AbstractThe redox sequences of sensitive aliphatic mono‐dithiolene complexes [MII(CO)2(cydt)(dppe)] (M=Mo, W) were studied with extensive cyclic voltammetrical and spectro‐electrochemical (SEC) investigations using UV‐vis and IR spectroscopy. With a newly developed matrix factorisation technique, the pure component spectra and temporal evolution of the developed species were ascertained, including sensitive and transient ones. The concentration of all involved compounds at the working electrode as dependent on the respective applied potential was derived with very high accuracy. The assignment of the species’ geometries and electronic structures was further verified by quantum chemical calculations. Overall, the combined electrochemical, spectroscopic, quantum chemical and mathematical approach facilitates a comprehensive understanding of the underlying electrochemical transformations and equilibria. Since only a single CV run is needed to obtain all data required to identify the individual species, the method presented here is expected to be applicable to a wide range of complicated electrochemically responsive systems and thus opens a path towards developing a deeper mechanistic understanding of the underlying chemistry.
The Quasi Curvature‐Dimension Condition with Applications to Sub‐Riemannian Manifolds
Authors: Milman Emanuel 
Published: December 2020

AbstractWe obtain the best known quantitative estimates for the Lp‐Poincaré and log‐Sobolev inequalities on domains in various sub‐Riemannian manifolds, including ideal Carnot groups and in particular ideal generalized H‐type Carnot groups and the Heisenberg groups, corank 1 Carnot groups, the Grushin plane, and various H‐type foliations, Sasakian and 3‐Sasakian manifolds. Moreover, this constitutes the first time that a quantitative estimate independent of the dimension is established on these spaces. For instance, the Li‐Yau / Zhong‐Yang spectral‐gap estimate holds on all Heisenberg groups of arbitrary dimension up to a factor of 4.We achieve this by introducing a quasi‐convex relaxation of the Lott‐Sturm‐Villani CD(K, N) condition we call the “quasi curvature‐dimension condition” QCD(Q, K, N). Our motivation stems from a recent interpolation inequality along Wasserstein geodesics in the ideal sub‐Riemannian setting due to Barilari and Rizzi. We show that on an ideal sub‐Riemannian manifold of dimension n, the measure contraction property MCP(K, N) implies QCD(Q, K, N) with Q = 2N − n ≥ 1, thereby verifying the latter property on the aforementioned ideal spaces; a result of Balogh‐Kristály‐Sipos is used instead to handle nonideal corank 1 Carnot groups. By extending the localization paradigm to completely general interpolation inequalities, we reduce the study of various analytic and geometric inequalities on QCD spaces to the one‐dimensional case. Consequently, we deduce that while (strictly) sub‐Riemannian manifolds do not satisfy any type of CD condition, many of them satisfy numerous functional inequalities with exactly the same quantitative dependence (up to a factor of Q) as their CD counterparts. © 2020 Wiley Periodicals LLC
Screening of suitable genotype for Bangladesh conditions based on genetic variability and path analysis in F2 white maize populations
Authors: Hasan Md. Mahmudul , Rahman Jamilur , Sultana Fahmida , Fatima Kaniz , Shahriar Saleh Ahmed , Imtiaz Abdullah All , Subramaniam Sreeramanan , Uddain Jasim 
Published: December 2020

AbstractWhite maize is the new maize (Zea mays L.) cultivar in Bangladesh. The country needs high‐yielding white maize varieties for farmers’ cultivation, but developing such variety requires appropriate inbred lines. Here, nine F2 populations of white maize were evaluated through assessment of their genetic variability, heritability, and character association for selection of promising lines based on yield and growth parameters. Analysis of genetic variability showed that there were significant variations among the various genotypes of F2 populations. High heritability coupled with large genetic advances in percentage means were obtained in plant height, cob height, number of branches per tassel, number of cobs bearing node, leaf blade area, and grain yield per plant. The analysis of path coefficient indicated positive direct contribution towards yield per plant through days to 50% tasseling, days to 50% silking, cob height, days to maturity, number of branches of the tassel, cob breadth, and number of grains per row. The results thus indicated that indirect selection based on plant height, days to maturity, cob height, leaves per plants, cob length, number of rows per cob, and number of grains per row are reliable to select the appropriate lines for yield improvement in white maize. In view of the yield and its contributing characteristics, the population of KS 510 has a high yield potential for improvement of the varietal performance of white maize.
Pregnancy‐specific glycoprotein 9 acts as both a transcriptional target and a regulator of the canonical TGF‐β/Smad signaling to drive breast cancer progression
Authors: Liu Ying‐Ying , Zhang Sa , Yu Tian‐Jian , Zhang Fang‐Lin , Yang Fan , Huang Yan‐Ni , Ma Ding , Liu Guang‐Yu , Shao Zhi‐Ming , Li Da‐Qiang 
Published: December 2020

AbstractPregnancy‐specific glycoprotein 9 (PSG9) is a placental glycoprotein essential for the maintenance of normal gestation in mammals. Bioinformatics analysis of multiple publicly available datasets revealed aberrant PSG9 expression in breast tumors, but its functional and mechanistic role in breast cancer remains unexplored. Here, we report that PSG9 expression levels were elevated in tumor tissues and plasma specimens from breast cancer patients, and were associated with poor prognosis. Gain‐ or loss‐of‐function studies demonstrated that PSG9 promoted breast cancer cell proliferation, migration, and invasionin vitro, and enhanced tumor growth and lung colonization in vivo. Mechanistically, transforming growth factor‐β1 (TGF‐β1) transcriptionally activated PSG9 expression through enhancing the enrichment of Smad3 and Smad4 onto PSG9 promoter regions containing two putative Smad‐binding elements (SBEs). Mutation of both SBEs in the PSG9 promoter, or knockdown of TGF‐β receptor 1 (TGFBR1), TGFBR2, Smad3, or Smad4 impaired the ability of TGF‐β1 to induce PSG9 expression. Consequently, PSG9 contributed to TGF‐β1‐induced epithelial‐mesenchymal transition (EMT) and breast cancer cell migration and invasion. Moreover, PSG9 enhanced the stability of Smad2, Smad3, and Smad4 proteins by blocking their proteasomal degradation, and regulated the expression of TGF‐β1 target genes involved in EMT and breast cancer progression, thus further amplifying the canonical TGF‐β/Smad signaling in breast cancer cells. Collectively, these findings establish PSG9 as a novel player in breast cancer progressionvia hijacking the canonical TGF‐β/Smad signaling, and identify PSG9 as a potential plasma biomarker for the early detection of breast cancer.
An insight into small extracellular vesicles: Their roles in colorectal cancer progression and potential clinical applications
Authors: He Xuefeng , Zhong Xinyang , Hu Zijuan , Zhao Senlin , Wei Ping , Li Dawei 
Published: December 2020

AbstractColorectal cancer (CRC) is one of the most common cancers and a leading cause of mortality worldwide. Small extracellular vesicles (sEVs) are nano‐sized extracellular vesicles containing a variety of bioactive molecules, such as nucleic acids, proteins, lipids, and metabolites. Recent evidence from CRC has revealed that sEVs contribute to tumorigenesis, progression, and drug resistance, and serve as a tool for “liquid biopsy” and a drug delivery system for therapy. In this review, we summarize information about the roles of sEVs in the proliferation, invasion, migration, epithelial‐mesenchymal transition, formation of the premetastatic niche, and drug resistance to elucidate the mechanisms governing sEVs in CRC and to identify novel targets for therapy and prognostic and diagnostic biomarkers.