bluuebunny/crossref_metadata_2025_split huggingface dataset:
SOX9 is a Target of miR-134-3p And miR-224-3p in Beast Cancer Cell Lines
Authors: Chao Tsu-Yang , Kordaß Theresa , Osen Wolfram , Eichmüller Stefan B. 
Published: October 2021

Abstract
SOX9 represents a transcription factor identified as an important mediator of cancer progression in breast cancer. miRNAs are small non-coding RNAs that can inhibit translation of target genes by binding to the 3’-UTR region of the respective mRNA molecule. Deregulated miRNA expression plays a pivotal role in hallmarks of cancer such as sustained proliferation and inhibition of apoptosis. In this study we investigated the miRNA-mediated regulation of SOX9 expression in two breast cancer cell lines providing further insights into cellular mechanisms driving breast cancer progression. The effect of miR-134-3p, miR-224-3p and miR-6859-3p on SOX9 expression was tested on mRNA as well as protein level in the human breast cancer cell line MDA-MB-231. Furthermore, direct binding of these miRNAs to the SOX9 3’-UTR was assessed by luciferase reporter assays and site-directed mutagenesis in MDA-MB-231 and MCF-7 cells. SOX9 expression was significantly reduced on mRNA and protein level by transfection of either miR-134-3p, miR-224-3p or miR-6859-3p. Luciferase reporter assays proved direct binding of miR-134-3p and miR-224-3p to the SOX9 3’-UTR in MDA-MB-231 and MCF-7 cells. Expression analysis performed in silico revealed reduced expression of both miRNAs in breast cancer tissues. We describe three novel miRNAs capable of targeting SOX9 in human breast cancer cell lines. For miR-134-3p and miR-224-3p direct interaction with the SOX9 3’-UTR was proven. Furthermore, miR-134-3p and miR-224-3p reduced breast cancer cell viability, which is in line with the tumorigenic effects reported for SOX9 in breast cancer.
Nomogram Predicting Overall Survival After Surgical Resection For Retroperitoneal Leiomyosarcoma Patients
Authors: Zhuang Aobo , Tong Hanxing , Fang Yuan , Ma Lijie , Lu Weiqi , Zhang Yong 
Published: October 2021

Abstract
Aim: To develop a survival nomogram for patients with retroperitoneal leiomyosarcoma (RLMS) after surgery.Methods: 118 patients with RLMS after surgical resection at the General Surgery Department, Shanghai Public Health Clinical Center, Fudan University were retrospectively analyzed. The nomogram was constructed based on COX regression model and discrimination was assessed using the concordance index (c-index). The predicted and actual survival was evaluated through calibration plots.Results: The c-index of the nomogram was 0.779 (95% CI, 0.659-0.898). The predicted and actual survival probabilities are in good agreement in all calibration curve.﻿Conclusion: This study built the first survival nomogram for patients with surgical resected RLMS.
Role of D-Dimer in the Risk Stratification of Acute Coronary Syndrome Patients: Implications for Antithrombotic Treatment. A Systematic Review and Exploratory Meta-analysis.
Authors: Biccirè Flavio Giuseppe , Farcomeni Alessio , Gaudio Carlo , Pignatelli Pasquale , Tanzilli Gaetano , Pastori Daniele 
Published: October 2021

Abstract
Background Data on the prognostic role of D-dimer in patients with acute coronary syndrome (ACS) are controversial. Our aim was to summarize current evidence on the association between D-dimer levels and short/long-term poor prognosis of ACS patients. We also investigated the association between D-Dimer and no-reflow (NR) phenomenon.Methods Systematic review and metanalysis of observational studies including ACS patients and reporting data on D-Dimer levels. PubMed and SCOPUS databases were searched. Data were combined with hazard ratio (HR) and metanalysed. The principal endpoint was a composite of cardiovascular events (CVEs) including myocardial infarction, all-cause and cardiovascular mortality. Results Overall, 32 studies included in the systematic review with 28,869 patients. Of them, 6 studies investigated in-hospital and 26 studies long-term outcomes. Overall, 23 studies showed positive association of high D-Dimer levels with CVEs. D-Dimer levels predicted poor prognosis in all studies reporting in-hospital outcomes. Five studies satisfied inclusion criteria and were included in the metanalysis, with a total of 8,616 patients. Median follow-up was 13.2 months with 626 CVEs. The pooled HR for D-dimer levels and CVEs was 1.264 (95% CI 1.134-1.409). Five out of 7 studies (4,195 STEMI patients) investigating the association between D-Dimer levels and NR showed a positive correlation of D-dimer levels with NR. Conclusions In patients with ACS D-Dimer was associated with higher in-hospital and short/long-term complications. D-Dimer was also higher in patients with NR phenomenon. The use of D-Dimer may help to identify patients with residual thrombotic risk after ACS.Trial registration: the review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews: CRD42021267233.
Inhibitory effect of naphthoquine phosphate against Babesia gibsoni in vitro and Babesia rodhaini in vivo
Authors: Ji Shengwei , Liu Mingming , Galon Eloiza May , Rizk Mohamed Abdo , Tuvshintulga Bumduuren , Li Jixu , Zafar Iqra , Hasegawa Yae , Yokoyama Naoaki , Xuan Xuenan 
Published: October 2021

Abstract
Background: Drug resistance and ﻿severe side effects are major challenges in the treatment of babesiosis as they lead to less choices for treatment. Development of new drugs to enrich the treatment strategies and delay the emergence of drug resistance in parasites is still needed. Naphthoquine (NQ) combined with artemisinin treats Plasmodium infection by ﻿rapid parasite clearance. The current study repurposed NQ as a babesiosis drug treatment by evaluating the effects of naphthoquine phosphate (NQP) as a single dose treatment for babesiosis. Methods: In vitro anti-Babesia activity of ﻿NQP was tested on Babesia gibsoni cultures. The inhibition of parasite growth was verified using a SYBR green I-based fluorescence assay. In vivo efficacy of NQP was evaluated using BALB/c mice infected with Babesia rodhaini. The parasitemia level and hematocrit values were monitored. Results: The half maximal inhibitory concentration of NQP against B. gibsoni in vitro was 3.3 ± 0.5 ﻿μM. Oral administration of NQP for 5 successive days at a dose of 40 mg/kg of body weight ﻿resulted in significant inhibition on parasite growth compared with the ﻿control group. All mice in NQP-treated group survived, whereas the mice in control group died between days 6 and 9 post infection. Conclusion: This is the first study to evaluate the anti-Babesia activity of NQP in vitro and in vivo. ﻿The results showed that NQP is a promising drug for babesiosis treatment and drug repurposing may provide new treatment strategies for babesiosis.
Flow Field Simulation And Experimental Investigation On Macro Electrolyte Jet Electrochemical Turning of TB6 Titanium Alloy
Authors: Liu Yang , Qu Ningsong , Qiu Zhi 
Published: October 2021

Abstract
Electrolyte jet electrochemical turning is an effective method to realize high-quality machining of titanium alloy rotating components; however, minimal research has been carried out in this field. This is because it is difficult to control the machining flow field, which leads to poor machining surface quality. In this work, numerical simulations were used to optimize the machining flow field and reduce the proportion of gas that mixed into the machining area. This can promote participation of the tool electrode tip in the electrochemical reaction and improve the machining efficiency. The effectiveness of the optimized machining flow field for jet electrochemical turning was verified experimentally. The results showed that all three kinds of revolving TB6 titanium alloy samples with different structures could maintain the original contour shape, with a contour error <1% and a machined surface roughness reaching Ra 2.414 μm. The results demonstrate the application potential of the jet electrochemical turning process.
Influenza’s plummeting and future dynamics: the roles of mask wearing, mobility change and SARS-CoV-2 interference
Authors: Han Shasha , Zhang Ting , Lyu Yan , Lai Shengjie , Dai Peixi , Zheng Jiandong , Yang Weizhong , Zhou Xiao-Hua , Feng Luzhao 
Published: October 2021

Abstract
Untangling lessons from the influenza’s plummeting during the COVID-19 pandemic is critical for mitigating seasonal and pandemic influenza. Here we explored a country-specific inference model to estimate the effects of mask-wearing, mobility changes (international and domestic) and SARS-CoV-2 interference in China, England and the United States. We found that mask wearing had a larger reduction than mobility changes in all the regions. Only in 2019-2020, SARS-CoV-2 interference had an observable effect, with values varying at the timing of the influenza season and the speed of SARS-CoV-2 community transmission. Compared to the epidemics in 2017–2019, longer and blunter rebounds could occur in the incoming 2021–2022 season, but the rebound would be smaller if less stringent mask mandates continued or the international mobility stayed low. Our results bear implications for understanding how influenza evolves under non-pharmaceutical interventions and other respiratory diseases, and will inform designing of tailored public health measures.
HELP-DKT: An Interpretable Cognitive Model of How Students Learn Programming Based on Deep Knowledge Tracing
Authors: Liang Yu , Peng Tianhao , Pu Yanjun , Wu Wenjun 
Published: October 2021

Abstract
Student cognitive models are playing an essential role in intelligent online tutoring for programming courses. These models capture students' learning interactions and store them in the form of a set of binary responses, thereby failing to utilize rich educational information in the learning process. Moreover, the recent development of these models has been focused on improving the prediction performance and tended to adopt deep neural networks in building the end-to-end prediction frameworks. Although this approach can provide an improved prediction performance, it may also cause difficulties in interpreting the student's learning status, which is crucial for providing personalized educational feedback. To address this problem, this paper provides an interpretable cognitive model named HELP-DKT, which can infer how students learn programming based on deep knowledge tracing. HELP-DKT has two major advantages. First, it implements a feature-rich input layer, where the raw codes of students are encoded to vector representations, and the error classifications as concept indicators are incorporated. Second, it can infer meaningful estimation of student abilities while reliably predicting future performance. The experiments confirm that HELP-DKT can achieve good prediction performance and present reasonable interpretability of student skills improvement. In practice, HELP-DKT can personalize the learning experience of novice learners.
Prediction and Prevention of Pandemics via Graphical Model Inference and ConvexProgramming
Authors: Krechetov Mikhail , Sikaroudi Amir Mohammad Esmaieeli , Efrat Alon , Polishchuk Valentin , Chertkov Michael 
Published: October 2021

Abstract
Hard-to-predict bursts of COVID-19 pandemic revealed significance of statistical modeling which would resolve spatio-temporal correlations over geographical areas, for example spread of the infection over a city with census tract granularity. In this manuscript, we provide algorithmic answers to the following two interrelated public health challenges of immense social impact which have not been adequately addressed (1) Inference Challenge: assuming that there are N census blocks (nodes) in the city, and given an initial infection at any set of nodes, e.g. any N of possible single node infections, any N(N − 1)/2 of possible two node infections, etc, what is the probability for a subset of census blocks to become infected by the time the spread of the infection burst is stabilized? (2) Prevention Challenge: What is the minimal control action one can take to minimize the infected part of the stabilized state footprint? To answer the challenges, we build a Graphical Model of pandemic of the attractive Ising (pair-wise, binary) type, where each node represents a census track and each edge factor represents the strength of the pairwise interaction between a pair of nodes, e.g. representing the inter-node travel, road closure and related, and each local bias/field represents the community level of immunization, acceptance of the social distance and mask wearing practice, etc. Resolving the Inference Challenge requires finding the Maximum-A-Posteriory (MAP), i.e. most probable, state of the Ising Model constrained to the set of initially infected nodes. (An infected node is in the +1 state and a node which remained safe is in the −1 state.) We show that almost all attractive Ising Models on dense graphs result in either of the two possibilities (modes) for the MAP state: either all nodes which were not infected initially became infected, or all the initially uninfected nodes remain uninfected (susceptible). This bi-modal solution of the Inference Challenge allows us to restate the Prevention Challenge as the following tractable convex programming: for the bare Ising Model with pair-wise and bias factors representing the system without prevention measures, such that the MAP state is fully infected for at least one of the initial infection patterns, find the closest, in l 1 norm, therefore prevention-optimal, set of factors resulting in all the MAP states of the Ising model, with the optimal prevention measures applied, to become safe.
ITS Sequence Analysis of Ophidascaris Baylisi from Burmese Pythons
Authors: Zhao Qi , Abuzeid Asmaa , Zhuang Tingting , He Long , Liu Jumei , Li Xiu , Li Guoqing 
Published: October 2021

Abstract
Members of genus Ophidascaris are common parasitic roundworms in snakes that cause gastric granulomas, adenocarcinomas, intestinal obstruction, death, and serious economic losses in snakes and their products. To identify molecular marker of Ophidascaris baylisi from the Burmese python (Python molurus bivittatus), we amplified internal transcribed spacer (ITS) sequence from this roundworm and analyzed their homology and phylogeny. The amplified ITS sequence length was 1140 bp, comprising the complete ITS1, 5.8S, and ITS2 sequences and a partial 28S sequence. The ITS1+ sequence was homologous (85.8% homology) to the related species Ophidascaris robertsi. The phylogenetic tree revealed a close genetic distance between O. baylisi and O. robertsi, which formed a separate branch within family Ascaridae clade. The results indicated that the identified ITS sequence could be a good molecular marker for further study on the molecular classification and genetic variation of Ophidascaris species.
Merkel Cell Carcinoma With Gastric Metastasis, A Rare Presentation: Case Report and Literature Review
Authors: Durastante Vittorio , Conte Antonello , Brollo Pier Paolo , Biddau Carlo , Graziano Michele , Bresadola Vittorio 
Published: October 2021

Abstract
Introduction.
Merkel cell carcinoma (MCC) is an infrequent, but highly aggressive neuroendocrine neoplasm of the skin with a propensity for recurrence and metastasis. We report a rare case of gastric metastatic localization of this cancer by focusing on the diagnostic, clinical and surgical approach to the patient.
Case report.
Clinical presentation begins with a peripheral lymphadenopathy whose immunohistochemical characterization identifies the lymphatic dissemination of the disease. Gradually the patient develops a severe anaemic state which requires several blood transfusions and surgical gastric resection to remove a large bleeding lesion of the antral region. The histopathological analysis of the specimen confirms the metastatic origin from MCC, but the primitive lesion remains unknown.
Discussion.
Since this clinical situation is very rare, we conducted a review of the literature selecting the few cases reported, in order to evaluate the current knowledge on this topic. Metastatic involvement of the stomach from Merkel cell carcinoma is a rare presentation of this disease progression with a frequent delay in formulating the correct diagnosis and in further treatment which may be life-threatening for the patient. As regards the local treatment, there is no specific guideline, and the therapeutic indication should be tailored on the specific case.
The relationship between net GHG emissions and radiative forcing with an application to Article 4.1 of the Paris Agreement.
Authors: Wigley Tom M. L. 
Published: October 2021

Abstract
This paper provides an assessment of Article 4.1 of the Paris Agreement on climate; the main goal of which is to provide guidance on how “to achieve the long-term temperature goal set out in Article 2”. Paraphrasing, Article 4.1 says that, to achieve this end, we should decrease greenhouse gas (GHG) emissions so that net anthropogenic GHG emissions fall to zero in the second half of this century. To aggregate net GHG emissions, 100-year Global Warming Potentials (GWP-100) are commonly used to convert non-CO2 emissions to equivalent CO2 emissions. As a test case using methane, temperature projections using GWP-100 scaling are shown to be seriously in error. This throws doubt on the use of GWP-100 scaling to estimate net GHG emissions. An alternative method to determine the net-zero point for GHG emissions based on radiative forcing is derived. This shows that the net-zero point needs to be reached as early as 2036, much sooner than in the Article 4.1 window. Other scientific flaws in Article 4.1 that further undermine its purpose to guide efforts to achieve the Article 2 temperature targets are discussed.
An improved droplet digital PCR assay reveals the stability of intrahepatic hepatitis B virus cccDNA.
Authors: Hayashi Sanae , Isogawa Masanori , Kawashima Keigo , Ito Kyoko , Chuaypen Natthaya , Morine Yuji , Shimada Mitsuo , Higashi-Kuwata Nobuyo , Tangkijvanich Pisit , Mitsuya Hiroaki , Tanaka Yasuhito 
Published: October 2021

Abstract
The persistence of covalently closed circular DNA (cccDNA) poses a major obstacle to curing chronic hepatitis B (CHB). Here, we used droplet digital PCR (ddPCR) for cccDNA quantitation. ddPCR measured a less than two-fold difference in the intrahepatic cccDNA content more accurately than conventional real-time PCR (qPCR), (R2=0.9416 and R2=0.8963, respectively) and had also higher sensitivity and specificity than qPCR. The results of ddPCR correlated closely with serum HB core-related antigen and HB surface antigen (HBsAg) in 24 HBV-infected human-liver-chimeric mice (PXB-mice). We demonstrated that the total cccDNA content did not change during liver repopulation, although the cccDNA content per hepatocyte was reduced in PXB-mice after entecavir treatment. In the 6 patients with HBV-related hepatocellular carcinoma, ddPCR detected cccDNA in both tumor and non-tumor tissues. In 13 HBeAg-negative CHB patients with pegylated interferon alpha-2a, cccDNA contents from paired biopsies were more significantly reduced in virological response (VR) than in non-VR at week 48 (p=0.0051). Interestingly, cccDNA levels were the lowest in VR with HBsAg clearance but remained detectable after the treatment. Collectively, ddPCR revealed that cccDNA content is stable during hepatocyte proliferation and persists at quantifiable levels, even after serum HBsAg clearance.
Identification and Molecular Mapping of a Major Quantitative Trait Locus Underlying Branch Angle in Soybean
Authors: Chance Clark , Wang Weidong , Wang Ying , Fear Gabriel , Wen Zixiang , Wang Dechun , Ren Bo , Ma Jianxin 
Published: October 2021

Abstract
Soybean branch angle is a critical architectural trait that affects many other traits of agronomic importance associated with the plant’s productivity and grain yield, and is thus a vital consideration in soybean breeding. However, the genetic basis for modulating this important trait in soybean and many other crops remain unknown. Previously, we developed a recombinant inbred line (RIL) population derived from a cross between a domesticated soybean (Glycine max) variety, Williams 82, and a wild soybean (Glycine soja) accession, PI 479752, and observed drastic variation in plant architecture including branch angle among individual RILs. In this study, one of the RILs possessing extremely wide branch angle (WBA) was crossed with an elite soybean cultivar (LD00-3309) possessing narrow branch angle (NBA) to produce an F2 population composed of 147 plants and F2-derived F3 families for inheritance analysis and QTL mapping. We found that branch angle is controlled by a major QTL located on chromosome 19, designated qGmBa1, and that WBA – derived from the wild soybean accession – is dominant over NBA. This locus was also detected as a major one underlying branch angle by QTL mapping using a subset of the soybean nested association mapping (SoyNAM) population composed of 140 RILs, which were derived from a cross between a landrace, PI 437169B, possessing WBA and an elite variety, IA3023, possessing NBA. Molecular markers located in the QTL region defined by both mapping populations can be used for marker-assisted selection of branch angle in soybean breeding.
Ninjinyoeito Ameliorated Cigarette Smoke Extract-induced Apoptosis and Inflammation Through JNK Signaling Inhibition in Human Lung Fibroblasts
Authors: Murata Kenta , Fujita Nina , Takahashi Ryuji 
Published: October 2021

Abstract
BackgroundCigarette smoke is a major risk factor for various lung diseases, such as chronic obstructive pulmonary disease (COPD). Ninjinyoeito (NYT), a traditional Chinese medicine, has been prescribed for patients with post-illness or post-operative weakness, fatigue, loss of appetite, rash, cold limbs, and anemia. In addition to its traditional use, NYT has been prescribed for treating frailty in gastrointestinal, respiratory, and urinary functions. Further, NYT treatment can ameliorate cigarette smoke-induced lung injury, which is a destructive index in mice; however, the detailed underlying mechanism remains unknown. PurposeThe purpose of this study was to investigate whether NYT ameliorates cigarette smoke-induced lung injury and inflammation in human lung fibroblasts and determine its mechanism of action. MethodsWe prepared a cigarette smoke extract (CSE) from commercially available cigarettes to induce cell injury and inflammation in the human lung fibroblast cell line HFL1. The cells were pretreated with NYT for 24 h prior to CSE exposure. Cytotoxicity and cell viability were measured by lactate dehydrogenase (LDH) cytotoxicity assay and cell counting kit (CCK)-8. IL-8 level in the cell culture medium was measured by performing Enzyme-Linked Immuno Sorbent Assay (ELISA). To clarify the mechanisms of NYT, we used CellROX Green Reagent for reactive oxygen species (ROS) production and western blotting analysis for cell signaling.ResultsExposure of HFL1 cells to CSE for 24 h induced apoptosis and interleukin (IL)-8 release. Pretreatment with NYT inhibited apoptosis and IL-8 release. Furthermore, CSE exposure for 24 h increased the production of ROS and phosphorylation levels of p38 and JNK. Pretreatment with NYT only inhibited CSE-induced JNK phosphorylation, and not ROS production and p38 phosphorylation. These results suggest that NYT acts as a JNK-specific inhibitor.ConclusionNYT treatment ameliorated CSE-induced apoptosis and inflammation by inhibiting the JNK signaling pathway. Finally, these results suggest that NYT may be a promising therapeutic agent for patients with COPD.