bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling
Authors: Gu Yang , Wang Yanying , He Luyun , Zhang Jiahang , Zhu Xiaoxiao , Liu Nian , Wang Jianyi , Lu Tiankun , He Lei , Tian Yong , Fan Zusen 
Published: October 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive.

Methods
CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology.

Results
CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development.

Conclusion
Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.
Zanubrutinib monotherapy in relapsed/refractory mantle cell lymphoma: a pooled analysis of two clinical trials
Authors: Zhou Keshu , Zou Dehui , Zhou Jianfeng , Hu Jianda , Yang Haiyan , Zhang Huilai , Ji Jie , Xu Wei , Jin Jie , Lv Fangfang , Feng Ru , Gao Sujun , Zhou Daobin , Tam Constantine S. , Simpson David , Wang Michael , Phillips Tycel J. , Opat Stephen , Huang Zhiyue , Lu Huafei , Song Yuqin , Song Yongping 
Published: October 2021

AbstractMantle cell lymphoma (MCL) is a mature B-cell neoplasm with a high initial response rate followed almost invariably by relapse. Here we report the pooled data from 2 studies, BGB-3111-AU-003 and BGB-3111-206, to explore the efficacy of zanubrutinib monotherapy in relapsed/refractory (R/R) MCL. A total of 112 patients were included. Median follow-up durations were 24.7 and 24.9 months for BGB-3111-AU-003 and BGB-3111-206, respectively. Overall response rate (ORR) and complete response (CR) rate were 84.8% and 62.5%, and median duration of response, progression-free survival (PFS) and overall survival (OS) were 24.9, 25.8 and 38.2 months, respectively. After weighting, the PFS (median: NE vs. 21.1 months,P = 0.235) and OS (median: NE vs. 38.2 months,P = 0.057) were similar but numerically better in the second-line than later-line group. Zanubrutinib was well-tolerated with treatment discontinuation and dose reduction for adverse events in 12.5% and 2.7% of patients, respectively. Hypertension, major hemorrhage and atrial fibrillation/flutter rates were 11.6%, 5.4% and 1.8%, respectively. Zanubrutinib is efficacious in R/R MCL, with a favorable safety profile.
Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases
Authors: De La Vega Francisco M. , Chowdhury Shimul , Moore Barry , Frise Erwin , McCarthy Jeanette , Hernandez Edgar Javier , Wong Terence , James Kiely , Guidugli Lucia , Agrawal Pankaj B. , Genetti Casie A. , Brownstein Catherine A. , Beggs Alan H. , Löscher Britt-Sabina , Franke Andre , Boone Braden , Levy Shawn E. , Õunap Katrin , Pajusalu Sander , Huentelman Matt , Ramsey Keri , Naymik Marcus , Narayanan Vinodh , Veeraraghavan Narayanan , Billings Paul , Reese Martin G. , Yandell Mark , Kingsmore Stephen F. 
Published: October 2021

Abstract
Background
Clinical interpretation of genetic variants in the context of the patient’s phenotype is becoming the largest component of cost and time expenditure for genome-based diagnosis of rare genetic diseases. Artificial intelligence (AI) holds promise to greatly simplify and speed genome interpretation by integrating predictive methods with the growing knowledge of genetic disease. Here we assess the diagnostic performance of Fabric GEM, a new, AI-based, clinical decision support tool for expediting genome interpretation.

Methods
We benchmarked GEM in a retrospective cohort of 119 probands, mostly NICU infants, diagnosed with rare genetic diseases, who received whole-genome or whole-exome sequencing (WGS, WES). We replicated our analyses in a separate cohort of 60 cases collected from five academic medical centers. For comparison, we also analyzed these cases with current state-of-the-art variant prioritization tools. Included in the comparisons were trio, duo, and singleton cases. Variants underpinning diagnoses spanned diverse modes of inheritance and types, including structural variants (SVs). Patient phenotypes were extracted from clinical notes by two means: manually and using an automated clinical natural language processing (CNLP) tool. Finally, 14 previously unsolved cases were reanalyzed.

Results
GEM ranked over 90% of the causal genes among the top or second candidate and prioritized for review a median of 3 candidate genes per case, using either manually curated or CNLP-derived phenotype descriptions. Ranking of trios and duos was unchanged when analyzed as singletons. In 17 of 20 cases with diagnostic SVs, GEM identified the causal SVs as the top candidate and in 19/20 within the top five, irrespective of whether SV calls were provided or inferred ab initio by GEM using its own internal SV detection algorithm. GEM showed similar performance in absence of parental genotypes. Analysis of 14 previously unsolved cases resulted in a novel finding for one case, candidates ultimately not advanced upon manual review for 3 cases, and no new findings for 10 cases.

Conclusions
GEM enabled diagnostic interpretation inclusive of all variant types through automated nomination of a very short list of candidate genes and disorders for final review and reporting. In combination with deep phenotyping by CNLP, GEM enables substantial automation of genetic disease diagnosis, potentially decreasing cost and expediting case review.
Integrating thousands of PTEN variant activity and abundance measurements reveals variant subgroups and new dominant negatives in cancers
Authors: Matreyek Kenneth A. , Stephany Jason J. , Ahler Ethan , Fowler Douglas M. 
Published: October 2021

Abstract
Background
PTEN is a multi-functional tumor suppressor protein regulating cell growth, immune signaling, neuronal function, and genome stability. Experimental characterization can help guide the clinical interpretation of the thousands of germline or somatic PTEN variants observed in patients. Two large-scale mutational datasets, one for PTEN variant intracellular abundance encompassing 4112 missense variants and one for lipid phosphatase activity encompassing 7244 variants, were recently published. The combined information from these datasets can reveal variant-specific phenotypes that may underlie various clinical presentations, but this has not been comprehensively examined, particularly for somatic PTEN variants observed in cancers.

Methods
Here, we add to these efforts by measuring the intracellular abundance of 764 new PTEN variants and refining abundance measurements for 3351 previously studied variants. We use this expanded and refined PTEN abundance dataset to explore the mutational patterns governing PTEN intracellular abundance, and then incorporate the phosphatase activity data to subdivide PTEN variants into four functionally distinct groups.

Results
This analysis revealed a set of highly abundant but lipid phosphatase defective variants that could act in a dominant-negative fashion to suppress PTEN activity. Two of these variants were, indeed, capable of dysregulating Akt signaling in cells harboring a WT PTEN allele. Both variants were observed in multiple breast or uterine tumors, demonstrating the disease relevance of these high abundance, inactive variants.

Conclusions
We show that multidimensional, large-scale variant functional data, when paired with public cancer genomics datasets and follow-up assays, can improve understanding of uncharacterized cancer-associated variants, and provide better insights into how they contribute to oncogenesis.
CDKN2B-AS1 participates in high glucose-induced apoptosis and fibrosis via NOTCH2 through functioning as a miR-98-5p decoy in human podocytes and renal tubular cells
Authors: Xiao Min , Bai Shoujun , Chen Jing , Li Yaxi , Zhang Shu , Hu Zhao 
Published: October 2021

Abstract
Background
Diabetic nephropathy (DN) is the most common causes of end-stage renal disease. Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is connected with the development of DN, but the role of CDKN2B-AS1 in DN has not been entirely elucidated.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to measure CDKN2B-AS1 and miR-98-5p levels. Cell viability, proliferation, and apoptosis were analyzed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) or flow cytometry assays. Protein levels were measured by western blotting. The relationship between CDKN2B-AS1 or notch homolog 2 (NOTCH2) and miR-98-5p was verified via dual-luciferase reporter assay.

Results
CDKN2B-AS1 and NOTCH2 were upregulated in the serum of DN patients and high glucose-disposed human podocytes (HPCs) and human renal tubular cells (HK-2), whereas miR-98-5p was downregulated. High glucose repressed viability and accelerated apoptosis of HPCs and HK-2 cells. CDKN2B-AS1 knockdown impaired high glucose-induced apoptosis and fibrosis of HPCs and HK-2 cells. Mechanistically, CDKN2B-AS1 sponged miR-98-5p to regulate NOTCH2 expression. Also, CDKN2B-AS1 inhibition-mediated effects on apoptosis and fibrosis of high glucose-disposed HPCs and HK-2 cells were weakened by miR-98-5p inhibitor. Also, NOTCH2 knockdown partly reversed miR-98-5p inhibitor-mediated impacts on apoptosis and fibrosis of high glucose-disposed HPCs and HK-2 cells.

Conclusion
High glucose-induced CDKN2B-AS1 promoted apoptosis and fibrosis via the TGF-β1 signaling mediated by the miR-98-5p/NOTCH2 axis in HPCs and HK-2 cells.
Connecting breast cancer survivors for exercise: protocol for a two-arm randomized controlled trial
Authors: Smith-Turchyn Jenna , McCowan Michelle E. , O’Loughlin Erin , Fong Angela J. , McDonough Meghan H. , Santa Mina Daniel , Arbour-Nicitopoulos Kelly P. , Trinh Linda , Jones Jennifer M. , Bender Jackie L. , Culos-Reed S. Nicole , Tomasone Jennifer R. , Vani Madison F. , Sabiston Catherine M. 
Published: October 2021

Abstract
Background
Peer-based exercise interventions that cultivate new opportunities for support with a fellow cancer survivor may result in increased exercise volume. It is not clear whether adding qualified exercise professional (QEP) support to peer-based interventions improves health outcomes. Therefore, the purpose of this study is to determine whether breast cancer survivor (BCS) dyads who receive 10 weekly sessions of virtually delivered QEP support have improved outcomes compared to BCS dyads who do not receive QEP support.

Methods
Participants Adult BCS with medical clearance for exercise, who have an internet-connected device, and currently engage in < 150 min of moderate-intensity exercise per week. Intervention BCS will be matched using evidence-based criteria. The intervention group will receive dyadic exercise information sessions and a program tailored by a QEP for 10 weeks (intervention period) and have access to the QEP for an additional 4 weeks (tapering period). The control will not receive any QEP support. Outcomes The primary outcome is post-intervention self-reported exercise volume. Secondary outcomes include device-assessed exercise volume (i.e., Fitbit), social support, and health-related quality of life. Randomization 108 participants, matched in dyads, will be randomized 1:1 to the MatchQEP or Match groups using a web-based scheme. Statistical analysis Outcomes will be measured at baseline, post-intervention, post-tapering, and at 12 weeks post-intervention follow-up.

Discussion
The findings from this RCT will determine if matched BCS dyads who receive 10 weeks of virtually delivered QEP support have higher levels of self-report and device-measured exercise, social support, and health related quality of life compared to matched dyads without QEP-delivered exercise guidance. To our knowledge this will be the first study to assess the combined effect of peer- and QEP support on exercise volume. Project findings will inform and optimize intervention methods aimed to increase exercise among BCS through accessible exercise supports.
Trial Registration: The study is registered on ClinicalTrials.gov (study identifier: NCT04771975, protocol Version Number: 2, date: July 22, 2021).
Mathematical analysis of hepatitis B epidemic model with optimal control
Authors: Zada Inam , Naeem Jan Muhammad , Ali Nigar , Alrowail Dalal , Sooppy Nisar Kottakkaran , Zaman Gul 
Published: October 2021

AbstractInfection of hepatitis B virus (HBV) is a global health problem. We provide the study about hepatitis B virus dynamics that can be controlled by education campaign (awareness), vaccination, and treatment. Initially we bring constant controls in considerations for treatment, vaccination, and education campaign (awareness). In the case of constant controls, we study the stability and existence of the disease-free and endemic equilibria model’s solutions. Afterwards, we take time as a control and formulate the suitable optimal control problem, acquire optimal control strategy in order to reduce the number of humans that are infected and the costs associated. At the end, results of numerical simulations show that the optimal combination of education campaign (awareness), treatment, and vaccination is the most efficient way to control the infection of hepatitis B virus (HBV) infection.
The efficacy and safety of high-flow nasal cannula therapy in patients with COPD and type II respiratory failure: a meta-analysis and systematic review
Authors: Xu Zhiping , Zhu Lingxia , Zhan Jingye , Liu Lijun 
Published: October 2021

Abstract
Background
High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) have been used for the treatment of COPD and respiratory failure in clinical settings. We aimed to evaluate the efficacy and safety of HFNC therapy in patients with COPD and type II respiratory failure, to provide evidence to the clinical COPD management.

Methods
We searched Cochrane et al. databases up to Dec 31, 2020 for randomized controlled trials (RCTs) on the use of HFNC therapy in patients with COPD and type II respiratory failure. Two researchers independently screened the literature according to the inclusion and exclusion criteria, and evaluated the quality of the literature and extracted data. We used Revman5.3 software for statistical analysis of collected data.

Results
A total of 6 RCTs involving 525 COPD and type II respiratory failure patients. Meta-analyses indicated that compared with NIV, HFNC could significantly reduce PaCO2 level (MD = − 2.64, 95% CI (− 3.12 to − 2.15)), length of hospital stay ((MD = – 1.19, 95 CI (− 2.23 to − 0.05)), the incidence of nasal facial skin breakdown ((OR = 0.11, 95% CI (0.03–0.41)). And there were no significant differences between the two groups in PaO2 ((MD = 2.92, 95% CI (− 0.05 to 5.90)), incidence of tracheal intubation ((OR = 0.74, 95% CI (0.34–1.59)) and mortality (OR = 0.77, 95% CI (0.28–2.11)).

Conclusions
HFNC is more advantageous over NIV in the treatment of COPD and type II respiratory failure. Future studies with larger sample size and strict design are needed to further elucidate the role of HFNC in COPD and respiratory failure.
Consumer reviews analysis on cycling pants in online shopping malls using text mining
Authors: Kim Chunjeong , Na Youngjoo 
Published: October 2021

AbstractThis study was investigated trends and consumer awareness on cycling pants by analyzing the reviews on bib shorts, bib tights, shorts, and tights in online shopping malls using text mining. The reviews and product information on cycling pants from Jan. 2017 to the first half of 2020 were crawled, and a total of 7241 cases were analyzed. The keywords of cycling pants were extracted using a Korean morphological analyzer (KoNLP), calculated to the term-document matrix, and then converted into a co-occurrence matrix. The number of reviews of cycling pants increased by 39% per year, and especially in the first half of 2020, the number of reviews has doubled over compared to the first half of last year. Bib shorts accounted for more than 50% of the number of reviews of cycling pants and received the highest rating, making them the most preferred. Positive reviews on cycling pants appeared 15 times over than that of negative reviews, and most of the cycling pants were evaluated positively. Size and cost-effective appeared as the important keywords both in positive and negative reviews. However, it was found that consumers have a difficult time choosing the size not only in the negative but also in the positive reviews. Pad was the keyword that appeared the most in negative reviews, and it was the most dissatisfied factor in the cycling pants. Therefore, in an internet shopping mall, it is necessary to provide intuitive and accurate information that is easy for consumers to understand about information on the size and pad of the cycle pants.
Sudden circulatory collapse caused by mechanical obstruction of the left main coronary trunk with infective endocarditis vegetation: a case report
Authors: Usui Rena , Mutsuga Masato , Narita Yuji , Tokuda Yoshiyuki , Terazawa Sachie , Ito Hideki , Uchida Wataru , Usui Akihiko 
Published: October 2021

Abstract
Background
Acute coronary syndrome (ACS) caused by mechanical obstruction of the coronary artery with a vegetation is extremely rare but associated with high mortality. The optimal management strategy of this condition remains controversial because of its scarcity. We experienced a case of sudden circulatory collapse due to mechanical occlusion of the left main coronary trunk with a vegetation.

Case presentation
A 68-year-old woman with aortic and mitral valve infective endocarditis suffered sudden dyspnea followed by heart arrest while awaiting surgery. Despite treatment with adequate antibiotic therapy, she had had multiple embolic infarctions and ruptured infectious cerebral aneurysms. We conducted transcatheter arterial embolization of the aneurysm and postponed the cardiac surgery due to residual aneurysmal blood flow. She suffered sudden cardiac arrest, and extracorporeal membrane oxygenation was applied after cardiopulmonary resuscitation. An echocardiogram revealed diffuse severe hypokinesis, and emergency coronary angiography was performed under suspicion of ACS. It revealed obstruction of the left main coronary trunk by a vegetation. Emergent cardiac surgery was performed. A vegetation had occluded the left coronary orifice. Aortic and mitral valve replacement with coronary artery bypass to the left antero-descending branch was performed. Regarding her cardiac function, she still required extracorporeal membrane oxygenation after surgery. She passed away 19 days after surgery due to multiple organ failure.

Conclusions
ACS caused by mechanical obstruction of the coronary artery with a vegetation is rare but associated with high mortality. When circulatory collapse acutely occurs in patients with aortic valve infective endocarditis, we should suspect acute coronary artery obstruction. Urgent coronary angiography is mandatory to rescue the patient while preparing for emergency surgery.
Adding value to food chain information: using data on pig welfare and antimicrobial use on-farm to predict meat inspection outcomes
Authors: Pessoa Joana , McAloon Conor , Rodrigues da Costa Maria , García Manzanilla Edgar , Norton Tomas , Boyle Laura 
Published: October 2021

AbstractBackgroundUsing Food Chain Information data to objectively identify high-risk animals entering abattoirs can represent an important step forward towards improving on-farm animal welfare. We aimed to develop and evaluate the performance of classification models, using Gradient Boosting Machine algorithms that utilise accurate longitudinal on-farm data on pig health and welfare to predict condemnations, pluck lesions and low cold carcass weight at slaughter.ResultsThe accuracy of the models was assessed using the area under the receiver operating characteristics (ROC) curve (AUC). The AUC for the prediction models for pneumonia, dorsocaudal pleurisy, cranial pleurisy, pericarditis, partial and total condemnations, and low cold carcass weight varied from 0.54 for pneumonia and 0.67 for low cold carcass weight. For dorsocaudal pleurisy, ear lesions assessed on pigs aged 12 weeks and antimicrobial treatments (AMT) were the most important prediction variables. Similarly, the most important variable for the prediction of cranial pleurisy was the number of AMT. In the case of pericarditis, ear lesions assessed both at week 12 and 14 were the most important variables and accounted for 33% of the Bernoulli loss reduction. For predicting partial and total condemnations, the presence of hernias on week 18 and lameness on week 12 accounted for 27% and 14% of the Bernoulli loss reduction, respectively. Finally, AMT (37%) and ear lesions assessed on week 12 (15%) were the most important variables for predicting pigs with low cold carcass weight.ConclusionsThe findings from our study show that on farm assessments of animal-based welfare outcomes and information on antimicrobial treatments have a modest predictive power in relation to the different meat inspection outcomes assessed. New research following the same group of pigs longitudinally from a larger number of farms supplying different slaughterhouses is required to confirm that on farm assessments can add value to Food Chain Information reports.