tbuckley/cabot-search huggingface dataset:
Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Authors: Yuanjie Sun, Yan Liu, Baoyan Liu, Kehua Zhou, Zenghui Yue, Wei Zhang, Wenbin Fu, Jun Yang, Ning Li, Liyun He, Zhiwei Zang, Tongsheng Su, Jianqiao Fang, Yulong Ding, Zongshi Qin, Hujie Song, Hui Hu, Hong Zhao, Qian Mo, Jing Zhou, Jiani Wu, Xiaoxu Liu, Weiming Wang, Ran Pang, Huan Chen, Xinlu Wang, Zhishun Liu
Journal: Annals of Internal Medicine (2021)

Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. To assess the long-term efficacy of acupuncture for CP/CPPS. Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938). Ten tertiary hospitals in China. Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported. Sham acupuncture might have had certain physiologic effects. Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment. China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.
Innate and adaptive immunity: the understudied driving force of heart valve disease
Authors: Francesca Bartoli-Leonard, Jonas Zimmer, Elena Aikawa
Journal: Cardiovascular Research (2021)

Calcific aortic valve disease (CAVD), and its clinical manifestation that is calcific aortic valve stenosis, is the leading cause for valve disease within the developed world, with no current pharmacological treatment available to delay or halt its progression. Characterized by progressive fibrotic remodelling and subsequent pathogenic mineralization of the valve leaflets, valve disease affects 2.5% of the western population, thus highlighting the need for urgent intervention. Whilst the pathobiology of valve disease is complex, involving genetic factors, lipid infiltration, and oxidative damage, the immune system is now being accepted to play a crucial role in pathogenesis and disease continuation. No longer considered a passive degenerative disease, CAVD is understood to be an active inflammatory process, involving a multitude of pro-inflammatory mechanisms, with both the adaptive and the innate immune system underpinning these complex mechanisms. Within the valve, 15% of cells evolve from haemopoietic origin, and this number greatly expands following inflammation, as macrophages, T lymphocytes, B lymphocytes, and innate immune cells infiltrate the valve, promoting further inflammation. Whether chronic immune infiltration or pathogenic clonal expansion of immune cells within the valve or a combination of the two is responsible for disease progression, it is clear that greater understanding of the immune systems role in valve disease is required to inform future treatment strategies for control of CAVD development.
Abstract 13565: A hs-CRP Level But Not Coronary Plaque Regression or Change in Plaque Composition Could Predict Future Cardiovascular Events in Statin-Treated Patients with Coronary Artery Disease -The Extended TRUTH Study-
Authors: Tsuyoshi Nozue, Kazuki Fukui, Shingo Yamamoto, Tomoyuki Kunishima, Shigeo Umezawa, Yuko Onishi, Shinichi Tohyama, Youichi Takeyama, Yoshihiro Morino, Takao Yamauchi, Kiyoshi Hibi, Takashi Sozu, Mitsuyasu Terashima, Ichiro Michishita
Journal: Circulation (2012)

Background: The TRUTH study was a prospective, open-labeled, randomized and multicenter trial to evaluate the effects of 8-month treatment with pitavastatin (aggressive lipid-lowering) versus prava...
高齢女性における上行大動脈の実効大動脈弾性率,全血管抵抗,脈波増大係数と左室拡張機能との関連性
Authors: Goto Toshihiko, Ohte Nobuyuki, Fukuta Hidekatsu, Wakami Kazuaki, Tani Tomomitsu, Kimura Genjiro
Journal: Circulation (2013)
Yap Promotes Noncanonical Wnt Signals From Cardiomyocytes for Heart Regeneration
Authors: Shijie Liu, Li Tang, Xiaolei Zhao, Bao Nguyen, Todd R. Heallen, Min Li, Jianxin Wang, Jun Wang, James F. Martin
Journal: Circulation Research (2021)

Rationale: During neonatal heart regeneration, the fibrotic response, which is required to prevent cardiac rupture, resolves via poorly understood mechanisms. Deletion of the Hippo pathway gene Sav in adult cardiomyocytes increases Yap activity and promotes cardiac regeneration, partly by inducing fibrosis resolution. Deletion of Yap in neonatal cardiomyocytes leads to increased fibrosis and loss of neonatal heart regeneration, suggesting that Yap inhibits fibrosis by regulating intercellular signaling from cardiomyocytes to cardiac fibroblasts (CFs). Objective: We investigated the role of Wntless ( Wls ), which is a direct target gene of Yap, in communication between cardiomyocytes and CFs during neonatal heart regeneration. Methods and Results: We generated 2 mouse models to delete Wls specifically in cardiomyocytes ( Myh6-Cas9 combined with AAV9-Wls-g RNAs, and Myh6 cre-ERT2/+ ; Wls flox/flox ). Reanalysis of single-cell RNA sequencing data revealed that Wnt ligands are expressed in cardiomyocytes, whereas Wnt receptors are expressed in CFs, suggesting that Wnt signaling is directional from cardiomyocytes to CFs during neonatal heart regeneration. Wls deletion in neonatal cardiomyocytes disrupted Wnt signaling, revealed by reduced noncanonical Wnt signaling in non-cardiomyocytes. Four weeks after neonatal heart myocardial infarction, heart function was measured by echocardiography. Wls deletion in neonatal cardiomyocytes after myocardial infarction impairs neonatal heart regeneration, marked by decreased contractile function and increased fibrosis. Wls mutant hearts display CF activation, characterized by increased extracellular matrix secretion, inflammation, and CF proliferation. Conclusions: These data indicate that during neonatal heart regeneration, intercellular signaling from cardiomyocytes to CFs occurs via noncanonical Wnt signaling to rebuild cardiac architecture after myocardial infarction.
Identification of asthma-associated microRNAs in bronchial biopsies
Authors: Mirjam P. Roffel, Ilse M. Boudewijn, Jos L.L. van Nijnatten, Alen Faiz, Corneel J. Vermeulen, Antoon J. van Oosterhout, Karen Affleck, Wim Timens, Ken R. Bracke, Tania Maes, Irene H. Heijink, Corry-Anke Brandsma, Maarten van den Berge
Journal: European Respiratory Journal (2021)

Background Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma. Methods Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA–mRNA interactions were analysed using mRNA data available from the same bronchial biopsies, and enrichment of pathways was identified with Enrichr and g:Profiler. Results In total, 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared with controls, of which 60 remained differentially expressed after controlling for smoking and inhaled corticosteroid treatment. We identified several asthma-associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly/organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies. Conclusion Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p as potential regulators that could contribute to the pathogenesis of asthma.
Slit2 Inhibits Breast Cancer Metastasis by Activating M1-Like Phagocytic and Antifibrotic Macrophages
Authors: Dinesh K. Ahirwar, Manish Charan, Sanjay Mishra, Ajeet K. Verma, Konstantin Shilo, Bhuvaneswari Ramaswamy, Ramesh K. Ganju
Journal: Cancer Research (2021)

Abstract Tumor-associated macrophages (TAM) are heterogeneous in nature and comprise antitumor M1-like (M1-TAM) or pro-tumor M2-like (M2-TAM) TAMs. M2-TAMs are a major component of stroma in breast tumors and enhance metastasis by reducing their phagocytic ability and increasing tumor fibrosis. However, the molecular mechanisms that regulate phenotypic plasticity of TAMs are not well known. Here we report a novel tumor suppressor Slit2 in breast cancer by regulating TAMs in the tumor microenvironment. Slit2 reduced the in vivo growth and metastasis of spontaneous and syngeneic mammary tumor and xenograft breast tumor models. Slit2 increased recruitment of M1-TAMs to the tumor and enhanced the ability of M1-TAMs to phagocytose tumor cells in vitro and in vivo. This Slit2-mediated increase in M1-TAM phagocytosis occurred via suppression of IL6. Slit2 was also shown to diminish fibrosis in breast cancer mouse models by increasing the expression of matrix metalloproteinase 13 in M1-TAMs. Analysis of patient samples showed high Slit2 expression strongly associated with better patient survival and inversely correlated with the abundance of CD163+ TAMs. Overall, these studies define the role of Slit2 in inhibiting metastasis by activating M1-TAMs and depleting tumor fibrosis. Furthermore, these findings suggest that Slit2 can be a promising immunotherapeutic agent to redirect TAMs to serve as tumor killers for aggressive and metastatic breast cancers. In addition, Slit2 expression along with CD163+ TAMs could be used as an improved prognostic biomarker in patients with breast cancer. Significance: This study provides evidence that the antitumor effect of Slit2 in breast cancer occurs by activating the phagocytic activity of M1-like tumor-associated macrophages against tumor cells and diminishing fibrosis.
Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
Authors: Jacek Hajda, Barbara Leuchs, Assia L. Angelova, Veronika Frehtman, Jean Rommelaere, Mieke Mertens, Maximilian Pilz, Meinhard Kieser, Ottheinz Krebs, Michael Dahm, Bernard Huber, Christine E. Engeland, Athanasios Mavratzas, Nicolas Hohmann, Jutta Schreiber, Dirk Jäger, Niels Halama, Oliver Sedlaczek, Matthias M. Gaida, Volker Daniel, Christoph Springfeld, Guy Ungerechts
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy. Patients and Methods: This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on 4 consecutive days and as an intralesional injection, 6 to 13 days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28. Results: ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had a confirmed partial response and one patient revealed an unconfirmed partial response according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T-cell responses to viral proteins. An interesting immunologic pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx. Conclusions: The trial met all primary objectives, revealed no environmental risks, and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.
Sensitivity and specificity of the antigen-based anterior nasal self-testing programme for detecting SARS-CoV-2 infection in schools, Austria, March 2021
Authors: Peter Willeit, Benoît Bernar, Christoph Zurl, Mariam Al-Rawi, Andrea Berghold, David Bernhard, Wegene Borena, Christian Doppler, Reinhold Kerbl, Alwin Köhler, Robert Krause, Bernd Lamprecht, Johannes Pröll, Hannes Schmidt, Ivo Steinmetz, Evelyn Stelzl, Heribert Stoiber, Dorothee von Laer, Johannes Zuber, Thomas Müller, Volker Strenger, Michael Wagner
Journal: Eurosurveillance (2021)

This study evaluates the performance of the antigen-based anterior nasal screening programme implemented in all Austrian schools to detect SARS-CoV-2 infections. We combined nationwide antigen-based screening data obtained in March 2021 from 5,370 schools (Grade 1-8) with an RT-qPCR-based prospective cohort study comprising a representative sample of 244 schools. Considering a range of assumptions, only a subset of infected individuals are detected with the programme (low to moderate sensitivity) and non-infected individuals mainly tested negative (very high specificity).
Cerebral blood flow in mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis
Authors: Heng Zhang, Yan Wang, Diyang Lyu, Yan Li, Wenwen Li, Qi Wang, Yan Li, Qi Qin, Xuechu Wang, Min Gong, Haishan Jiao, Wenying Liu, Jianping Jia
Journal: Ageing Research Reviews (2021)
Sfaira accelerates data and model reuse in single cell genomics
Authors: David S. Fischer, Leander Dony, Martin König, Abdul Moeed, Luke Zappia, Lukas Heumos, Sophie Tritschler, Olle Holmberg, Hananeh Aliee, Fabian J. Theis
Journal: Genome biology (2021)

Abstract Single-cell RNA-seq datasets are often first analyzed independently without harnessing model fits from previous studies, and are then contextualized with public data sets, requiring time-consuming data wrangling. We address these issues with sfaira, a single-cell data zoo for public data sets paired with a model zoo for executable pre-trained models. The data zoo is designed to facilitate contribution of data sets using ontologies for metadata. We propose an adaption of cross-entropy loss for cell type classification tailored to datasets annotated at different levels of coarseness. We demonstrate the utility of sfaira by training models across anatomic data partitions on 8 million cells.
Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma
Authors: C. Elizabeth Boudreau, Hinda Najem, Martina Ott, Craig Horbinski, Dexing Fang, Chase M. DeRay, Jonathan M. Levine, Michael A. Curran, Amy B. Heimberger
Journal: Clinical Cancer Research (2021)

Activation of STING (
Estimated Cost-effectiveness of Endoscopic Screening for Upper Gastrointestinal Tract Cancer in High-Risk Areas in China
Authors: Ruyi Xia, Hongmei Zeng, Wenjun Liu, Li Xie, Mingwang Shen, Peng Li, He Li, Wenqiang Wei, Wanqing Chen, Guihua Zhuang
Journal: JAMA Network Open (2021)

Upper gastrointestinal tract cancer, including esophageal and gastric cancers, in China accounts for 50% of the global burden. Endoscopic screening may be associated with a decreased incidence of and mortality from upper gastrointestinal tract cancer.To evaluate the cost-effectiveness of endoscopic screening for esophageal and gastric cancers among people aged 40 to 69 years in areas of China where the risk of these cancers is high.For this economic evaluation, a Markov model was constructed for initial screening at different ages from a health care system perspective, and 5 endoscopic screening strategies with different frequencies (once per lifetime and every 10 years, 5 years, 3 years, and 2 years) were evaluated. The study was conducted between January 1, 2019, and October 31, 2020. Model parameters were estimated based on this project, government documents, and published literature. For each initial screening age (40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a closed cohort of 100 000 participants was assumed to enter the model and follow the alternative strategies.Cost-effectiveness was measured by calculating the incremental cost-effectiveness ratio (ICER), and the willingness-to-pay threshold was assumed to be 3 times the per capita gross domestic product in China (US $10 276). Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of model findings.The study included a hypothetical cohort of 100 000 individuals aged 40 to 69 years. All 5 screening strategies were associated with improved effectiveness by 1087 to 10 362 quality-adjusted life-years (QALYs) and increased costs by US $3 299 000 to $22 826 000 compared with no screening over a lifetime, leading to ICERs of US $1343 to $3035 per QALY. Screening at a higher frequency was associated with an increase in QALYs and costs; ICERs for higher frequency screening compared with the next-lower frequency screening were between US $1087 and $4511 per QALY. Screening every 2 years would be the most cost-effective strategy, with probabilities of 90% to 98% at 3 times the per capita gross domestic product of China. The model was the most sensitive to utility scores of esophageal cancer- or gastric cancer-related health states and compliance with screening.The findings suggest that combined endoscopic screening for esophageal and gastric cancers may be cost-effective in areas of China where the risk of these cancers is high; screening every 2 years would be the optimal strategy. These data may be useful for development of policies targeting the prevention and control of upper gastrointestinal tract cancer in China.
28194 Patient-reported outcomes of ruxolitinib cream for the treatment of atopic dermatitis: Pooled results from two phase 3 studies
Authors: Eric L. Simpson, Matthias Augustin, Diamant Thaçi, Laurent Misery, Jonathan I. Silverberg, April W. Armstrong, Zelma C. Chiesa Fuxench, Michael E. Kuligowski, May E. Venturanza, Kang Sun, Kim Papp
Journal: Journal of the American Academy of Dermatology (2021)
25843 Tapinarof cream 1% once daily for plaque psoriasis: Patient-reported outcomes from two pivotal phase 3 trials
Authors: Robert Bissonnette, Bruce Strober, Mark Lebwohl, Jerry Bagel, James Del Rosso, Joseph F. Merola, Neal Bhatia, Paul Yamauchi, Philip M. Brown, David S. Rubenstein, Anna M. Tallman
Journal: Journal of the American Academy of Dermatology (2021)
A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation
Authors: Zhen-xing Liang, Hua-shan Liu, Li Xiong, Xin Yang, Feng-wei Wang, Zi-wei Zeng, Xiao-wen He, Xian-rui Wu, Ping Lan
Journal: Molecular Cancer (2021)

Abstract Background Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. Methods We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC–MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. Results A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Conclusions circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.
Downregulation of ID4 by promoter hypermethylation in colorectal cancer cell lines and cancer tissues
Authors: Jin-Sung Choi, Kyung-Hee Kim, Il-Jin Kim, Ja-Lok Ku, Jae-Gahb Park
Journal: Cancer Research (2005)

920  It has been recognized that hypermethylation of the CpG island of the promoter region silences some genes as effectively as inactivation of the gene by mutations or deletions. Recently it has been found that the human ID4 gene, one of the ID family of the helix-loop-helix (HLH) transcription factors, did not significantly expressed in 82% and 30% in human gastric cancer cell lines and cancer tissues due to hypermethylation of the promoter region. Little is known, however, about the expression and hypermethylation status of ID4 in colorectal cancer cell lines and cancer tissues. To verify the expression and methylation status of ID4 gene in colorectal carcinogenesis, we checked promoter hypermethylation status by RT-PCR analysis and methylation specific PCR (MS-PCR) and sequencing analysis after sodium bisulfite modification in 32 colorectal cancer cell lines and 76 cancer tissues. We have also analyzed the hypermethylation status of hMLH1 gene and microsatellite instability status in cancer cell lines and cancer. Of 32 lines, ID4 expression was significantly reduced in 15 cell lines (47%) by RT-PCR. After sodium bisulfite modification and direct sequencing analysis, the promoter hypermethylation of ID4 was confirmed in 17 cell lines (17 out of 27 cell lines, 63%). Promoter hypermethylatoin of ID4 in colorectal cancer tissues and corresponding normal tissues was found in 63% and 1.3%, respectively. The promoter region of hMLH1 gene was hypermethylated in 31.2% in cancer cell lines and 29% in cancer tissues. There was no correlation between promoter hypermethylation of ID4 and hMLH1 gene, and hypermethylation of ID4 gene and microsatellite instability status. These results suggest that promoter hypermethylation of ID4 down-regulates its expression in colorectal carcinomas as well as gastric cancers and might play an important role the development and progression of human colorectal carcinomas.