tbuckley/cabot-search huggingface dataset:
Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer
Authors: Yiqing Tan, Ran Sun, Lei Liu, Dejuan Yang, Qin Xiang, Li Li, Jun Tang, Zhu Qiu, Weiyan Peng, Yuanyuan Wang, Lin Ye, Guosheng Ren, Tingxiu Xiang
Journal: Theranostics (2021)

Rationale: Breast cancer (BrCa) is the most common cancer worldwide, and the 5-year relative survival rate has declined in patients diagnosed at stage IV. Advanced BrCa is considered as incurable, which still lack effective treatment strategies. Identifying and characterizing new tumor suppression genes is important to establish effective prognostic biomarkers or therapeutic targets for late-stage BrCa. Methods: RNA-seq was applied in BrCa tissues and normal breast tissues. Through analyzing differentially expressed genes, DRD2 was selected for further analysis. And expression and promoter methylation status of DRD2 were also determined. DRD2 functions were analyzed by various cell biology assays in vitro. Subcutaneous tumor model was used to explore DRD2 effects in vivo. A co-cultivated system was constructed to investigate interactions of DRD2 and macrophages in vitro. WB, IHC, IF, TUNEL, qRT-PCR, Co-IP, Antibody Array, and Mass Spectrum analysis were further applied to determine the detailed mechanism. Results: In BrCa, DRD2 was found to be downregulated due to promoter methylation. Higher expression of DRD2 positively correlated with longer survival times especially in HER2-positive patients. DRD2 also promoted BrCa cells sensitivity to Paclitaxel. Ectopic expression of DRD2 significantly inhibited BrCa tumorigenesis. DRD2 also induced apoptosis as well as necroptosis in vitro and in vivo. DRD2 restricted NF-κB signaling pathway activation through interacting with β-arrestin2, DDX5 and eEF1A2. Interestingly, DRD2 also regulated microenvironment as it facilitated M1 polarization of macrophages, and triggered GSDME-executed pyroptosis. Conclusion: Collectively, this study novelly manifests the role of DRD2 in suppressing BrCa tumorigenesis, predicting prognosis and treatment response. And this study further reveals the critical role of DRD2 in educating M1 macrophages, restricting NF-κB signaling pathway and triggering different processes of programmed cell death in BrCa. Taking together, those findings represent a predictive and therapeutic target for BrCa.
P78.12 A Rare Case of Dermatomyositis as Late Immune-Related Toxicity During Anti-PD1 Treatment for Advanced Lung Cancer
Authors: A. Catino, D. Galetta, L. Lospalluti, M. Tampoia, G. Cazzato, F. Ambrogio, M. Montrone, P. Pizzutilo, V. Longo, F. Pesola, A. Mastrandrea, D. Ricci
Journal: Journal of Thoracic Oncology (2021)
Abstract 14850: The Impact of Sacubitril/Valsartan and ACEi/ARB on Renal Outcomes in Heart Failure: Evidence From Real World Clinical Practice
Authors: Nicholas Y Tan, Xiaoxi Yao, Lindsey R Sangaralingham, Nilay D Shah, Andrew D Rule, John C Burnett, Shannon M Dunlay, S J Sangaralingham
Journal: Circulation (2018)

Introduction: Renal function is an important consideration in patients with HF and is modulated by RAAS inhibition. Post-hoc analyses from the PARADIGM-HF trial suggest that sacubitril-valsartan (r...
Nowcasting epidemics of novel pathogens: lessons from COVID-19
Authors: Joseph T. Wu, Kathy Leung, Tommy T. Y. Lam, Michael Y. Ni, Carlos K. H. Wong, J. S. Malik Peiris, Gabriel M. Leung
Journal: Nature Medicine (2021)

Epidemic nowcasting broadly refers to assessing the current state by understanding key pathogenic, epidemiologic, clinical and socio-behavioral characteristics of an ongoing outbreak. Its primary objective is to provide situational awareness and inform decisions on control responses. In the event of large-scale sustained emergencies, such as the COVID-19 pandemic, scientists need to constantly update their aims and analytics with respect to the rapidly evolving emergence of new questions, data and findings in order to synthesize real-time evidence for policy decisions. In this Perspective, we share our views on the functional aims, rationale, data requirements and challenges of nowcasting at different stages of an epidemic, drawing on the ongoing COVID-19 experience. We highlight how recent advances in the computational and laboratory sciences could be harnessed to complement traditional approaches to enhance the scope, timeliness, reliability and utility of epidemic nowcasting.
Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials
Authors: Shilong Yang, Yan Li, Lianpan Dai, Jianfeng Wang, Peng He, Changgui Li, Xin Fang, Chenfei Wang, Xiang Zhao, Enqi Huang, Changwei Wu, Zaixin Zhong, Fengze Wang, Xiaomin Duan, Siyu Tian, Lili Wu, Yan Liu, Yi Luo, Zhihai Chen, Fangjun Li, Junhua Li, Xian Yu, Hong Ren, Lihong Liu, Shufang Meng, Jinghua Yan, Zhongyu Hu, Lidong Gao, George F Gao
Journal: The Lancet Infectious Diseases (2021)
P09.08 Age-Related Outcomes of First-Line Pembrolizumab in a Real-World Non-Small-Cell Lung Cancer (NSCLC) Cohort
Authors: S. Dolter, H. Grosjean, D. Meyers, O. Javizian, I. Stukalin, S. Goutam, D. Morris, D.G. Bebb, A. Pabani
Journal: Journal of Thoracic Oncology (2021)
Academics are balloted on industrial action over Liverpool University’s “unethical” plans to cut jobs
Authors: Matthew Limb
Journal: BMJ (2021)

International concern is growing over a UK university’s “callous” and “unethical” plans to cut jobs among clinician scientists and researchers, including those doing key covid related work.

More than 2000 external academics have signed an open letter saying that restructuring plans by the University of Liverpool, which could see 47 jobs lost in its Faculty of Health and Life Sciences, “can only have a chilling effect on UK research.”1

They said that faculty staff were identified and targeted for possible redundancy by “grant income and citation metrics” without being able to review the criteria or the information held about them. They argue that the “irresponsible” use of quantitative metrics violates the San Francisco Declaration of Research Assessment,2 which the university is signed up to, and other internationally agreed principles. The university has denied this accusation.

The metrics have been deployed against staff who have received consistently positive annual appraisals and have been “working harder than ever during a global pandemic,” they wrote.

“Everyone is shocked this is happening—it’s a very unacceptable way of handling staff,” said Jeremy Turnbull, who is Johnston professor of biochemistry at the university and faces losing his job as “one of the 47” under the proposals (see case study below). Also under threat are staff producing research that is considered …
<i>QuickStats</i>: Percentage* of Adults Aged ≥18 Years Who Have Seen or Talked to a Doctor or Other Health Care Professional About Their Own Health in the Past 12 Months,† by Sex and Age Group — National Health Interview Survey,§ United States, 2015
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In 2015, women aged ≥18 years were more likely than men, overall and for each age group except those aged ≥65 years, to have seen or talked to a doctor or other health professional about their own health in the past 12 months. For both sexes, visits to a doctor or other health care professional increased with age, from 63.1% among men aged 18-29 years to 93.2% among men aged ≥65 years and from 82.4% among women aged 18-29 years to 94.3% among women ≥65 years.
Long-term persistence of RBD+ memory B cells encoding neutralizing antibodies in SARS-CoV-2 infection
Authors: Arunasingam Abayasingam, Harikrishnan Balachandran, David Agapiou, Mohamed Hammoud, Chaturaka Rodrigo, Elizabeth Keoshkerian, Hui Li, Nicholas A. Brasher, Daniel Christ, Romain Rouet, Deborah Burnet, Branka Grubor-Bauk, William Rawlinson, Stuart Turville, Anupriya Aggarwal, Alberto Ospina Stella, Christina Fichter, Fabienne Brilot, Michael Mina, Jeffrey J. Post, Bernard Hudson, Nicky Gilroy, Dominic Dwyer, Sarah C. Sasson, Fiona Tea, Deepti Pilli, Anthony Kelleher, Nicodemus Tedla, Andrew R. Lloyd, Marianne Martinello, Rowena A. Bull
Journal: Cell Reports Medicine (2021)

Considerable concerns relating to the duration of protective immunity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist, with evidence of antibody titers declining rapidly after infection and reports of reinfection. Here, we monitor the antibody responses against SARS-CoV-2 receptor-binding domain (RBD) for up to 6 months after infection. While antibody titers are maintained, ∼13% of the cohort's neutralizing responses return to background. However, encouragingly, in a selected subset of 13 participants, 12 have detectable RBD-specific memory B cells and these generally are increasing out to 6 months. Furthermore, we are able to generate monoclonal antibodies with SARS-CoV-2 neutralizing capacity from these memory B cells. Overall, our study suggests that the loss of neutralizing antibodies in plasma may be countered by the maintenance of neutralizing capacity in the memory B cell repertoire.
P26.07 Video-Assisted Thoracoscopic Surgery for Stage I Thymoma: Short-Term Outcomes and Appropriate Indications
Authors: T. Suzuki, T. Hishida, Maeda C., K. Matsuda, T. Nakagomi, S. Omura, H. Tanaka, K. Masai, K. Kaseda, K. Asakura, H. Asamura
Journal: Journal of Thoracic Oncology (2021)
Single-Cell RNA Sequencing Reveals the Cellular Origin and Evolution of Breast Cancer in <i>BRCA1</i> Mutation Carriers
Authors: Li Hu, Liming Su, Hainan Cheng, Chunling Mo, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Jianguang Zhang, Yuntao Xie
Journal: Cancer Research (2021)

Abstract The cell of origin and the development of breast cancer are not fully elucidated in BRCA1 mutation carriers, especially for estrogen receptor (ER)–positive breast cancers. Here, we performed single-cell RNA sequencing (RNA-seq) on 82,122 cells isolated from the breast cancer tissues and adjacent or prophylactic normal breast tissues from four BRCA1 mutation carriers and three noncarriers. Whole-exome sequencing was performed on breast tumors from the four BRCA1 mutation carriers; for validation, bulk RNA-seq was performed on adjacent normal breast tissues from eight additional BRCA1 mutation carriers and 14 noncarriers. Correlation analyses suggested that breast cancers in BRCA1 mutation carriers might originate from luminal cells. The aberrant luminal progenitor cells with impaired differentiation were significantly increased in normal breast tissues in BRCA1 mutation carriers compared with noncarriers. These observations were further validated by the bulk RNA-seq data from additional BRCA1 mutation carriers. These data suggest that the cell of origin of basal-like breast tumors (ERneg) in BRCA1 mutation carriers might be luminal progenitor cells. The expression of TP53 and BRCA1 was decreased in luminal progenitor cells from normal breast tissue in BRCA1 mutation carriers, which might trigger the basal/mesenchymal transition of luminal progenitors and might result in basal-like tumor development. Furthermore, ERhigh luminal tumors might originate from mature luminal cells. Our study provides in-depth evidence regarding the cells of origin of different breast cancer subtypes in BRCA1 mutation carriers. Significance: Single-cell RNA-seq data indicate that basal-like breast cancer (ERneg) might originate from luminal progenitors, and ERhigh luminal breast cancer might originate from mature luminal cells in BRCA1 mutation carriers.
Novel Suture Systems: An Accelerated Wound‐Healing Surgical Suture Engineered with an Extracellular Matrix (Adv. Healthcare Mater. 6/2021)
Authors: Agustina Setiawati, Dongyoon Jang, Daeyon Cho, Shingyu Cho, Hayan Jeong, Sungmin Park, Jungsug Gwak, Soo Ryeon Ryu, Won Hee Jung, Bong‐Gun Ju, Kwang‐Hwan Jung, Oh‐Sun Kwon, Kwanwoo Shin
Journal: Advanced Healthcare Materials (2021)

During surgery to suture injured tissue, friction occurs at the interface between the tissue and the suture, which often causes serious “secondary trauma” to fragile tissue and can lead to inflammation and infection. In article number 2001686, Kwanwoo Shin and co-workers develope a novel surgical suture system that accelerates wound healing. The presence of fibronectin fibrils on the engineered sutures improves cell migration and adhesion in wound tissues, especially while minimizing friction at the surgery site.
Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut‐Off Approach
Authors: Laura Cristoferi, Vincenza Calvaruso, Diletta Overi, Mauro Viganò, Cristina Rigamonti, Elisabetta Degasperi, Vincenzo Cardinale, Sara Labanca, Nicola Zucchini, Anna Fichera, Vito Di Marco, Monica Leutner, Rosanna Venere, Antonino Picciotto, Martina Lucà, Giacomo Mulinacci, Andrea Palermo, Alessio Gerussi, Daphne D’Amato, Sarah Elisabeth O’Donnell, Federica Cerini, Carla De Benedittis, Federica Malinverno, Vincenzo Ronca, Clara Mancuso, Nora Cazzagon, Antonio Ciaccio, Donatella Barisani, Marco Marzioni, Annarosa Floreani, Domenico Alvaro, Eugenio Gaudio, Pietro Invernizzi, Guido Carpino, Alessandra Nardi, Marco Carbone
Journal: Hepatology (2021)

Background and Aims Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration‐controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. Approach and Results We collected data from 167 consecutive treatment‐naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and &gt;11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. Conclusions In a multicenter study of treatment‐naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and &gt;11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.
Impact of sodium glucose cotransporter 2 (SGLT2) inhibitors on atherosclerosis: from pharmacology to pre-clinical and clinical therapeutics
Authors: Zhenghong Liu, Xiaoxuan Ma, Iqra Ilyas, Xueying Zheng, Sihui Luo, Peter J. Little, Danielle Kamato, Amirhossein Sahebkar, Weiming Wu, Jianping Weng, Suowen Xu
Journal: Theranostics (2021)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new oral drugs for the therapy of patients with type 2 diabetes mellitus (T2DM).Research in the past decade has shown that drugs of the SGLT2i class, such as empagliflozin, canagliflozin, and dapagliflozin, have pleiotropic effects in preventing cardiovascular diseases beyond their favorable impact on hyperglycemia.Of clinical relevance, recent landmark cardiovascular outcome trials have demonstrated that SGLT2i reduce major adverse cardiovascular events, hospitalization for heart failure, and cardiovascular death in T2DM patients with/without cardiovascular diseases (including atherosclerotic cardiovascular diseases and various types of heart failure).The major pharmacological action of SGLT2i is through inhibiting glucose re-absorption in the kidney and thus promoting glucose excretion.Studies in experimental models of atherosclerosis have shown that SGLT2i ameliorate the progression of atherosclerosis by mechanisms including inhibition of vascular inflammation, reduction in oxidative stress, reversing endothelial dysfunction, reducing foam cell formation and preventing platelet activation.Here, we summarize the anti-atherosclerotic actions and mechanisms of action of SGLT2i, with an aim to emphasize the clinical utility of this class of agents in preventing the insidious cardiovascular complications accompanying diabetes.
Association between Personal Activity Intelligence (PAI) and body weight in a population free from cardiovascular disease – The HUNT study
Authors: Sophie K. Kieffer, Javaid Nauman, Kari Syverud, Hege Selboskar, Stian Lydersen, Ulf Ekelund, Ulrik Wisløff
Journal: The Lancet Regional Health - Europe (2021)

Personal Activity Intelligence (PAI) is a new metric for physical activity tracking, and is associated with reduced risk of all-cause and cardiovascular mortality. We prospectively investigated whether PAI is associated with lower body weight gain in a healthy population.
Emerging noninvasive methylation biomarkers of cancer prognosis and drug response prediction
Authors: Javier Oliver, Marilina Garcia-Aranda, Patricia Chaves, Emilio Alba, Manuel Cobo-Dols, Juan Luis Onieva, Isabel Barragan
Journal: Seminars in Cancer Biology (2021)

Cancer is the second leading cause of death worldwide being responsible for 9.6 million deaths in 2018. Epigenetic alterations are key in directing the aberrant expression of tumor-associated genes that drive cellular malignant transformation and cancer progression. Among epigenetic alterations, DNA methylation is the most deeply studied one in relation to environmental exposure. Tissue biopsies have traditionally been the main procedure by which a small sample of body tissue is excised to confirm cancer diagnosis or to indicate the primary site when cancer has spread. In contrast, the analysis of circulating tumor-derived material, or tumor circulome, by means of liquid biopsy of peripheral blood, urine, saliva or sputum is a noninvasive, fast and reproducible alternative to tissue biopsy. Recently, the assessment of epigenetic alterations such as DNA methylation and hydroxymethylation in circulating free DNA has been proved possible. These marks can be associated to prognosis and response to a variety of treatments including chemotherapy, hormonotherapy or immunotherapy. Epigenetic biomarkers may offer some advantages over RNA or genetic biomarkers given their stability in bodily fluids and their high tissue-specificity. While many challenges are still ahead, the unique advantages of these types of biomarkers is urging the scientific community to persevere in their clinical validation and integration into reliable prediction models. This review aims at recapitulating the emerging noninvasive DNA methylated biomarkers of importance for prediction of prognosis and drug response in cancer.
Covid-19: Eight in 10 Wuhan residents with antibodies had no symptoms, finds study
Authors: Susan Mayor
Journal: BMJ (2021)

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High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults With Acute Sinusitis
Authors: Jennifer Gregory, Bichtram Huynh, Brittany Tayler, Chaitali Korgaonkar-Cherala, Gina Garrison, Ashar Ata, Paul Sorum
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit. <h3>Objective</h3> To confirm the previous finding that high-dose amoxicillin plus clavulanate (with double the amount of amoxicillin) may be superior to standard-dose amoxicillin plus clavulanate in adults. <h3>Design, Setting, and Participants</h3> This double-blind, comparative-effectiveness randomized clinical trial was conducted from February 26, 2018, through May 10, 2020, at the academic primary care internal medicine and pediatrics practice of Albany Medical Center, located in Cohoes, New York. Participants included adults aged 18 years or older who were prescribed amoxicillin plus clavulanate for acute bacterial sinusitis diagnosed in accordance with the Infectious Diseases Society of America guidelines. <h3>Interventions</h3> Amoxicillin 875 mg with clavulanate 125 mg plus either placebo (standard dose) or amoxicillin 875 mg (high dose) twice a day for 7 days. <h3>Main Outcomes and Measures</h3> The primary efficacy outcome was a global rating of "a lot better" or "no symptoms" at the end of 3 days of treatment using a Global Rating of Improvement scale, with outcomes ranging from 1 (a lot worse) to 6 (no symptoms). The primary adverse effect outcome was severe diarrhea at 3 or 10 days after the start of treatment. <h3>Results</h3> At an unplanned interim analysis prompted by COVID-19 restrictions, 157 of a projected 240 participants had been enrolled (mean age, 48.5 [range, 18.7-84.0] years; 117 women [74.5%]), with 79 randomized to the standard dose and 78 to the high dose; 9 and 12, respectively, withdrew or were lost to follow-up before the assessment of the primary outcome. At day 3, 31 of 70 participants (44.3%) in the standard-dose group reported a global rating of "a lot better" or "no symptoms," as did 24 of 66 (36.4%) in the high-dose group, for a difference of −7.9% (95% CI, −24.4% to 8.5%;<i>P</i> = .35). The study was, therefore, stopped for futility. Diarrhea was common in both groups by day 3, with any diarrhea reported in 29 of 71 participants (40.8%) receiving the standard dose and 28 of 65 (43.1%) receiving the high dose and severe diarrhea reported in 5 of 71 (7.0%) and 5 of 65 (7.7%), respectively. <h3>Conclusions and Relevance</h3> The results of this randomized clinical trial suggest that adults treated for clinically diagnosed acute sinusitis did not appear to benefit from taking high-dose compared with standard-dose amoxicillin plus clavulanate. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03431337
<i>Candida albicans</i> disorder is associated with gastric carcinogenesis
Authors: Mengya Zhong, Yubo Xiong, Jiabao Zhao, Zhi Gao, Jingsong Ma, Zhengxin Wu, Yongxi Song, Xuehui Hong
Journal: Theranostics (2021)

Bacterial infection is associated with gastric carcinogenesis. However, the relationship between nonbacterial components and gastric cancer (GC) has not been fully explored. We aimed to characterize the fungal microbiome in GC.
FP12.12 Lung Cancer in Women Never-Smokers: A Genomics Perspective of the Women’s Health Initiative (WHI) Cohort.
Authors: S. Moorthi, A. Paguirigan, G. Anderson, P. Porter, M. Herndon, E. Jhingan, G. Ha, A. Berger
Journal: Journal of Thoracic Oncology (2021)