tbuckley/cabot-search huggingface dataset:
All‐trans retinoic acid induces leukemia resistance to NK cell cytotoxicity by down‐regulating B7‐H6 expression via c‐Myc signaling
Authors: Guoshuai Cao, Ying Cheng, Xiaodong Zheng, Haiming Wei, Zhigang Tian, Rui Sun, Haoyu Sun
Journal: Cancer Communications (2021)

Abstract Background The interaction between activating receptor NKp30 and its major tumor ligand B7‐H6 is important for NK cell‐mediated tumor rejection. However, the regulation of B7‐H6 by tumor therapeutics remains largely unknown. In this study, we investigated the regulation of B7‐H6 by all‐trans retinoic acid (atRA), a terminal differentiation inducer of tumor cells that is extensively used for clinical leukemia therapy. Methods We investigated the role of NKp30:B7‐H6 axis in NK cell‐mediated tumor lysis against leukemia cells and the influence of atRA treatment on the cytotoxicity of NK cells using NK cell lines (NK92 and NKG) and leukemia cell lines (U‐937 and THP‐1). We evaluated the effect of atRA treatment on the expression of B7‐H6 using real‐time PCR, flow cytometry and western blotting. We used CRISPR/Cas9 to knockdown B7‐H6 expression and siRNA to knockdown c‐Myc in U‐937 cells to evaluate the role of B7‐H6 and c‐Myc in atRA‐induced tumor resistance against NK cells. Results NK cell‐mediated U‐937 cell lysis was mainly dependent on NKp30/B7‐H6 interaction. Blockade of B7‐H6 by monoclonal antibody significantly impaired NK cytotoxicity. atRA treatment induced U‐937 resistance to NK cell cytotoxicity by reducing B7‐H6 expression, and showed no effect on NK cytotoxicity against B7‐H6 knockdown U‐937 cells. Epigenetic modifications, such as DNA methylation and histone deacetylase (HDAC), were not responsible for atRA‐mediated B7‐H6 down‐regulation as inhibitors of these pathways could not restore B7‐H6 mRNA expression. On the other hand, atRA treatment reduced c‐Myc expression, which in turn inhibited the transcription of B7‐H6 on leukemia cells. Conclusion atRA treatment promotes tumor cell resistance against NK cell‐mediated lysis by down‐regulating B7‐H6 expression via the c‐Myc signaling pathway, suggesting that more attention needs to be paid to the immunological adverse effects in the clinical use of atRA treatment.
Blockade of AIM2 inflammasome or α1-AR ameliorates IL-1β release and macrophage-mediated immunosuppression induced by CAR-T treatment
Authors: Dan Liu, Xiyue Xu, Yulian Dai, Xuan Zhao, Shunshun Bao, Wen Ma, Li Zha, Shuci Liu, Yuchen Liu, Junnian Zheng, Ming Shi
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Interleukin (IL) 1 released from monocytes/macrophages is one of the critical determinants in mediating the adverse events of chimeric antigen receptor T cell (CAR-T) therapy, including cytokine release syndrome and neurotoxicity. However, the molecular mechanisms of IL-1 production during CAR-T therapy remain unknown. Methods The roles of AIM2 and α1-adrenergic receptor (α1-AR) in CAR-T treatment-induced IL-1β release were evaluated by gene silencing, agonist or antagonist treatment. The phenotype switch of macrophages in response to CAR-T treatment was analyzed concerning cytotoxicity of CAR-T cells and proliferation of activated T cells. Results This study provided the experimental evidence that CAR-T treatment-induced activation of AIM2 inflammasome of macrophages resulted in the release of bioactive IL-1β. CAR-T treatment-induced α1-AR-mediated adrenergic signaling augmented the priming of AIM2 inflammasome by enhancing IL-1β mRNA and AIM2 expression. Meanwhile, tumor cell DNA release triggered by CAR-T treatment potentiated the activation of AIM2 inflammasome in macrophages. Interestingly, an apparent phenotypic switch in macrophages occurred after interacting with CAR-T/tumor cells, which greatly inhibited the cytotoxicity of CAR-T cells and proliferation of activated T cells through upregulation of programmed cell death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) in the macrophages. Blockade of AIM2 inflammasome or α1-AR reversed the upregulation of PD-L1 and IDO and the phenotypic switch of the macrophages. Conclusion Our study implicates that CAR-T therapy combined with the blockade of AIM2 inflammasome or α1-AR may relieve IL-1β-related toxic side effects of CAR-T therapy and ensure antitumor effects of the treatment.
UK will miss healthy ageing targets without urgent action, inquiry concludes
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The UK government will miss key targets to improve healthy ageing unless it acts now to tackle “stark” inequalities in healthy life expectancy, a House of Lords inquiry has concluded.1

In a report published on 15 January the House of Lords Science and Technology Committee concluded that new science had the potential to delay the onset of age related disease and improve healthy ageing to the benefit of individuals, the NHS, and society. But while it noted that the UK was a world leader in drug development and in technologies, with promising advances, the inquiry found that this had yet to translate …
Covid-19: High level of non-covid deaths may reflect health system pressures
Authors: Shaun Griffin
Journal: BMJ (2021)

Covid-19: High level of non-covid deaths may health system pressures Shaun GriffinExcess deaths were higher than deaths involving covid-19 in the week leading up to Christmas, the first time this has occurred during the second wave of the pandemic, show the latest provisional figures.Experts said that this may reflect the pressure on care pathways for patients with non-covid conditions.
Comprehensive integrative profiling of upper tract urothelial carcinomas
Authors: Xiaoping Su, Xiaofan Lu, Sehrish Khan Bazai, Eva Compérat, Roger Mouawad, Hui Yao, Morgan Rouprêt, Jean-Philippe Spano, David Khayat, Irwin Davidson, Nizar N. Tannir, Fangrong Yan, Gabriel G. Malouf
Journal: Genome biology (2021)

Abstract Background Crosstalk between genetic, epigenetic, and immune alterations in upper tract urothelial carcinomas and their role in shaping muscle invasiveness and patient outcome are poorly understood. Results We perform an integrative genome- and methylome-wide profiling of diverse non-muscle-invasive and muscle-invasive upper tract urothelial carcinomas. In addition to mutations of FGFR3 and KDM6A , we identify ZFP36L1 as a novel, significantly mutated tumor suppressor gene. Overall, mutations of ZFP36 family genes ( ZFP36 , ZFP36L1 , and ZFP36L2 ) are identified in 26.7% of cases, which display a high mutational load. Unsupervised DNA methylation subtype classification identifies two epi-clusters associated with distinct muscle-invasive status and patient outcome, namely, EpiC-low and EpiC-high. While the former is hypomethylated, immune-depleted, and enriched for FGFR3 -mutated, the latter is hypermethylated, immune-infiltrated, and tightly associated with somatic mutations of SWI/SNF genes. Conclusions Our study delineates for the first time the key role for convergence between genetic and epigenetic alterations in shaping clinicopathological and immune upper tract urothelial carcinoma features.
Lack of relationship of AT1001 to zonulin and prehaptoglobin-2: clinical implications
Authors: Ludvig M Sollid, Frits Koning
Journal: Gut (2020)

We read with interest the letter to the editor by Massier et al 1 and the accompanying response by Fasano.2 We would like to point out one critical issue that has not been addressed, namely, the relationship between AT1001, zonulin and prehaptoglobin-2. AT1001 is an octapeptide that was thought to represent the N-terminal sequence of zonulin.3 4 However, in all likelihood this octapeptide sequence (GGVLVQPG) derives from immunoglobulin. In their attempt to identify the human homolog of the Vibrio cholera zonula occludens …
Changes in Plant-Based Diet Indices and Subsequent Risk of Type 2 Diabetes in Women and Men: Three U.S. Prospective Cohorts
Authors: Zhangling Chen, Jean-Philippe Drouin-Chartier, Yanping Li, Megu Y. Baden, JoAnn E. Manson, Walter C. Willett, Trudy Voortman, Frank B. Hu, Shilpa N. Bhupathiraju
Journal: Diabetes Care (2021)

OBJECTIVE We evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We prospectively followed 76,530 women in the Nurses’ Health Study (NHS) (1986–2012), 81,569 women in NHS II (1991–2017), and 34,468 men in the Health Professionals Follow-up Study (1986–2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis. RESULTS We documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (&amp;gt;10%) in PDI and hPDI over 4 years had a 12–23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7–9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0–35.6% of the associations between changes in PDI and hPDI and diabetes risk. CONCLUSIONS Improving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.
How the pan-genome is changing crop genomics and improvement
Authors: Rafael Della Coletta, Yinjie Qiu, Shujun Ou, Matthew B. Hufford, Candice N. Hirsch
Journal: Genome biology (2021)

Abstract Crop genomics has seen dramatic advances in recent years due to improvements in sequencing technology, assembly methods, and computational resources. These advances have led to the development of new tools to facilitate crop improvement. The study of structural variation within species and the characterization of the pan-genome has revealed extensive genome content variation among individuals within a species that is paradigm shifting to crop genomics and improvement. Here, we review advances in crop genomics and how utilization of these tools is shifting in light of pan-genomes that are becoming available for many crop species.
The longitudinal relationship between loneliness, social isolation, and frailty in older adults in England: a prospective analysis
Authors: Katie Davies, Asri Maharani, Tarani Chandola, Chris Todd, Neil Pendleton
Journal: The Lancet Healthy Longevity (2021)

It is estimated that about 10% of people aged 65 and older are frail. Loneliness and social isolation are linked to increased mortality and poorer functional capacity. We assessed trends in frailty status associated with loneliness and social isolation over 14 years in a representative sample of English older adults.In this longitudinal study, we used data from the English Longitudinal Study of Ageing (ELSA), which was designed to recruit a representative sample of adults aged 50 years and older living in private households in England. We analysed Waves 2-8 (covering June, 2004, to June, 2017). Frailty was defined using the frailty index, analysed continuously and as pre-specified categories, to categorise individuals as being non-frail (≤0·08), pre-frail (>0·08 to <0·25), or frail (≥0·25 to 1·00). Loneliness was measured using the UCLA 3-item Loneliness Scale and social isolation was measured following a previous ELSA approach, and both sets of scores were categorised into low, medium, or high. Linear mixed methods and Cox proportional hazard modelling were used, adjusted for confounders.The study sample consisted of 9171 participants at the baseline of Wave 2 (4083 male and 5088 female), with similar numbers in subsequent waves. In the fixed effect model, adjusted for marital status, age, gender, wealth, and smoking status, respondents with higher levels of loneliness had a higher frailty index score (β coefficient 0·006, 95% CI 0·006 to 0·007; p<0·0001), as did those with a higher level of social isolation (β 0·002, <0·001 to 0·002; p<0·0001). Increasing age was associated with an increased frailty index, adjusted for loneliness and social isolation independently. Compared with a low level of loneliness, there was a higher risk of developing frailty with medium loneliness (hazard ratio [HR] 1·57, 95% CI 1·49 to 1·65; p<0·0001) and high loneliness (HR 2·62, 2·49 to 2·76; p<0·0001). Compared with a low level of social isolation, there was a higher risk of developing frailty with medium social isolation (HR 1·12, 1·05 to 1·20; p<0·0001) and high social isolation (HR 1·32, 1·22 to 1·43; p<0·0001).Both loneliness and social isolation increase the risk of developing frailty. Understanding these mechanisms might offer opportunities to attenuate this risk.None.
Association of Pertuzumab, Trastuzumab, and Docetaxel Combination Therapy With Overall Survival in Patients With Metastatic Breast Cancer
Authors: Sreeram V. Ramagopalan, Riccardo Pisoni, Lokendra Singh Rathore, Joshua Ray, Cormac Sammon
Journal: JAMA Network Open (2021)

This cohort study compares the findings of combined pertuzumab, trastuzumab, and docetaxel therapy in women with metastatic breast cancer with those in the CLEOPATRA trial.
Evaluation for Myocarditis in Competitive Student Athletes Recovering From Coronavirus Disease 2019 With Cardiac Magnetic Resonance Imaging
Authors: Jitka Starekova, David A. Bluemke, William S. Bradham, Lee L. Eckhardt, Thomas M. Grist, Joanna E. Kusmirek, Christopher S. Purtell, Mark L. Schiebler, Scott B. Reeder
Journal: JAMA Cardiology (2021)

The utility of cardiac magnetic resonance imaging (MRI) as a screening tool for myocarditis in competitive student athletes returning to training after recovering from coronavirus disease 2019 (COVID-19) infection is unknown.To describe the prevalence and severity of cardiac MRI findings of myocarditis in a population of competitive student athletes recovering from COVID-19.In this case series, an electronic health record search was performed at our institution (University of Wisconsin) to identify all competitive athletes (a consecutive sample) recovering from COVID-19, who underwent gadolinium-enhanced cardiac MRI between January 1, 2020, and November 29, 2020. The MRI findings were reviewed by 2 radiologists experienced in cardiac imaging, using the updated Lake Louise criteria. Serum markers of myocardial injury and inflammation (troponin-I, B-type natriuretic peptide, C-reactive protein, and erythrocyte sedimentation rate), an electrocardiogram, transthoracic echocardiography, and relevant clinical data were obtained.COVID-19 infection, confirmed using reverse transcription-polymerase chain reaction testing.Prevalence and severity of MRI findings consistent with myocarditis among young competitive athletes recovering from COVID-19.A total of 145 competitive student athletes (108 male and 37 female individuals; mean age, 20 years; range, 17-23 years) recovering from COVID-19 were included. Most patients had mild (71 [49.0%]) or moderate (40 [27.6%]) symptoms during the acute infection or were asymptomatic (24 [16.6%]). Symptoms were not specified or documented in 10 patients (6.9%). No patients required hospitalization. Cardiac MRIs were performed a median of 15 days (range, 11-194 days) after patients tested positive for COVID-19. Two patients had MRI findings consistent with myocarditis (1.4% [95% CI, 0.4%-4.9%]). Of these, 1 patient had marked nonischemic late gadolinium enhancement and T2-weighted signal abnormalities over multiple segments, along with an abnormal serum troponin-I level; the second patient had 1-cm nonischemic mild late gadolinium enhancement and mild T2-weighted signal abnormalities, with normal laboratory values.In this case series study, based on MRI findings, there was a low prevalence of myocarditis (1.4%) among student athletes recovering from COVID-19 with no or mild to moderate symptoms. Thus, the utility of cardiac MRI as a screening tool for myocarditis in this patient population is questionable.
Response to: ‘Correspondence on ‘EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups’’ by Irfan<i>et al</i>
Authors: Ingrid E Lundberg, Frederick W Miller, Lisa G Rider, Victoria P Werth, Anna Tjärnlund, Matteo Bottai
Journal: Annals of the Rheumatic Diseases (2021)

Figure 1 Differences in the prevalence of skin manifestations between Caucasian and Asian dermatomyositis (DM) and amyopathic DM (ADM) patients based on data from the International Myositis Classification Criteria Project. 2 P values are derived from significance of difference between Caucasian DM patients and Asian DM patients, and between Caucasian ADM patients and Asian ADM patients, respectively.*p<0.05
68Ga-PSMA-HBED-CC PET/CT Findings in a Patient of Polyostotic Fibrous Dysplasia
Authors: Gaurav Malhotra, Pratibha Pawal Aute, Sushama Awasare, Ramesh V. Asopa
Journal: Clinical Nuclear Medicine (2021)

Abstract A 43-year-old man diagnosed with fibrous dysplasia with McCune-Albright syndrome was subjected to 18 F-fluoride bone scan and 68 Ga-PSMA-HBED-CC PET/CT as per the institution protocol. 18 F-bone scan revealed extensive involvement of axial and appendicular skeleton confirming polyostotic fibrous dysplasia. 68 Ga-PSMA PET/CT showed increased tracer uptake in corresponding lesions of fibrous dysplasia. PSMA uptake in fibrous dysplasia lesions has been rarely described with literature evidence being limited to anecdotal case reports. Nevertheless, due to increasing use of PSMA PET/CT, one should be aware of this false-positive finding to avoid misinterpretation of the scans.
Autism Spectrum Disorder and the Risk of Substance Use Disorder
Authors: Sarah Ann R. Anderson, Marina Catallozzi
Journal: JAMA Pediatrics (2021)

Screening for substance use is a priority in adolescent health care.1 There has long been an acknowledgment of the link between psychiatric diagnoses and substance use disorders (SUDs).2,3 One of the cornerstones of the approaches to decreasing SUDs is to screen for and treat these other illnesses.
Abstract 13398: High-Resolution micro-OCT for Endothelial Cell Visualization in the Coronary Arteries
Authors: Kensuke Nishimiya, Biwei Yin, Zhonglie Piao, Jiheun Ryu, Hany Osman, Gargi Sharma, Hui Min Leung, Chia-Pin Liang, Joseph A Gardecki, Guillermo J Tearney
Journal: Circulation (2018)

Background: Coronary arteries are covered by a thin layer of endothelial cells (ECs). Impairment of ECs is at the origin of coronary atherosclerosis. More recently, endothelial erosion has emerged ...
A mathematical model for the quantification of a patient’s sensitivity to checkpoint inhibitors and long-term tumour burden
Authors: Joseph D. Butner, Zhihui Wang, Dalia Elganainy, Karine A. Al Feghali, Marija Plodinec, George A. Calin, Prashant Dogra, Sara Nizzero, Javier Ruiz-Ramírez, Geoffrey V. Martin, Hussein A. Tawbi, Caroline Chung, Eugene J. Koay, James W. Welsh, David S. Hong, Vittorio Cristini
Journal: Nature Biomedical Engineering (2021)
Under starters orders: NHS’s biggest ever vaccine drive
Authors: Alison Shepherd
Journal: BMJ (2021)

Patients receive covid-19 vaccines at an NHS vaccination centre set up in the grounds of Epsom Downs racecourse in Surrey.The site, with six other mass vaccination centres in London, Newcastle, Manchester, Birmingham, Bristol, and Stevenage, forms part of the government's attempts to ramp up its ambitious covid vaccination programme.It has announced plans to offer at least two million vaccinations a week at over 2700 sites in the UK, with the target to offer every adult a vaccine by the autumn.The priority of the Epsom site as it opened was to offer vaccinations to healthcare and social workers and people aged over 80 living within a 45 minute drive of the racecourse.
Biomarkers in lung cancer screening: the importance of study design
Authors: David R. Baldwin, Matthew E. Callister, Philip A. Crosbie, Emma L. O'Dowd, Robert C. Rintoul, Hilary A. Robbins, Robert J.C. Steele
Journal: European Respiratory Journal (2021)

<b>Use of biomarkers to select participants for lung cancer CT screening could improve clinical and cost effectiveness. It is crucial to design research that evaluates biomarkers against LDCT and to test them in the population in which they will be used.</b>https://bit.ly/3gPHAPu
Beta2-Adrenergic Receptor Gene Polymorphisms: Will the Important One Please Step Forward?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Martin C. Michel, Rainer Büscher
Journal: Journal of the American College of Cardiology (2008)
Cholinergic Capsules and Academic Admonitions
Authors: Palmer Taylor
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Herein, I intend to capture highlights shared with my academic and research colleagues over the 60 years I devoted initially to my graduate and postdoctoral training and then to academic endeavors starting as an assistant professor in a new medical school at the University of California, San Diego (UCSD). During this period, the Department of Pharmacology emerged from a division within the Department of Medicine to become the first basic science department, solely within the School of Medicine at UCSD in 1979. As part of the school's plans to reorganize and to retain me at UCSD, I was appointed as founding chair. Some years later in 2002, faculty, led largely within the Department of Pharmacology and by practicing pharmacists within UCSD Healthcare, started the independent Skaggs School of Pharmacy and Pharmaceutical Sciences with a doctor of pharmacy (PharmD) program, where I served as the founding dean. My career pathway, from working at my family-owned pharmacy to chairing a department in a school of medicine and then becoming the dean of a school of pharmacy at a research-intensive, student-centered institution, involved some risky decisions. But the academic, curricular, and accreditation challenges posed were met by a cadre of creative faculty colleagues. I offer my experiences to individuals confronted with a multiplicity of real or imagined opportunities in academic health sciences, the related pharmaceutical industry, and government oversight agencies.
Point-of-Care Platelet Function Analysis: Ready for Prime Time?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Elisabeth Mahla, Mark J. Antonino, Udaya S. Tantry, Paul A. Gurbel
Journal: Journal of the American College of Cardiology (2009)
Magnetic Resonance Labeling of Stem Cells: Is Positive Tracking a Plus or a Minus?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Dara L. Kraitchman, Peter Caravan
Journal: JACC. Cardiovascular imaging (2009)
Predicting Clinical Response and Safety of JCAR017 in B-NHL Patients: Potential Importance of Tumor Microenvironment Biomarkers and CAR T-Cell Tumor Infiltration
Authors: Christina Swanson, Trevor Do, Samantha Merrigan, Shaparak Lonning, Kim Merriam, Joshua Prentiss, Janani Sridar, Claire L Sutherland, Benhuai Xie, Minh Pham, Daniel Li, Tina Albertson, Howard M Stern, Sharon Moulis
Journal: Blood (2017)