tbuckley/cabot-search huggingface dataset:
Genome‐wide analysis identifies gallstone‐susceptibility loci including genes regulating gastrointestinal motility
Authors: Cameron J. Fairfield, Thomas M. Drake, Riinu Pius, Andrew D. Bretherick, Archie Campbell, David W. Clark, Jonathan A. Fallowfield, Caroline Hayward, Neil C. Henderson, Andrii Iakovliev, Peter K. Joshi, Nicholas L. Mills, David J. Porteous, Prakash Ramachandran, Robert K. Semple, Catherine A. Shaw, Cathie L. W. Sudlow, Paul R. H. J. Timmers, James F. Wilson, Stephen J. Wigmore, Athina Spiliopoulou, Ewen M. Harrison
Journal: Hepatology (2021)

Abstract Background and Aims Genome‐wide association studies (GWAS) have identified several risk loci for gallstone disease. As with most polygenic traits, it is likely that many genetic determinants are undiscovered. The aim of this study was to identify genetic variants that represent new targets for gallstone research and treatment. Approach and Results We performed a GWAS of 28,627 gallstone cases and 348,373 controls in the UK Biobank, replicated findings in a Scottish cohort (1089 cases, 5228 controls), and conducted a GWA meta‐analysis (43,639 cases, 506,798 controls) with the FinnGen cohort. We assessed pathway enrichment using gene‐based then gene‐set analysis and tissue expression of identified genes in Genotype‐Tissue Expression project data. We constructed a polygenic risk score (PRS) and evaluated phenotypic traits associated with the score. Seventy‐five risk loci were identified ( p &lt; 5 × 10 −8 ), of which 46 were new. Pathway enrichment revealed associations with lipid homeostasis, glucuronidation, phospholipid metabolism, and gastrointestinal motility. Anoctamin 1 ( ANO1 ) and transmembrane Protein 147 ( TMEM147 ), both in novel, replicated loci, are expressed in the gallbladder and gastrointestinal tract. Both regulate gastrointestinal motility. The gallstone risk allele rs7599‐A leads to suppression of hepatic TMEM147 expression, suggesting that the protein protects against gallstone formation. The highest decile of the PRS demonstrated a 6‐fold increased odds of gallstones compared with the lowest decile. The PRS was strongly associated with increased body mass index, serum liver enzymes, and C‐reactive protein concentrations, and decreased lipoprotein cholesterol concentrations. Conclusions This GWAS demonstrates the polygenic nature of gallstone risk and identifies 46 novel susceptibility loci. We implicate genes influencing gastrointestinal motility in the pathogenesis of gallstones.
P15.01 Phase II Prospective Study of Adjuvant Pembrolizumab in N2 Positive NSCLC Treated With Neoadjuvant CCRT Followed by Surgery
Authors: S. Park, H.A. Jung, J.H. Cho, J. Sun, S. Lee, Y.S. Choi, J.S. Ahn, J. Kim, K. Park, J.I. Zo, Y.M. Shim, H.K. Kim, M. Ahn
Journal: Journal of Thoracic Oncology (2021)
Biomaterial scaffolds for clinical procedures in endodontic regeneration
Authors: He Liu, Jing Lu, Qianzhou Jiang, Markus Haapasalo, Junrong Qian, Franklin R. Tay, Ya Shen
Journal: Bioactive Materials (2021)

Regenerative endodontic procedures have been rapidly evolving over the past two decades and are employed extensively in clinical endodontics. These procedures have been perceived as valuable adjuvants to conventional strategies in the treatment of necrotic immature permanent teeth that were deemed to have poor prognosis. As a component biological triad of tissue engineering (i.e., stem cells, growth factors and scaffolds), biomaterial scaffolds have demonstrated clinical potential as an armamentarium in regenerative endodontic procedures and achieved remarkable advancements. The aim of the present review is to provide a broad overview of biomaterials employed for scaffolding in regenerative endodontics. The favorable properties and limitations of biomaterials organized in naturally derived, host-derived and synthetic material categories were discussed. Preclinical and clinical studies published over the past five years on the performance of biomaterial scaffolds, as well as current challenges and future perspectives for the application of biomaterials for scaffolding and clinical evaluation of biomaterial scaffolds in regenerative endodontic procedures were addressed in depth.
Coronary calcification detected by electron-beam computed tomography and non-coronary measures of atherosclerosis:
Authors: Jacqueline CM Witteman
Journal: Circulation (2001)

0004 Coronary calcification as detected by electron-beam tomography (EBT) is a measure of coronary atherosclerosis. We investigated whether coronary artery calcium is associated with non-coronary measures of atherosclerosis, using data from the population-based Rotterdam Study. Participants in the third phase of the study were invited to undergo EBT scanning for detection of coronary calcifications. EBT scans were obtained from 2263 participants (47% men, mean age (SD), 71.3 (5.7)). Quantification of coronary calcifications was performed using Agatston’s method, and resulted in a calcium score. Calcium scores were available for 1874 subjects. Measures of non-coronary atherosclerosis included presence of aorta calcification detected by X-ray, presence of plaques in carotid arteries and intima-media thickness of the common carotid artery, both detected by ultrasonography, and ankle to brachial blood pressure index as a measure of peripheral arterial disease. Three calcium score categories were considered: 0 - 100, 101 - 500, and &gt;500. The calcium score showed a graded association with the measures of non-coronary atherosclerosis. Using logistic regression analysis, age and sex adjusted odds ratios for aorta calcification were 3.2 (95% confidence interval, 2.0 - 5.2) in subjects with calcium score 101 - 500 and 12.0 (7.6 - 18.9) in subjects with calcium score &gt; 500, when compared to subjects in the lowest calcium score category. The corresponding odds ratios for carotid plaques were 2.4 (1.6 - 3.5) and 5.8 (3.9 - 8.6). In a general linear model adjusted for age and sex, mean intima-media thickness increased with increasing calcium score category, while mean ankle to brachial blood pressure index decreased. These results indicate that known measures of non-coronary atherosclerosis are strongly related to coronary atherosclerosis, as measured by EBT calcium.
P14.05 Phase 2, Study of Iovance Autologous Tumor Infiltrating Lymphocytes (Lifileucel, LN-144, LN-145, LN-145-S1) In Patients With Solid Tumors
Authors: S. Gettinger, H. Kluger, A. Schoenfeld, A. Betof Warner, K. He, A. Sukari, S. Thomas, B. Doger, S. Lee, S. Haefliger, Z. Goldberg, A. Cacovean, R. Fiaz, G. Chen, M. Jagasia, F. Graf Finckenstein, M. Fardis, A. Jimeno
Journal: Journal of Thoracic Oncology (2021)
PTPMT1 Is Required for Embryonic Cardiac Cardiolipin Biosynthesis to Regulate Mitochondrial Morphogenesis and Heart Development
Authors: Ze’e Chen, Siting Zhu, Hong Wang, Li Wang, Jianlin Zhang, Yusu Gu, Changming Tan, Mehul Dhanani, Eric Wever, Xinru Wang, Boyu Xie, Shijia Wang, Lei Huang, Antoine H.C. van Kampen, Jie Liu, Zhen Han, Hemal H. Patel, Frédéric M. Vaz, Xi Fang, Ju Chen, Kunfu Ouyang
Journal: Circulation (2021)
Addressing the nephrology workforce shortage via a novel undergraduate pipeline program: the Kidney Disease Screening and Awareness Program (KDSAP) at 10 years
Authors: Ming-Yan Jiang, Rui Song, Rebecca Chen, Andrew Cho, Sirine Bellou, Min Zhuo, Jiahua Li, Edward Krupat, Suraj Sarvode Mothi, Kavya Shah, Jeremy Policht, Andrew Rosenblatt, Jeffrey Berns, Delphine S. Tuot, Michael Heung, Li-Li Hsiao
Journal: Kidney International (2021)
Clinical Perspectives on IgG4-Related Disease and Its Classification
Authors: Guy Katz, John H. Stone
Journal: Annual Review of Medicine (2021)

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease. Since its discovery nearly two decades ago, our understanding of its pathophysiology and clinical manifestations has grown substantially. Early diagnosis and treatment of this elusive disease can prevent substantial organ damage from end-stage fibrosis, emphasizing the need for prompt recognition and accurate characterization of IgG4-RD. The classification criteria endorsed by the American College of Rheumatology and the European Alliance of Associations for Rheumatology in 2019 provide a framework for establishing the diagnosis in the clinical setting. This process involves recognizing the typical manifestations of the disease and incorporating clinical, radiological, serological, and histopathological information as well as excluding disease mimickers. Glucocorticoids and rituximab are effective at inducing remission in IgG4-RD in most patients, but the optimal approach to long-term management of IgG4-RD remains an area of active clinical research.
A rapid assay provides on-site quantification of tetrahydrocannabinol in oral fluid
Authors: Hojeong Yu, Hoyeon Lee, Jiyong Cheong, Sang Won Woo, Juhyun Oh, Hyun-Kyung Oh, Jae-Hyun Lee, Hui Zheng, Cesar M. Castro, Yeong-Eun Yoo, Min-Gon Kim, Jinwoo Cheon, Ralph Weissleder, Hakho Lee
Journal: Science Translational Medicine (2021)

The express probe for on-site cannabis inhalation (EPOCH) system is able to quantitate tetrahydrocannabinol concentrations in oral fluid.
Abstract 9740: Factors Associated With Performing Urgent Coronary Angiography in Out-of-Hospital Cardiac Arrest
Authors: David H Lam, Lauren M Glassmoyer, Roger B Davis, Donald E Cutlip, Michael W Donnino, Michael N Cocchi, Duane S Pinto
Journal: Circulation (2015)

Introduction: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality and is most commonly caused by cardiovascular disease. Current guidelines recommend urgent coronary angiography (UCA) if ST-elevation myocardial infarction (STEMI) or high suspicion of acute myocardial infarction exist. Some have advocated for UCA in all OHCA without an obvious non-cardiac cause of arrest. The reasons for large clinical variation in performance of UCA in OHCA are not well understood. Objective: We sought to identify factors associated with performing UCA in OHCA. Methods: A retrospective chart review was conducted on 535 consecutive cardiac arrest patients who achieved return of spontaneous circulation (ROSC) and were admitted at a tertiary academic medical center from January 2008 to August 2014. Exclusion criteria included in-hospital cardiac arrests (201), outside hospital UCA (8), and lack of medical records (1). Univariable analysis followed by multivariable forward selection forcing age and gender were used to determine correlates of performing UCA, defined as within 6 hours of presentation. Results: Out of 325 resuscitated OHCA patients (mean age, 64; women, 35%), 69 were taken to UCA. Factors associated with performing UCA were history of coronary artery disease (CAD) (OR 2.76, 95% CI 1.22-6.28), initial shockable rhythm (OR 3.04, 95% CI 1.31-7.06), following commands post-ROSC (OR 2.77, 95% CI 1.06-7.25), and STEMI (OR 15.17, 95% CI 6.57-35.04). Increasing age (OR 0.97, 95% CI 0.95-0.999) and obvious non-cardiac cause of arrest (OR 0.10, 95% CI 0.03-0.37) were negatively associated. Gender, prior stroke, dementia, bystander cardiopulmonary resuscitation, hypotension, contraindication to anticoagulant, presenting from nursing home or rehabilitation, do not resuscitate order prior to admission, non-English primary language, and presenting during off-hours were not associated with the decision for UCA. Conclusions: In resuscitated out-of-hospital cardiac arrest patients, history of CAD, shockable rhythm, ability to follow commands, and STEMI were associated with performing urgent coronary angiography. Older patients and those with an obvious non-cardiac cause of arrest were less likely to receive coronary angiography.
Thiazole antibiotics that inhibit FoxM1 are potential anticancer drugs
Authors: Andrei Gartel, Marianna Halasi, Senthil Radhakrishnan, Uppoor Bhat
Journal: Cancer Research (2008)

2663  The oncogenic transcription factor forkhead box M1 (FoxM1) is overexpressed in a number of different carcinomas, whereas its expression is turned off in terminally differentiated cells. For this reason, FoxM1 is an attractive target for therapeutic intervention in cancer treatment. As a first step toward realizing this goal, in this study, using a high-throughput, cell based assay system, we screened for and isolated the antibiotic thiazole compound Siomycin A as an inhibitor of FoxM1 transcriptional activity. Interestingly, we observed that Siomycin A was able to down-regulate the transcriptional activity as well as the protein and mRNA levels of FoxM1. Consequently, we found that the downstream target genes of FoxM1, such as Cdc25B, Survivin, and CENPB, were also repressed. However, thiazole antibiotics did not affect transcriptional activity of p53, TCF/Lef or GLI suggesting that they specifically target FoxM1. Furthermore, we found that thiazole antibiotics were able inhibit the growth of human cancer cells of different origin with IC50 between 0.5 and 5 I¼M. Siomycin A induced apoptosis selectively in transformed, but not in normal human fibroblasts. Treatment of human cancer cell lines of different origin with 1-5 I¼M of thiazole antibiotics led to predominant down-regulation of FoxM1 and apoptosis. Taken together, our data suggest that thiazole antibiotics that inhibit FoxM1 could represent a useful starting point for the development of anticancer therapeutics against human neoplasia.
Who should pay for social care and how?
Authors: John Appleby
Journal: BMJ (2021)

The government’s announcement in September that the NHS and adult social care services across the UK will receive more money over the next few years is potentially an historic change.1

To do so, the government has decided to find the extra cash from an increase in national insurance contributions (NICs) paid by employees and employers, and then to separate out these new sums as a “health and social care levy” in 2023. This essentially introduces a new tax hypothecated to spending on the NHS and social care. Although the new tax will fund only a small proportion (less than 10%) of the total spending on the NHS and social care, it marks an important shift in how we pay for care.

On the one hand, the use of NICs as a source of extra health funding is not new. In 2002 Gordon Brown, the then chancellor, raised NICs by one percentage point to increase NHS spending, for example.2 On the other hand, such moves were …
Delta variant: what is the real risk of hospital admission?
Authors: Roland Salmon
Journal: BMJ (2021)

Wise reports on the finding that patients with the delta variant of SARS-CoV-2 are more than twice as likely to be admitted to hospital than those infected with the alpha variant.12

This news item, along with other coverage of the study, emphasises the adjusted odds ratio of 2.26 (95% confidence interval 1.32 to 3.89), an apparent doubling of risk of hospital admission …
A systematic review of parent report measures assessing the psychosocial impact of food allergy on patients and families
Authors: Kaitlin B. Proctor, Katherine Tison, Hayley H. Estrem, Jinhee Park, Lawrence Scahill, Brian P. Vickery, William G. Sharp
Journal: Allergy (2021)

Abstract Background Reducing the psychosocial impact of food allergy (FA) represents a top patient‐centered research priority. This priority recognizes that psychosocial impact is an important outcome of current FA therapies (eg, oral immunotherapy), as well as interventions aimed at improving overall quality of life and illness adaptation. Reliable and valid measurement is a necessary prerequisite to developing and evaluating current and emerging FA therapies and potential changes in psychosocial impact. Methods In this systematic review, we applied the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement to evaluate available parent report measures assessing the psychosocial impact of pediatric IgE‐mediated FA. Results The systematic search yielded 64 articles involving 13 unique measures. Measures were evaluated through the lens of the Patient Reported Outcomes Measurement Information System (PROMIS) guidelines. Findings indicated that available measures show some evidence of reliability and validity; however, none completely adhere to PROMIS guidelines for measure development. Conclusion Results highlight a continued need to dedicate research to develop a measurement approach that assesses the full range of psychosocial impact that parents and families may experience as a result of FA, as well as serve as a research outcome as the field continues to develop effective treatments, including immunotherapy.
PB1856 HEPATITIS ASSOCIATED APLASTIC ANEMIA: ETIOLOGY, CLINICAL CHARACTERISTICS AND OUTCOME
Authors: Ö. Tüfekçi, H. Hekimci Özdemir, B. Malbora, N.Y. Özbek, N. Yaralı, A. Erdem, M. Evim, B. Baytan, T. Karapınar, Y. Oymak, S. Yılmaz, D. Yılmaz Karapınar
Journal: HemaSphere (2019)

Background: Hepatitis associated aplastic anemia (HAA); is a form of acquired aplastic anemia in which bone marrow failure develops after an acute attack of hepatitis. Aplastic anemia can also be seen after liver transplantation due to acute fulminant hepatitis. Aims: In this study, we aimed to define clinical and labarotory characteristics, possible causes, treatment strategies and and clinical outcome in patients with HAA. Methods: Seventeen children from six centers throughout Turkey were enrolled in the study. Clinical data were retrieved from the medical records. Results: The median age at time of diagnosis of acute hepatisis was 8.9 years (min: 5‐max:17). Search for etiology revealed highly positive CMV‐DNA in one patient and HCV‐RNA in one patient. One other patient was found to be positive for EBV, CMV and parvovirus DNA. Besides, one patient had the diagnosis of autoimmune hepatitis. The median time from diagnosis of hepatitis to diagnosis of aplastic anemia was 30 days (min:0‐max:322). Pancytopenia was simultaneously present in 5 out of 17 (29%) patients. Liver transplantation due to acute fulminant hepatitis was performed in 5 patients (29%). Aplastic anemia developed before liver transplantation in two patients and after liver transplantation in three patients. In terms of treatment for aplastic anemia; 8 patients (47%) received immunsuppressive treatment (IST) with anti‐thymocyte globulin and cyclosporine. HLA identical hematopetic stem cell transplantation (HSCT) was performed in 5 patients (29%). Two patients who received IST later underwent HSCT. The median time from diagnosis of AA to IST and HSCT were 45 days (min:1‐max:218) and 104 days (min:86‐max:1282), respectively. At the end; 9 out of 17 patients (52%) were alive, in remission and transfusion free. Those who were alive either received HSCT and/or IST, except one patient who received no treatment. Eight patients (48%) died mainly due to infectious causes. Summary/Conclusion: Although there have been limited number of patients in the present study, it was noteworthy that approximately one‐third of patients presented with pancytopenia at the time of diagnosis of hepatitis. Further research is needed to investigate the effect of some etiological agents on the clinical outcome. The loss of patients who did not undergo IST and HSCT revealed once again the importance of initiating IST at the appropriate time together with donor search for HSCT in this group of patients.
MA04.07 Clinical Characteristics and Outcomes in Patients With Malignant Pleural Mesothelioma (MPM) with COVID-19 Infection
Authors: S. Cedres, J.D. Assaf, P. Iranzo, N. Pardo, A. Martinez-Marti, A. Navarro, D. Marmolejo, A. Rezqallah, J. Gonzalo, C. Carbonell, J. Frigola, R. Amat, C. Viaplana, R. Dienstmann, E. Felip
Journal: Journal of Thoracic Oncology (2021)
Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner
Authors: Roanne Keeton, Simone I. Richardson, Thandeka Moyo-Gwete, Tandile Hermanus, Marius B. Tincho, Ntombi Benede, Nelia P. Manamela, Richard Baguma, Zanele Makhado, Amkele Ngomti, Thopisang Motlou, Mathilda Mennen, Lionel Chinhoyi, Sango Skelem, Hazel Maboreke, Deelan Doolabh, Arash Iranzadeh, Ashley D. Otter, Tim Brooks, Mahdad Noursadeghi, James C. Moon, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Jonathan Blackburn, Nei-Yuan Hsiao, Carolyn Williamson, Catherine Riou, Ameena Goga, Nigel Garrett, Linda-Gail Bekker, Glenda Gray, Ntobeko A.B. Ntusi, Penny L. Moore, Wendy A. Burgers
Journal: Cell Host & Microbe (2021)
Effect of silver in thermal treatments of Fe-Mn-C degradable metals: Implications for stent processing
Authors: Sergio Loffredo, Sofia Gambaro, Francesco Copes, Carlo Paternoster, Nicolas Giguère, Maurizio Vedani, Diego Mantovani
Journal: Bioactive Materials (2021)

Twinning-induced plasticity (TWIP) steels are considered excellent materials for manufacturing products requiring extremely high mechanical properties for various applications including thin medical devices, such as biodegradable intravascular stents. It is also proven that the addition of Ag can guarantee an appropriate degradation while implanted in human body without affecting its bioactive properties. In order to develop an optimized manufacturing process for thin stents, the effect of Ag on the recrystallization behavior of TWIP steels needs to be elucidated. This is of major importance since manufacturing stents involves several intermediate recrystallization annealing treatments. In this work, the recrystallization mechanism of two Fe-Mn-C steels with and without Ag was thoroughly investigated by microstructural and mechanical analyses. It was observed that Ag promoted a finer microstructure with a different texture evolution, while the recrystallization kinetics resulted unaffected. The presence of Ag also reduced the effectiveness of the recrystallization treatment. This behavior was attributed to the presence of Ag-rich second phase particles, precipitation of carbides and to the preferential development of grains possessing a {111} orientation upon thermal treatment. The prominence of {111} grains can also give rise to premature twinning, explaining the role of Ag in reducing the ductility of TWIP steels already observed in other works. Furthermore, in vitro biological performances were unaffected by Ag. These findings could allow the design of efficient treatments for supporting the transformation of Fe-Mn-C steels alloyed with Ag into commercial products.