tbuckley/cabot-search huggingface dataset:
TIAMMAt: Leveraging Biodiversity to Revise Protein Domain Models, Evidence from Innate Immunity
Authors: Michael G Tassia, Kyle T David, James P Townsend, Kenneth M Halanych
Journal: Molecular Biology and Evolution (2021)

Sequence annotation is fundamental for studying the evolution of protein families, particularly when working with nonmodel species. Given the rapid, ever-increasing number of species receiving high-quality genome sequencing, accurate domain modeling that is representative of species diversity is crucial for understanding protein family sequence evolution and their inferred function(s). Here, we describe a bioinformatic tool called Taxon-Informed Adjustment of Markov Model Attributes (TIAMMAt) which revises domain profile hidden Markov models (HMMs) by incorporating homologous domain sequences from underrepresented and nonmodel species. Using innate immunity pathways as a case study, we show that revising profile HMM parameters to directly account for variation in homologs among underrepresented species provides valuable insight into the evolution of protein families. Following adjustment by TIAMMAt, domain profile HMMs exhibit changes in their per-site amino acid state emission probabilities and insertion/deletion probabilities while maintaining the overall structure of the consensus sequence. Our results show that domain revision can heavily impact evolutionary interpretations for some families (i.e., NLR's NACHT domain), whereas impact on other domains (e.g., rel homology domain and interferon regulatory factor domains) is minimal due to high levels of sequence conservation across the sampled phylogenetic depth (i.e., Metazoa). Importantly, TIAMMAt revises target domain models to reflect homologous sequence variation using the taxonomic distribution under consideration by the user. TIAMMAt's flexibility to revise any subset of the Pfam database using a user-defined taxonomic pool will make it a valuable tool for future protein evolution studies, particularly when incorporating (or focusing) on nonmodel species.
Oral and periodontal implications of tobacco and nicotine products
Authors: Benjamin W. Chaffee, Elizabeth T. Couch, Manali V. Vora, Richard S. Holliday
Journal: Periodontology 2000 (2021)

Tobacco use contributes to more mortality and morbidity globally than any other behavioral risk factor. Adverse effects do not spare the oral cavity, with many oral diseases more common, and treatments less successful, in the tobacco-using patient. Many of the oral health effects of cigarette smoking are well established, but other forms of tobacco, including cigars and smokeless tobacco, merit dental professionals' attention. Recently, an expanding variety of new or emerging tobacco and/or nicotine products has been brought to market, most prominently electronic cigarettes, but also including heated tobacco and other noncombustible nicotine products. The use of cannabis (marijuana) is increasing and also has risks for oral health and dental treatment. For the practicing periodontist, and all dental professionals, providing sound patient recommendations requires knowledge of the general and oral health implications associated with this wide range of tobacco and nicotine products and cannabis. This review provides an overview of selected tobacco and nicotine products with an emphasis on their implications for periodontal disease risk and clinical management. Also presented are strategies for tobacco use counselling and cessation support that dental professionals can implement in practice.
The Urgent Need for Rigorous Studies of Telehealth for Older Adults Who Are Homebound
Authors: Lauren R. Moo, Andrea Wershof Schwartz
Journal: JAMA Network Open (2021)

Arkers Kwan Ching Wong, PhD, RN; Frances Kam Yuet Wong, PhD, RN; Karen Kit Sum Chow, MSc, RSW; Siu Man Wong, MSc, RSW; Paul Hong Lee, PhD, PStat
Quantifying and Interpreting Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Cancer Control for Advanced Gastroesophageal Cancer Among an Older Population—Reply
Authors: Peter S. Hall, David A. Cairns, Matthew T. Seymour
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Alveolar macrophages and epithelial cells: The art of living together
Authors: Derek Clements, Juliana Idoyaga
Journal: The Journal of Experimental Medicine (2021)

In this issue of JEM, Gschwend et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210745) reveal the indispensable role of alveolar epithelial cells type 2 in controlling the density of alveolar macrophages. This study highlights the intricate crosstalk that lung stroma and macrophages undergo to maintain homeostasis.
Immunologic resilience and COVID-19 survival advantage
Authors: Grace C. Lee, Marcos I. Restrepo, Nathan Harper, Muthu Saravanan Manoharan, Alisha M. Smith, Justin A. Meunier, Sandra Sanchez-Reilly, Aamir Ehsan, Anne P. Branum, Caitlyn Winter, Lauryn Winter, Fabio Jimenez, Lavanya Pandranki, Andrew Carrillo, Graciela L. Perez, Antonio Anzueto, Hanh Trinh, Monica Lee, Joan M. Hecht, Celida Martinez-Vargas, Raj T. Sehgal, Jose Cadena, Elizabeth A. Walter, Kimberly Oakman, Raymond Benavides, Jacqueline A. Pugh, Scott Letendre, Maristella Steri, Valeria Orrù, Edoardo Fiorillo, Francesco Cucca, Alvaro G. Moreira, Nu Zhang, Elizabeth Leadbetter, Brian K. Agan, Douglas D. Richman, Weijing He, Robert A. Clark, Jason F. Okulicz, Sunil K. Ahuja, Mohamed I. Abdalla, Sandra G. Adams, Joseph Agnew, Saleem Ali, Jennifer Barker, Angela Birdwell, Stephen Bradford, Heather Briggs, Judith Marin Corral, Jennifer J. Dacus, Patrick J. Danaher, Scott A. DePaul, Jill Dickerson, Jollynn Doanne, Samantha Elbel, Corina Escamilla, Robert Farrar, David Feldman, Julianne Flynn, Delvina Ford, Joanna D. Foy, Megan Freeman, Samantha Galley, Maritza Garza, Sherraine Gilman, Jennifer Gomez, Varun K. Goyal, Sally Grassmuck, Joshua Hanson, Brande Harris, Gabrielyd Hastings, Audrey Haywood, Cecilia Hinojosa, Tony T. Ho, Teri Hopkins, Pamela Jewell, Thomas B. Johnson, Vasiliki Kotogiannes, Austin C. Lawler, Chadwick S. Lester, Stephanie M. Levine, Haidee V. Lewis, Angel Louder, Charmaine Mainor, Rachel Maldonado, Yvette Martinez, Neil McElligott, Laura Medlin, Myra Mireles, Kathleen Morneau, Samuel B. Munro, Anoop Nambiar, Daniel Nassery, Robert Nathanson, Jane O’Rorke, Cheryl Padgett, Sergi Pascual-Guardia, Marisa Patterson, Rogelio Perez, Robert E. Phillips, Patrick B. Polk, Michael A. Pomager, Kristy J. Preston, Kevin C. Proud, Michelle Rangel, Temple A. Ratcliffe, Renee L. Reichelderfer, Evan M. Renz, Jeanette Ross, Teresa Rudd, Maria E. Sanchez, Tammy Sanders, Kevin C. Schindler, David Schmit, Claudio Solorzano, Nilam Soni, Win S. Tam, Edward J. Tovar, Anna R. Tyler, Anjuli Vasquez, Maria C. Veloso, Steven G. Venticinque, Jorge A. Villalpando, Melissa Villanueva, Lauren Villegas, Andrew Wallace, Emily Wang, Andreia Williamson, Sadie A. Trammell Velasquez, Andrea Yunes, Katharine H. Zentner
Journal: Journal of Allergy and Clinical Immunology (2021)

The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR).
Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex
Authors: Nida Haider, Jasmin Lebastchi, Ashok Kumar Jayavelu, Thiago M. Batista, Hui Pan, Jonathan M. Dreyfuss, Ivan Carcamo-Orive, Joshua W. Knowles, Matthias Mann, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2021)

Insulin resistance is present in one-quarter of the general population, predisposing these people to a wide range of diseases. Our aim was to identify cell-intrinsic determinants of insulin resistance in this population using induced pluripotent stem cell–derived (iPSC–derived) myoblasts (iMyos). We found that these cells exhibited a large network of altered protein phosphorylation in vitro. Integrating these data with data from type 2 diabetic iMyos revealed critical sites of conserved altered phosphorylation in IRS-1, AKT, mTOR, and TBC1D1 in addition to changes in protein phosphorylation involved in Rho/Rac signaling, chromatin organization, and RNA processing. There were also striking differences in the phosphoproteome in cells from men versus women. These sex-specific and insulin-resistance defects were linked to functional differences in downstream actions. Thus, there are cell-autonomous signaling alterations associated with insulin resistance within the general population and important differences between men and women, many of which also occur in diabetes, that contribute to differences in physiology and disease.
Intraarticular versus systemic administration of etanercept in antigen-induced temporomandibular joint arthritis in the rabbit
Authors: KD Kristensen, P Stoustrup, A Kueseler, TK Pedersen, PM Cattaneo, J Gelineck, EM Hauge, JR Nyengaard, T Herlin
Journal: Annals of the Rheumatic Diseases (2007)
Integrated prognostic and histogenomic justification of stage-directed therapy for single large hepatocellular carcinoma: a Korean nationwide registry study
Authors: Jihyun An, Ha Il Kim, Bora Oh, Yoo-Jin Oh, Ji-Hye Oh, Wonkyung Kim, Chang Ohk Sung, Ju Hyun Shim
Journal: Gut (2021)

Early diagnosis of hepatocellular carcinoma (HCC) increases the chances of curative treatment and long-term survival.1 2 We read with interest the analytical study by Zhang et al presenting nomogram models predicting recurrence-free survival and guiding therapeutic decisions in a patient-tailored approach to treatment of early-stage HCC within Milan criteria.3 The refined Barcelona Clinic Liver Cancer (BCLC) guidelines no longer limit the size of solitary nodules in the definition of stage A HCC. However, there is continuing debate about the need to restrict the maximum diameter of single HCCs to inside the Milan limit (≤5 cm).4–6 In a survival-based confirmatory investigation, we primarily used a Korean nationwide cancer registry database of 10 510 new HCC cases. These cases were randomly sampled and registered in 54 hospitals, and investigated by the Korea Liver Cancer Study Group and the governmental organisation of the Korea Central Cancer Registry in 2008–2014. We included in the final analysis 1610 asymptomatic HCC subjects with BCLC stage A or stage B who had preserved liver function levels referred to as Child-Pugh class A without ascites and who initially received standard treatments as per BCLC stage (online supplemental figure S1).4 The population was divided into four groups: group 1, stage A disease fulfilling Milan criteria undergoing liver resection or transplantation, or local ablation; group 2, potential stage A with single nodules >5 cm undergoing resection; group 3, potential stage B with single nodules >5 cm undergoing transarterial chemoembolisation (TACE); and group 4, stage B undergoing TACE. Five-year overall survival (OS) rates were significantly different across the four groups (p<0.001; figure 1A). The …
Early Menopause and Cardiovascular Disease Risk in Women With or Without Type 2 Diabetes: A Pooled Analysis of 9,374 Postmenopausal Women
Authors: Yilin Yoshida, Zhipeng Chen, Robin L. Baudier, Marie Krousel-Wood, Amanda H. Anderson, Vivian A. Fonseca, Franck Mauvais-Jarvis
Journal: Diabetes Care (2021)

Early menopause may be associated with higher cardiovascular disease (CVD) risk. Type 2 diabetes mellitus (T2DM), coupled with early menopause, may result in even greater CVD risk in women. We examined CVD risk in women with early compared with normal-age menopause, with and without T2DM overall, and by race/ethnicity.
Eosinophil morphology in the reactive eosinophilia of Hodgkin lymphoma
Authors: Wenchee Siow, Francis Matthey, Barbara J. Bain
Journal: American Journal of Hematology (2021)

A 35-year-old woman with stage IVB refractory Hodgkin lymphoma, mixed cell type, who had initially presented 18 months earlier, developed marked leukocytosis with striking eosinophilia with disease progression. The eosinophils showed notable morphological abnormalities (all images, ×100 objective) including degranulation, vacuolation, granules that were smaller than normal and granules in mature eosinophils that had basophilic staining characteristics. There were some hyperlobated nuclei, some non-segmented nuclei (top right) and some ring nuclei (bottom right). Striking eosinophilia with marked cytological abnormalities often gives rise to the suspicion of eosinophilic leukemia. However it is important to be aware that marked cytological abnormalities can also occur when eosinophilia is reactive. A systematic study comparing reactive and neoplastic cases reported that, although there was a tendency to more marked morphological abnormalities in those with clonal neoplastic eosinophils, there was considerable overlap.1 The feature most strongly associated with neoplasia, particularly because of its association with inv(16), was the presence of immature basophilic granules but as demonstrated in this patient, even this is not specific for neoplasia. The authors declare no conflict of interest.
Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk
Authors: Anita M. van den Hoek, Jelle C.B.C. de Jong, Nicole Worms, Anita van Nieuwkoop, Marijke Voskuilen, Aswin L. Menke, Serene Lek, Martien P.M. Caspers, Lars Verschuren, Robert Kleemann
Journal: Metabolism (2021)

Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5-7%) can already have a beneficial effect on NASH. However, the underlying molecular mechanisms of exercise and diet interventions remain largely elusive, and it is unclear whether they exert their health effects via similar or different pathways.Ldlr-/-.Leiden mice received a high fat diet (HFD) for 30 weeks to establish a severe state of NASH/fibrosis with simultaneous atherosclerosis development. Groups of mice were then either left untreated (control group) or were treated for 20 weeks with exercise (running wheel), diet change (switch to a low fat chow diet) or the combination thereof. The liver and distant organs including heart, white adipose tissue (WAT) and muscle were histologically examined. Comprehensive transcriptome analysis of liver, WAT and muscle revealed the organ-specific effects of exercise and diet and defined the underlying pathways.Exercise and dietary change significantly reduced body weight, fat mass, adipocyte size and improved myosteatosis and muscle function with additive effects of combination treatment. WAT inflammation was significantly improved by diet change, tended to be reduced with exercise, and combination therapy had no additive effect. Hepatic steatosis and inflammation were almost fully reversed by exercise and diet change, while hepatic fibrosis tended to be improved with exercise and was significantly improved with diet change. Additive effects for the combination therapy were shown for liver steatosis and associated liver lipids, and atherosclerosis, but not for hepatic inflammation and fibrosis. Pathway analysis revealed complementary effects on metabolic pathways and lipid handling processes, thereby substantiating the added value of combined lifestyle treatment.Exercise, diet change and the combination thereof can reverse established NASH/fibrosis in obese Ldlr-/-.Leiden mice. In addition, the lifestyle interventions had beneficial effects on atherosclerosis, WAT inflammation and muscle function. For steatosis and other parameters related to adiposity or lipid metabolism, exercise and dietary change affected more distinct pathways that acted complementary when the interventions were combined resulting in an additive effect for the combination therapy on important endpoints including NASH and atherosclerosis. For inflammation, exercise and diet change shared several underlying pathways resulting in a net similar effect when the interventions were combined.
Corrigendum to “Celastrol nanoemulsion induces immunogenicity and downregulates PD-L1 to boost abscopal effect in melanoma therapy” [Biomaterials 269 (2021) 120604]
Authors: Nasha Qiu, Yun Liu, Qi Liu, Yanzuo Chen, Limei Shen, Mengying Hu, Xuefei Zhou, Youqing Shen, Jianqing Gao, Leaf Huang
Journal: Biomaterials (2021)
Comparison of Classification of Indications for Allogeneic and Autologous Transplant for Adults in ASTCT Guidelines and Evidence Available in Published Literature
Authors: Myung S. Kim, Johnny Cai, Ashray Maniar, Thomas Kartika, Alyson Haslam, Vinay Prasad
Journal: JAMA Internal Medicine (2021)

Hematopoietic stem cell transplantation (HCT) is a common procedure, with 22 000 cases performed in the US per year at a total cost of 1.3 billion dollars per year. 1 To our knowledge, an evaluation of the quality and level of evidence of society guidelines in HCT has not been performed.In the 1980s, oncologists adopted autologous stem cell transplant for metastatic breast cancer following high-dose chemotherapy based on uncontrolled studies only to find no clinical benefit in randomized clinical trials (RCTs). 2,3In this study, we seek to quantify the number of RCTs in the literature for each indication by disease type and status.We then describe the published literature of the past 5 years. Methods |We reviewed evidence according to the American Society for Transplantation and Cellular Therapy (ASTCT) 2020 guidelines 4 for indications with S (standard of care) or C (clinical evidence available, standard of care) level recommendations for hematologic malignant diseases.Randomized clinical trials published in peer-reviewed journals were identified using the Ovid MEDLINE database.All publications under relevant medical subject headings (MeSH) were combined with results from keyword "transplantation" using the Boolean operator "AND."We limited the search to RCTs.We reviewed all articles from 2016 to present using Google Scholar by searching disease type and keyword "transplantation" (eTables 1 and 2 in the Supplement).We reviewed the first 100 results of each search.This study was exempt from institutional review board approval because it involved publicly available data and did not involve individual patient data.Results | In total there are 103 recommendations in the ASTCT 2020 guidelines for allogeneic transplant and autologous transplant. 4For allogeneic transplant, there are 43 S indications and 27 C indications.For autologous transplant, there are 23 S indications and 18 C indications.There were 4 RCTs for
Work Loss in Patients With Celiac Disease: A Population-based Longitudinal Study
Authors: Soran R. Bozorg, Jonas Söderling, Åsa H. Everhov, Benjamin Lebwohl, Peter H.R. Green, Martin Neovius, Jonas F. Ludvigsson, Karl Mårild
Journal: Clinical Gastroenterology and Hepatology (2021)

Celiac disease (CD) affects around 1% of the population worldwide. Data on work disability in patients with CD remain scarce. We estimated work loss in patients with CD, including its temporal relationship to diagnosis.Through biopsy reports from Sweden's 28 pathology departments, we identified 16,005 working-aged patients with prevalent CD (villus atrophy) as of January 1, 2015, and 4936 incident patients diagnosed with CD in 2008 to 2015. Each patient was matched to up to 5 general-population comparators. Using nationwide social insurance registers, we retrieved prospectively recorded data on compensation for sick leave and disability leave to assess work loss in patients and comparators.In 2015, patients with prevalent CD had a mean of 42.5 lost work days as compared with 28.6 in comparators (mean difference, 14.7; 95% confidence interval [CI], 13.2-16.2), corresponding to a relative increase of 49%. More than one-half of the work loss (60.1%) in patients with CD was derived from a small subgroup (7%), whereas 75.4% had no work loss. Among incident patients, the annual mean difference between patients and comparators was 8.0 days (range, 5.4-10.6 days) of lost work 5 years before CD diagnosis, which grew to 13.7 days (range, 9.1-18.3 days) 5 years after diagnosis. No difference in work loss was observed between patients with or without mucosal healing at follow-up.Patients with CD lost more work days than comparators before their diagnosis, and this loss increased after diagnosis. Identifying patients with an increased risk of work loss may serve as a target to mitigate work disability, and thereby reduce work loss, in patients with CD.
High expression of tenascin-C extra domains, markers of angiogenesis, in human lung cancer
Authors: Sven Hillinger, Michela Silacci, Stephan Arni, Simon Brack, Walter Weder, Dario Neri
Journal: Cancer Research (2007)

191  Background:  Tumor-associated extracellular matrix molecules are isoforms of proteins with a wide distribution in normal adult tissues, such as fibronectin and tenascin. Large Tenascin-C isoforms are present in almost all normal adult tissues but are upregulated in fetal, regenerating, and neoplastic tissues. In this study we investigated the expression of three tenascin isoforms in tumor tissue samples from lung cancer patients to evaluate the diagnostic and therapeutic value for clinical applications.  Methods:  In total, 35 corresponding tissue samples (tumor and normal lung tissue of the same patient) have been analyzed by immunohistochemistry using three different human monoclonal antibodies to domains A1 (F16), C (G11) and D (P12). All tumor specimens have been non-small cell lung cancer types.  Results:  Three isoforms G11, F16 and P12 have exhibited a very intense staining of different histological types of lung cancer. More than 80% of squamous cell carcinomas, adenocarcinomas and large cell carcinoma samples have been positively stained. None of the corresponding normal lung tissue specimens showed an expression of either tenascin domains.  Conclusions:  The results show that tenascin-C isoforms are highly expressed around the neovasculature and in the stroma of the majority of non-small cell lung cancers but is undetectable in the normal lung tissue. Therefore these isoforms could represent valuable candidates for the development of antibody based biopharmaceuticals for the treatment of lung cancer.