tbuckley/cabot-search huggingface dataset:
Pathogen diversity, immunity, and the fate of infections: lessons learned from Trypanosoma cruzi human–host interactions
Authors: Luísa M D Magalhães, Kenneth J Gollob, Bianca Zingales, Walderez O Dutra
Journal: The Lancet Microbe (2022)

The complexity of host–pathogen interactions often leads to distinct clinical outcomes upon infection with different pathogen strains. In this Review, we explore the interactions between the highly diverse Trypanosoma cruzi population and the human host. At least 30% of the 7 million individuals with Chagas disease will develop a severe cardiopathy that is among the deadliest heart diseases known. The diversity of the T cruzi population also creates major hurdles for therapy and vaccine development. We also discuss the ecoepidemiological and geographical distribution of T cruzi strains, their susceptibility to treatment, their antigenic diversity, and their effect on the immune response and on disease outcome. Furthermore, we highlight the importance of understanding the T cruzi host–pathogen relationship for guiding new approaches towards development of therapies and vaccines for Chagas disease, and how the information gained by studying this relationship can inspire solutions for other host–pathogen interactions.
55P Potential benefits of extensive genomic analysis in patients with KRAS mutated solid tumors: Concurrent alterations and potential targets
Authors: I.C. Jacobsen, I. Spanggaard, M. Hoejgaard, L. Belcaid, C. Qvortrup, C.W. Yde, A.Y. Schmidt, F.C. Nielsen, G.L. Willemoe, M.S. Dam, U. Lassen, K.S. Rohrberg
Journal: Annals of Oncology (2022)
Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias
Authors: Yan Yi, Shenglei Ge
Journal: Journal of Hematology & Oncology (2022)

Disrupting the methylation of telomeric silencing 1-like (DOT1L)-mediated histone H3 lysine 79 has been implicated in MLL fusion-mediated leukemogenesis. Recently, DOT1L has become an attractive therapeutic target for MLL-rearranged leukemias. Rigorous studies have been performed, and much progress has been achieved. Moreover, one DOT1L inhibitor, EPZ-5676, has entered clinical trials, but its clinical activity is modest. Here, we review the recent advances and future trends of various therapeutic strategies against DOT1L for MLL-rearranged leukemias, including DOT1L enzymatic activity inhibitors, DOT1L degraders, protein-protein interaction (PPI) inhibitors, and combinatorial interventions. In addition, the limitations, challenges, and prospects of these therapeutic strategies are discussed. In summary, we present a general overview of DOT1L as a target in MLL-rearranged leukemias to provide valuable guidance for DOT1L-associated drug development in the future. Although a variety of DOT1L enzymatic inhibitors have been identified, most of them require further optimization. Recent advances in the development of small molecule degraders, including heterobifunctional degraders and molecular glues, provide valuable insights and references for DOT1L degraders. However, drug R&D strategies and platforms need to be developed and preclinical experiments need to be performed with the purpose of blocking DOT1L-associated PPIs. DOT1L epigenetic-based combination therapy is worth considering and exploring, but the therapy should be based on a thorough understanding of the regulatory mechanism of DOT1L epigenetic modifications.
CLASSIFICATION AND IMPLICATIONS OF HEART FAILURE EVENTS FROM THE VICTORIA TRIAL
Authors: G. Michael Felker, Rebecca North, W. Schuyler Jones, Kevin J. Anstrom, Mahesh J. Patel, Javed Butler, Justin A. Ezekowitz, Carolyn S.P. Lam, Christopher M. O’Connor, Lothar Roessig, Adrian F. Hernandez, Paul Wayne Armstrong
Journal: Journal of the American College of Cardiology (2022)
Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer
Authors: Dave J Gibson, Mayenaaz Sidhu, Simon Zanati, David J Tate, Dileep Mangira, Alan Moss, Rajvinder Singh, Luke F Hourigan, Spiro Raftopoulos, Alan Pham, Phil Kostos, M Priyanthi Kumarasinghe, Andrew Ruszkiewicz, Duncan McLeod, Gregor J E Brown, Michael J Bourke
Journal: Gut (2022)

Objective Management of covert submucosal invasive cancer (SMIC) discovered after piecemeal endoscopic mucosal resection (pEMR) of large (&gt;20 mm) non-pedunculated colorectal polyps is challenging. The residual cancer risk is largely unknown. We sought to evaluate this in a large tertiary referral cohort. Design Cases of covert SMIC following pEMR were identified and followed. Oncological outcomes after surgery were divided based on residual intramural cancer, lymph node metastases (LNM) or both. Risk factors for residual intramural cancer and LNM were analysed based on the original pEMR histological variables. Risk parameters were analysed with respect to low and high-risk variables for residual intramural cancer and LNM. Results Among 3372 cases of large non-pedunculated colorectal polyps, 143 cases of covert SMIC (4.2%) were identified. 109 underwent surgical resection. Histological analysis of pEMR histology was available in 98 of 109 (90%) cases. 62 cases (63%) had no residual malignancy. 36 cases had residual malignancy (residual intramural cancer n=24; LNM n=5; both n=7). All cases of residual intramural cancer could be identified by a R1 histological deep margin. Cases with poor differentiation (PD) and/or lymphovascular invasion (LVI) had a high risk of LNM (12/33), with a very low risk without these criteria (&lt;1%; 0/65). Cases at low risk for LNM with R0 deep margin have a low risk of residual intramural cancer (&lt;1%; 0/35). Conclusion The majority of cases of large non-pedunculated colorectal polyps with covert SMIC following pEMR will have no residual malignancy. The risk of residual malignancy can be ascertained from three key variables: PD, LVI and R1 deep margin.
PROGNOSTIC VALUE OF HIGH SENSITIVITY C-REACTIVE PROTEIN AMONG CHRONIC KIDNEY DISEASE PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Davis B. Jones, Carlo Pivato, Davide Cao, Samantha Sartori, Johny Nicolas, Frans Beerkens, Victor Razuk, Daniel Feldman, Mohan Satish, Clayton Snyder, Gennaro Giustino, Prakash Krishnan, Nitin Barman, Joseph M. Sweeny, Usman Baber, George D. Dangas, Samin K. Sharma, Annapoorna Subhash Kini, Roxana Mehran
Journal: Journal of the American College of Cardiology (2022)
Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment
Authors: Hongyu Wu, Hong Yao, Chen He, Yilin Jia, Zheying Zhu, Shengtao Xu, Dahong Li, Jinyi Xu
Journal: Acta Pharmaceutica Sinica B (2022)

Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions. In recent years, molecular glues have been widely used as protein degraders. In addition, however, molecular glues play a variety of vital roles, such as complex stabilization, interactome modulation and transporter inhibition, enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery. Since most molecular glues are identified serendipitously, exploration of their systematic discovery and rational design are important. In this review, representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization, homo-polymerization and hetero-dimerization according to their aggregation modes, and we attempt to elucidate their mechanisms of action. In particular, we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development: starting point, optimization and identification.
FEASIBILITY OF EVALUATING ENDOTHELIAL WALL SHEAR STRESS FROM CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Inge J. van den Hoogen, Jussi Schultz, Jurrien Kuneman, Michiel Alexander De Graaf, Vasileios Kamperidis, Alexander Broersen, J. Wouter Jukema, Antonis Sakellarios, Sotirios Nikopoulos, Savvas Kyriakidis, Katerina K. Naka, Lampros K. Michalis, Dimitrios I. Fotiadis, Teemu Maaniitty, Antti Saraste, Jeroen J. Bax, Juhani M. Knuuti
Journal: Journal of the American College of Cardiology (2022)
EPR22-112: Risk of Prostate Cancer for Metformin Versus Sulphonylurea Monotherapy in Type 2 Diabetes Mellitus: A Propensity Score-Matched Retrospective Cohort Study
Authors: Yan Hiu Athena Lee, Jiandong Zhou, Jeremy Man Ho Hui, Xuejin Liu, Teddy Tai Loy Lee, Kyle Hui, Abraham Ka Chung Wai, Wing Tak Wong, Tong Liu, Kenrich Ng, Sharen Lee, Edward Christopher Dee, Jeffrey Shi Kai Chan, Qingpeng Zhang, Gary Tse
Journal: Journal of the National Comprehensive Cancer Network (2022)

"EPR22-112: Risk of Prostate Cancer for Metformin Versus Sulphonylurea Monotherapy in Type 2 Diabetes Mellitus: A Propensity Score-Matched Retrospective Cohort Study" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Rate of pancreatic cancer following a negative endoscopic ultrasound and associated factors
Authors: Dominic King, Umair Kamran, Amandeep Dosanjh, Ben Coupland, Jemma Mytton, John S. Leeds, Manu Nayar, Prashant Patel, Kofi W. Oppong, Nigel J. Trudgill
Journal: Endoscopy (2022)

BACKGROUND : Data are limited regarding pancreatic cancer diagnosed following a pancreaticobiliary endoscopic ultrasound (EUS) that does not diagnose pancreatic cancer. We have studied the frequency of, and factors associated with, post-EUS pancreatic cancer (PEPC) and 1-year mortality. METHODS : Between 2010 and 2017, patients with pancreatic cancer and a preceding pancreaticobiliary EUS were identified in a national cohort using Hospital Episode Statistics. Patients with a pancreaticobiliary EUS 6-18 months before a later pancreatic cancer diagnosis were the PEPC cases; controls were those with pancreatic cancer diagnosed within 6 months of pancreaticobiliary EUS. Multivariable logistic regression models examined the factors associated with PEPC and a Cox regression model examined factors associated with 1-year cumulative mortality. RESULTS : 9363 pancreatic cancer patients were studied; 93.5 % identified as controls (men 53.2 %; median age 68 [interquartile range (IQR) 61-75]); 6.5 % as PEPC cases (men 58.2 %; median age 69 [IQR 61-77]). PEPC was associated with older age (≥ 75 years compared with &lt; 65 years, odds ratio [OR] 1.42, 95 %CI 1.15-1.76), increasing co-morbidity (Charlson co-morbidity score &gt; 5, OR 1.90, 95 %CI 1.49-2.43), chronic pancreatitis (OR 3.13, 95 %CI 2.50-3.92), and diabetes mellitus (OR 1.58, 95 %CI 1.31-1.90). Metal biliary stents (OR 0.57, 95 %CI 0.38-0.86) and EUS-FNA (OR 0.49, 95 %CI 0.41-0.58) were inversely associated with PEPC. PEPC was associated with a higher cumulative mortality at 1 year (hazard ratio 1.12, 95 %CI 1.02-1.24), with only 14 % of PEPC patients (95 %CI 12 %-17 %) having a surgical resection, compared with 21 % (95 %CI 20 %-22 %) of controls. CONCLUSIONS : PEPC occurred in 6.5 % of patients and was associated with chronic pancreatitis, older age, more co-morbidities, and specifically diabetes mellitus. PEPC was associated with a worse prognosis and lower surgical resection rates.
“THE WEEKEND EFFECT:” A NATIONWIDE ANALYSIS OF DIFFERENCE IN OUTCOMES AMONG PATIENTS WITH NON-ST ELEVATION MYOCARDIAL INFARCTION ADMITTED DURING THE WEEKEND
Authors: Rezwan F. Munshi, James Pellegrini, Narois Nehru, Aditya Iyer, Kashyap Shah, Samarthkumar Thakkar, Amgad N. Makaryus, Ofek Hai, Roman Zeltser
Journal: Journal of the American College of Cardiology (2022)
Where Americans Die — Is There Really “No Place Like Home”?
Authors: Melissa W. Wachterman, Elizabeth A. Luth, Robert S. Semco, Joel S. Weissman
Journal: New England Journal of Medicine (2022)

Interview with Dr. Melissa Wachterman on cultural factors and financial incentives driving where people in the United States choose to die. (10:09)Download The perception that a good death is one that occurs at home is ingrained in our cultural and social history. But palliative care clinicians have begun to question this idea. What is needed is high-quality end-of-life care that aligns with individual goals and needs.
Biomarker analysis from CheckMate 214: nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma
Authors: Robert J Motzer, Toni K Choueiri, David F McDermott, Thomas Powles, Yann-Alexandre Vano, Saurabh Gupta, Jin Yao, Celine Han, Ron Ammar, Simon Papillon-Cavanagh, Shruti S Saggi, M Brent McHenry, Petra Ross-Macdonald, Megan Wind-Rotolo
Journal: Journal for ImmunoTherapy of Cancer (2022)

The phase 3 CheckMate 214 trial demonstrated higher response rates and improved overall survival with nivolumab plus ipilimumab versus sunitinib in first-line therapy for advanced clear-cell renal cell carcinoma (RCC). An unmet need exists to identify patients with RCC who are most likely to benefit from treatment with nivolumab plus ipilimumab.In exploratory analyses, pretreatment levels of programmed death ligand 1 were assessed by immunohistochemistry. Genomic and transcriptomic biomarkers (including tumor mutational burden and gene expression signatures) were also investigated.Biomarkers previously associated with benefit from immune checkpoint inhibitor-containing regimens in RCC were not predictive for survival in patients with RCC treated with nivolumab plus ipilimumab. Analysis of gene expression identified an association between an inflammatory response and progression-free survival with nivolumab plus ipilimumab.The exploratory analyses reveal relationships between molecular biomarkers and provide supportive data on how the inflammation status of the tumor microenvironment may be important for identifying predictive biomarkers of response and survival with combination immunotherapy in patients with RCC. Further validation may help to provide biomarker-driven precision treatment for patients with RCC.
Efficacy and safety of a universal influenza A vaccine (MVA-NP+M1) in adults when given after seasonal quadrivalent influenza vaccine immunisation (FLU009): a phase 2b, randomised, double-blind trial
Authors: Thomas G Evans, Louise Bussey, Elizabeth Eagling-Vose, Kathryn Rutkowski, Chris Ellis, Chris Argent, Paul Griffin, Joshua Kim, Susan Thackwray, Sepehr Shakib, Julia Doughty, John Gillies, Jian Wu, Julian Druce, Melinda Pryor, Sarah Gilbert
Journal: The Lancet Infectious Diseases (2022)
Long-term evolution of humoral immune response after SARS-CoV-2 infection
Authors: Elisa Teyssou, Karen Zafilaza, Sophie Sayon, Stéphane Marot, Margot Dropy, Cathia Soulie, Basma Abdi, Florence Tubach, Pierre Hausfater, Anne-Geneviève Marcelin, David Boutolleau
Journal: Clinical Microbiology and Infection (2022)
Comments on Surgeon-Patient Sex Concordance and Postoperative Outcomes—Reply
Authors: Christopher J. D. Wallis, Angela Jerath, Raj Satkunasivam
Journal: JAMA Surgery (2022)

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 Surgery 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 Surgery journal
Assessment of SARS-CoV-2 Mu Variant Emergence and Spread in Colombia
Authors: Juan Hernandez-Ortiz, Andres Cardona, Karl Ciuoderis, Francisco Averhoff, Maria-Angelica Maya, Gavin Cloherty, Jorge E. Osorio
Journal: JAMA Network Open (2022)

e The median age was 39 years (range, 0-99 years); the mean (SD) age was 42.4 (20.
Health Needs and Use of Services Among Children with Developmental Disabilities — United States, 2014–2018
Authors: Mary E. Cogswell, Eric Coil, Lin H. Tian, Sarah C. Tinker, A. Blythe Ryerson, Matthew J. Maenner, Catherine E. Rice, Georgina Peacock
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Developmental delays, disorders, or disabilities (DDs) manifest in infancy and childhood and can limit a person's function throughout life* (1-3). To guide strategies to optimize health for U.S. children with DDs, CDC analyzed data from 44,299 participants in the 2014-2018 National Health Interview Survey (NHIS). Parents reported on 10 DDs,† functional abilities, health needs, and use of services. Among the approximately one in six (17.3%) U.S. children and adolescents aged 3-17 years (hereafter children) with one or more DDs, 5.7% had limited ability to move or play, 4.7% needed help with personal care, 4.6% needed special equipment, and 2.4% received home health care, compared with ≤1% for each of these measures among children without DDs. Children with DDs were two to seven times as likely as those without DDs to have taken prescription medication for ≥3 months (41.6% versus 8.4%), seen a mental health professional (30.6% versus 4.5%), a medical specialist (26.0% versus 12.4%), or a special therapist, such as a physical, occupational, or speech therapist, (25.0% versus 4.5%) during the past year, and 18 times as likely to have received special education or early intervention services (EIS) (41.9% versus 2.4%). These percentages varied by type of disability and by sociodemographic subgroup. DDs are common, and children with DDs often need substantial health care and services. Policies and programs that promote early identification of children with developmental delays and facilitate increased access to intervention services can improve health and reduce the need for services later in life.§ Sociodemographic inequities merit further investigation to guide public health action and ensure early and equitable access to needed care and services.
Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance
Authors: Amr R. Elhamamsy, Brandon J. Metge, Heba A. Alsheikh, Lalita A. Shevde, Rajeev S. Samant
Journal: Cancer Research (2022)

Abstract Ribosomes are a complex ensemble of rRNA and ribosomal proteins that function as mRNA translation machines. Ribosome biogenesis is a multistep process that begins in the nucleolus and concludes in the cytoplasm. The process is tightly controlled by multiple checkpoint and surveillance pathways. Perturbations in these checkpoints and pathways can lead to hyperactivation of ribosome biogenesis. Emerging evidence suggests that cancer cells harbor a specialized class of ribosomes (onco-ribosomes) that facilitates the oncogenic translation program, modulates cellular functions, and promotes metabolic rewiring. Mutations in ribosomal proteins, rRNA processing, and ribosome assembly factors result in ribosomopathies that are associated with an increased risk of developing malignancies. Recent studies have linked mutations in ribosomal proteins and aberrant ribosomes with poor prognosis, highlighting ribosome-targeted therapy as a promising approach for treating patients with cancer. Here, we summarize various aspects of dysregulation of ribosome biogenesis and the impact of resultant onco-ribosomes on malignant tumor behavior, therapeutic resistance, and clinical outcome. Ribosome biogenesis is a promising therapeutic target, and understanding the important determinants of this process will allow for improved and perhaps selective therapeutic strategies to target ribosome biosynthesis.
Associations of Internalized Skin Bias With Age, Adverse Psychopathology, and Health-Related Quality of Life Among Patients With Hidradenitis Suppurativa
Authors: Melissa Butt, Andrea Rigby, Douglas L. Leslie, Galen T. Foulke, Alexandra Flamm, Joslyn S. Kirby, Vernon M. Chinchilli
Journal: JAMA Dermatology (2022)

<h3>Importance</h3> Hidradenitis suppurativa (HS) is a chronic autoinflammatory disease that is highly associated with affective disorders such as depression and anxiety. Recent studies have shown that patients with HS may also endorse high levels of internalized skin bias (ISB). This redirection of skin disease−related social stigma toward oneself may also play an important role in the associations between adverse psychopathology (eg, depression, anxiety) and health-related quality of life (HRQOL). <h3>Objectives</h3> To evaluate the associations of ISB with other core outcomes in HS and to determine if ISB may mediate the associations between adverse psychopathological outcomes and impaired HRQOL. <h3>Design, Setting, and Participants</h3> A cross-sectional study of adult patients with HS recruited from 1 academic medical center as well as through virtual social and recruitment networks. Eligible participants completed an online survey comprised of 4 survey instruments along with demographic and disease history information from April 1, 2021, to July 15, 2021. <h3>Main Outcomes and Measures</h3> Measures included the Internalized Skin Bias Questionnaire (ISBQ), Burns Anxiety Inventory, the Beck Depression Inventory−II, the Hidradenitis Suppurativa Quality of Life (HiSQOL) instrument, along with demographic and disease history information. The primary outcome was HRQOL as measured by the HiSQOL. Data were analyzed in July through August 2021. <h3>Results</h3> The survey was completed by 230 of 279 patients (82.4%; mean [SD] age, 39.2 [11.2] years; 209 [90.9%] identified as female, 203 [88.7%] as not Hispanic, 178 [77.7%] as White). Depression and anxiety were shown to be a substantial burden in this sample, with 56.5% of participants' scores qualifying for moderate or greater anxiety and 45.7% moderate or greater depression. The mean (SD) HRQOL scores were moderately high at 34.5 (16.7), indicating strong levels of impairment. There was a moderate correlation between ISBQ score and depression (<i>r</i> = 0.67); and fair correlations with HRQOL (<i>r</i> = 0.52) and anxiety (<i>r</i> = 0.56). Therefore, ISB appears to positively mediate the associations between depression and anxiety (estimated proportions of total effect that were mediated, 38.7% and 24.9%, respectively) and HRQOL. After controlling for age, disease severity, and disease duration, both ISB and anxiety were positive predictors of impaired HRQOL. <h3>Conclusions and Relevance</h3> This cross-sectional study found that ISB was associated with adverse psychopathology and impaired HRQOL in patients with HS. Furthermore, ISB appears to mediate the associations of depression and anxiety with HRQOL. Future studies are needed to design interventions targeted at addressing adverse psychopathology associated with ISB and improving HRQOL and well-being for patients with HS.