tbuckley/cabot-search huggingface dataset:
Abstract P089: Fitness and Fatness Are Both Associated With Cardiometabolic Health in 8-10 Year Old New Zealand Children
Authors: Lee Stoner, Nicholas Castro, Paula Skidmore, Sally Lark, James Faulkner, Michaelle Williams
Journal: Circulation (2018)

Introduction: In adults, low cardiorespiratory fitness (CRF) and overweight-obesity are associated with greater cardiometabolic disease risk. However, the association between measures of CRF and overweight-obesity upon cardiometabolic risk in youth, particularly pre-adolescents, is less clear. Further, previous studies in children have predominantly examined the relationships between CRF and overweight-obesity upon individual cardiometabolic risk factors. The clustering of cardiometabolic risk factors has been recognized for over two decades, including in young children. Hypothesis: We tested the null hypothesis of no association between clustered cardiometabolic risk factors and high CRF or overweight-obesity. Methods: This cross-sectional study recruited 392 children (50% F) aged 8-10 years from three representative sample sites across New Zealand. Overweight-obesity was classified according to 2007 WHO criteria for Body Mass Index. CRF was estimated using a shuttle run test, and high CRF was categorized as a maximum oxygen uptake exceeding 35 ml/kg/min in girls, and 42 ml/kg/min in boys. Eleven traditional and novel cardiometabolic risk factors were measured: peripheral blood pressures, central systolic blood pressure, heart rate, augmentation index, fasting total cholesterol, high density lipoproteins, low density lipoproteins, triglycerides, serum glucose, and glycosylated haemoglobin. Principal component analysis identified underlying cardio-metabolic factors, and a 2-way (high fitness, overweight-obese) analysis of co-variance was used to determine associations between cardio-metabolic risk factors with fitness and overweight-obesity. Covariates were: age, sex, ethnicity, socio-economic status. Results: Principle component analysis revealed four underling factors: blood pressure, cholesterol, vascular, and carbohydrate-metabolism. Using these factors, a cumulative risk score was also calculated. Only high CRF (P=0.001, Eta=0.028) was significantly associated with the blood pressure factor. Only overweight-obesity associated with vascular (P=0.010, Eta=0.018) and carbohydrate-metabolism (P=0.005, Eta=0.021) factors. Neither high fitness (p=0.728) nor overweight-obesity (P=0.121) significantly associated with cholesterol. For the cumulative risk score, there was an interaction effect (P=0.038, Eta=0.012). High CRF improved cardiometabolic risk in overweight-obese children (P=0.006, Eta=0.02), but not in normal weight children. Conversely, being overweight-obese increased cardiometabolic health risk in children with low fat levels (P&lt;0.001, Eta=0.039), but not in high fit children. Conclusions: In pre-adolescent children, fitness and fatness associate with different cardio-metabolic risk. With regards to overall cardio-metabolic risk, high fitness may protect against overweight-obesity.
Workload, setting of clinics often far from ideal
Authors: T. F. Kirn
Journal: JAMA (1988)

THE PRAIRIE HOUSE is an old mansion on a street that years ago was lined with what then were Chicago's most expensive homes. When the heyday of the mansions was over, the warehouses and meat-packing plants moved in, only to become casualties in turn of the invention of the refrigerated railroad car. Today, the streets are strewn with broken glass and even the big commercial buildings stand empty. Prairie House, which is run by Substance Abuse Services, Inc, is typical of methadone clinics. It stands in a neighborhood so desolate that the rent is cheap and there is no one around to oppose the clinic's presence. Right now, it is handling patients from another clinic as well—one that lost its lease. Four hundred thirty patients are being treated. The facility is overcrowded, but fortunately no patients were lost when the other clinic was forced to move. Willie McCullough has been
High plasma and lingual uroguanylin as potential contributors to changes in food preference after sleeve gastrectomy
Authors: Gema Frühbeck, Sara Becerril, Marina Martín, Beatriz Ramírez, Víctor Valentí, Rafael Moncada, Victoria Catalán, Javier Gómez-Ambrosi, Camilo Silva, María A. Burrell, Javier Escalada, Amaia Rodríguez
Journal: Metabolism (2022)
Reply to Eoin Dinneen, Jon Oxley, and Greg Shaw’s Letter to the Editor re: Bernardo Rocco, Luca Sarchi, Simone Assumma, et al. Digital Frozen Sections with Fluorescence Confocal Microscopy During Robot-assisted Radical Prostatectomy: Surgical Technique. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2021.03.021
Authors: Bernardo Rocco, Alessia Cimadamore, Maria Chiara Sighinolfi, Simone Assumma, Rodolfo Montironi
Journal: European Urology (2021)
FDA Approval Summary: Pralsetinib for the Treatment of Lung and Thyroid Cancers With <i>RET</i> Gene Mutations or Fusions
Authors: Janice Kim, Diana Bradford, Erin Larkins, Lee H. Pai-Scherf, Somak Chatterjee, Pallavi S. Mishra-Kalyani, Emily Wearne, Whitney S. Helms, Amal Ayyoub, Youwei Bi, Jielin Sun, Rosane Charlab, Jiang Liu, Hong Zhao, Dun Liang, Soma Ghosh, Reena Philip, Richard Pazdur, Marc R. Theoret, Julia A. Beaver, Harpreet Singh
Journal: Clinical Cancer Research (2021)

Abstract The FDA granted accelerated approval for pralsetinib on September 4, 2020 for non–small cell lung cancer (NSCLC) and December 1, 2020 for thyroid cancer, for: (i) adult patients with metastatic RET fusion–positive NSCLC, (ii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, and (iii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate). Approval was based on the results of a multicenter, open-label, multi-cohort clinical trial (ARROW, NCT03037385), demonstrating substantial overall response rates (ORR) and durable responses in patients with RET-altered tumors. ORRs within the approved patient populations ranged from 57% [95% confidence interval (CI), 46–68] in patients with RET fusion–positive NSCLC previously treated with platinum chemotherapy to 89% (95% CI, 52–100) in patients with RET fusion–positive thyroid cancer, with response duration of at least 6 months in most responders. The product label includes warnings and precautions for pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, tumor lysis syndrome, risk of impaired wound healing, and embryo-fetal toxicity. This article summarizes the major considerations during FDA review leading to the approval of pralsetinib.
Beta blockade is tolerated and improves cardiac function in elderly heart failure patients Guillermo B. Clintron, Juan M. Aranda, Barry H. Greenberg, Ming Heng, Dale G. Renlund, Surai Thaneemit0Chen, Heidi Krause-Steinrauf, for the BEST Investigators. VA Medical Center, Tampa, FL, University of South Florida, Tampa, FL
Journal: Journal of the American College of Cardiology (2001)
A systematic review of post-transplant lymphoproliferative disorder after lung transplant.
Authors: Mobeen Zaka Haider, Zarlakhta Zamani, Fnu Kiran, Hasan Mehmood Mirza, Muhammad Taqi, Hafsa Shahid, Deepak Kumar, Karun Neupane, Yousra Khalid, Mohsin Sheraz Mughal, Muhammad Salman Faisal, Muhammad Umair Mushtaq, Faiz Anwer
Journal: Journal of Clinical Oncology (2021)

e19046 Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. This study aims to explore the association of PTLD diagnosed after lung transplant with infectious agents and immunosuppression regimen, explore types of PTLD, and their outcome. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and included five studies. Results: We analyzed data from five studies, n=13,643 transplant recipients with n=287 (2.10%) developed PTLD. Four studies showed that 32/63 (51%) PTLD patients were male and 31 (49%) were female. Three studies reported 53/55 (96.4%) patients were EBV positive at PTLD diagnosis. Courtwright. et al, reported that 217/224 (97%) PTLD was associated with either EBV positive donor or recipient. Four studies showed that the monomorphic B cell type 48/63 (76%) was the most common histological type of PTLD diagnosed with DLBCL the most common subtype 31/48 (64.6%). Data from 3 studies showed that the onset of PTLD following lung transplant varies with a median duration of 18.3 months (45 days to 20.2 years). Three studies showed that 26/55 (47.3%) patients had early-onset (≤ 1 yr of Tx) and 29/55 (52.7%) patients had late-onset PTLD (&gt; 1 yr of Tx). Management of PTLD included a reduction in immunosuppression including corticosteroids, CNI, purine synthesis inhibitors, Rituximab, and chemotherapeutic agents. Three studies showed a mortality rate of 30/45 (66.7%) and 13/30 (43.3%) deaths were PTLD related. Conclusions: Our review concludes that PTLD is a serious complication, only 2% of lung transplant recipients developed PTLD. EBV seropositivity is the most factor associated with PTLD diagnosis. Monomorphic PTLD was reported as the most common type in the adult population and no association between gender and PTLD was found. The analysis shows that there is a slightly lower incidence of early (≤ 1 yr of Tx) than late-onset (&gt; 1 yr of Tx) PTLD. Table 1 PTLD after a Lung transplant in adults - a review. [Table: see text]
Optical substrates for drug-metabolizing enzymes: Recent advances and future perspectives
Authors: Qiang Jin, JingJing Wu, Yue Wu, Hongxin Li, Moshe Finel, Dandan Wang, Guangbo Ge
Journal: Acta Pharmaceutica Sinica B (2022)

Drug-metabolizing enzymes (DMEs), a diverse group of enzymes responsible for the metabolic elimination of drugs and other xenobiotics, have been recognized as the critical determinants to drug safety and efficacy. Deciphering and understanding the key roles of individual DMEs in drug metabolism and toxicity, as well as characterizing the interactions of central DMEs with xenobiotics require reliable, practical and highly specific tools for sensing the activities of these enzymes in biological systems. In the last few decades, the scientists have developed a variety of optical substrates for sensing human DMEs, parts of them have been successfully used for studying target enzyme(s) in tissue preparations and living systems. Herein, molecular design principals and recent advances in the development and applications of optical substrates for human DMEs have been reviewed systematically. Furthermore, the challenges and future perspectives in this field are also highlighted. The presented information offers a group of practical approaches and imaging tools for sensing DMEs activities in complex biological systems, which strongly facilitates high-throughput screening the modulators of target DMEs and studies on drug/herb‒drug interactions, as well as promotes the fundamental researches for exploring the relevance of DMEs to human diseases and drug treatment outcomes.
An Introduction to Clinical Perimetry.
Journal: JAMA (1928)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Cancer Etiology and Prevention Principle: “1 + X”
Authors: Hui Liu, Zigang Dong
Journal: Cancer Research (2021)

Abstract Cancer was previously thought to be an inevitable aspect of human health with no effective treatments. However, the results of in-depth cancer research suggest that most types of cancer may be preventable. Therefore, a comprehensive understanding of the disparities in cancer burden caused by different risk factors is essential to inform and improve cancer prevention and control. Here, we propose the cancer etiology and prevention principle “1 + X,” where 1 denotes the primary risk factor for a cancer and X represents the secondary contributing risk factors for the cancer. We elaborate upon the “1 + X” principle with respect to risk factors for several different cancer types. The “1 + X” principle can be used for precise prevention of cancer by eliminating the main cause of a cancer and minimizing the contributing factors at the same time.
Abstract 312: Visualization of Cardiomyocyte cGMP Dynamics in Hypoxia/Reoxygenation
Authors: Nadja I Bork, Viacheslav O Nikolaev
Journal: Circulation Research (2017)

The second messenger cyclic guanosine 3′5′-monophosphate (cGMP) plays an important role in the regulation of multiple physiologic processes in the cardiovascular system for example it is known to inhibit hypertrophy and to protect against ischemia-reperfusion injury. As a consequence of hypoxia in the heart, maladaptive signaling cascades are activated that can result in cardiac damage and finally lead to heart failure. However, cellular responses to hypoxia/reoxygenation (H/R) are still incompletely understood and almost nothing is known about cGMP dynamics in the context of H/R. The aim of this project was to investigate the effects of H/R on cGMP dynamics in mammalian cardiomyocytes. Therefore transgenic mice with cardiomyocyte-specific expression of the cytosolic Förster resonance energy transfer (FRET)-based cGMP sensor red cGES-DE5 were used to study cGMP dynamics in single adult cardiomyocytes exposed to H/R. In addition, a Langendorff system was used for FRET measurements in whole-heart. Basal cGMP levels in single adult cardiomyocytes exposed to H/R were increased. This increase was generated already during the hypoxic period and was maintained during reoxygenation. PDE3 protein expression and activity were significantly downregulated after H/R, however RNA expression level of PDE3 was not significantly changed. At the same time, protein levels of the soluble guanylyl cyclase β-subunit showed a tendency towards downregulation during H/R. In whole heart measurements, we could show that cGMP levels increase during anoxia and decrease during reoxygenation. This indicates that there is also an influence of other cell-types on cGMP dynamics or on cGMP cell-cell transfer. In conclusion, we developed FRET-based cGMP measurements in single cardiomyocytes and whole hearts in context of H/R and found an increase of intracellular cGMP in hypoxia. This offers great opportunities to dissect the molecular mechanism of cGMP signaling regulation during ischemic injury and should help to distinguish between direct protective effects on cardiomyocytes and indirect mechanisms such as cell-cell interactions in cGMP signaling during and after H/R.
A study of pembrolizumab (pembro) in combination with Y90 radioembolization in patients (pts) with poor prognosis hepatocellular carcinoma (HCC) with preserved liver function.
Authors: Autumn Jackson McRee, Paul R. Helft, William Proctor Harris, Hanna Kelly Sanoff, Matthew Johnson, Menggang Yu, Bert O'Neil
Journal: Journal of Clinical Oncology (2022)

422 Background: HCC is an aggressive cancer that is challenging to treat due to the concomitant diagnosis of cirrhosis. For HCC pts with no extrahepatic metastases and well-compensated liver function, Y90 radioembolization is a standard therapy. In observational studies, pts with multifocal disease or portal vein thrombosis (PVT) had worse outcomes with short disease control intervals of less than 6 months. Pembro is an anti-PD-1 monoclonal antibody that is FDA-approved for advanced HCC pts who have progressed on sorafenib. Given pre-clinical evidence that radiotherapy can increase PD-L1 expression and enhance tumoral T-cell recruitment, this study explored the safety and efficacy of pembro with Y90 radioembolization in pts with poor prognosis HCC. Methods: GI15-225 was a multi-center, single-arm study in poor prognosis HCC pts, defined as having multifocal disease, branch PVT and/or diffuse disease (NCT03099564). Pts with extrahepatic metastatic disease were excluded; eligible pts had disease amenable to 1-2 embolization procedures. Pts had Child Pugh A/B7 cirrhosis with no prior Y90 treatment; previous TAE, TACE, SBRT, liver resection or ablation were allowed. Treatment consisted of pembro 200mg every 3 weeks with Y90 radioembolization performed 7-10 days after first dose of pembro. The primary objective was to estimate the progression free survival (PFS) rate at 6 months per RECIST 1.1; secondary endpoints included safety, time to progression (TTP), overall response rate (ORR) and overall survival (OS). Results: A total of 29 pts were enrolled 10/23/17 to 11/24/20. Median age 66 years, 89% male, and 47% with PVT. 26 pts were evaluable for primary endpoint having received Y90 and at least one dose of pembro. The 6 month PFS rate was 57.7% (95% CI 36.9 – 76.6). Median PFS was 8.6 months (95% CI 4.1 – 13.4) and median TTP was 9.9 months (95% 4.2 – NR). Median OS was 22 months (95% CI 8.4 – 32.0). The ORR was 27% (Table). Most common treatment related grade 3-4 AEs were decreased lymphocytes (18%), increased bilirubin (11%), hypertension (11%), ascites (7%), and AST/ALT elevation (7%). One pt experienced grade 5 toxicity of hepatic failure after receiving one dose of pembro and Y90 that was attributed to Y90 and disease progression. Conclusions: Concurrent administration of pembro with Y90 radioembolization in pts with poor prognosis HCC demonstrated promising clinical activity with median TTP and OS that exceeds historical data reported in similar patients treated with Y90 alone. With a 6 month PFS rate of 57.7% and a favorable toxicity profile, the combination of immune checkpoint blockade and Y90 deserves further evaluation in larger randomized clinical trials. Clinical trial information: NCT03099564. [Table: see text]
Real-world cost-effectiveness of first-line gemcitabine + nab-paclitaxel versus FOLFIRINOX in patients with advanced pancreatic cancer: A population-based retrospective cohort study in Ontario, Canada.
Authors: Vanessa Arciero, Jin Luo, Ambika Parmar, Wei Fang Dai, Jaclyn M. Beca, Michael J. Raphael, Wanrudee Isaranuwatchai, Steven Habbous, Mina Tadrous, Craig Earle, Jim Biagi, Nicole Mittmann, Jessica Arias, Scott Gavura, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2022)

529 Background: Currently, there are no direct randomized control trials (RCTs) comparing gemcitabine and nab-paclitaxel (Gem-Nab) and FOLFIRINOX for advanced pancreatic cancer (APC). Thus, previous model-based cost-effectiveness analyses were based on indirect comparisons of RCT data. While it is well known that RCT-based efficacy does not often translate to real-world effectiveness, there is limited literature investigating the comparative cost-effectiveness of Gem-Nab versus FOLFIRINOX for APC in the real-world. The objective of this study is to examine the real-world cost-effectiveness of Gem-Nab versus FOLFIRINOX in patients with APC in Ontario, Canada. Methods: This population-based retrospective cohort study compared all patients treated with first-line Gem-Nab or FOLFIRINOX for APC with ECOG performance status 0-1 in Ontario from April 2015 to March 2019. Patients were linked to administrative databases to identify key characteristics and costing data. Using propensity scores and a stabilizing weights method, an inverse probability of treatment weighted cohort was developed. Mean survival and total costs were calculated over a 5-year time horizon, adjusted for censoring and discounted at 1.5% (per Canadian guidelines). Incremental cost-effectiveness ratio and net monetary benefit were computed (measured in life-years and quality-adjusted life years) to estimate cost-effectiveness from the public healthcare payer’s perspective. A sensitivity analysis was conducted using the propensity score matching method. Results: 1,988 patients were identified (Gem-Nab: 928, FOLFIRINOX: 1,060). Mean survival was lower for patients in the Gem-Nab group than the FOLFIRINOX group (0.98 versus 1.26 life-years, incremental -0.28 (95% confidence interval -0.47, -0.13)). Patients in the Gem-Nab group also incurred greater mean 5-year total costs (Gem-Nab: $103,884, FOLFIRINOX: $101,518). Key cost contributors include ambulatory cancer care, acute in-patient hospitalization, and systemic therapy drug acquisition. Gem-Nab was dominated by FOLFIRINOX, as it is less effective and more costly. Results from the sensitivity analysis were similar. Conclusions: In routinely treated unselected patients, Gem-Nab is likely more costly and less effective than FOLFIRINOX and therefore, not considered cost-effective at any commonly accepted willingness-to-pay threshold.
Reply
Authors: Stefan H. Ostermayer, Yves Bayard, Kai Billinger, Thomas Trepels, Ulrike Krumsdorf, Horst Sievert, Mark Reisman, Paul H. Kramer, Ray V. Matthews, Peter C. Block, Heyder Omran, Antonio L. Bartorelli, Paolo Della Bella, Carlo DiMario, Carlo Pappone, Paul N. Casale, William A. Gray, Jeffery W. Moses, Athena Poppas, David O. Williams, Bernhard Meier, Allan Skanes, Paul S. Teirstein, Michael D. Lesh, Toshiko Nakai, Horst Sievert
Journal: Journal of the American College of Cardiology (2006)
Horizontally Acquired Cellulases Assist the Expansion of Dietary Range in <i>Pristionchus</i> Nematodes
Authors: Ziduan Han, Bogdan Sieriebriennikov, Vladislav Susoy, Wen-Sui Lo, Catia Igreja, Chuanfu Dong, Aileen Berasategui, Hanh Witte, Ralf J Sommer
Journal: Molecular Biology and Evolution (2021)

Horizontal gene transfer (HGT) enables the acquisition of novel traits via non-Mendelian inheritance of genetic material. HGT plays a prominent role in the evolution of prokaryotes, whereas in animals, HGT is rare and its functional significance is often uncertain. Here, we investigate horizontally acquired cellulase genes in the free-living nematode model organism Pristionchus pacificus. We show that these cellulase genes 1) are likely of eukaryotic origin, 2) are expressed, 3) have protein products that are secreted and functional, and 4) result in endo-cellulase activity. Using CRISPR/Cas9, we generated an octuple cellulase mutant, which lacks all eight cellulase genes and cellulase activity altogether. Nonetheless, this cellulase-null mutant is viable and therefore allows a detailed analysis of a gene family that was horizontally acquired. We show that the octuple cellulase mutant has associated fitness costs with reduced fecundity and slower developmental speed. Furthermore, by using various Escherichia coli K-12 strains as a model for cellulosic biofilms, we demonstrate that cellulases facilitate the procurement of nutrients from bacterial biofilms. Together, our analysis of cellulases in Pristionchus provides comprehensive evidence from biochemistry, genetics, and phylogeny, which supports the integration of horizontally acquired genes into the complex life history strategy of this soil nematode.