tbuckley/cabot-search huggingface dataset:
Extracellular Vesicles from Pancreatic Cancer Stem Cells Lead an Intratumor Communication Network (EVNet) to fuel tumour progression
Authors: Carolina F Ruivo, Nuno Bastos, Barbara Adem, Ines Batista, Cecilia Duraes, Carlos A Melo, Stephanie A Castaldo, Francisco Campos‐Laborie, Pedro Moutinho-Ribeiro, Barbara Morão, Ana Costa-Pinto, Soraia Silva, Hugo Osorio, Sergio Ciordia, Jose Luis Costa, David Goodrich, Bruno Cavadas, Luisa Pereira, Tony Kouzarides, Guilherme Macedo, Rui Maio, Fatima Carneiro, Marília Cravo, Raghu Kalluri, Jose Carlos Machado, Sonia A Melo
Journal: Gut (2022)

Intratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour.
HIV Prevention in US Correctional System, 1991
Journal: JAMA (1992)

During 1990, an estimated 4,350,000 adults--2.4% of the total U.S. adult population--were under correctional supervision* in the United States, a 75% increase since 1983 (1). From 1983 through 1989, the number of juveniles (aged 10-17 years) in custody increased 25%, from 80,091 to 99,846 (U.S. Department of Justice, personal communication, 1992). By November 1990, 4519 cases of acquired immunodeficiency syndrome (AIDS) had been reported among inmates in federal and 45 state prisons, and 2466 cases had been reported by 25 city/county jail systems (U.S. Department of Justice, unpublished data, 1991); these totals include both cases of AIDS reported among persons before their incarceration as well as those reported by prison systems. This report characterizes efforts to prevent human immunodeficiency virus (HIV) transmission within correctional systems.
TCT-734 Influence of Platelet Reactivity and Inflammation on Peri-procedural Myonecrosis in East Asian Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Young-Hoon Jeong, Yongwhi Park, Jin-Sin Koh, Choong Hwan Kwak, Jin-Yong Hwang, Udaya Tantry, Paul Gurbel
Journal: Journal of the American College of Cardiology (2012)
Bempegaldesleukin Stimulates Immune Response
Journal: Cancer Discovery (2019)

Abstract In two clinical trials, the CD122-preferential IL2 pathway agonist bempegaldesleukin increased proliferation and activation of tumor-infiltrating lymphocytes in patients with solid tumors. Despite the lack of response to the agent as a monotherapy in the first-in-human trial, patients with metastatic urothelial carcinoma in the subsequent PIVOT-02 trial did respond when the drug was combined with the PD-1 inhibitor nivolumab.
Progranulin as a therapeutic target in neurodegenerative diseases
Authors: Herve Rhinn, Nadine Tatton, Stella McCaughey, Michael Kurnellas, Arnon Rosenthal
Journal: Trends in Pharmacological Sciences (2022)

Progranulin (PGRN, encoded by the GRN gene) plays a key role in the development, survival, function, and maintenance of neurons and microglia in the mammalian brain. It regulates lysosomal biogenesis, inflammation, repair, stress response, and aging. GRN loss-of-function mutations cause neuronal ceroid lipofuscinosis or frontotemporal dementia-GRN (FTD-GRN) in a gene dosage-dependent manner. Mutations that reduce PGRN levels increase the risk for developing Alzheimer's disease, Parkinson's disease, and limbic-predominant age-related transactivation response DNA-binding protein 43 encephalopathy, as well as exacerbate the progression of amyotrophic lateral sclerosis (ALS) and FTD caused by the hexanucleotide repeat expansion in the C9orf72 gene. Elevating and/or restoring PGRN levels is an attractive therapeutic strategy and is being investigated for neurodegenerative diseases through multiple mechanisms of action.
TCTAP A-042 Immediate &amp; Intermediate Follow Up of Percutaneous Treatment of Bifurcation Lesion Using Drug Eluting Stent for Main Branch and Drug Eluting Balloon for the Side Branch, Inbifurcational Coronanary Artery Disease
Authors: Saad Al Kasab, Menwar Mutared Al Anazi, Rida Mustafa Nourallah, Mohamed Al Kasab, Ali Al Masood
Journal: Journal of the American College of Cardiology (2014)
Low-dose $beta;-blocker therapy improves left ventricular function during exercise in elderly patients with myocardial ischemia and preserved left ventricular function Joao B. Serro-Azul, Mauricio Wajngarten, Maria C. Giorgio, Jose C. Meneghetti, Creuza Dal Bo, Humberto Pierri, Amit Nussbacher, Otavio Gebara, Ligia B. Pinto, Nubia W. Vieira. HEART INSTITUTE (InCor) UNIVERSITY OF SAO PAULO, MEDICAL SCHOOL, SAO PAULO, Brazil
Journal: Journal of the American College of Cardiology (2001)
TFEB signaling attenuates NLRP3‐driven inflammatory responses in severe asthma
Authors: Efthymia Theofani, Maria Semitekolou, Konstantinos Samitas, Annie Mais, Ioanna E. Galani, Vasiliki Triantafyllia, Joanna Lama, Ioannis Morianos, Athanasios Stavropoulos, Se‐Jin Jeong, Evangelos Andreakos, Babak Razani, Nikoletta Rovina, Georgina Xanthou
Journal: Allergy (2022)

Abstract Background NLRP3‐driven inflammatory responses by circulating and lung‐resident monocytes are critical drivers of asthma pathogenesis. Autophagy restrains NLRP3‐induced monocyte activation in asthma models. Yet, the effects of autophagy and its master regulator, transcription factor EB (TFEB), on monocyte responses in human asthma remain unexplored. Here, we investigated whether activation of autophagy and TFEB signaling suppress inflammatory monocyte responses in asthmatic individuals. Methods Peripheral blood CD14 + monocytes from asthmatic patients ( n = 83) and healthy controls ( n = 46) were stimulated with LPS/ATP to induce NLRP3 activation with or without the autophagy inducer, rapamycin. ASC specks, caspase‐1 activation, IL‐1β and IL‐18 levels, mitochondrial function, ROS release, and mTORC1 signaling were examined. Autophagy was evaluated by LC3 puncta formation, p62/SQSTM1 degradation and TFEB activation. In a severe asthma (SA) model, we investigated the role of NLRP3 signaling using Nlrp3 −/− mice and/or MCC950 administration, and the effects of TFEB activation using myeloid‐specific TFEB‐overexpressing mice or administration of the TFEB activator, trehalose. Results We observed increased NLRP3 inflammasome activation, concomitant with impaired autophagy in circulating monocytes that correlated with asthma severity. SA patients also exhibited mitochondrial dysfunction and ROS accumulation. Autophagy failed to inhibit NLRP3‐driven monocyte responses, due to defective TFEB activation and excessive mTORC1 signaling. NLRP3 blockade restrained inflammatory cytokine release and linked airway disease. TFEB activation restored impaired autophagy, attenuated NLRP3‐driven pulmonary inflammation, and ameliorated SA phenotype. Conclusions Our studies uncover a crucial role for TFEB‐mediated reprogramming of monocyte inflammatory responses, raising the prospect that this pathway can be therapeutically harnessed for the management of SA.
Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access
Authors: Francesca Fumagalli, Valeria Calbi, Maria Grazia Natali Sora, Maria Sessa, Cristina Baldoli, Paola Maria V Rancoita, Francesca Ciotti, Marina Sarzana, Maddalena Fraschini, Alberto Andrea Zambon, Serena Acquati, Daniela Redaelli, Vanessa Attanasio, Simona Miglietta, Fabiola De Mattia, Federica Barzaghi, Francesca Ferrua, Maddalena Migliavacca, Francesca Tucci, Vera Gallo, Ubaldo Del Carro, Sabrina Canale, Ivana Spiga, Laura Lorioli, Salvatore Recupero, Elena Sophia Fratini, Francesco Morena, Paolo Silvani, Maria Rosa Calvi, Marcella Facchini, Sara Locatelli, Ambra Corti, Stefano Zancan, Gigliola Antonioli, Giada Farinelli, Michela Gabaldo, Jesus Garcia-Segovia, Laetitia C Schwab, Gerald F Downey, Massimo Filippi, Maria Pia Cicalese, Sabata Martino, Clelia Di Serio, Fabio Ciceri, Maria Ester Bernardo, Luigi Naldini, Alessandra Biffi, Alessandro Aiuti
Journal: The Lancet (2022)
Abstract 10: Increasing Cardiac Fatty Acid Oxidation Protects Against High Fat Diet Induced Cardiomyopathy in Mice
Authors: Dan Shao, Stephen C Kolwicz, Nathan Roe, Outi Villet, Loreta D Tomasi, Alyssa N Braun, Rong Tian
Journal: Circulation Research (2017)

In the obese and diabetic heart, an imbalance between fatty acid uptake and fatty acid oxidation (FAO) promotes the development of cardiac lipotoxicity. We previously demonstrated that cardiac-specific deletion of ACC2 in adult mice was effective in increasing myocardial FAO while maintaining normal cardiac function and energetics. In this study, we tested the hypothesis that ACC2 deletion in an adult heart would prevent the cardiac lipotoxic phenotype in a mouse model of diet-induced obesity. ACC2 flox/flox (CON) and ACC2 flox/flox-MerCreMer+ (iKO) were injected with tamoxifen and subjected to a high fat diet (HFD) for 24 weeks. HFD induced similar body weight gain and glucose intolerance in CON and iKO. In isolated Langendorff-perfused heart experiments, HFD feeding increased FAO 1.6-fold in CON mice which was further increased to 1.9-fold in iKO mice compared with CON on chow diet. HFD induced systolic and diastolic dysfunction was abolished in iKO mice compared with CON mice (Fractional shortening 32.8±2.8% (CON) vs. 39.2±3.2% (iKO), E’/A’ ratio 0.91±0.09 (CON) vs. 1.11±0.08 (iKO), p&lt; 0.05, n=5-6). Heart weight /Tibia length ratio was significantly higher in CON than iKO mice after HFD feeding (7.19±0.22 vs. 6.47±0.28, p&lt;0.05, n=6). These data indicate that elevated myocardial FAO per se does not cause the development of cardiac dysfunction in obese animals. In fact, enhancing FAO via ACC2 deletion prevents HFD induced cardiac dysfunction and attenuates pathological hypertrophy. Molecular markers for ER stress such as p-PERK (1.5 fold) and p-JNK (2 fold) was elevated in CON-HFD hearts, which was completely attenuated in iKO-HFD hearts. Impairment of autophagy was also observed in CON-HFD hearts evidenced by decreases in LC3 II (60%) and increases in P62 (75%) level, while no difference in autophagy were observed in iKO-HFD hearts compared to iKO-chow. Therefore, the beneficial effect for enhancing cardiac fatty oxidation in HFD induced obesity model may be mediated, in part, by maintenance of cellular homeostasis and survival through regulating ER stress and autophagy. Taken together, our findings suggest that promoting cardiac FAO is an effective strategy to resist the development of cardiac lipotoxicity during diet-induced obesity.
The Noble and Often Nobel Role Played by Insulin-Focused Research in Modern Medicine
Authors: Victor S. Harrison, Mahfuzul H. Khan, Christine E. Chamberlain, David M. Harlan
Journal: Diabetes Care (2021)

Since diabetes was first described over 3,000 years ago, clinicians and scientists alike have sought ever improving treatments en route to a cure. As we approach the 100th anniversary of insulin's first therapeutic use, this article will recount the glorious history associated with research surrounding insulin's isolation, purification, cloning, and subsequent modification. The discovery path we will relate tells the story of many relentless and passionate investigators pursuing ground-breaking research. The fruits of their labor include several Nobel Prizes, new technology, and, more importantly, ever improving treatments for one of humankind's greatest medical scourges.
Interplay of Dinner Timing and<i>MTNR1B</i>Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial
Authors: Marta Garaulet, Jesus Lopez-Minguez, Hassan S. Dashti, Céline Vetter, Antonio Miguel Hernández-Martínez, Millán Pérez-Ayala, Juan Carlos Baraza, Wei Wang, Jose C. Florez, Frank A.J.L. Scheer, Richa Saxena
Journal: Diabetes Care (2022)

OBJECTIVE We tested whether the concurrence of food intake and elevated concentrations of endogenous melatonin, as occurs with late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes–associated G allele in the melatonin receptor-1B gene (MTNR1B). RESEARCH DESIGN AND METHODS In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime (“early dinner timing”) and a late condition scheduled 1 h prior to habitual bedtime (“late dinner timing”), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses between early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method. RESULTS Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. The effect of late eating impairing glucose tolerance was stronger in the MTNR1B G-allele carriers than in noncarriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint disposition index = 0.018). CONCLUSIONS Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects.
Physicians who move and why they move
Authors: S. R. Steiber
Journal: JAMA (1982)

Physicians in the United States migrate across county lines more often than nonphysicians, but their migration parallels that of the population at large: from the northern "Frost Belt" to the southern "Sun Belt." The data presented herein show that mobile physicians ("movers") are more often younger and female than nonmobile physicians ("stayers"). Stayers are more likely to be primary care or self-employed physicians, and movers more often are in nonprimary care or in medical administration, research, teaching, or other medical employment modalities. County-level characteristics such as population income and size also help determine whether a physician will be a mover or stayer. (<i>JAMA</i>1982;248:1490-1492)
From the Editor’s Desk…
Authors: Patrizia Burra, Frank Tacke, Vlad Ratziu, Stefan Zeuzem, Bruno Sangro, Paolo Angeli
Journal: Journal of Hepatology (2021)

Despite the large number of clinical trials on COVID-19 vaccines, only a few participants with pre-existing liver diseases were included. In this issue of the Journal, 2 separate studies analyse the safety and efficacy of COVID-19 vaccines in patients with non-alcoholic fatty liver disease (NAFLD) and in liver transplant recipients. Wang et al. reported that neutralising antibodies against SARS-CoV-were detected in 364 (95.5%) patients with NAFLD, based on an analysis of the CHESS2101 study from China.
A platelet glycoprotein IIb/IIIa receptor blocker-coated stent inhibits porcine coronary stent thrombosis and restenosis Myung Ho Jeong, Kyung Tae Kang, Young Keun Ahn, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang. Chonnam National University Hospital, Kwang Ju, South Korea
Journal: Journal of the American College of Cardiology (2001)
Women and Health: the key for sustainable development
Authors: Ana Langer, Afaf Meleis, Felicia M Knaul, Rifat Atun, Meltem Aran, Héctor Arreola-Ornelas, Zulfiqar A Bhutta, Agnes Binagwaho, Ruth Bonita, Jacquelyn M Caglia, Mariam Claeson, Justine Davies, France A Donnay, Jewel M Gausman, Caroline Glickman, Annie D Kearns, Tamil Kendall, Rafael Lozano, Naomi Seboni, Gita Sen, Siriorn Sindhu, Miriam Temin, Julio Frenk
Journal: The Lancet (2015)
More physician involvement in future Olympic programs
Authors: P. Gunby
Journal: JAMA (1980)

As the 1980 Olympics approach, some medical preparations already are under way for the 1984 Games. "The Olympics no longer can be a quadrennial affair," says Irving I. Dardik, MD, chairman of the Council on Sports Medicine for the US Olympic Committee. "Instead of waiting until shortly before the 1984 games to begin another Olympic medical support effort, we are planning a continuing program over the intervening years, involving more physicians than ever before, to benefit American athletes generally." Two days after the close of the Winter Games, Dardik will help direct the first Olympic Sports Medicine Conference (Feb 26 through 29) in Boston. There some of the medical plans for the 1984 games will be discussed with attending physicians, some of whom will have been at the Lake Placid, NY, games. In the meantime, the US Olympic Committee has established an athletic training and research center on a 50-acre
In This Issue
Journal: Cancer Discovery (2020)

See article, [p. 198][1] . </br>![][2]</img> In breast cancer, some mutations in ERBB2 (encoding HER2) are associated with oncogenic addiction to HER2 signaling. Building on a phase II trial of single-agent treatment with the irreversible pan-HER inhibitor neratinib in patients with ERBB2 -
Experimental results with a sirolimus eluting stent: A comprehensive histological analysis Takeshi Suzuki, Gregory Kopia, Lynn R. Bailey, Gerard Llanos, Jennifer Lyons, Pallassana Narayan, George Papandreou, Robert Falotico, Fermin Tio, Andrew J. Carter. Stanford University Medical Center, Stanford, CA, University Texas San Antonio, San Antonio, TX
Journal: Journal of the American College of Cardiology (2001)
<i>Fusobacterium nucleatum</i> Promotes Metastasis in Colorectal Cancer by Activating Autophagy Signaling via the Upregulation of CARD3 Expression: Erratum
Authors: Yongyu Chen, Yan Chen, Jixiang Zhang, Pan Cao, Wenhao Su, Yunchao Deng, Na Zhan, Xiangsheng Fu, Yun Huang, Weiguo Dong
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.38870.].
On the Pathology and Treatment of Ovarian Diseases
Authors: L. Tait
Journal: BMJ (1874)

position of the tongue.In a fcetus .9 of an inch long, this arch, which may be called the lingual, consists of a globular cartilage, connected with the periotic tissue below and behind the root of Meckel's cartilage (part of the mandibular arch).In a foetus i.8 of an inch long, this arch con- sists of five portions, cartilage and membrane alternating; the lowest nodule of cartilage joining the hyoid arch, and constituting, in the adult, the lesser horn of the hyoid bone: from this the tongue rises.It is not necessary here to refer in any detail to the remaining arches connected with the base of the skull: they are the hyoid, the laryngeal, and the exoccipital.In their development they follow the growth of the cerebral nerves ; the most remarkable being, perhaps, that of the laryngeal, with its extension into the thorax, in association with the pneumogastric nerve, and the development, from the single tube of which it at first consists, of the larynx with the trachea, and of the lower part of the pharynx with the Esophagus. (For a description of these arches, see the Philoso1hical Transactions, 1871, p. I21, pl.i.)
Clinical research: further COVID-19 collateral damage
Authors: None The Lancet Gastroenterology & Hepatology
Journal: The Lancet. Gastroenterology & hepatology (2020)

More than 1500 clinical studies run by the NHS have been permanently closed in Britain in the wake of COVID-19, with a further 9000 suspended, representing a disruption of 70% of NHS research, according to a report in The Observer. Elsewhere, an analysis of trials registered with ClinicalTrials.gov since 2017 indicated the rate of trial closure has increased significantly during the pandemic period versus the pre-pandemic era.
Prognostic utility of preoperative and postoperative circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.
Authors: Ali Alqahtani, Abdurahman Alloghbi, Chao Yin, Reetu Mukherji, Benjamin Adam Weinberg
Journal: Journal of Clinical Oncology (2022)

595 Background: Surgical resection offers the only chance of cure for localized pancreatic ductal adenocarcinoma (PDAC). Despite surgical resection, 80% of patients experience disease recurrence. There is growing evidence that support the prognostic role of perioperative KRAS-mutated circulating tumor DNA (ctDNA). We conducted a systematic review and meta-analysis to investigate the prognostic utility of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search of PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was performed in September 2021. We included studies that reported on the effects of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse free survival (RFS) in resected PDAC. The random-effects model was used to calculate pooled OS and RFS hazard ratios (HRs) and 95% confidence intervals (CIs). Publication bias was assessed by visual inspection of a funnel plot of the included studies. Results: We identified 6,986 studies, and 13 studies were eligible for analysis. A total of 954 patients were included for the final evaluation. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95% CI, 1.346-3.174; P &lt; 0.001) and worse OS in 10 studies (HR, 2.170; 95% CI, 1.451-3.245; P &lt; 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 7 studies (HR, 2.986; 95% CI, 1.897-4.699; P &lt;.001), and worse OS in 5 studies (HR, 5.812; 95% CI, 1.757-19.228; P = 0.004) compared to negative ctDNA. There was visible symmetry in the funnel plot of the studies included, suggesting no publication bias. Conclusions: In resected PDAC, preoperative and postoperative KRAS-mutated ctDNA positivity may be useful markers of poor prognosis in terms of RFS and OS. Clinically, KRAS-mutated ctDNA testing may also have implications when considering the aggressiveness and duration of adjuvant therapy in PDAC, although prospective trials are needed to assess this utility.
THE DIRTY RESTAURANT KITCHEN.
Journal: JAMA (1905)

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