tbuckley/cabot-search huggingface dataset:
Abstract P343: Sex Differences in Cardiovascular/Cerebrovascular Mortality Risk Associated With Chronic Insomnia
Authors: Julio Fernandez-Mendoza, Fan He, Alexandros N Vgontzas, Duanping Liao, Edward O Bixler
Journal: Circulation (2018)

Introduction: It remains unknown whether individuals with chronic insomnia are at increased risk of mortality, particularly cardiovascular or cerebrovascular (CVD/CBV) mortality. Given the higher prevalence of insomnia in women than in men, it is unknown whether its prognosis in terms of mortality is also different across sexes. Hypothesis: The risk of CVD/CBV mortality associated with chronic insomnia is significantly higher than in non-complaining individuals and this risk is modified by sex. Methods: We addressed this question in the Penn State Adult Cohort, a random, general population sample of 1,741 men and women (48.7 ± 13.5 years) who were studied in the sleep laboratory and followed-up for their cause of death up to 15 years. Sleep difficulty was assessed based on three levels of severity: chronic insomnia (i.e., a complaint of chronic sleep difficulties lasting at least 1 year), poor sleep (i.e., moderate-to-severe sleep difficulties at any given time) and none (i.e., absence of either of the two categories). Cox regression models controlled for potential confounders, including age, race, body mass index, years of education, smoking, sleep disordered breathing, alcohol use, mental health problems, hypertension, diabetes, heart disease, stroke and other physical health problems. Results: Poor sleep and chronic insomnia were significantly more prevalent in females (26.7% and 10.7%, respectively) than males (17.6% and 4.1%, respectively). A significant interaction (p = 0.04) showed that the risk of CVD/CBV mortality associated with chronic insomnia was modified by male sex, while poor sleep was not significantly associated with increased risk of CVD/CBV mortality in either males or females. Chronic insomnia was associated with a 2.9-fold (95%CI=1.53-5.61) increased risk of CVD/CBV mortality in males even after adjusting for all confounders, while this risk was not significantly elevated in females (HR=1.13, 95%CI=0.56-2.31). Conclusions: Chronic insomnia is associated with increased risk of CVD/CBV mortality in males, while it has a better prognosis in females despite its higher prevalence. These data suggest potential sex-related vulnerabilities in the underlying mechanisms linking chronic insomnia with CVD/CBV morbidity and mortality.
Seeing for ourselves: Insights into the development of moral behaviour from models of visual perception and misperception
Authors: Daniel Collerton, Elaine Perry
Journal: Behavioral and Brain Sciences (2018)

Abstract Parallels from visual processing support Doris's cognitive architecture underlying moral agency. Unconscious visual processes change with conscious reflection. The sparse and partial representations of vision, its illusions, and hallucinations echo biases in moral reasoning and behaviour. Traditionally, unconscious moral processes are developed by teaching and reflection. Modern neuroscience could bypass reflection and directly influence unconscious processes, creating new dangers.
Circulating and Tumor Myeloid-derived Suppressor Cells in Resectable Non–Small Cell Lung Cancer
Authors: Yoshikane Yamauchi, Seyer Safi, Carolin Blattner, Anchana Rathinasamy, Ludmila Umansky, Simone Juenger, Arne Warth, Martin Eichhorn, Thomas Muley, Felix J. F. Herth, Hendrik Dienemann, Michael Platten, Philipp Beckhove, Jochen Utikal, Hans Hoffmann, Viktor Umansky
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Myeloid-derived suppressor cell (MDSC) expansion has been found to play a role in disease progression in patients with cancer. However, the characteristics of MDSCs in lung cancer are poorly understood.Objectives: We prospectively investigated MDSCs and inflammatory factors in tumor and peripheral blood samples from patients with resectable non–small cell lung cancer and studied their correlations with the disease prognosis.Methods: A complex analysis of MDSC subsets and inflammatory mediators was performed using flow cytometry and a Bio-Plex assay.Measurements and Main Results: A significant increase in the frequency of circulating monocytic (M)-MDSCs was observed in the patients with non–small cell lung cancer compared with the healthy donors (HDs). Moreover, the frequencies of M- and polymorphonuclear (PMN)-MDSCs were higher in tumors than in the peripheral blood of the same patients. This accumulation was associated with elevated concentrations of inflammatory mediators involved in MDSC migration to and activation in the tumor microenvironment. An analysis of the MDSC immunosuppressive pattern showed increased programmed death-ligand 1 expression on circulating cells from patients compared with HDs. Tumor PMN-MDSCs displayed higher programmed death-ligand 1 expression levels than the same cells in the peripheral blood. The frequency of CCR5 (C-C chemokine receptor 5) expression on circulating M-MDSCs was significantly higher in the patients than in the HDs. Clinical data analysis revealed negative correlations between recurrence-free survival and the frequencies of PMN-MDSCs and CCR5+ M-MDSCs in the circulation but not in tumors.Conclusions: Our findings suggest that the level of MDSCs in the peripheral blood but not in tumor tissues predicts recurrence after surgery.
Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Michael J. Morris, R. Bryan Rumble, Ethan Basch, Sebastien J. Hotte, Andrew Loblaw, Dana Rathkopf, Paul Celano, Rick Bangs, Matthew I. Milowsky
Journal: Journal of Clinical Oncology (2018)

Purpose This clinical practice guideline addresses abiraterone or docetaxel with androgen-deprivation therapy (ADT) for metastatic prostate cancer that has not been treated (or has been minimally treated) with testosterone-lowering agents. Methods Standard therapy for newly diagnosed metastatic prostate cancer has been ADT alone. Three studies have compared ADT alone with ADT and docetaxel, and two studies have compared ADT alone with ADT and abiraterone. Results Three prospective randomized studies (GETUG-AFU 15, STAMPEDE, and CHAARTED) examined overall survival (OS) with adding docetaxel to ADT. STAMPEDE and CHAARTED favored docetaxel (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; n = 2,962 and HR, 0.73; 95% CI, 0.59 to 0.89; n = 790, respectively). GETUG-AFU 15 was negative. LATITUDE and STAMPEDE examined the impact on OS of adding abiraterone (with prednisone or prednisolone) to ADT. LATITUDE and STAMPEDE favored abiraterone (HR, 0.62; 95% CI, 0.51 to 0.76; n = 1,199 and HR, 0.63; 95% CI, 0.52 to 0.76; n = 1,917, respectively). Recommendations ADT plus docetaxel or abiraterone in newly diagnosed metastatic non-castrate prostate cancer offers a survival benefit as compared with ADT alone. The strongest evidence of benefit with docetaxel is in men with de novo high-volume (CHAARTED criteria) metastatic disease. Similar survival benefits are seen using abiraterone acetate in high-risk patients (LATITUDE criteria) and in the metastatic population in STAMPEDE. ADT plus abiraterone and ADT plus docetaxel have not been compared, and it is not known if some men benefit more from one regimen as opposed to the other. Fitness for chemotherapy, patient comorbidities, toxicity profiles, quality of life, drug availability, and cost should be considered in this decision. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .
Physician Burnout—Overdiagnosis and Unproven Interventions—Reply
Authors: Tait Shanafelt, Joel Goh, Christine Sinsky
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Cardiovascular Disease and Risk Management: Review of the American Diabetes Association Standards of Medical Care in Diabetes 2018
Authors: James J. Chamberlain, Eric L. Johnson, Sandra Leal, Andrew S. Rhinehart, Jay H. Shubrook, Lacie Peterson
Journal: Annals of Internal Medicine (2018)

The American Diabetes Association (ADA) annually updates its Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes.For the 2018 standards, the ADA Professional Practice Committee searched MEDLINE through November 2017 to add, clarify, or revise recommendations on the basis of new evidence. The committee rated the recommendations as A, B, or C depending on the quality of evidence or E for expert consensus or clinical experience. The standards were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community informed revisions.This synopsis focuses on guidance relating to cardiovascular disease and risk management in nonpregnant adults with diabetes. Recommendations address diagnosis and treatment of cardiovascular risk factors (hypertension and dyslipidemia), aspirin use, screening for and treatment of coronary heart disease, and lifestyle interventions.
Prediction of the First Variceal Hemorrhage in Patients with Cirrhosis of the Liver and Esophageal Varices
Journal: New England Journal of Medicine (1988)

We conducted a prospective study of 321 patients with cirrhosis of the liver and esophageal varices with no history of bleeding to see whether a comprehensive analysis of their clinical features and of the endoscopic appearances of their varices could help to identify those at highest risk for bleeding. Varices were classified endoscopically as suggested by the Japanese Research Society for Portal Hypertension. Patients were followed for 1 to 38 months (median, 23), during which 85 patients (26.5 percent) bled. Multiple regression analysis (Cox's model) revealed that the risk of bleeding was significantly related to the patient's modified Child class (an index of liver dysfunction based on serum albumin concentration, bilirubin level, prothrombin time, and the presence of ascites and encephalopathy), the size of the varices, and the presence of red wale markings (longitudinal dilated venules resembling whip marks) on the varices. A prognostic index based on these variables was devised that enabled us to identify a subset of patients with a one-year incidence of bleeding exceeding 65 percent. The index was prospectively validated on an independent sample of 75 patients with varices and no history of bleeding. We conclude that our prognostic index, which identifies groups of patients with one-year probabilities of bleeding ranging from 6 to 76 percent, can be used to identify candidates for prophylactic treatment. (N Engl J Med 1988; 319:983–9.)
Differences in molecular profiles of males and females with colorectal cancer (CRC).
Authors: Afsaneh Barzi, Mohamed E. Salem, Joanne Xiu, Wolfgang Michael Korn, John Marshall, Anthony Frank Shields, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2018)

623 Background: Females (F) have a lower incidence of CRC and carry a better overall prognosis than males(M). We explored the differences in the molecular profile of CRC as an explanation for the differences in the outcome. Methods: CRC cases submitted to Caris Life Sciences from 2015 to 2017 were analyzed. These cases were tested with next generation sequencing (NGS) of 592 genes and a panel of IHC and copy number variation assessment. Microsatellite instability (MSI) was evaluated with NGS for known MSI loci in the target regions. High Tumor mutational load (TML-H) was defined as ≥17 mutations/megabase. Results: Data from a total of 1768 CRC tumors (F: 859; M: 909) was available for analysis. The mean age at testing was similar between the two groups (F 59 vs. M 60 years). Tumor location was unknown in more than 40% of the cases. For those with known tumor location (1056) F had a higher rate in right sided than left sided and rectal tumors (51% vs. 47% vs. 40%, p = 0.006). Overall, F carried significantly lower frequency of mutation in APC (68% vs. 74%, p = 0.02), higher frequency of BRAF (11% vs. 6.6%, p = 0.003) and BRCA1 (2% vs. 0.6%, p = 0.007). PDL1 expression was higher in F (4.5% vs. 2.1%, p = 0.006) and MGMT expression was higher in M (63% vs. 56%, p = 0.04). There was no significant difference in the TML-H (F:6.4% vs. M:5.9%) and MSI-high (F:6.2% in vs M:4.8%). When primary (877) and metastatic tumors (838) were investigated separately, mutations in APC was higher in M primary tumors (74% vs. 68% p = 0.03) while not different in metastatic sites. On the contrary, BRCA1 mutations were higher in the metastatic sites for F (2% vs. 0.2%, p = 0.02). PD-L1 was higher in the primary tumor of F (5.2% vs. 1.8%, p = 0.008) and PD-1 on tumor infiltrating lymphocyte in metastatic tumors in F (48% vs. 30%, p = 0.01). Conclusions: The profile of female patients (higher rates of PDL1 in primary and PD1 in metastatic tumors) supports a higher degree of immune evasion. The differences in the profile of metastatic vs. primary sites may be due to the differences in the mechanism of metastasis in females vs. males and may have implications for PDX models.
RECIST 1.1 versus immune-related RECIST and immune-related response criteria in assessing response to nivolumab in patients with lung, renal, and head and neck cancers.
Authors: Surabhi Pathak, Marina Messinger, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2017)

e14609 Background: Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is reported to underestimate response to immunotherapeutic drugs. Therefore, immune related RECIST (iRECIST) based on RECIST 1.1 and immune related response criteria (IRRC) based on WHO response criteria have been studied, mainly in patients with melanoma. Whether RECIST 1.1 underestimates responses in other cancers is not well known. Aim of the present study is to assess response rates to PDL-1 inhibitor Nivolumab in lung, renal and head and neck (H&amp;N) cancers using RECIST 1.1, iRECIST and IRRC. Methods: We reviewed patients from 2012 to present with lung, renal, H&amp;N cancers treated with Nivolumab at John h Stroger Jr. Hospital of Cook County. Incomplete charts and those treated for less than 4 cycles of Nivolumab were excluded. Data was analyzed using descriptive statistics and Fisher exact test. Results: 47 charts were reviewed, 27 met the inclusion criteria. 17 lung (14 adeno, 3 squamous), 7 renal (5 clear cell) and 3 H&amp;N cancer patients were included. Average age was 58.2yrs, 20(74%) were male. Average treatment was for 13 cycles. Response was assessed after at least 4 cycles. Disease control rate for lung, renal, head and neck cancer was 70%,58%, 33% respectively with RECIST 1.1 criteria compared to 77%, 71% and 66% respectively using immune RECIST or IRRC (P &gt; 0.05). No patient developed pseudoprogression. Two had progressive disease per RECIST 1.1 but stable disease with iRECIST and IRRC. 26 of the 27 patients showed concordance between iRECIST and IRRC. One patient had stable disease per iRECIST but partial response per IRRC. Average survival after treatment initiation was 8.3 months for lung, 9.1 months for renal and 5.6 months for H&amp;N cancer. Treatment was discontinued in 2 patients based on progression per RECIST 1.1, both patients had stable disease per iRECIST&amp; IRRC. Conclusions: Trend towards underestimation of treatment response using RECIST 1.1 criteria compared to iRECIST or IRRC was observed. Strong concordance was observed between iRECIST and IRRC. Given relative ease of use, iRECIST might be favored over IRRC in response evaluation for immunotherapeutic drugs.
ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis
Authors: Yan Chen, Bo Zhang, Lei Bao, Lai Jin, Mingming Yang, Yan Peng, Ashwani Kumar, Jennifer E. Wang, Chenliang Wang, Xuan Zou, Chao Xing, Yingfei Wang, Weibo Luo
Journal: Journal of Clinical Investigation (2018)

Altered epigenetic reprogramming contributes to breast cancer progression and metastasis. How the epigenetic reader mediates breast cancer progression remains poorly understood. Here, we showed that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) is induced by HIF-1 and HIF-2 in breast cancer cells and also upregulated in human breast tumors, and is correlated with poor survival of patients with breast cancer. Genetic deletion of ZMYND8 decreases breast cancer cell colony formation, migration, and invasion in vitro, and inhibits breast tumor growth and metastasis to the lungs in mice. The ZMYND8's oncogenic effect in breast cancer requires HIF-1 and HIF-2. We further showed that ZMYND8 interacts with HIF-1α and HIF-2α and enhances elongation of the global HIF-induced oncogenic genes by increasing recruitment of BRD4 and subsequent release of paused RNA polymerase II in breast cancer cells. ZMYND8 acetylation at lysines 1007 and 1034 by p300 is required for HIF activation and breast cancer progression and metastasis. These findings uncover a primary epigenetic mechanism of HIF activation and HIF-mediated breast cancer progression, and discover a possible molecular target for the diagnosis and treatment of breast cancer.
Groin Hernia Surgery in Low-Resource Settings — A Problem Still Unsolved
Authors: Jenny Löfgren, Jessica Beard, Thomas Ashley
Journal: New England Journal of Medicine (2018)

Low-Cost Mesh for Hernia Repair A trial performed in Uganda supported the efficacy and safety of a low-cost mosquito net mesh for use in hernia repair. Experience since then indicates that the mesh currently supplied by the same company differs from the one that was studied and should not be used.
The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma
Authors: Yaojie Fu, Shanshan Liu, Shan Zeng, Hong Shen
Journal: Molecular Cancer (2018)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a "partner in crime" to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure. In addition to multiple paracrine signaling pathways, recent research has confirmed that PSCs-mediated tumor microenvironment may influence behaviors of PDAC via diverse mechanisms, such as rewiring metabolic networks, suppressing immune responses. These new activities are closely linked with treatment and prognosis of PDAC. In this review, we discuss the recent advances regarding new functions of activated PSCs, including PSCs-cancer cells interaction, mechanisms involved in immunosuppressive regulation, and metabolic reprogramming. It's clear that these updated experimental or clinical studies of PSCs may provide a promising approach for PDAC treatment in the near future.
A limited skeptical threat
Authors: Joshua May
Journal: Behavioral and Brain Sciences (2018)

Abstract Doris argues that our choices are heavily influenced by forces that we wouldn't count as genuine reasons. This unsettling conclusion is motivated by a debunking argument so wide-ranging that it isn't foisted upon us by the sciences. Doris sometimes seems to lower his ambitions when offering instead a skeptical hypothesis argument, but that conflicts with his aims in the book.
Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein
Authors: Luise Linsenmeier, Behnam Mohammadi, Sebastian Wetzel, Berta Puig, Walker S. Jackson, Alexander Hartmann, Keiji Uchiyama, Suehiro Sakaguchi, Kristina Endres, Jörg Tatzelt, Paul Saftig, Markus Glatzel, Hermann C. Altmeppen
Journal: Molecular Neurodegeneration (2018)

Proteolytic processing of the prion protein (PrP<superscript>C</superscript>) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous system and in brain diseases. Shedding of almost full-length PrP<superscript>C</superscript> into the extracellular space by the metalloprotease ADAM10 is of peculiar relevance since soluble PrP stimulates axonal outgrowth and is protective in neurodegenerative conditions such as Alzheimer’s and prion disease. However, molecular determinates and mechanisms regulating the shedding of PrP are entirely unknown.We produced an antibody recognizing the neo-epitope of shed PrP generated by ADAM10 in biological samples and used it to study structural and mechanistic aspects affecting the shedding. For this, we investigated genetically modified cellular and murine models by biochemical and morphological approaches.We show that the novel antibody specifically detects shed PrP in cell culture supernatants and murine brain. We demonstrate that ADAM10 is the exclusive sheddase of PrP<superscript>C</superscript> in the nervous system and reveal that the glycosylation state and type of membrane-anchorage of PrP<superscript>C</superscript> severely affect its shedding. Furthermore, we provide evidence that PrP shedding can be modulated by pharmacological inhibition and stimulation and present data suggesting that shedding is a relevant part of a compensatory network ensuring PrP<superscript>C</superscript> homeostasis of the cell.With the new antibody, our study introduces a new tool to reliably investigate PrP-shedding. In addition, this study provides novel and important insight into the regulation of this cleavage event, which is likely to be relevant for diagnostic and therapeutic approaches even beyond neurodegeneration.
Pharmacokinetics of rifapentine and rifampin in a rabbit model of tuberculosis and correlation with clinical trial data
Authors: Dalin Rifat, Brendan Prideaux, Radojka M. Savic, Michael E. Urbanowski, Teresa L. Parsons, Brian Luna, Mark A. Marzinke, Alvaro A. Ordonez, Vincent P. DeMarco, Sanjay K. Jain, Veronique Dartois, William R. Bishai, Kelly E. Dooley
Journal: Science Translational Medicine (2018)

A rabbit model of pulmonary cavitary tuberculosis helps to explain phase 2 clinical trial results for the rifamycin class of TB drugs.