tbuckley/cabot-search huggingface dataset:
Methyl‐Sensing Nuclear Receptor Liver Receptor Homolog‐1 Regulates Mitochondrial Function in Mouse Hepatocytes
Authors: Sungwoo Choi, Bingning Dong, Chih‐Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C. Wang, David D. Moore
Journal: Hepatology (2019)

Background and Aims Liver receptor homolog‐1 (LRH‐1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH‐1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid through the Kennedy pathway and trimethylation of phosphatidylethanolamine through phosphatidylethanolamine N ‐methyl transferase (PEMT). Approach and Results Here, we report that a PEMT–LRH‐1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh‐1 reduces mitochondrial number, basal respiration, beta‐oxidation, and adenosine triphosphate production in hepatocytes and decreases expression of mitochondrial biogenesis and beta‐oxidation genes. In contrast, activation of LRH‐1 by its phosphatidylcholine agonists exerts opposite effects. While disruption of the Kennedy pathway does not affect the LRH‐1‐mediated regulation of mitochondrial activities, genetic or pharmaceutical inhibition of the PEMT pathway recapitulates the effects of Lrh‐1 knockdown on mitochondria. Furthermore, we show that S ‐adenosyl methionine, a cofactor required for PEMT, is sufficient to induce Lrh‐1 transactivation and consequently mitochondrial biogenesis. Conclusions A PEMT–LRH‐1 axis regulates mitochondrial biogenesis and beta‐oxidation in hepatocytes.
Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial
Authors: Gerard J. Criner, Antoine Delage, Kirk Voelker, D. Kyle Hogarth, Adnan Majid, Michael Zgoda, Donald R. Lazarus, Roberto Casal, Sadia B. Benzaquen, Robert C. Holladay, Adam Wellikoff, Karel Calero, Mark J. Rumbak, Paul R. Branca, Muhanned Abu-Hijleh, Jorge M. Mallea, Ravi Kalhan, Ashutosh Sachdeva, C. Matthew Kinsey, Carla R. Lamb, Michael F. Reed, Wissam B. Abouzgheib, Phillip V. Kaplan, Gregory X. Marrujo, David W. Johnstone, Mario G. Gasparri, Arturo A. Meade, Christopher A. Hergott, Chakravarthy Reddy, Richard A. Mularski, Amy Hajari Case, Samir S. Makani, Ray W. Shepherd, Benson Chen, Gregory E. Holt, Simon Martel
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).
Balance Deficits and Functional Disability in Cancer Survivors Exposed to Neurotoxic Cancer Treatments
Authors: J. Matt McCrary, David Goldstein, Terry Trinh, Hannah C. Timmins, Tiffany Li, Jasmine Menant, Michael Friedlander, Craig R. Lewis, Mark Hertzberg, Siobhan O’Neill, Tracy King, Annmarie Bosco, Michelle Harrison, Susanna B. Park
Journal: Journal of the National Comprehensive Cancer Network (2019)

Chemotherapy-induced peripheral neuropathy (CIPN) persists after treatment in up to 40% of cancer survivors and has been linked with increased balance deficits, disabilities, and fall occurrences. This study aimed to comprehensively assess the links between CIPN, balance deficits, and functional disability and to inform the development of clinical screening tools for patients at risk of these events.A total of 190 cancer survivors exposed to neurotoxic chemotherapies (age, 57 ± 13 years; average time from completion of neurotoxic therapy, 12 ± 11 months) attended a neurology research clinic for a single cross-sectional assessment of patient-reported and objective CIPN, standing balance in 4 conditions of increasing difficulty, and functional disability.Most patients (68%) reported CIPN symptoms at assessment. Symptomatic patients displayed increased functional disability (F=39.4; P<.001) and balance deficits (F=34.5; P<.001), with degree of balance impairments consistent with a healthy elderly population (age ≥65 years) reporting multiple falls over the subsequent year. Increasing CIPN severity correlated with increasing functional disability (clinically assessed R2=0.46; patient-reported R2=0.49; P<.001) and balance deficits (clinically assessed R2=0.41; patient-reported R2=0.30; P<.001). A 5-factor model of key independent correlates-patient-reported numbness/tingling, weakness, and balance deficit; age; and vibration perception-was strongly linked to balance deficits (R2=0.46; P<.001) and functional disability (R2=0.56; P<.001).This study confirms links between increasing CIPN severity and increasing balance deficits and functional disability using comprehensive CIPN assessment methodology. The extent of balance deficits in patients with CIPN underscores the functional consequences of neurotoxicity. A 5-factor model provides a foundation for clinical screening tools to assess balance deficits and functional disability in patients exposed to neurotoxic chemotherapies.
Comparison of the Harms, Advantages, and Costs Associated With Alternative Guidelines for the Evaluation of Hematuria
Authors: Mihaela V. Georgieva, Stephanie B. Wheeler, Daniel Erim, Rebecca Smith-Bindman, Ronald Loo, Casey Ng, Tullika Garg, Mathew Raynor, Matthew E. Nielsen
Journal: JAMA Internal Medicine (2019)

Existing recommendations for the diagnostic testing of hematuria range from uniform evaluation of varying intensity to patient-level risk stratification. Concerns have been raised about not only the costs and advantages of computed tomography (CT) scans but also the potential harms of CT radiation exposure.To compare the advantages, harms, and costs associated with 5 guidelines for hematuria evaluation.A microsimulation model was developed to assess each of the following guidelines (listed in order of increasing intensity) for initial evaluation of hematuria: Dutch, Canadian Urological Association (CUA), Kaiser Permanente (KP), Hematuria Risk Index (HRI), and American Urological Association (AUA). Participants comprised a hypothetical cohort of patients (n = 100 000) with hematuria aged 35 years or older. This study was conducted from August 2017 through November 2018.Under the Dutch and CUA guidelines, patients received cystoscopy and ultrasonography if they were 50 years or older (Dutch) or 40 years or older (CUA). Under the KP and HRI guidelines, patients received different combinations of cystoscopy, ultrasonography, and CT urography or no evaluation on the basis of risk factors. Under the AUA guidelines, all patients 35 years or older received cystoscopy and CT urography.Urinary tract cancer detection rates, radiation-induced secondary cancers (from CT radiation exposure), procedural complications, false-positive rates per 100 000 patients, and incremental cost per additional urinary tract cancer detected.The simulated cohort included 100 000 patients with hematuria, aged 35 years or older. A total of 3514 patients had urinary tract cancers (estimated prevalence, 3.5%; 95% CI, 3.0%-4.0%). The AUA guidelines missed detection for the fewest number of cancers (82 [2.3%]) compared with the detection rate of the HRI (116 [3.3%]) and KP (130 [3.7%]) guidelines. However, the simulation model projected 108 (95% CI, 34-201) radiation-induced cancers under the KP guidelines, 136 (95% CI, 62-229) under the HRI guidelines, and 575 (95% CI, 184-1069) under the AUA guidelines per 100 000 patients. The CUA and Dutch guidelines missed detection for a larger number of cancers (172 [4.9%] and 251 [7.1%]) but had 0 radiation-induced secondary cancers. The AUA guidelines cost approximately double the other 4 guidelines ($939/person vs $443/person for Dutch guidelines), with an incremental cost of $1 034 374 per urinary tract cancer detected compared with that of the HRI guidelines.In this simulation study, uniform CT imaging for patients with hematuria was associated with increased costs and harms of secondary cancers, procedural complications, and false positives, with only a marginal increase in cancer detection. Risk stratification may optimize the balance of advantages, harms, and costs of CT.
Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma
Authors: Jiabin Cai, Lei Chen, Zhou Zhang, Xinyu Zhang, Xingyu Lu, Weiwei Liu, Guoming Shi, Yang Ge, Pingting Gao, Yuan Yang, Aiwu Ke, Linlin Xiao, Ruizhao Dong, Yanjing Zhu, Xuan Yang, Jiefei Wang, Tongyu Zhu, Deping Yang, Xiaowu Huang, Chengjun Sui, Shuangjian Qiu, Feng Shen, Huichuan Sun, Weiping Zhou, Jian Zhou, Ji Nie, Chang Zeng, Emily Kunce Stroup, Xu Zhang, Brian C-H Chiu, Wan Yee Lau, Chuan He, Hongyang Wang, Wei Zhang, Jia Fan
Journal: Gut (2019)

Objective The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC. Design Applying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 patients with HCC, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularisation for feature selection. Results The 5hmC-Seal data from patients with HCC showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer staging system from non-HCC (validation set: area under curve (AUC)=88.4%; (95% CI 85.8% to 91.1%)), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumours (eg, ≤2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC=84.6%; (95% CI 80.6% to 88.7%)), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (eg, smoking/alcohol intake history). Conclusion We have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.
Retrospective evaluation of resected ampulla of vater adenocarcinoma (AOVA): Clinicopathologic variables and long-term outcomes—REAL study.
Authors: Neelam Vijay Desai, Tania Zuluaga Toro, Lizette Vila Duckworth, Alex Sommerfeld, Ahmad Alkhasawneh, Wei Hou, Alison Ivey, Thomas J. George
Journal: Journal of Clinical Oncology (2012)

e14612 Background: AOVA accounts for about 1% of GI cancers. 30% of patients receive curative intent resection with 5-year survival between 20-50%. Limited data are available concerning the value of adjuvant therapy. AOVA may be intestinal or biliary based on histology with each associated with a different natural history and prognosis. This study aims to characterize clinicopathologic features of this disease and associate these with outcomes. Methods: An IRB-approved retrospective review of all patients at the University of Florida between 2000-2011 was undertaken to identify patients with resected AOVA. Periampullary tumors were excluded. Independent histologic review to define intestinal versus biliary subtype and molecular phenotype (including CK 7, 19, 20, SMAD4, CDX2 and MUC1) was undertaken. Chi-square test was used to determine significance between variables. Results: 68 total patients were identified and analyzed. Clinical variables, relapse and survival data are presented (Table). For patients &lt;70 years old, median OS was 69 months vs 13 months for patients &gt;70 years (P=0.0115). Histologic and molecular subgroup analysis is ongoing. Conclusions: AOVA long-term outcomes are consistent with previous publications with 5-year survival of 32%. Age and stage appear to have a substantial impact on survival. Histologic and molecular analysis may further define patient subsets and will be reported. [Table: see text]
Myeloproliferative Neoplasms in Asia, Including Middle East, Turkey, and Algeria: Epidemiological Indices and Treatment Practice Patterns from the Multinational, Multicenter, Observational MERGE Registry
Authors: Mohamed A Yassin, Ali Taher, Vikram Mathews, Hsin-An Hou, Tahir Shamsi, Tulin Tuglular, Zhijian Xiao, Soo-Jeong Kim, Depei Wu, Junmin Li, Gerd Rippin, Islam Sadek, Asif Siddiqui, Raymond S Wong
Journal: Blood (2018)
Screening for Thyroid Cancer
Authors: Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Michael J. Barry, Karina W. Davidson, Chyke A. Doubeni, John W. Epling, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, Maureen G. Phipps, Michael Silverstein, Melissa A. Simon, Albert L. Siu, Chien-Wen Tseng
Journal: JAMA (2017)

<h3>Importance</h3> The incidence of thyroid cancer detection has increased by 4.5% per year over the last 10 years, faster than for any other cancer, but without a corresponding change in the mortality rate. In 2013, the incidence rate of thyroid cancer in the United States was 15.3 cases per 100 000 persons. Most cases of thyroid cancer have a good prognosis; the 5-year survival rate for thyroid cancer overall is 98.1%. <h3>Objective</h3> To update the US Preventive Services Task Force (USPSTF) recommendation on screening for thyroid cancer. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the benefits and harms of screening for thyroid cancer in asymptomatic adults, the diagnostic accuracy of screening (including neck palpation and ultrasound), and the benefits and harms of treatment of screen-detected thyroid cancer. <h3>Findings</h3> The USPSTF found inadequate direct evidence on the benefits of screening but determined that the magnitude of the overall benefits of screening and treatment can be bounded as no greater than small, given the relative rarity of thyroid cancer, the apparent lack of difference in outcomes between patients who are treated vs monitored (for the most common tumor types), and observational evidence showing no change in mortality over time after introduction of a mass screening program. The USPSTF found inadequate direct evidence on the harms of screening but determined that the overall magnitude of the harms of screening and treatment can be bounded as at least moderate, given adequate evidence of harms of treatment and indirect evidence that overdiagnosis and overtreatment are likely to be substantial with population-based screening. The USPSTF therefore determined that the net benefit of screening for thyroid cancer is negative. <h3>Conclusions and Recommendation</h3> The USPSTF recommends against screening for thyroid cancer in asymptomatic adults. (D recommendation)
Expectations of healthcare quality: A cross-sectional study of internet users in 12 low- and middle-income countries
Authors: Sanam Roder-DeWan, Anna D. Gage, Lisa R. Hirschhorn, Nana A. Y. Twum-Danso, Jerker Liljestrand, Kwanele Asante-Shongwe, Viviana Rodríguez, Talhiya Yahya, Margaret E. Kruk
Journal: PLoS Medicine (2019)

Background High satisfaction with healthcare is common in low- and middle-income countries (LMICs), despite widespread quality deficits. This may be due to low expectations because people lack knowledge about what constitutes good quality or are resigned about the quality of available services. Methods and findings We fielded an internet survey in Argentina, China, Ghana, India, Indonesia, Kenya, Lebanon, Mexico, Morocco, Nigeria, Senegal, and South Africa in 2017 (N = 17,996). It included vignettes describing poor-quality services—inadequate technical or interpersonal care—for 2 conditions. After applying population weights, most of our respondents lived in urban areas (59%), had finished primary school (55%), and were under the age of 50 (75%). Just over half were men (51%), and the vast majority reported that they were in good health (73%). Over half (53%) of our study population rated the quality of vignettes describing poor-quality services as good or better. We used multilevel logistic regression and found that good ratings were associated with less education (no formal schooling versus university education; adjusted odds ratio [AOR] 2.22, 95% CI 1.90–2.59, P < 0.001), better self-reported health (excellent versus poor health; AOR 5.19, 95% CI 4.33–6.21, P < 0.001), history of discrimination in healthcare (AOR 1.47, 95% CI 1.36–1.57, P < 0.001), and male gender (AOR 1.32, 95% CI 1.23–1.41, P < 0.001). The survey did not reach nonusers of the internet thus only representing the internet-using population. Conclusions Majorities of the internet-using public in 12 LMICs have low expectations of healthcare quality as evidenced by high ratings given to poor-quality care. Low expectations of health services likely dampen demand for quality, reduce pressure on systems to deliver quality care, and inflate satisfaction ratings. Policies and interventions to raise people's expectations of the quality of healthcare they receive should be considered in health system quality reforms.
Oral anticancer therapy: Does the patient understand?
Authors: Donna M. Graham, Richard Martin Bambury, Jeffri R. M. Ismail, Margaret O'Keefe, Catherine Drake, Alan O'Shea, Eugene J. Moylan, Derek Gerard Power, Seamus O'Reilly
Journal: Journal of Clinical Oncology (2012)

e16506 Background: Oral anti-cancer therapy (OAT) prescribing is increasing. Safety and adherence issues surrounding OAT are causing a shift in the traditional roles and responsibilities of oncologists, nurses and pharmacists. This study aims to investigate patients’ perception of education and safety surrounding OAT use. Methods: Over a 6-month period an anonymous cross-sectional survey was offered to all patients (pts) attending for cancer treatment with OAT at Irish hospitals with cancer services in the South-West region. Data was prospectively analyzed using standard statistical tools for non-parametric data. Results: A total of 172 surveys were distributed and 101 pts responded (59%). Of these, 53 (54%) were female. Median age was 62 (range 29-80 yrs). Diagnosis was colorectal cancer in 49 pts (48%), breast cancer in 13 (13%) and glioma in 12 (12%). Of treatments used, 85% were oral chemotherapy and 15% oral biological therapy. The most commonly used agent was capecitabine (61%). When commencing OAT, 17 (17%) of respondents felt they did not understand it. Understanding was improved by pt education by a doctor (p=0.03) or hospital-based nurse (p=0.04) and provision of information booklets (p=0.04). Pts were unaware of interactions in 30% of cases and 20% were not aware of any safety issues. Pts who had been given information leaflets were significantly more aware of safety including careful handling (p&lt;0.001), storage conditions (p=0.02) and safe disposal (p&lt;0.001). Pts attending nurse-led oral chemotherapy clinics (NOCC) were significantly more aware of safety issues (p=0.04). Of respondents, 1% reported taking too many tablets and 15% had forgotten to take OAT on ≥1 occasion. NOCC improved adherence (p=0.03). Conclusions: OAT, when indicated, is an option for selected pts who are compliant and educated about complications. This study highlights issues with pt education and safety awareness. To our knowledge the factors influencing this have not been previously explored. A significant proportion of our pts were sub-optimally educated regarding medication interactions, storage needs, handling and disposal precautions. Educational tools to aid healthcare professionals in pt instruction and NOCC significantly improve patient understanding.
Annals Graphic Medicine - Dr. Mom: Working the Weekend
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2019)

Web Exclusives6 August 2019Annals Graphic Medicine - Dr. Mom: Working the WeekendFREEGrace E. Farris, MDGrace E. Farris, MDMount Sinai School of Medicine, New York, New York (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0048 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0042.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Icahn School of Medicine at Mount Sinai and chief of hospital medicine at Mount Sinai West hospital in New York, New York. You can view her work at her Web site: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 August 2019Volume 171, Issue 3Page: W9-W10KeywordsConflicts of interestDisclosureHospital medicineHospitalists ePublished: 6 August 2019 Issue Published: 6 August 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...