tbuckley/cabot-search huggingface dataset:
Progress on Decreasing Salt Consumption
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2017)

Excess salt consumption is associated with hypertension, stroke, and heart disease.One way to avoid excess salt is to eat fresh foods and do your own food preparation.However, for many reasons, with convenience being a key consideration, many Americans commonly eat packaged food, which is a major source of salt.Unlike homemade food, consumers cannot control how much salt is in the packaged foods.Thus, decreasing the salt content in packaged food has been a principal focus of public health efforts.Therefore, it is gratifying to read the study by Poti and colleagues 1 in this issue looking at temporal trends in the salt content of packaged food and beverages purchased by a nationally representative panel of households.The investigators found that the per capita quantity of salt (milligrams per
The gathering storm: hydroxychloroquine retinopathy screening in the U.K.
Authors: W.R. Tucker, J. Galloway, S. Walsh
Journal: British Journal of Dermatology (2017)

Hydroxychloroquine (HCQ) is a quinolone thought to downregulate the immune response by interfering with the ability of antigen‐presenting cells to process autoantigens.1 The licenced indications for HCQ use are rheumatoid arthritis, including juvenile idiopathic arthritis, systemic and discoid lupus erythematosus, and2 certain dermatological conditions caused or aggravated by sunlight. Recent evidence that it can reduce mortality and morbidity in systemic lupus erythematous3 has led to greater use in rheumatology, dermatology and increasingly oncology.4 Prescribing in the U.K. has increased from approximately 50 000 patients in 20104,5,6,7,8 to 90 000 patients in 2015.8,9,10,11 Such rapid shifts in prescribing practice have refocused attention on the most devastating side‐effect of HCQ: toxic retinopathy, which can be irreversible if not detected early. The mechanism of retinal toxicity is not well understood but HCQ appears to cross the blood–retinal barrier and affect photoreceptors of the retina initially, changes which may be anatomically and clinically invisible, before later binding to melanin in the retinal pigment epithelium (RPE) when the classical pigmented bull's eye maculopathy can occur.12 The low incidence (0·5%) of reported toxicity in previous studies may be explained by having to use these visible signs of end‐stage retinopathy as the biomarker.13
Abstract P015: Hypoxia Regulates Embryonic Cardiac Myocyte Proliferation and Differentiation
Authors: Alexander Zambon, Jennifer Stowe
Journal: Circulation Research (2011)

Mammalian cardiac myocytes (CM) proliferate readily during development but exit the cell cycle perinatally. The molecular mechanism for this is poorly understood could lead to new approaches for cardiac regeneration. We employed a novel bioinformatics approach to identify transcription factors that may control perinatal cell-cycle arrest and identified hypoxia inducible factor 1α (Hif1α) as a potential regulator of CM proliferation and differentiation. To test our hypothesis, e12.5d embryonic heart cells were cultured in atmospheric (17%) or hypoxic (3%) [O2] and then assessed for proliferation over 4 days. Total cell numbers were significantly increased (∼2 fold, P&lt;0.005) in cells cultured in 3% vs. 17% [O2] after 4 days. Hypoxia increased numbers of cTn+ cells labeled with p-Histone-H3 indicating an increase in CM proliferation. Carboxyfluorescein succinimidyl ester staining indicated that the majority (70%) of cells cultured in 3% [O2] divided 2–3 times while the majority (73%) of cells in 17% [O2] divided 0–1 times after 3 days of culture. As expected, hypoxia stabilized the Hif1α protein and induced the expression of Vegf. Messenger RNA for the G1-S phase cyclin dependent kinase Ccnd2 was increased (&gt;2 fold) in hypoxic vs. atmospheric cultured cells indicating that hypoxia my increase proliferation by regulating the expression of cell cycle machinery. Furthermore, early mesodermal transcription factors Brachyury and Mesp1 and the CM progenitor marker Nkx2.5 were induced (&gt;5 fold) in hypoxic vs. atmospheric [O2] cultured cells suggesting that hypoxia positively regulates early mesodermal and CM progenitor cell differentiation. To validate this hypothesis, we differentiated mouse embryonic stem cells in atmospheric and hypoxic [O2] and observed similar increases in the expression of Brachyury, Mesp1 and Nkx2.5 in hypoxic differentiated cells. Transient culture (2 d) of embryoid bodies (EBs) in hypoxia increased the frequency of beating EBs and the % of cTn+ cells compared to cells differentiated in atmospheric O2. Taken together these data suggest that the hypoxic environment in which CMs develop may serve as a key signal that regulates mesodermal progenitor marker expression and CM progenitor cell differentiation and proliferation.
Cellular analysis in bronchoalveolar lavage: inherent limitations of current standard procedure
Authors: Benjamin-Alexander Bollmann, Benjamin Seeliger, Nora Drick, Tobias Welte, Jens T. Gottlieb, Mark Greer
Journal: European Respiratory Journal (2017)

Bronchoalveolar lavage (BAL) is an established procedure for diagnosing respiratory infections and characterising non-infective lung diseases [1]. Increasingly, emphasis has been placed on BAL cellular composition in the diagnostic algorithms for interstitial lung disease [2] and chronic lung allograft dysfunction following lung transplantation [3]. The "dead-space" concept: bronchoscope size and instillation protocol significantly alter BAL cellular composition <http://ow.ly/ZEaj30be7HV>
16 Outcomes for home parenteral nutrition patients in northern ireland – a ten year review (2006–2016)
Authors: E Gardiner, E Murray, G Rafferty, GB Turner
Journal: Gut (2017)

Background  Intestinal failure (IF) patients in Northern Ireland requiring home parenteral nutrition (hPN) are managed in the Belfast Trust by the Nutrition team at Belfast City Hospital.  Aim  The aims of this review were to analyse the aetiology of IF; admission rates (particularly those due to catheter related blood stream infections (CRBSI)) and patient outcomes.  Method  Electronic records including radiology and microbiology results for all patients on hPN in Northern Ireland from 2006–2016 were reviewed.  Results  86 patients used hPN between 2006–2016. One patient was excluded due to incomplete data. The average age at presentation was 51 (range 19–78). The mean number of days hPN was administered was 1072 (range 23–3834). The most common causes of IF were Crohn’s disease (29%), surgical complications (22%) and mesenteric ischaemia (18%). There were 414 admissions in the timescale – 137 admissions were due to CRBSI. The CRBSI rate was 1.5 per 1000 catheter days (previously 1.81 (1994–2014)). 43 patients had no infections (51%) and 10 had >5 infections, accounting for 55% of all CRSBI admissions. The most common organisms identified were Gram negative organisms (38%) Coagulase Negative Staphylococci (34%); and Yeasts (11%). 28% of patients remain on home parenteral nutrition; 21 patients have had restoration of intestinal continuity.  Conclusions  Parenteral nutrition remains a safe treatment in the management of intestinal failure. Our CRBSI rate has reduced in the past 10 years, likely due to ongoing patient education and training.
Abstract 58: The Quality of Prearrival Cardiopulmonary Resuscitation: A Performance Review of Regional Dispatchers and Bystanders
Authors: Hidetada Fukushima, Hideki Asai, Hironori KItaoka, Asami Iwamura, Tadahiko Seki, Yasuyuki Kawai, Kazunobu Norimoto, Yasuyuki Urisono, Kenji Nishio, Masami Imanishi, Kazuo Okuchi
Journal: Circulation (2014)

Background:  Emergency Medical Service (EMS) dispatchers and bystanders play key roles in EMS pre-arrival cardiopulmonary resuscitation (CPR). There is, however, no standardized review process for evaluating the performance of dispatchers and bystanders.   Method:  We conducted a performance review of pre-arrival CPR in Nara city (276.8km2, 364,000 residents). Dispatch instruction for CPR was defined as ‘Complete Instruction’ (dispatchers recognized first compression) or ‘Incomplete Instruction’ (dispatchers failed to recognize first compression). Based on evaluation by EMS at the scene, bystander CPR continuing until EMS arrival was classified as ‘Continuous Compression’. Bystander CPR with hard and fast chest compressions was classified as ‘Good Compression’.   Results:  We reviewed 197 cardiac arrest calls between Nov. 2013 and Mar. 2014. CPR was already in progress in 51 cases. In the remaining 146 cases, CPR need was recognized in 129. Due to barriers preventing CPR instruction, dispatchers provided instruction in 106 cases and bystanders performed CPR in 51 cases. Among these, dispatchers provided ‘Complete Instruction’ in 33 cases and ‘Incomplete Instruction’ in 18 cases. ‘Continuous Compression’ was performed in 37 cases and significantly more often in the ‘Complete Instruction’ than the ‘Incomplete Instruction’ group (28/33[84.8%] vs 9/18[50.0%], Chi-square test p=0.008*). The median elapsed time before first compression was 145 seconds in the ‘Continuous Compression’ with ‘Complete Instruction’ group (N=28). ‘Good Compression’ was performed in only 15 cases.   Conclusion:  Our performance review found that ‘Complete Instruction’ was strongly associated with immediate and continuous bystander CPR until EMS arrival. Unfortunately, ‘Good Compression’ was not frequently provided. Performance reviews of both dispatchers and bystanders can yield useful information for improving the quality of pre-arrival CPR.
Uptake and patterns of use of gemcitabine for stage IV pancreatic cancer.
Authors: Paul Eliezer Oberstein, Dawn L. Hershman, John A. Chabot, Lauren Khanna, Beverly J. Insel, Alfred I. Neugut
Journal: Journal of Clinical Oncology (2013)

e15074 Background: Gemcitabine was approved by the FDA in 1996 and subsequently became the standard of care for patients with advanced pancreatic cancer. We investigated the frequency and predictors of gemcitabine use among the elderly with stage IV pancreatic cancer. Methods: We used the SEER-Medicare database to identify subjects &gt;65 years who were diagnosed with stage IV pancreatic cancer between 1/1/98-12/31/05, and survived for &gt;30 days following diagnosis. After excluding patients who received non-gemcitabine chemotherapy, we used multivariate logistic regression models to analyze the association between patient and tumor characteristics and receipt of gemcitabine compared to no chemotherapy. Results: Among 3,208 patients analyzed, 1,614 (50.3%) received gemcitabine chemotherapy, 1,480 (46.1%) received no chemotherapy; 114 (3.5%) received non-gemcitabine therapy and were excluded from multivariate analysis. Among patients diagnosed early in the study period (1998-2000) the rate of gemcitabine use was 44.9%. In multivariate analysis, gemcitabine use was not associated with gender, race, tumor histology, or increasing comorbidities. Unmarried patients were less likely to receive gemcitabine (OR=0.65, 95% CI 0.55-0.76), and use decreased with increasing age (for those 75-79, OR=0.72. 95% CI 0.58-0.90, for those 80-84, OR=0.38, 95% CI 0.30-0.49, for those &gt;84, OR=0.21 95%CI 0.15-0.30) compared to those 65-69. Patients diagnosed in 2004-2005 (OR= 1.51, 95% CI 1.23-1.84) were more likely to receive gemcitabine compared to those diagnosed in 1998-2000. Higher socioeconomic status were associated with increased utilization of gemcitabine (highest quintile OR=2.14, 95% CI 1.60-2.85, second and third quintile OR=1.45, 95%CI 1.10-1.93, compared to lowest quintile.) Conclusions: Although chemotherapy for stage IV pancreatic cancer confers a small survival benefit, uptake of gemcitabine was rapid with 55% of elderly patients receiving this therapy by 2004-2005. Future studies should explore the reasons behind the increased use in patients with higher socioeconomic status.
General practitioners' views about managing depression in patients with chronic obstructive pulmonary disease
Authors: Abebaw Yohannes
Journal: European Respiratory Journal (2011)

Introduction: Depression is common in patients with chronic obstructive pulmonary disease (COPD). COPD patients consult their general practitioners at least once or twice a year because of acute exacerbations. There is little data available on the management of depression in patients with COPD.  Aims: The study investigated general practitioners (GP9s) views about recognising and treating depression in patients with COPD.  Methods: We conducted a postal survey of 3,957 GP9s in England about their views on recognising and treating depression in patients with COPD. The survey examined the GP9s views using a likert scale (0 = strongly disagree, 2 = neither agree or disagree, 4 = strongly agree). The questions were prioritising treatment, value of screening for depression, difficulty of treating depression, best way of treating depression, depression exacerbates and interferes self-managment of COPD.  Results: 3,957 general practitioners were mailed. Of these, 857 (22%) complete responses were received. Seventy-two percent of GPs agree screening for depression regularly, 9% disagree and neutral 19%. Prioritising treatment of COPD symptoms over depression disagree 21%, neutral 46% and 33% agree. Convincing COPD patients that depression needs treatment: disagree 27%, neutral 30% and agree 43%. Depression exacerbates COPD symptoms: disagree 9%, neutral 24%, and agree 67%. Depression impairs self-management of COPD: disagree 4% and agree 96%.  Conclusions: Most GPs reported the importance of screening for depression regularly and depression impedes the self-management of COPD. Over two-fifths of the GPs find it difficult to convince patients to offer treatment. Further studies are required.
Coffee and herbal tea consumption is associated with lower liver stiffness in the general population: The Rotterdam study
Authors: Louise J.M. Alferink, Juliana Fittipaldi, Jessica C. Kiefte-de Jong, Pavel Taimr, Bettina E. Hansen, Herold J. Metselaar, Josje D. Schoufour, M. Arfan Ikram, Harry L.A. Janssen, Oscar H. Franco, Sarwa Darwish Murad
Journal: Journal of Hepatology (2017)
What's hot that the other lot got
Authors: B. Soar
Journal: Thorax (2015)

This Croatian retrospective case control study compared patients who had undergone talc pleurodesis with a control group of matched patients who were treated with serial thoracentesis.1 One hundred and seven patients with proven malignant pleural effusions (metastatic breast and lung cancer) were included. Fifty-six were treated with talc pleurodesis and a control group of 51 patients matched in age, sex and disease underwent serial thoracentesis. The overall and subgroup survival with different tumour types and different performance status (PS) 1, 2 and 3 were compared. Patients undergoing talc pleurodesis had a longer average survival interval (MS) than the patients who underwent thoracentesis (MS 21.5 and MS 9 weeks respectively, p<0.001). The best results were observed in those with PS 1 (MS 35.5 and MS 11 weeks) and PS 2 (MS 21 and MS 10 weeks). There was no difference in groups at PS 3. The authors conclude that patients treated with …
Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: A randomized, double-blind trial of olanzapine versus haloperidol (American Journal of Psychiatry (2003) 160, (1396-1404))
Authors: J. A. Lieberman, G. Tollefson, M. Tohen, A. I. Green, R. E. Gur, R. Kahn, J. McEvoy, D. Perkins, T. Sharma, R. Zipursky, H. Wei, R. M. Hamer
Journal: American Journal of Psychiatry (2009)
Annotated Bibliography of Cause-of-Death Validation Studies: 1958-1980.
Journal: Annals of Internal Medicine (1984)

This bibliography contains an annotated listing of 128 published and unpublished papers on the quality of cause-of-death   Items selected for inclusion are limited to those available in English written or published since 1957 and based on substantive data.  The geographical focus of the bibliography is worldwide.  It is noted that no country has a well-defined program for systematically assessing the quality of medical certifications being reported on death certificates or for measuring the error effects on the levels and trends of cause-of-death statistics.  (EXCERPT)
Japan's worst nuclear accident leave two fighting for life
Authors: J. Lamar
Journal: BMJ (1999)

Forty nine people were exposed to radiation—two with a potentially lethal dose—after Japan's worst nuclear accident struck a uranium processing plant on 30 September.

The accident occurred at a facility run by JCO, an affiliate of Sumitomo Metal Mining, in Tokaimura, 70 miles north west of Tokyo, as a result of an attempted short cut.

In the process of purifying reactor fuel, workers were supposed to use an automatic pump to mix up to 2.4 kg of enriched uranium with nitric acid Instead, they manually used a stainless steel bucket and mixed 16 kg of the fissile …
Abstract 374: Cardiac Fibroblasts are Essential During Pathological Stress
Authors: Jill T Kuwabara
Journal: Circulation Research (2015)

Cardiac fibroblasts reportedly play a role in normal heart function and are responsible for adverse remodeling after heart injury. Although fibroblast activities can be detrimental during disease, a basal level of cardiac fibroblast activity is required to maintain structural integrity and prevent rupture. We use transgenic mouse models to demonstrate that reduced fibroblasts numbers have serious consequences during pathological stress. At baseline, we observe a dramatic loss of the cardiac fibroblast lineage, which results in vasculature alterations, such as capillary dilation and decreased capillary density. Baseline changes in basement membrane (laminin) and cardiomyocyte structure have also been identified in fibroblast deficient hearts. These phenotypic changes become exacerbated after surgery indicating that fibroblasts are necessary for crosstalk between other cell types in the heart. In addition, we predict that the loss of fibroblasts will cause enhanced deterioration in cardiac function after injury due to reduced structural integrity of the heart. We will use transverse aortic constriction (TAC) as a pressure-overload model. After 5 weeks of TAC, we observe a ~50% (Baseline 71.99±6.06, TAC5wks 22.09±1.89) decrease in ejection fraction in fibroblast deficient hearts compared to a ~16% (Baseline 76.21±7.08, TAC5wks 59.59) decrease in control hearts. Our data suggest that a specific level of cardiac fibroblast activity is required to maintain normal heart function. Our goal is to identify both deleterious and beneficial roles of fibroblasts in the response of the heart to the types of pathological stress commonly encountered in patients.
A pretrained neural network shows similar diagnostic accuracy to medical students in categorizing dermatoscopic images after comparable training conditions
Authors: P. Tschandl, H. Kittler, G. Argenziano
Journal: British Journal of Dermatology (2017)

Automated image classification by machine vision is evolving, largely because of the increasing efficiency of neural networks with special architectures such as convolutional neural networks (CNN)1. A recent study comparing board certified dermatologists with CNN suggested that CNN may achieve diagnostic accuracies similar to human experts2. We demonstrated that medical students without prior knowledge of dermatoscopy learn equally well from an analytic or heuristic teaching approach3.

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Next-generation sequencing (NGS)-based profiling of pancreatic acinar cell carcinoma for identification of a recurrent <i>SND1-BRAF</i> fusion.
Authors: Vincent A. Miller, Juliann Chmielecki, Katherine Hutchinson, Garrett Michael Frampton, Siraj M. Ali, Jeffrey S. Ross, Chanjuan Shi, William Pao, David S. Klimstra, Roman Yelensky, Doron Lipson, Phil Stephens
Journal: Journal of Clinical Oncology (2014)

11029 Background: Pancreatic acinar cell carcinoma (ACC) is a rare subtype of pancreatic cancer with a poor prognosis. Chemotherapy and radiation therapy have limited efficacy against these tumors, and novel treatment strategies are needed. Previous whole exome sequencing studies have classified these tumors as genomically heterogeneous with distinct genomic profiles from other pancreatic cancers (Jiao et al., 2013). To identify genomic alterations that could serve as potential therapeutic targets, we profiled a small set (n=3) of pancreatic ACC tumors. Methods: Extracted tumor DNA underwent hybrid capture for 3,769 exons from 236 cancer-related genes plus 47 introns of 19 genes frequently rearranged in cancer and was sequenced to an average median depth of 728x. Sequences were assessed for base substitutions, insertions and deletions, rearrangements, and copy number changes. We characterized signaling properties of confirmed molecular alterations by ectopic expression of engineered cDNAs in 293H cells. Results: We observed an average of two genomic alterations per tumor. A recurrent SND1-BRAF rearrangement was identified in two samples that lacked other known driver events. This fusion was similar in structure to other reported BRAF fusions, and preserves the serine-threonine kinase domain of the protein. In vitro studies of SND1-BRAF suggest that it activates MAPK signaling, which can be inhibited by trametinib and sorafenib. Conclusions: Although the number of samples in this study is small, fusions involving BRAF potentially occur at a high frequency in pancreatic ACC and may represent a novel therapeutic target in this disease. These alterations occur within intronic regions, and may be missed by sequencing methods that investigate exonic regions only. Preclinical data suggest that SND1-BRAF driven activation of MAPK signaling can be inhibited with existing targeted agents, suggesting that a subset of this virulent disease may be amenable to treatment with available therapies. NGS-based profiling of an expanded cohort of pancreatic ACC tumors is ongoing to determine the overall frequency of BRAF fusions in this disease.
Ubiquitin ligase RNF146 coordinates bone dynamics and energy metabolism
Authors: Yoshinori Matsumoto, Jose La Rose, Melissa Lim, Hibret A. Adissu, Napoleon Law, Xiaohong Mao, Feng Cong, Paula Mera, Gerard Karsenty, David Goltzman, Adele Changoor, Lucia Zhang, Megan Stajkowski, Marc D. Grynpas, Carsten Bergmann, Robert Rottapel
Journal: Journal of Clinical Investigation (2017)

Cleidocranial dysplasia (CCD) is an autosomal dominant human disorder characterized by abnormal bone development that is mainly due to defective intramembranous bone formation by osteoblasts. Here, we describe a mouse strain lacking the E3 ubiquitin ligase RNF146 that shows phenotypic similarities to CCD. Loss of RNF146 stabilized its substrate AXIN1, leading to impairment of WNT3a-induced β-catenin activation and reduced Fgf18 expression in osteoblasts. We show that FGF18 induces transcriptional coactivator with PDZ-binding motif (TAZ) expression, which is required for osteoblast proliferation and differentiation through transcriptional enhancer associate domain (TEAD) and runt-related transcription factor 2 (RUNX2) transcription factors, respectively. Finally, we demonstrate that adipogenesis is enhanced in Rnf146-/- mouse embryonic fibroblasts. Moreover, mice with loss of RNF146 within the osteoblast lineage had increased fat stores and were glucose intolerant with severe osteopenia because of defective osteoblastogenesis and subsequent impaired osteocalcin production. These findings indicate that RNF146 is required to coordinate β-catenin signaling within the osteoblast lineage during embryonic and postnatal bone development.