tbuckley/cabot-search huggingface dataset:
Part 7: Neonatal Resuscitation
Authors: Jeffrey M. Perlman, Jonathan Wyllie, John Kattwinkel, Myra H. Wyckoff, Khalid Aziz, Ruth Guinsburg, Han-Suk Kim, Helen G. Liley, Lindsay Mildenhall, Wendy M. Simon, Edgardo Szyld, Masanori Tamura, Sithembiso Velaphi, David W. Boyle, Steve Byrne, Chris Colby, Peter Davis, Hege L. Ersdal, Marilyn B. Escobedo, Qi Feng, Maria Fernanda de Almeida, Louis P. Halamek, Tetsuya Isayama, Vishal S. Kapadia, Henry C. Lee, Jane McGowan, Douglas D. McMillan, Susan Niermeyer, Colm P. F. O’Donnell, Yacov Rabi, Steven A. Ringer, Nalini Singhal, Ben J. Stenson, Marya L. Strand, Takahiro Sugiura, Daniele Trevisanuto, Enrique Udaeta, Gary M. Weiner, Cheo L. Yeo
Journal: Circulation (2015)

GRADEThe task force performed a detailed systematic review based on the recommendations of the Institute of Medicine of the National Academies 4 and using the methodological approach proposed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. 5fter identification and prioritization of the questions to be addressed (using the PICO [population, intervention, comparator, outcomes] format), 6 with the assistance of information specialists, a detailed search for relevant articles was
Expression of PD-1 and PD-L1 in patients with renal cell carcinoma with sarcomatoid dedifferentiation (sRCC).
Authors: Fumi Kawakami, Kanishka Sircar, Jaime Rodriguez-Canales, Pheroze Tamboli, Nizar M. Tannir, Eric Jonasch, Ignacio Ivan Wistuba, Christopher G. Wood, Jose A. Karam
Journal: Journal of Clinical Oncology (2016)

582 Background: sRCC is a very aggressive malignancy, with limited treatment options. Given the recent surge in novel immunotherapeutic agents targeting PD-1 and PD-L1, we decided to investigate the expression of these markers in patients with sRCC. Methods: PD-1 and PD-L1 immunohistochemistry was performed on whole sections from nephrectomy specimens in 118 patients with sRCC and 92 patients with clear cell RCC without sarcomatoid dedifferentiation(ccRCC). PD-1 staining was manually evaluated. PD-1 cell numbers ≥ 1/HPF was defined as positive. PD-L1 staining was evaluated with semiquantitative method (H-score = 0-300) with digital analysis. Results: Of the 118 patients with sRCC, 94 had clear cell epithelioid component and 24 had non-clear cell epithelioid component. In the cohort with ccRCC, 20 were grade 4, 58 were grade 3, and 14 were grade 2. 21 cases of sRCC that received neoadjuvant therapy and 2 sRCC and 1 ccRCC where digitally calculated H-score was at variance with manual evaluation were eliminated from the study. 98.6% (73/74) of clear cell sRCC were positive for PD-1. Similarly, 100% (20/20) of the non-clear cell sRCC, 95% (19/20) of the grade 4, and 55/58 (94.8%) of grade 3 ccRCC were positive for PD-1, whereas 9/14 (64.3%) of the grade 2 ccRCC expressed PD-1 (P= 0.0002). 43.2% (32/74) of clear cell sRCC and 55.0% (11/20) of the non-clear cell sRCC were positive for PD-L1, whereas only 10% of the grade 4 non-sarcomatoid ccRCC were positive for PD-L1 (P= 0.0047). None of the grade 2 and 3 ccRCC expressed PD-L1. All the PD-L1 positive cases except 1 clear cell sRCC case were also PD-1 positive. We found a threshold H-score ≥ 25 in sRCC to stratify patient groups with worse prognosis (P= 0.0435) with 29.3% of the cases showing H-score ≥ 25. High PD-L1 H-score was significantly associated with presence of metastatic disease (P= 0.0284). Conclusions: sRCC (both clear and non-clear cell) showed higher frequency and stronger expression of PD-L1 and higher PD-1 positive cell density compared to ccRCC without sarcomatoid component. High expression of PD-L1 is at significant risk of cancer related mortality for sRCC patients. These findings form a rationale to study PD-1 and PD-L1 targeting agents in patients with sRCC.
Annals On Being a Doctor Story Slam - Playlist for an Organ Donor
Authors: Mohammed "Zeeshan" Nayeemuddin
Journal: Annals of Internal Medicine (2016)

Web Exclusives19 January 2016Annals On Being a Doctor Story Slam - Playlist for an Organ DonorFREEMohammed "Zeeshan" Nayeemuddin, MDMohammed "Zeeshan" Nayeemuddin, MDFrom Temple University Hospital, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/V15-0022 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals On Being a Doctor Story Slam - Playlist for an Organ Donor This story, "Playlist for an Organ Donor," by Dr. Mohammed "Zeeshan" Nayeemuddin, is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation. (Duration 5:52)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.Attendees of the 18 November 2015 Annals On Being a Doctor Story Slam voted this story as one of their 3 favorites.For more videos from and information on Annals On Being a Doctor Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Temple University Hospital, Philadelphia, Pennsylvania.Note: This story is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation. Attendees voted this story as one of their 3 favorites.Corresponding Author: Mohammed "Zeeshan" Nayeemuddin, MD, Temple University Hospital, 3322 North Broad Strett, Philadelphia, PA 19140; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 January 2016Volume 164, Issue 2Page: SS11 ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
PTH-100 A comparative gene expression study between individuals with apparent resistance, spontaneous clearance, or chronic infection from hcv
Authors: P Mandalou, MW Robinson, D Felmlee, C Sieberhagen, T Mindos, D Hegazy, J MacLaughlan, ME Cramp
Journal: Gut (2015)

<h3>Introduction</h3> We have identified a group of high risk injection drug users who share needles, syringes and other injecting paraphernalia over a long period of time yet who remain uninfected by hepatitis C virus (HCV). These individuals appear to be resistant to HCV infection and we have termed them exposed uninfected (EU). Defining factors that may prevent HCV infection in these cohorts could give valuable insight into the mechanisms of natural resistance to HCV. <h3>Method</h3> Individuals at high risk of recurrent exposure to HCV infection from long term IDU were recruited in Plymouth and if HCV antibody and HCV RNA negative were termed exposed uninfected (EU). We have compared the transcriptional profiles of intravenous drug users (IDU) with 3 different outcomes following HCV exposure – chronic hepatitis C infection (CHCV; n = 6), spontaneously resolution of HCV (SR; HCV Ab positive but HCV RNA negative, n = 6) and exposed but uninfected (EU; n = 6). Agilent single channel microarray was performed on RNA isolated from peripheral blood mononuclear cells and the results were analysed on Ingenuity Pathway Analysis software (Qiagen). The identified targets were subsequently validated at a protein level. <h3>Results</h3> 1465 genes between the EU and CHCV group, 4377 between the CHCV and SR group and 4510 between the SR and EU group were significantly up or down regulated. Of the differentially regulated genes, the association with resistance to HCV was strongest for IL27 and CXCL7 which were significantly upregulated in EU (IL27 log fold change EU vs SR: 1.943, p = 1.72E-04 and CXCL7 log fold change EU vs CHCV 2.359, p = 6.04E-03) relative to the other 2 groups. At a protein level, the median IL27 serum level in the EU group (n = 13), detected by sandwich ELISA, was significantly higher (p = 0.008) compared to CHCV (n = 14), healthy control (HC; n = 8) and SR (n = 14) groups. The CD28 mediated T-helper cell signalling pathway was significantly upregulated in SR (ratio 0.348, p = 2.77E-05) relative to the 2 other groups. <h3>Conclusion</h3> Significant differences in gene expression were found in injection drug users with different outcomes from exposure to HCV infection. EU and SR exhibit differences related to innate and adaptive immunity compared to CHCV that likely contribute to natural resistance and spontaneous clearance of HCV. <h3>Disclosure of interest</h3> None Declared.
Phagocytosis
Authors: Thomas P. Stossel
Journal: New England Journal of Medicine (1974)

PHAGOCYTOSIS, the process whereby single cells internalize objects that they encounter, is a matter of survival for primitive unicellular organisms, which use it to gain nourishment. Nearly a century ago Metchnikoff deduced that phagocytic cells protected higher creatures from assault by the ubiquitous microorganisms in the internal and external environment, and championed the cause of phagocytosis as the basis of survival against pyogenic infection.1 Metchnikoff's crusade provoked opposition from the proponents of humoral mechanisms of host protection, but from this controversy arose the realization that humoral factors and phagocytes co-operate,2 a concept popularized by George Bernard Shaw in The Doctor's . . .
Management of the investigation by Enter-net of international foodborne outbreaks of gastrointestinal organisms
Authors: J C Desenclos, I. S.T. Fisher, N Gill
Journal: Eurosurveillance (1999)

The free circulation of people, goods, and foods within the European Union (EU) states has increased the opportunity for international outbreaks of foodborne infections despite prevention efforts to reduce microbiological contamination of foodstuffs. The
Peer counseling in a general hospital
Authors: F G Guggenheim, S O'Hara
Journal: American Journal of Psychiatry (1976)

Self-help groups can aid an individual in coping with and adapting to catastrophic illness. The authors describe a therapeutic technique in which a member of a medical team serves as a catalyst in introducing a "veteran" patient to a newly disabled patient with the same disease or problem so that they can share feelings, experiences, and strategies. Two cases are presented in which patients who were severely depressed benefited from peer counseling. Short-term or "one-shot" encounters can be a valuable way to help some disabled patients deal with the anxiety and helplessness they feel in the acute states of serious disease or injury.
Soundings: The good old days
Authors: Liam Farrell
Journal: BMJ (2004)

After I started in general practice I worked a one-in-two night rota for 12 years. By the end, I was thoroughly burnt out and had so little empathy left that I could sit through Spencer Tracy's death scene in Captains Courageous without blubbering. I hated being called out of bed and calling me was as pointless as Tantalus's mother shouting, “Come on, son, eat your dinner.” My only remaining virtues were sarcasm and lust, my only emotions apathy and self pity, and I was ready to start slaughtering my staff—only I wasn't sure how to hide their still-quivering bodies from the fuzz.

But when the opportunity of joining an out-of-hours cooperative arose, instead of jumping on it like a health insurance company on the occasional perfectly genuine claim, my feelings were curiously equivocal. Would the patients stand for it? Would there be marching in the streets? Or would they just be quietly hurt and disappointed? He's not the same calibre as old Doc Jackson, they'd be saying—he doesn't really care, he's let us down, after our thinking so much of him and nominating him for that award, The Best Doctor In The World... Ever. There is no joy in Mudville, mighty Casey has struck out.

In the end, despite my reservations, I joined the coop and it has proved a smart move. It saved my sanity, allowing me to spend more time with my family, drink more heavily, and join an extreme fascist organisation that considers global warming to be a good thing. I'm also now so chock-full of empathy that when I say, “Have a nice day,” I sometimes actually mean it.

Yet there remains a small stubborn part of me that misses the old days, like a successful artist yearning for his lonely days in the garret eating muffins soaked in spit. My great sin is nostalgia, and time has softened the memories, so I tend to forget the unrelenting long hours, the trivial calls, the physical exhaustion, the wanting to kick somebody. Instead I miss the intimacy, the being there, the always knowing what was going on, the always feeling in control.

Unfortunately, I've found that my patients are getting along very well without me, thanks very much; any competent doctor is quite acceptable, even if he or she doesn't know their seed, breed, and generation. I guess that, most of all, I miss being needed.
Nonclinical Evaluations of Small-Molecule Oncology Drugs: Integration into Clinical Dose Optimization and Toxicity Management
Authors: Donna M. Dambach, Natalie E. Simpson, Thomas W. Jones, Richard J. Brennan, Richard Pazdur, Todd R. Palmby
Journal: Clinical Cancer Research (2016)

Abstract Multidisciplinary approaches that incorporate nonclinical pharmacologic and toxicologic characterization of small-molecule oncology drugs into clinical development programs may facilitate improved benefit–risk profiles and clinical toxicity management in patients. The performance of the current nonclinical safety-testing scheme was discussed, highlighting current strengths and areas for improvement. While current nonclinical testing appears to predict the clinical outcome where the prevalence of specific adverse effects are high, nonclinical testing becomes less reliable for predicting clinical adverse effects that occur infrequently, as with some kinase inhibitors. Although adverse effects associated with kinase inhibitors can often be predicted on the basis of target biology, drugs can be promiscuous and inhibit targets with poorly defined function and associated risks. Improvements in adverse effect databases and better characterization of the biologic activities of drug targets may enable better use of computational modeling approaches in predicting adverse effects with kinase inhibitors. Assessing safety of a lead candidate in parallel with other drug properties enables incorporation of a molecule's best features during chemical design, eliminates the worst molecules early, and permits timely investigation/characterization of toxicity mechanisms for identified liabilities. A safety lead optimization and candidate identification strategy that reduces intrinsic toxicity and metabolic risk and enhances selectivity can deliver selective kinase inhibitors that demonstrate on-target adverse effects identified nonclinically. Integrating clinical and nonclinical data during drug development can facilitate better identification and management of oncology drugs. Follow-up nonclinical studies may be used to better understand the risks in a given patient population and minimize or manage these risks more appropriately. Clin Cancer Res; 22(11); 2618–22. ©2016 AACR. See all articles in this CCR Focus section, “New Approaches for Optimizing Dosing of Anticancer Agents.”
Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies
Authors: Dagfinn Aune, NaNa Keum, Edward Giovannucci, Lars T Fadnes, Paolo Boffetta, Darren C Greenwood, Serena Tonstad, Lars J Vatten, Elio Riboli, Teresa Norat
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality. <b>Data sources</b>&nbsp;PubMed and Embase searched up to 3 April 2016. <b>Study selection</b>&nbsp;Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality. <b>Data synthesis</b>&nbsp;Summary relative risks and 95% confidence intervals calculated with a random effects model. <b>Results</b>&nbsp;45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I<sup>2</sup>=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I<sup>2</sup>=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I<sup>2</sup>=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I<sup>2</sup>=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I<sup>2</sup>=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I<sup>2</sup>=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I<sup>2</sup>=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I<sup>2</sup>=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I<sup>2</sup>=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I<sup>2</sup>=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains. <b>Conclusions</b>&nbsp;This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality.
Hypothyroidism and survival during sunitinib therapy in metastatic renal cell carcinoma (mRCC): A prospective observational analysis.
Authors: F. Bladou, G. Gravis, R. Sabatier, J. Deville, J. Walz, H. Narbonne, M. Marcy, N. Salem, S. Brunelle, J. Eymard
Journal: Journal of Clinical Oncology (2010)

e15013 Background: Sunitinib is currently a standard of care for the treatment of mRCC. Hypothyroidism was frequently observed with sunitinib therapy. This study was conducted to determine the thyroid function and progression-free survival (PFS) of patients (pts) treated for mRCC. Methods: Between October 2005 and March 2009 111 pts treated by sunitinib (50 mg/day, 4 weeks followed by 2 weeks rest) for advanced or mRCC were evaluated for serum TSH, T3 and T4 levels before treatment and every 6 weeks during treatment. Survival was analyzed according to the Landmark method with a day 180 cut off; excluding pts presenting an early progression or censored before day 180. Significance was evaluated with a Log rank test. Results: Median age was 61.7 years. Out of 58 patients (52.3%) developing an alteration of thyroid function, 55 presented a hypothyroidism. Median time to TSH alteration was 294 days and PFS was 342 days for the whole population. Of the 55 hypothyroidism pts, 51 (92.7%) received L-Thyroxin replacement with a median dose of 75 mg/day (range 25-250). The group with abnormal thyroid function at day 180 had a median PFS of 575 days versus 481 days for the group without thyroid abnormality (p=0.94, HR=1.024 (95 CI= [0.544-1.930])). Conclusions: As it was previously described, more than half of our population developed a dysthyroidism under sunitinib therapy. Dysthyroid patients with systematic T4 replacement do not have a significant different PFS (p=0.94) compare to patients without dysthyroidism. Dysthyroidism with systematic hormonal substitution does not influence outcome in sunitinib treated hypothyroidism suffering pts. Nevertheless these conclusions have to be validated by larger comparative studies and biological mechanisms connecting sunitinib and thyroid dysfunction need to be deeply explored. No significant financial relationships to disclose.
Activated Dyes as Antitumor Agents
Authors: Thomas J. Dougherty
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Activated Dyes as Antitumor Agents Get access Thomas J. Dougherty Thomas J. Dougherty Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 4, April 1974, Pages 1333–1336, https://doi.org/10.1093/jnci/52.4.1333 Published: 01 April 1974 Article history Received: 10 December 1973 Accepted: 18 December 1973 Published: 01 April 1974
AB0988 Validation of the Systemic Lupus International Collaborating Clinics (SLICC) Classification Criteria in Juvenile Systemic Lupus Erythematosus
Authors: K.J.N. Kimseng, L.F. Dans, C.A. Tee
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The current use of the SLICC classification criteria for juvenile systemic lupus erythematosus (jSLE) is extrapolated from an adult-validated study.<sup>1</sup> Efforts have been conducted to validate its applicability in the pediatric population.<sup>2,3</sup> <h3>Objectives</h3> To validate the SLICC classification criteria among juvenile SLE patients <h3>Methods</h3> A diagnostic criteria validity study was conducted. Medical records of &lt;19 years old patients, who were seen in a tertiary hospital from June 2012 to June 2014, were reviewed to make 300 case summaries. Included were 150 jSLE and 150 non-jSLE cases. Non-jSLE cases, with jSLE as a consideration, comprised the control group. Patients who had no definite diagnosis, or who were lost to follow-up, were excluded. Each case summary was evaluated by at least 3 of 7 pediatric rheumatologists by utilizing the SLICC criteria. A consensus diagnosis for each case was reached based on majority agreement (&gt;50%) of the individual subspecialist assessments. The clinical diagnosis of the team of attending physicians, with at least 1 pediatric rheumatologist, was used as the gold standard. The sensitivity, specificity and number of misclassified cases were determined. <h3>Results</h3> The sensitivity of the SLICC criteria is at 94.0% (95%CI 88.9-97.2), and specificity at 96.7% (95%CI 92.4-98.9) in the cohort of Filipino jSLE patients. One-forty-one cases were correctly classified as jSLE, while 145 controls were correctly classified as non-jSLE. There were 9 false negatives, while 5 controls were false positives. <h3>Conclusions</h3> The SLICC classification criteria is a valid guide for clinical practitioners to diagnose patients afflicted with jSLE. <h3>References</h3> Petri, M et al. Arthritis &amp; Rheumatism 2012; 64: 2677-2686. Fonesca, AR et al. Rheumatology. 2014. doi:10.1093/rheumatology/keu278. Sag, E at al. Clinical and Experimental Rheumatology. 2014 June; 32 (3): 440-444. <h3>Acknowledgements</h3> Dr. Pauline Camposano, Dr. Carien-Gulay-Carvajal, Dr. Christine Bernal, Dr. Karen Cruz, Dr. Shanida Camomot, and Dr. Maria Kristine Belen-Ciabal <h3>Disclosure of Interest</h3> None declared
Heart failure1150th AnniversaryHistorical ArticleIntroductionIn this edition of the Journal, we release the second in a series of reviews of influential articles that have been previously published in ACC journals, including the American Journal of Cardiology(from 1958 to 1982), and JACC(from 1983 to the present). The publication of these articles is only one aspect of the ACC’s 50th anniversary commemoration, which highlights 50 years of leadership in cardiovascular care and education. The …
Authors: G S Francis
Journal: Journal of the American College of Cardiology (1999)