tbuckley/cabot-search huggingface dataset:
Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease
Authors: Pelin O. Simsek Kiper, Hiroaki Saito, Francesca Gori, Sheila Unger, Eric Hesse, Kei Yamana, Riku Kiviranta, Nicolas Solban, Jeff Liu, Robert Brommage, Koray Boduroglu, Luisa Bonafé, Belinda Campos-Xavier, Esra Dikoglu, Richard Eastell, Fatma Gossiel, Keith Harshman, Gen Nishimura, Katta M. Girisha, Brian J. Stevenson, Hiroyuki Takita, Carlo Rivolta, Andrea Superti-Furga, Roland Baron
Journal: New England Journal of Medicine (2016)

Cortical-bone fragility is a common feature in osteoporosis that is linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments.We evaluated four patients with Pyle's disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger sequencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture.In all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4, like persons with Pyle's disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect.Our study showed that Pyle's disease was caused by a deficiency of sFRP4, that cortical-bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross-regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss National Foundation and the National Institutes of Health.).
Endoscopic resection of a giant ileal inflammatory fibroid polyp by retrograde double-balloon enteroscopy
Authors: Faidon-Marios Laskaratos, Erasmia Vlachou, Tu Luong, Peter Wylie, Mark Hamilton, Charles Murray, Edward Despott
Journal: Endoscopy (2016)

A 70-year-old woman with a longstanding history of ileocolonic Crohn's disease was reviewed in our inflammatory bowel disease clinic. Although her Crohn's disease-related symptoms were well controlled on azathioprine and 5-aminosalicylic acid therapy, computed tomography enterography (CTE) demonstrated active disease affecting the distal ileum and right colon with an ileal polyp that had increased in size from 14 mm to 30 mm over a 2-year follow-up period ([Fig. 1]). Histopathology of biopsies taken from the distal ileal polyp were consistent with an inflammatory etiology but, because of its increasing size and the risk of intussusception, the lesion was deemed to merit endoscopic excision.
Evidence from prospective cohort studies did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review
Authors: Zoë Harcombe, Julien S Baker, Bruce Davies
Journal: British Journal of Sports Medicine (2016)

National dietary guidelines were introduced in 1977 and 1983, by the USA and UK governments to reduce coronary heart disease (CHD) mortality by reducing dietary fat intake. Our 2015 systematic review examined randomised controlled trial (RCT) evidence available to the dietary committees at the time; we found no support for the recommendations to restrict dietary fat. What epidemiological evidence was available to the dietary guideline committees in 1983?A systematic review of prospective cohort studies, published prior to 1983, which examined the relationship between dietary fat, serum cholesterol and the development of CHD.Across 6 studies, involving 31 445 participants, there were 1521 deaths from all-causes and 360 deaths from CHD during the mean follow-up of 7.5±6.2 years. The death rates were 4.8% and 1.1% from all-causes and CHD respectively. One study included men with previous heart disease. The death rate from CHD for those with, and without previous myocardial infarction was 20.9% and 1.0% respectively. None of the six studies found a significant relationship between CHD deaths and total dietary fat intake. One of the six studies found a correlation between CHD deaths and saturated dietary fat intake across countries; none found a relationship between CHD deaths and saturated dietary fat in the same population.1983 dietary recommendations for 220 million US and 56 million UK citizens lacked supporting evidence from RCT or prospective cohort studies. The extant research had been undertaken exclusively on males, so lacked generalisability for population-wide guidelines.
Rapid molecular diagnostics of severe primary immunodeficiency determined by using targeted next-generation sequencing
Authors: Hui Yu, Victor Wei Zhang, Asbjørg Stray-Pedersen, Imelda Celine Hanson, Lisa R. Forbes, M. Teresa de la Morena, Ivan K. Chinn, Elizabeth Gorman, Nancy J. Mendelsohn, Tamara Pozos, Wojciech Wiszniewski, Sarah K. Nicholas, Anne B. Yates, Lindsey E. Moore, Knut Erik Berge, Hanne Sorte, Diana K. Bayer, Daifulah ALZahrani, Raif S. Geha, Yanming Feng, Guoli Wang, Jordan S. Orange, James R. Lupski, Jing Wang, Lee-Jun Wong
Journal: Journal of Allergy and Clinical Immunology (2016)
Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) case reporting in the World Health Organization European Region in 2006
Authors: I Devaux, J Alix, G Likatavicius, M Herida, S Nielsen, F  F Hamers, A Nardone
Journal: Eurosurveillance (2008)

This article presents information on HIV and AIDS case reporting systems as part of a survey on HIV/AIDS surveillance practices in the World Health Organization (WHO) European Region. A standardised questionnaire was sent to the 53 national correspondents of the European Centre for the Epidemiological Monitoring of AIDS (EuroHIV). The HIV and AIDS case reporting section of the questionnaire comprised four parts: data collection system, HIV/AIDS case definition for surveillance, variables collected, and evaluation of surveillance systems). Individual-based data collection systems for HIV case reports have been implemented in 43 of 44 countries in the WHO European Region and for AIDS case reports in all the countries. For HIV case reports, a coded identifier is used in 28 countries, and full names are used in 11 countries. The European AIDS case definition has been adopted in 35 countries (80%). Information on molecular epidemiology is available in 30 countries, and HIV drug resistance is monitored in 11 countries. HIV/AIDS case reporting systems have been evaluated for under-reporting in 17 countries and for completeness in 11 countries. This article outlines the future needs for HIV/AIDS surveillance and presents recommendations on how to improve data comparability across European countries in the WHO region
Early assessment of distress in cancer patients treated in DH setting
Authors: A. Di Liscia, M. Schellino, A. Balbo, A.M. Bandiera, S. Cimino, T. Di Lonardo, M. Floccia, M. Mura, F. Salamone, R. Ravera, L.M. Repetto
Journal: Annals of Oncology (2015)
Abstract 10235: Fractional Flow Reserve and Long-Term Outcomes in Consecutive 'Real-World' Patients
Authors: Damian J Kelly, Michael L Liang, Aniket Puri, Suresh Perera, Madhav Menon, Gerard Devlin
Journal: Circulation (2010)

Background: Coronary pressure-derived fractional flow reserve (FFR) is an invasive physiological index of the functional severity of coronary artery stenoses. Randomised trial data has demonstrated...
Clinical relevance of circulating cell-free microRNAs in ovarian cancer
Authors: Koji Nakamura, Kenjiro Sawada, Akihiko Yoshimura, Yasuto Kinose, Erika Nakatsuka, Tadashi Kimura
Journal: Molecular Cancer (2016)

Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening. Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. This review summarizes the current knowledge regarding the potential clinical relevance of circulating cell-free miRNA for ovarian cancer diagnosis, prognosis, and therapeutics. Despite the high levels of ribonucleases in many types of body fluids, most of the circulating miRNAs are packaged in microvesicles, exosomes, or apoptotic bodies, are binding to RNA-binding protein such as argonaute 2 or lipoprotein complexes, and are thus highly stable. Cell-free miRNA signatures are known to be parallel to those from the originating tumor cells, indicating that circulating miRNA profiles accurately reflect the tumor profiles. Since it is well established that the dysregulation of miRNAs is involved in the tumorigenesis of ovarian cancer, cell-free miRNAs circulating in body fluids such as serum, plasma, whole blood, and urine may reflect not only the existence of ovarian cancer but also tumor histology, stage, and prognoses of the patients. Several groups have successfully demonstrated that serum or plasma miRNAs are able to discriminate patients with ovarian cancer patients from healthy controls, suggesting that the addition of these miRNAs to current testing regimens may improve diagnosis accuracies for ovarian cancer. Furthermore, recent studies have revealed that changes in levels of cell-free circulating miRNAs are associated with the condition of cancer patients. Discrepancies between the results across studies due to the lack of an established endogenous miRNA control to normalize for circulating miRNA levels, as well as differing extraction and quantification methods, are the pitfalls to be resolved before clinical application. There is still a long way, however, before this can be achieved, and further evidence would make it possible to apply circulating cell-free miRNAs not only as biomarkers but also as potential therapeutic targets for ovarian cancer in the future.
Chloroplast genomes: diversity, evolution, and applications in genetic engineering
Authors: Henry Daniell, Choun-Sea Lin, Ming Yu, Wan-Jung Chang
Journal: Genome biology (2016)

Chloroplasts play a crucial role in sustaining life on earth. The availability of over 800 sequenced chloroplast genomes from a variety of land plants has enhanced our understanding of chloroplast biology, intracellular gene transfer, conservation, diversity, and the genetic basis by which chloroplast transgenes can be engineered to enhance plant agronomic traits or to produce high-value agricultural or biomedical products. In this review, we discuss the impact of chloroplast genome sequences on understanding the origins of economically important cultivated species and changes that have taken place during domestication. We also discuss the potential biotechnological applications of chloroplast genomes.
Assessment of Accuracy of Patient-Initiated Differential Diagnosis Generation by Google Reverse Image Searching
Authors: Julia D. Ransohoff, Shufeng Li, Kavita Y. Sarin
Journal: JAMA Dermatology (2016)

increasingly self-generate differential diagnoses for medical conditions by both text and image searches, we highlight the present inadequacies and risk associated with the use of Google Reverse Image Search; while the present algorithms perform better with lesions representing or concerning for malignancy as well as with text cues, the error rate remains, at best, too high for the data to be safely used by those without dermatologic training.These data highlight the need for a more medically oriented toolkit, offering caution against use of the current technology.We propose Google's partnership with the medical community in developing a hybrid approach to synergize computer learning with human medical expertise, and caution widely against the present inaccuracies and danger of patient-initiated differential diagnosis generation from input photo matches.
Web: Is there a future for links pages?
Authors: Douglas Carnall
Journal: BMJ (2004)

It has been almost 10 years since the internet exploded into common use. Those who were going to learn html and install servers have done so, institutions have found their internet policies and are sticking to them, and users have settled down into comfortable patterns of behaviour. The internet is no longer “hot”: like plumbing, we'll certainly miss it if it's not there, but the grand visions of those heady days seem wrecked on the rocks of institutions just continuing to do what they have always done.

In the mid-1990s, when search engines' relevance ranking worked poorly, it seemed to make sense to aggregate pages of links to help yourself, and others with similar interests, to capture the rare jewels of excellence amid a seemingly random deluge. Sheffield University's School of Health and Related Research (ScHARR) has long maintained an extensive series of links in evidence based health information worldwide, now reorganised as Netting the Evidence (www.nettingtheevidence.org.uk/).

These web chefs produce a rich soup: nourishing chunks of online database float in a rich broth of the critical appraisal teaching materials assembled by centres and units. However, as a search facility it is next to useless. The average BMJ reader (if such a thing exists) does not scan down the list of links, alight upon, for example, the Canadian Coordinating Office for Health Technology Assessment and then wander through to read an evaluation of spinal manipulation for infantile colic (little evidence for or against the notion that it might work, apparently).

In the age of Google, producing pages of links has arguably been an activity of increasing futility. Google's underlying ranking mechanisms depend on human webmasters' linking activities to push the better quality pages to the head of the results page. So it is thanks to efforts of webmasters such as ScHARR's that entering the search term “Cochrane” in Google delivers the homepage of the Cochrane collaboration as its number one hit rather than, for instance, the Cochrane Group, a firm of Canadian civil engineers (ranked 37th).

Netting the Evidence is a plentiful source of materials for anyone attending a critical appraisal course to teach or learn. However, like most pages of links on the net, the site delivers its fair share of “page not found” messages, as the originators of the linked materials reorganise their materials, endure server upgrades, leave, retire, die, or lose enthusiasm for the never ending maintenance that any quality web resource must have to flourish.

ScHARR's persistence and energy is commendable when similar projects have been quietly forgotten, but this is not the web resource of the future. For that we need a project that combines both social and technical imagination: that harnesses the energy of the questioner, as well as the efforts of the traditional custodians of information.
Skin examination training can help patients and their partners find new melanomas
Authors: Jacqui Wise
Journal: BMJ (2016)

Patients with melanoma and their partners can effectively perform skin checks to identify new melanomas if given suitable training, a study published in JAMA Dermatology has shown.1

Patients with melanoma are at increased risk of developing a second primary melanoma. The risk of a second melanoma is elevated for as …
Mitochondrial Dysfunction in the Liver and Antiphospholipid Antibody Production Precede Disease Onset and Respond to Rapamycin in Lupus‐Prone Mice
Authors: Zachary Oaks, Thomas Winans, Tiffany Caza, David Fernandez, Yuxin Liu, Steve K. Landas, Katalin Banki, Andras Perl
Journal: Arthritis & Rheumatology (2016)

Objective Antiphospholipid antibodies (aPL) constitute a diagnostic criterion of systemic lupus erythematosus (SLE), and aPL have been functionally linked to liver disease in patients with SLE. Since the mechanistic target of rapamycin (mTOR) is a regulator of oxidative stress, a pathophysiologic process that contributes to the development of aPL, this study was undertaken in a mouse model of SLE to examine the involvement of liver mitochondria in lupus pathogenesis. Methods Mitochondria were isolated from lupus‐prone MRL/lpr, C57BL/6.lpr, and MRL mice, age‐matched autoimmunity‐resistant C57BL/6 mice as negative controls, and transaldolase‐deficient mice, a strain that exhibits oxidative stress in the liver. Electron transport chain (ETC) activity was assessed using measurements of oxygen consumption. ETC proteins, which are regulators of mitochondrial homeostasis, and the mTOR complexes mTORC1 and mTORC2 were examined by Western blotting. Anticardiolipin (aCL) and anti–β 2 ‐glycoprotein I (anti‐β 2 GPI) autoantibodies were measured by enzyme‐linked immunosorbent assay in mice treated with rapamycin or mice treated with a solvent control. Results Mitochondrial oxygen consumption was increased in the livers of 4‐week‐old, disease‐free MRL/lpr mice relative to age‐matched controls. Levels of the mitophagy initiator dynamin‐related protein 1 (Drp1) were depleted while the activity of mTORC1 was increased in MRL/lpr mice. In turn, mTORC2 activity was decreased in MRL and MRL/lpr mice. In addition, levels of aCL and anti‐β 2 GPI were elevated preceding the development of nephritis in 4‐week‐old MRL, C57BL/6.lpr, and MRL/lpr mice. Transaldolase‐deficient mice showed increased oxygen consumption, depletion of Drp1, activation of mTORC1, and elevated expression of NADH:ubiquinone oxidoreductase core subunit S3 (NDUFS3), a pro‐oxidant subunit of ETC complex I, as well as increased production of aCL and anti‐β 2 GPI autoantibodies. Treatment with rapamycin selectively blocked mTORC1 activation, NDUFS3 expression, and aPL production both in transaldolase‐deficient mice and in lupus‐prone mice. Conclusion In lupus‐prone mice, mTORC1‐dependent mitochondrial dysfunction contributes to the generation of aPL, suggesting that such mechanisms may represent a treatment target in patients with SLE.
Clinical Studies with Feather Dust
Authors: L J HALPIN, H E PRINCE
Journal: JAMA (1963)

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Peripheral blood gene expression predicts clinical benefit from anti–IL-13 in asthma
Authors: David F. Choy, Guiquan Jia, Alexander R. Abbas, Katrina B. Morshead, Nicholas Lewin-Koh, Rajiv Dua, Pauline Rivera, Priscilla Moonsamy, Marcel Fontecha, Aarthi Balasubramanyam, Chris Santini, Ekaterina Bassett, Jill M. Ray, Christopher R. Cabanski, Mary S. Bradley, Romeo Maciuca, Sofia Mosesova, Heleen Scheerens, Joseph R. Arron
Journal: Journal of Allergy and Clinical Immunology (2016)
Turkish Breast Cancer Registry: A multicenter epidemiologic study.
Authors: Ugur Coskun, Mahmut Gumus, Dogan Uncu, Metin Ozkan, Irfan Cicin, Kadri Altundag, Tamer Elkiran, Murat Kocer, Aziz Karaoglu, Nilufer Avci, Feyyaz Ozdemir, Erdem Cubukcu, Melih Cem Boruban, Alper Sevinc, Berna Oksuzoglu, Hande Turna, Bulent Yalcin, Esra Dumanli, Fatih Ozdener, Mustafa Benekli
Journal: Journal of Clinical Oncology (2014)

e12518 Background: Breast cancer (BC) is the most common cancer in women in Turkey. Studies investigating the epidemiology of BC in Turkey are retrospective case series providing limited information. We developed a BC registry to assess these issues. First analysis results are presented. Methods: Pts presenting to medical oncology clinics were prospectively registered in 25 centers. Clinical and pathological characteristics were recorded. Results: 8,199 pts (77 males [0.9%]) were registered. Median age was 53 yrs (20-92). 4,167 females (50.8%) were postmenopausal. 6,937 pts (84.6 CI: 83.8-85.4%) had invasive ductal BC with grades I (n=741, 9%), II (n=3,801, 46.4%), III (n=2,458, 30%). Hormone receptors (HR) were positive in 6300 (76.8 CI:75.9-77.7%) pts. Her2 was positive in 2,307 pts (28.1, CI:27.2-29.1%) by IHC and/or FISH. Triple negative BC was less than expected (n=760, 9.2 CI:8.7-9.9%). Initial stages at diagnosis were: I (15.6%), II (45%), III (25.3%), IV (6.6%). 1303 pts developed metastasis: bone (57.2%), liver (25%), lung (23.2%) and others. Most pts had single organ metastasis (n=868, 66.6%). Curative/palliative surgery was done in 7,577 pts (92.4 CI:91.8-93.0%): modified radical mastectomy (n=4,999, 66%), breast-conserving surgery (BCS, n=1,993, 26.3%), simple mastectomy (n=459, 6.1%). 762 patients (9.3%) received neoadjuvant therapy. Only 124 pts (16.3%) received neoadjuvant trastuzumab. 6,346 pts received adjuvant chemo with anthracyclines (92.3%) and taxanes (44.5%). 1,221 pts (19.2 CI:18.3-20.2%) used adjuvant trastuzumab. Endocrine therapies were used in 4,611 pts with tamoxifen (n=2,714, 58.9 CI:57.4-60.3%), aromatase inhibitors and others. 4,082 pts received adjuvant radiotherapy after mastectomy (n=2,624, 64%) or BCS (n=1,350, 33%). 1,119 pts (86 CI:83.9-87.7%) with metastatic BC detected either at diagnosis or follow up received first-line chemo. Most pts received taxane-based regimens while 417 pts (37.3 CI:34.5-40.2%) received anti-Her2 therapy. Conclusions: This study is the first comprehensive BC registry performed in Turkey with HR and Her2 status. Patient characteristics and demographics are similar to Western countries including biomarker data. Low rates of breast conserving surgery should be further explored.
Unrelated Bone Marrow Transplantation for Children with Chronic Myeloid Leukemia (CML): A Report from the Japan Marrow Donor Program (JMDP).
Authors: Hideki Muramatsu, Seiji Kojima, Ayami Yoshimi, Yoshiko Atsuta, Chikako Tono, Koji Kato, Yoshihisa Nagatoshi, Masami Inoue, Kazutoshi Koike, Takakazu Kawase, Keisei Kawa, Hiroyuki Shimada
Journal: Blood (2008)
MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome
Authors: Vaia Stavropoulou, Susanne Kaspar, Laurent Brault, Mathijs A. Sanders, Sabine Juge, Stefano Morettini, Alexandar Tzankov, Michelina Iacovino, I-Jun Lau, Thomas A. Milne, Hélène Royo, Michael Kyba, Peter J.M. Valk, Antoine H.F.M. Peters, Juerg Schwaller
Journal: Cancer Cell (2016)
Purine Analogues Based Induction Regimen Followed By Allo-HSCT Is An Effective Treatment Modality Of Philadelphia Chromosome-Positive Acute Myeloid Leukemia-Retrospective Analysis Of Polish Adult Leukemia Group (PALG)
Authors: Agnieszka Wierzbowska, Anna Szmigielska-Kaplon, Agnieszka Pluta, Ewa Wawrzyniak, Sebastian Grosicki, Grzegorz Helbig, Wanda Knopinska-Posluszny, Tomasz Gromek, Ilona Seferynska, Ewa Lech-Maranda, Jerzy Holowiecki, Tadeusz Robak
Journal: Blood (2013)