tbuckley/cabot-search huggingface dataset:
The Joubert Syndrome Protein Inpp5e Controls Ciliogenesis by Regulating Phosphoinositides at the Apical Membrane
Authors: Wenyan Xu, Miaomiao Jin, Ruikun Hu, Hong Wang, Fan Zhang, Shiaulou Yuan, Ying Cao
Journal: Journal of the American Society of Nephrology (2016)

Phosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in inositol polyphosphate 5-phosphatase E ( INPP5E ) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear. Here, we utilized an in vivo vertebrate model of renal cystogenesis to show that Inpp5e enzymatic activity at the apical membrane directs apical docking of basal bodies in renal epithelia. Knockdown or knockout of inpp5e led to ciliogenesis defects and cystic kidneys in zebrafish. Furthermore, knockdown of inpp5e in embryos led to defects in cell polarity, cortical organization of F-actin, and apical segregation of PtdIns(4,5)P 2 and PtdIns(3,4,5)P 3 . Knockdown of the ezrin gene, which encodes an ezrin/radixin/moesin (ERM) protein that crosslinks PtdIns(4,5)P 2 and F-actin, phenocopied inpp5e knockdowns. Notably, overexpression of the ezrin gene rescued inpp5e morphants. Finally, treatment with the PI 3-kinase inhibitor LY294002, which decreases PtdIns(3,4,5)P 3 levels, rescued the cellular, phenotypic, and renal functional defects in inpp5e -knockdown embryos. Together, our data indicate that Inpp5e functions as a key regulator of cell polarity in the renal epithelia, by inhibiting PtdIns(3,4,5)P 3 and subsequently stabilizing PtdIns(4,5)P 2 and recruiting Ezrin, F-actin, and basal bodies to the apical membrane, and suggest a possible novel approach for treating human ciliopathies.
Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study
Authors: Bo Abrahamsen, Pia Eiken, Daniel Prieto-Alhambra, Richard Eastell
Journal: BMJ (2016)

To determine the skeletal safety and efficacy of long term (≥10 years) alendronate use in patients with osteoporosis. Open register based cohort study containing two nested case control studies. Nationwide study of population of Denmark. 61 990 men and women aged 50-94 at the start of treatment, who had not previously taken alendronate, 1996-2007. Treatment with alendronate. Incident fracture of the subtrochanteric femur or femoral shaft (ST/FS) or the hip. Non-fracture controls from the cohort were matched to fracture cases by sex, year of birth, and year of initiation of alendronate treatment. Conditional logistic regression models were fitted to calculate odds ratios with and without adjustment for comorbidity and comedications. Sensitivity analyses investigated subsequent treatment with other drugs for osteoporosis. 1428 participants sustained a ST/FS (incidence rate 3.4/1000 person years, 95% confidence interval 3.2 to 3.6), and 6784 sustained a hip fracture (16.2/1000 person years, 15.8 to 16.6). The risk of ST/FS was lower with high adherence to treatment with alendronate (medication possession ratio (MPR, a proxy for compliance) >80%) compared with poor adherence (MPR <50%; odds ratio 0.88, 0.77 to 0.99; P=0.05). Multivariable adjustment attenuated this association (adjusted odds ratio 0.88, 0.77 to 1.01; P=0.08). The risk was no higher in long term users (≥10 dose years; 0.70, 0.44 to 1.11; P=0.13) or in current compared with past users (0.91, 0.79 to 1.06; P=0.22). Similarly, MPR >80% was associated with a decreased risk of hip fracture (0.73, 0.68 to 0.78; P<0.001) as was longer term cumulative use for 5-10 dose years (0.74, 0.67 to 0.83; P<0.001) or ≥10 dose years (0.74, 0.56 to 0.97; P=0.03). These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use.
Evidence That a Bioactive Lipid, Ceramide-1 Phosphate (C1P), Is Upregulated In Bone Marrow Microenvironment After Myeloablative Therapy and Is a Potential Novel Homing Factor for Hematopoietic Stem Cells
Authors: Chihwa Kim, Wu Wan, Ahmed Abdel-Latif, Marcin Wysoczynski, Magdalena Kucia, Janina Ratajczak, Mariusz Z Ratajczak
Journal: Blood (2010)
Case 51-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Richard M. Rose, Eugene J. Mark
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 44-year-old man was admitted to the hospital because of back pain, anemia, and an abnormal x-ray film of the chest.The patient was well until six months earlier, when he began to experience low-back pain that gradually became more severe and was aggravated by weight-bearing and sitting. Three months before admission he was no longer able to continue his work, which involved heavy lifting. Generalized weakness and fatigue developed. Three weeks before entry he awoke with more severe lumbar pain that occasionally radiated down the left leg and interfered with walking, and he had one episode . . .
Surface functionality affects the biodistribution and microglia-targeting of intra-amniotically delivered dendrimers
Authors: Fan Zhang, Elizabeth Nance, Zhi Zhang, Venkatasai Jasty, Siva P. Kambhampati, Manoj K. Mishra, Irina Burd, Roberto Romero, Sujatha Kannan, Rangaramanujam M. Kannan
Journal: Journal of Controlled Release (2016)
Statins and Reduced Risk of Liver Cancer: Evidence for Confounding: Table 1.
Authors: Gary D. Friedman, Ninah Achacoso, Bruce Fireman, Laurel A. Habel
Journal: JNCI Journal of the National Cancer Institute (2016)

A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects enrolled in Kaiser Permanente Northern California. Addressing confounding by indication by restricting subjects to those with elevated cholesterol greatly attenuated the negative association; eg, the multivariable-adjusted odds ratio (OR) rose from 0.41 (95% confidence interval [CI] = 0.35 to 0.49) to 0.87 (95% CI = 0.55 to 1.39) for receipt of 18 or more prescriptions. Confounding by contraindication was addressed by controlling for degree of abnormality of liver function tests, alanine or aspartate transaminase, measured within one year of the elevated cholesterol and strongly related to risk. The negative association of statins disappeared for all numbers of prescriptions received, with an odds ratio of 1.21 (95% CI = 0.53 to 2.75) for 18 or more prescriptions. Findings cast doubt on the causality of the frequently observed preventive association.
Hymenoptera stings in the head region induce impressive, but not severe sting reactions
Authors: L. Arzt, D. Bokanovic, I. Schwarz, C. Schrautzer, C. Massone, M. Horn, W. Aberer, G. Sturm
Journal: Allergy (2016)

Stings in the head region are considered to be a risk factor for severe systemic reactions to hymenoptera stings. We supposed that stings in skin areas, which are well supplied with blood, lead to more severe reactions and tested our hypothesis in 847 patients with confirmed hymenoptera venom allergy. However, symptom severity was independent from sting site: only 16.3% of patients with severe reactions were stung on the head (P = 0.017). But we confirmed age > 40 years (P < 0.001) as well as elevated basal tryptase levels (P = 0.001) as risk factors. Taking antihypertensive drugs seemed to have an influence: 41.7% of patients taking antihypertensive drugs experienced a severe reaction compared to 29.5% of patients, not taking such drugs (P = 0.019). However, considering patients' age in regression analysis, taking antihypertensive drugs had no effect on symptom severity (P = 0.342). Importantly, in most patients with severe reactions, cutaneous signs were absent (P < 0.001).
La surveillance des infections sexuellement transmissibles en Angleterre et au Pays de Galles
Authors: Gwenda Hughes, Thomas Paine, Daniel Thomas
Journal: Eurosurveillance (1998)

La surveillance des infections sexuellement transmissibles (IST) en Angleterre et au Pays de Galles s'est basee, dans le passe, principalement sur des donnees statistiques agregees soumises par toutes les cliniques de medecine genito-urinaire au Centre de surveillance des maladies transmissibles, ainsi que par les differents systemes de declaration des laboratoires. Bien que ces systemes fournissent des donnees de surveillance comparativement fiables, ils ne produisent pas d'informations suffisantes sur les facteurs de risque pour cibler correctement les programmes de prevention et de controle de ces infections. Ces dernieres annees, l'augmen-tation considerable des IST, l'emergence de nombreuses epidemies de IST, et les changements des profils de resistance gonococciques ont entraine la mise en place de methodes de surveillance plus sophistiquees. Cet article decrit les systemes actuels de surveillance des IST en Angleterre et au Pays de Galles, y compris les systemes recemment instaures ou en cours de developpement, afin de repondre a la necessite d'obtenir des donnees de surveillance plus detaillees sur les IST.
HOTAIR to induce EGFR-TKIs resistance in non-small cell lung cancer via epithelial-mesenchymal transition.
Authors: Ningning Cheng, Weijing Cai, Xuefei Li, Qi Wang, Mingchuan Zhao, Jiayu Li, Chao Zhao, Caicun Zhou
Journal: Journal of Clinical Oncology (2015)

e19079 Background: Previous research found that HOTAIR, a long non-coding RNA, aberrantly expressed and associated with tumor invasion, metastasis and chemo-resistance in many cancers. The aim of this study was to investigate the role of HOTAIR in resistance of EGFR-TKIs in NSCLC. Methods: HOTAIR expression level was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC cell lines or tumor tissues. A total of 52 samples with EGFR-mutant and EGFR-TKI-sensitive NSCLCs, 42 with acquired resistance and 46 with primary resistance to EGFR-TKIs were analyzed. The effect of HOTAIR on cell proliferation and apoptosis was undergone by CCK-8 and flow cytometry assays. The expression of EMT proteins was assessed by western blot. Results: HOTAIR was significantly down-regulated in lung cancer cells (PC9/R, H1975, H1299 and A549) and patients with primary and acquired resistance to EGFR-TKIs. In clinical setting, high levels of HOTAIR expression was significantly correlated with longer progression-free survival (PFS) [P< 0.01] compared with low HOTAIR expression subgroup in tumors with respond to EGFR-TKIs. In vitro, over-expression HOTAIR could restore gefitinib sensitivity in gefitinib-resistant cells (PC9/R, H1299 and A549), but this change in sensitivity was not observed in H1975. Up-regulated HOTAIR induced cell apoptosis in PC9/R, H1299 and A549, and activated epithelial-mesenchymal transition (EMT). Conclusions: HOTAIR expression was associated with primary and acquired resistance to EGFR-TKIs and could regulate cell proliferation through activating cell apoptosis and EMT, which suggest that HOTAIR might be act as a biomarker to predict the EGFR-TKIs resistance.
When banding fails; investigation hails
Authors: F Arnold, D Patch, D Yu, R H Westbrook
Journal: Gut (2016)

A 67-year-old man presented to our centre 5 years ago with a short history of jaundice and weight loss. A diagnosis of autoimmune hepatitis was made following laboratory investigations, imaging and a trans-jugular liver (TJ) biopsy. He was treated with prednisolone and azathioprine, which resulted in normalisation of his transaminases and bilirubin. Four years later, he was diagnosed with cirrhosis (Childs class A) based on clinical, biochemical and radiological parameters. He underwent a screening endoscopy, which revealed grade III oesophageal varices with multiple red signs and was started on propranolol as primary prophylaxis. He was unable to tolerate β blockers and oesophageal endoscopic band ligation (EBL) was subsequently undertaken. He underwent six further upper GI endoscopies with repeated EBL of his oesophageal varices; however, the grade III varices with red signs …
P-110 Efficacy of percutaneous transhepatic gallbladder drainage for acute cholecystitis in patients with unresectable Klatskin tumor
Authors: D.H. Kang, H.W. Kim, C.W. Choi, S.B. Park, S.J. Kim, H.S. Nam, H.H. Jang, W.H. Choi, Y.H. Choi, K.J. Oh
Journal: Annals of Oncology (2016)
Disclosing drug companies payments should be compulsory, say top earners
Authors: Duncan Jarvies
Journal: BMJ (2016)

The doctors who declared the most earnings from drug companies in the United Kingdom’s new database have said that being transparent about payments should be mandatory.

The database showed that 70% of healthcare professionals who received payments from drug companies agreed to have the information disclosed on Disclosure UK (www.disclosureuk.org.uk), which is hosted by the Association of the British Pharmaceutical Industry. But the 30% who didn’t agree to disclosure received more than half (52%) of the payments registered.1

From the data posted it is possible to find the top earners, but because of the way that the undeclared data are presented it is not possible to tell how they rank overall.

Ian Pavord, …
PD-031 An exploratory study-level meta-analysis assessing the impact of early tumour shrinkage on overall survival in patients with RAS wild-type metastatic colorectal cancer receiving first-line treatment in three randomised panitumumab trials
Authors: F. Rivera, M. Karthaus, M. Valladares-Ayerbes, J. Gallego, R. Koukakis, G. Demonty, J.-Y. Douillard
Journal: Annals of Oncology (2016)
Effect of sentinel lymph-node biopsy alone on the morbidity of the surgical treatment of early cervical cancer: Results from the prospective randomized study Senticol2.
Authors: Patrice Mathevet, Fabrice Lecuru
Journal: Journal of Clinical Oncology (2015)

5521 Background: Sentinel lymph node (SLN) biopsy is now part of the management of early cervical cancer. Feasibility and low false negative rate in case of bilateral detection have been demonstrated by several studies. However, patients’ benefits have not been demonstrated after SLN biopsy only. Methods: A multicenter prospective randomized study comparing SLN biopsy alone (Arm A) versus SLN biopsy + pelvic lymph-node dissection (Arm B) in early cervical cancer, has been carried out in France. Patient’s eligibility criteria were: 1) FIGO stage IA/IB1/IIA1 cervical cancer, 2) squamous or adenocarcinoma histology, 3) non pregnant patients aged > 18. All patients underwent SLN identification with a combined method (technetium + Patent blue). Patients with negative SLN at per-operative assessment were randomized. The primary objective was to compare the surgical morbidity of the 2 arms. The planned sample size was 124 patients per arm for a type I error rate of 5% and a one sided test. The protocol has been funded by the French NCI and has been reviewed by an Ethical Committee. Results: 267 patients were included between March 2009 and July 2012, and 61 patients were not randomized due to: unilateral or no SLN detection, positive SLN at frozen sections and other reasons. Of the remaining 206 patients, 105 were in arm A and 101 in arm B. The analysis was performed in intention-to-treat. The median number of SLN was 3 per patient and 1 per side. No false negative case was identified in arm B. The surgical morbidity related to the lymph-node dissection was largely and significantly reduced in arm A: 33 cases (31.4%) vs 52 cases (51.5%) in arm B, (p = 0.0046, X2test) and major morbidity related to the lymph-node dissection was also reduced: 1 case in arm A vs 6 cases in arm B (p = 0.06). The rate of early post-operative neurological symptoms was significantly reduced in arm A (7.8% vs 20.6% in arm B, p = 0.01). Conclusions: SLN biopsy may improve the management of early cervical cancer, as it induced less surgical morbidity than full pelvic lymphadenectomy. This study leads to morbidity-sparing approaches in cervical cancer treatment incorporating SLN biopsy alone in negative SLN patients. Clinical trial information: NCT01639820.
Bioresorbable Vascular Scaffolds for Coronary Revascularization
Authors: Dean J. Kereiakes, Yoshinobu Onuma, Patrick W. Serruys, Gregg W. Stone
Journal: Circulation (2016)

Contemporary metallic drug-eluting stents are associated with very good 1-year outcomes but an ongoing risk of stent-related adverse events (thrombosis, myocardial infarction, restenosis) after 1 year. The pathogenesis of these very late events is likely related to the permanent presence of the metal stent frame or polymer. Bioresorbable scaffolds have been developed to provide drug delivery and mechanical support functions similar to metallic drug-eluting stents, followed by complete resorption with recovery of more normal vascular structure and function, potentially improving very late clinical outcomes. A first-generation bioresorbable scaffold has been demonstrated to be noninferior to a contemporary metallic drug-eluting stents for overall 1-year patient-oriented and device-oriented outcomes. Increased rates of scaffold thrombosis and target vessel-related myocardial infarction were noted that may be mitigated by improved patient and lesion selection, procedural technique, and device iteration. Large-scale, randomized, clinical trials are ongoing to determine the long-term relative efficacy and safety of bioresorbable scaffolds compared with current metallic drug-eluting stents.
Results of a Phase I-II Clinical Trial of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab (OFAR) Combination Therapy In Patients with Aggressive, Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Richter Syndrome (RS)
Authors: Apostolia Maria Tsimberidou, William G. Wierda, Sijin Wen, William Plunkett, Susan O'Brien, Thomas J. Kipps, Jeffrey A. Jones, Hagop M. Kantarjian, Michael J. Keating
Journal: Blood (2010)
Are We Ready for a Potential Increase in Parkinson Incidence?
Authors: Honglei Chen
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
GRADUATE MEDICAL EDUCATION IN THE UNITED STATES
Authors: F C Wilson
Journal: JAMA (1966)

This paper discusses graduate medical education in the United States under the headings of History, Goals and Incentives, Curricula, Influences, and Essentials. The factors that influence graduate medical education are: evolving knowledge and technology; local, state, and national organizations; class size and composition; changing student specialty preferences; methods of health care delivery; economic constraints; and governmental regulation. Given the desirability for change, those aspects of the graduate medical education experience that must be preserved include control of the educational process by educators, the primacy of education over service, adequate supervision, continuity of care, stable funding, educational breadth, and high standards.
Structure Prediction of Membrane Proteins
Authors: Chunlong Zhou, Yao Zheng, Yan Zhou
Journal: Genomics Proteomics & Bioinformatics (2004)

Abstract There is a large gap between the number of membrane protein (MP) sequences and that of their decoded 3D structures, especially high-resolution structures, due to difficulties in crystal preparation of MPs. However, detailed knowledge of the 3D structure is required for the fundamental understanding of the function of an MP and the interactions between the protein and its inhibitors or activators. In this paper, some computational approaches that have been used to predict MP structures are discussed and compared.
Anterior Cruciate Ligament Tear
Authors: Nicola Maffulli, Umile Giuseppe Longo, Vincenzo Denaro
Journal: New England Journal of Medicine (2009)

n engl j med 360;14 nejm.org april 2, 2009 1463 daily for up to 4 years. Novelose was used because it was relatively easy to mix with a variety of foods. The dose used was as much as we thought we could ask participants to add to their diet. There were 97 withdrawals on the basis of “minor disorders,” as compared with 76 among participants receiving placebo starch. The difference was attributable to symptoms of bloating, suggesting that we had delivered a clinically significant dose. Analysis of crypt-cell proliferation and dissected crypt dimensions in mucosal-biopsy specimens (unpublished data) revealed no difference between the placebo group and either of the treatment groups. We agree that the literature supports the case for an antineoplastic effect of resistant starch. The lack of support for this hypothesis in our trial may simply reflect the major challenge of testing nutritional chemoprevention with the use of the traditional approach of a randomly assigned supplement. D. Timothy Bishop, M.D.
SAFE USE OF PESTICIDES
Authors: L I GOLDBERG
Journal: JAMA (1964)

Although a recently published book advocated elimination of all pesticide application in the United States, it is apparent that a majority of agriculturists feel that these agents are necessary to our present economy and food production. Therefore, it becomes the responsibility of the general population and of the medical profession to see that these pesticides are used in the safest manner and that appropriate therapy is always available. Pesticide toxicity concerns two major groups of our population: those working directly with the pesticides and their agricultural application, and those having contact because they live in areas where such agents are being applied. According to data from California, approximately 75% of the systemic poisoning from occupational exposures to agricultural chemicals is due to organophosphorus insecticides,<sup>1</sup>for which diagnostic blood tests are available and specific therapy is effective. A report in a recent issue of the<i>Archives of Environmental Health</i>indicates