tbuckley/cabot-search huggingface dataset:
Evaluating Industry Payments Among Dermatology Clinical Practice Guideline Authors
Authors: Alex M. Glazer, Daniel M. Siegel, Darrell S. Rigel
Journal: JAMA Dermatology (2018)

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 Dermatology 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 Dermatology journal
Depression in patients treated with haemodialysis: a cross-sectional study
Authors: Samah W Al-Jabi, Ansam Sous, Fatimah Jorf, Mahmoud Taqatqa, Mahdi Allan, Lamees Sawalha, Enas Lubadeh, Sa'ed H Zyoud, Waleed M Sweileh
Journal: The Lancet (2018)
Association of polymorphisms of genes involved in the androgen metabolism and signaling pathways with familial prostate cancer risk in a Japanese population
Authors: Silvia Casadei, Ian Seymour, Simonetta Rosato, Elena Lucchi, Fabio Falcini, Miria Strada, Nori Morini, Carlo Naldoni, Dino Amadori, Daniele Calistri
Journal: Cancer Research (2005)

1321  In recent years, mutations in the putative tumor suppressor genes BRCA1 and BRCA2 have been considered the most common predisposing factors for hereditary breast (BC) and ovarian cancer (OC). However, additional, unidentified low penetrance alleles, including common polymorphisms, are also believed to be involved. Common sequence variants in the BRCA1 and BRCA2genes have been reported to exert either a protective effect against BC and OC, to have no discernable effect, or to be a significant risk factor. Despite the large number of studies published to date, there is still no conclusive proof on the role of these polymorphisms in modifying BC and OC risk. In the present study 9 BRCA1 and 11 BRCA2 sequence variants, located in both coding and non-coding regions, were analyzed by the Multiple-Dye Cleavase Fragment Length Polymorphism (MD-CFLP) method and direct sequencing in 278 healthy individuals, familial (high-risk), and sporadic (low-risk) BC patients. No notable associations were observed for any of the BRCA1 polymorphisms. Meanwhile, evidence for a main effect on BC risk was found for the BRCA2N372H (exon 10) and IVS21-66 T>C (exon 22 intronic) polymorphisms. The presence of the IVS21-66 C allele was associated with an almost 2-fold increase in BC risk (Odds Risk [OR] adjusted for age and family history) in both high- and low- risk families (95% Confidence Interval [CI] = 0.85-3.87). Moreover, this risk difference was found to be independent of family history but dependent on the presence of BC. Moreover, the 372 H allele was associated with an increased risk of BC in high-risk families only. Interestingly, this effect was modulated according to genotype. The heterozygote and rare homozygote 372 N/H and H/H individuals from high-risk families were at a 2.06- (CI = 1.02-4.16) and 5.43- (CI = 0.60-47.66) fold increased risk of disease, respectively compared with N/N homozygotes. In exploring two-way gene interactions, we found a markedly elevated risk for the co-existence of both the 372 H and IVS21-66 C alleles [OR = 7.27, 95% CI = 2.15-24.59] in high-risk families.Our results suggest that the BRCA2372 H and IVS21-66 C alleles exert a modest positive effect on BC risk, however, this effect differs according to family history. The presence of one (N/H) or two (H/H) copies of the 372 H allele modulated the BC incidence in high-risk families only. Interestingly, the IVS21-66 C allele responded in a family history-independent manner and was linked to the presence of sporadic tumors.
Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol
Authors: Saskia L. Gooskens, Norbert Graf, Rhoikos Furtwängler, Filippo Spreafico, Christophe Bergeron, Gema L. Ramírez-Villar, Jan Godzinski, Christian Rübe, Geert O. Janssens, Gordan M. Vujanic, Ivo Leuschner, Aurore Coulomb-L'Hermine, Anne M. Smets, Beatriz de Camargo, Sara Stoneham, Harm van Tinteren, Kathy Pritchard-Jones, Marry M. van den Heuvel-Eibrink
Journal: Nature Reviews Urology (2018)

The International Society of Paediatric Oncology–Renal Tumour Study Group (SIOP–RTSG) has developed a new protocol for the diagnosis and treatment of childhood renal tumours, the UMBRELLA SIOP–RTSG 2016 (the UMBRELLA protocol). In this Consensus Statement, members of the SIOP–RTSG outline the rationale for the recommendations for treatment of CCSK in the protocol. The International Society of Paediatric Oncology–Renal Tumour Study Group (SIOP–RTSG) has developed a new protocol for the diagnosis, treatment, and follow-up monitoring of childhood renal tumours — the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). This protocol has been designed to continue international collaboration in the treatment of childhood renal tumours and will be implemented in over 50 different countries. Clear cell sarcoma of the kidney, which is a rare paediatric renal tumour that most commonly occurs in children between 2 and 4 years of age, is specifically addressed in the UMBRELLA protocol.
Long-Term Correction of Diabetes in Mice by In Vivo Reprogramming of Pancreatic Ducts
Authors: Yuhan Wang, Craig Dorrell, Willscott E. Naugler, Michael Heskett, Paul Spellman, Bin Li, Feorillo Galivo, Annelise Haft, Leslie Wakefield, Markus Grompe
Journal: Molecular Therapy (2018)

Direct lineage reprogramming can convert readily available cells in the body into desired cell types for cell replacement therapy. This is usually achieved through forced activation or repression of lineage-defining factors or pathways. In particular, reprogramming toward the pancreatic β cell fate has been of great interest in the search for new diabetes therapies. It has been suggested that cells from various endodermal lineages can be converted to β-like cells. However, it is unclear how closely induced cells resemble endogenous pancreatic β cells and whether different cell types have the same reprogramming potential. Here, we report in vivo reprogramming of pancreatic ductal cells through intra-ductal delivery of an adenoviral vector expressing the transcription factors Pdx1, Neurog3, and Mafa. Induced β-like cells are mono-hormonal, express genes essential for β cell function, and correct hyperglycemia in both chemically and genetically induced diabetes models. Compared with intrahepatic ducts and hepatocytes treated with the same vector, pancreatic ducts demonstrated more rapid activation of β cell transcripts and repression of donor cell markers. This approach could be readily adapted to humans through a commonly performed procedure, endoscopic retrograde cholangiopancreatography (ERCP), and provides potential for cell replacement therapy in type 1 diabetes patients. Direct lineage reprogramming can convert readily available cells in the body into desired cell types for cell replacement therapy. This is usually achieved through forced activation or repression of lineage-defining factors or pathways. In particular, reprogramming toward the pancreatic β cell fate has been of great interest in the search for new diabetes therapies. It has been suggested that cells from various endodermal lineages can be converted to β-like cells. However, it is unclear how closely induced cells resemble endogenous pancreatic β cells and whether different cell types have the same reprogramming potential. Here, we report in vivo reprogramming of pancreatic ductal cells through intra-ductal delivery of an adenoviral vector expressing the transcription factors Pdx1, Neurog3, and Mafa. Induced β-like cells are mono-hormonal, express genes essential for β cell function, and correct hyperglycemia in both chemically and genetically induced diabetes models. Compared with intrahepatic ducts and hepatocytes treated with the same vector, pancreatic ducts demonstrated more rapid activation of β cell transcripts and repression of donor cell markers. This approach could be readily adapted to humans through a commonly performed procedure, endoscopic retrograde cholangiopancreatography (ERCP), and provides potential for cell replacement therapy in type 1 diabetes patients.
Updated overall survival (OS) results of randomized phase III trial of erlotinib (E) versus (v) docetaxel (D) as second- or third-line therapy in patients with advanced non-small cell lung cancer (NSCLC): Docetaxel and Erlotinib Lung Cancer Trial (DELTA).
Authors: Hidenori Ibata, Masahiko Ando, Kazuhiro Asami, Yoshio Okano, Masaaki Fukuda, Hideyuki Nakagawa, Toshiyuki Kozuki, Tateo Endo, Atsuhisa Tamura, Mitsuhiro Kamimura, Kazuhiro Sakamoto, Michihiro Yoshimi, Yoshifumi Soejima, Yoshio Tomizawa, Shun-ichi Isa, Minoru Takada, Hideo Saka, Akihito Kubo, Tomoya Kawaguchi
Journal: Journal of Clinical Oncology (2014)

e19003 Background: The DELTA study demonstrated that there was no significant difference in PFS between D and E arms in epidermal growth factor receptor (EGFR)-unselected NSCLC, while D was better than E in EGFR wild type tumors. (Kawaguchi et al., JCO in press). This report represents the final OS results. Methods: OS was re-evaluated using updated data (data cutoff, 31 October, 2013, median follow-up, 12.7 months [interquartile range, 7.0-23.3]) for 301 patients. This study was sponsored by the Japanese National Hospital Organization. Results: A total of 232 events occurred (77.1 %). Median OS for E v D were 13.8 m (95% CI: 9.0-17.8) v 12.3 m (9.7-15.2) in patients with EGFR-unselected tumor [log-rank P = .934; HR = 0.989, 95% CI: 0.764-1.280], and 9.0 m (7.3-13.8) v 10.3 m (7.3-12.4) in patients with EGFR wild type tumor [P = .949; HR = 1.010, 95% CI: 0.742-1.379], respectively. The number of patients who received any post-study treatment was 106 (70.1 %) in E group and 96 (63.6 %) in D group (P = .220). No difference in OS was observed between E and D arms when comparing patients treated with any subsequent chemotherapy (HR = 1.137, 95% CI, 0.765-1.699; P = .879). Similarly, no difference was observed when comparing patients without subsequent chemotherapy (HR =1.408, 95% CI, 0.889-2.219; P = .710). On the other hand, patients with EGFR wild-type tumors who received D and did not receive subsequent therapy had a trend towards longer OS when compared with those treated with E and no subsequent therapy (HR = 1.567, 95% CI, 0.922-2.653; P = .064). However, no significant difference in OS was seen in patients who received any subsequent treatment (HR = 0.877, 95% CI, 0.540-1.457; P = 1.139). Conclusions: This updated OS analysis showed no significant difference between D and E arms in patients with EGFR wild type as well as EGFR-unselected NSCLC. Active post-study chemotherapy may have prolonged survival post-progression particularly in patients with EGFR wild type tumor. Clinical trial information: UMIN000002314.
Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures
Authors: Fabian Stemmler, David Simon, Anna-Maria Liphardt, Matthias Englbrecht, Juergen Rech, Axel J Hueber, Klaus Engelke, Georg Schett, Arnd Kleyer
Journal: Annals of the Rheumatic Diseases (2018)

Bone loss is a well-established consequence of rheumatoid arthritis (RA). To date, bone disease in RA is exclusively characterised by bone density measurements, while the functional properties of bone in RA are undefined. This study aimed to define the impact of RA on the functional properties of bone, such as failure load and stiffness.Micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone based on high-resolution peripheral quantitative CT data from the distal radius of anti-citrullinated protein antibody (ACPA)-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC). In addition, total, trabecular and cortical bone densities as well as microstructural parameters of bone were recorded. Correlations and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength as well as its relation to prevalent fractures.276 individuals were analysed. Failure load and stiffness (both P<0.001) of bone were decreased in RA+, but not RA-, compared with HC. Lower bone strength affected both female and male patients with RA+, was related to longer disease duration and significantly (stiffness P=0.020; failure load P=0.012) associated with the occurrence of osteoporotic fractures. Impaired bone strength was correlated with altered bone density and microstructural parameters, which were all decreased in RA+. Multivariate models showed that ACPA status (P=0.007) and sex (P<0.001) were independently associated with reduced biomechanical properties of bone in RA.In summary, µFEA showed that bone strength is significantly decreased in RA+ and associated with fractures.
Translational repression of HIF2α expression in mice with Chuvash polycythemia reverses polycythemia
Authors: Manik C Ghosh, De-Liang Zhang, Hayden Ollivierre, Michael A Eckhaus, Tracey A Rouault
Journal: Journal of Clinical Investigation (2018)

Chuvash polycythemia is an inherited disease caused by a homozygous germline VHLR200W mutation, which leads to impaired degradation of HIF2α, elevated levels of serum erythropoietin, and erythrocytosis/polycythemia. This phenotype is recapitulated by a mouse model bearing a homozygous VhlR200W mutation. We previously showed that iron-regulatory protein 1-knockout (Irp1-knockout) mice developed erythrocytosis/polycythemia through translational derepression of Hif2α, suggesting that IRP1 could be a therapeutic target to treat Chuvash polycythemia. Here, we fed VhlR200W mice supplemented with Tempol, a small, stable nitroxide molecule and observed that Tempol decreased erythropoietin production, corrected splenomegaly, normalized hematocrit levels, and increased the lifespans of these mice. We attribute the reversal of erythrocytosis/polycythemia to translational repression of Hif2α expression by Tempol-mediated increases in the IRE-binding activity of Irp1, as reversal of polycythemia was abrogated in VhlR200W mice in which Irp1 was genetically ablated. Thus, a new approach to the treatment of patients with Chuvash polycythemia may include dietary supplementation of Tempol, which decreased Hif2α expression and markedly reduced life-threatening erythrocytosis/polycythemia in the VhlR200W mice.
Les critères de l'EPAGE pour l'évaluation de la pertinence de l'indication de l'endoscopie digestive haute: est-il nécessaire de les réactualiser? A propos de 627 cas
Authors: A Sabbek, A Guediche, F Aissaoui, W Ben Mansour, W Bouhlel, MH Loghmari, L Safer
Journal: Endoscopy (2018)

La fibroscopie oesogastroduodénale (FOGD) étant le principal examen permettant l'exploration du tractus digestif haut, voit sa prescription en constante augmentation, alourdissant le coût de la prise en charge et allongeant les listes d'attente. Les critères de l'EPAGE (European Panel on the Appropriateness of Gastrointestinal Endoscopy) ont été élaborés afin d'évaluer la pertinence des indications de la FOGD et d'en rationaliser la prescription. Ces critères ont été réactualisés en 2008 pour la coloscopie alors que la dernière mise à jour pour l'endoscopie digestive haute remonte à 2002.
Rapid Onset of Action on Nasal Symptoms and Ocular Symptom Improvement With Olopatadine/Mometasone Combination Nasal Spray in Patients With Seasonal Allergic Rhinitis
Authors: Gary Berman, Niran J. Amar, Craig F. LaForce, Aurora Breazna, Cynthia F. Caracta, Sudeesh K. Tantry
Journal: Journal of Allergy and Clinical Immunology (2018)
In vitro conditions promoting the formation of both microtubules and spirals by the natural product (-)-rhazinilam
Authors: Michael C. Edler, Guangli Yang, William G. Bornmann, Ernest Hamel
Journal: Cancer Research (2004)

5414   The natural product (-)-rhazinilam, isolated from several Apocynaceae species and  Kopsia singapurensis  Ridlay, a plant from Malaysia, is an axially chiral phenylpyrrole known to have activity against tubulin. Previous work with (-)-rhazinilam revealed unique, seemingly contradictory effects on tubulin. The effects of (-)-rhazinilam on mammalian cells were similar to the effects of paclitaxel. Mitotic cells had multiple aster-like structures, and interphase cells had prominent microtubule bundles. With purified tubulin, (-)-rhazinilam usually produces spirals. Previous work (Bruno et al., Cell Motility and the Cytoskeleton 1994 28:317) showed that (-)-rhazinilam binds to tubulin, and that this binding is inhibited by both vinblastine and maytansine. (-)-Rhazinilam does not appear to bind to preformed microtubules. In the process of developing a quantitative assay for measuring the activity of (-)rhazinilam analogues, we observed conditions where both spirals and microtubules were simultaneously induced by (-)-rhazinilam. This observation suggests that (-)-rhazinilam may possess dual binding characteristics dependent on buffer conditions. If so, the cellular effects of (-)-rhazinilam may be due to binding in the paclitaxel site, while some of the  in vitro  effects may be due to binding in the vinca domain. Conversely, this observation may reinforce the argument that (-)-rhazinilam mimics the cellular effects of paclitaxel by inducing mi crotubule formation by a different mechanism of action. We are attempting to find  in vitro  conditions where only microtubules are induced by (-)-rhazinilam. This should clarify the binding site of (-)-rhazinilam on tubulin.
Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes
Authors: Ikram Ullah, Govindasamy-Muralidharan Karthik, Amjad Alkodsi, Una Kjällquist, Gustav Stålhammar, John Lövrot, Nelson-Fuentes Martinez, Jens Lagergren, Sampsa Hautaniemi, Johan Hartman, Jonas Bergh
Journal: Journal of Clinical Investigation (2018)

Metastatic breast cancers are still incurable. Characterizing the evolutionary landscape of these cancers, including the role of metastatic axillary lymph nodes (ALNs) in seeding distant organ metastasis, can provide a rational basis for effective treatments. Here, we have described the genomic analyses of the primary tumors and metastatic lesions from 99 samples obtained from 20 patients with breast cancer. Our evolutionary analyses revealed diverse spreading and seeding patterns that govern tumor progression. Although linear evolution to successive metastatic sites was common, parallel evolution from the primary tumor to multiple distant sites was also evident. Metastatic spreading was frequently coupled with polyclonal seeding, in which multiple metastatic subclones originated from the primary tumor and/or other distant metastases. Synchronous ALN metastasis, a well-established prognosticator of breast cancer, was not involved in seeding the distant metastasis, suggesting a hematogenous route for cancer dissemination. Clonal evolution coincided frequently with emerging driver alterations and evolving mutational processes, notably an increase in apolipoprotein B mRNA–editing enzyme, catalytic polypeptide-like–associated (APOBEC-associated) mutagenesis. Our data provide genomic evidence for a role of ALN metastasis in seeding distant organ metastasis and elucidate the evolving mutational landscape during cancer progression.
Tumor-Treating Fields
Authors: Lia M. Halasz, Timur Mitin
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
There but for the grace of God . . .
Authors: Fiona Godlee
Journal: BMJ (2018)

Who of us has not made mistakes that have harmed patients? Some years ago I and other senior doctors were asked to write about a serious error we had made (doi:10.1136/bmj.331.7517.595-b; http://bit.ly/2DOHE1K). 

I’m sure each of us had many to choose from. I wrote about a patient in whom I correctly diagnosed necrotising fasciitis but then sent to a general ward rather than intensive care. The patient survived but only after arresting and losing fingers and toes from disseminated intravascular coagulation. The then president of the UK General Medical Council, Graeme …
Coffee consumption and gout: a Mendelian randomisation study
Authors: Susanna C Larsson, Mattias Carlström
Journal: Annals of the Rheumatic Diseases (2018)

Observational studies have found that coffee consumption is inversely associated with risk of incident gout but inconsistently with serum uric acid concentrations.1–3 The causality of the associations is, however, uncertain since observational studies are susceptible to confounding and reverse causation bias. Genetic variants with an explicit impact on a modifiable exposure, such as a biomarker or habitual behaviour like coffee consumption, can be used as instrumental variables (proxies) for the exposure to improve causal inference.4 This method, known as Mendelian randomisation, builds on Mendel’s second law and the fact that genetic variants are randomly assorted during meiosis. Therefore, results from Mendelian randomisation studies are less prone to bias due to confounding and reverse causality. We used the Mendelian randomisation approach to examine whether coffee consumption is associated with gout and whether the association may be mediated by serum uric acid concentrations.

A genome-wide association study from the Coffee and Caffeine Genetics Consortium identified 10 single-nucleotide polymorphisms (SNPs), at eight loci, associated with coffee …
Re: Zhangqun Ye, Guohua Zeng, Huan Yang, et al. Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Eur Urol 2018;73:385–91
Authors: Andrew J. Portis, Matthew F. Bultitude
Journal: European Urology (2018)