tbuckley/cabot-search huggingface dataset:
Effect of Physical Activity on Frailty
Authors: Andrea Trombetti, Mélany Hars, Fang-Chi Hsu, Kieran F. Reid, Timothy S. Church, Thomas M. Gill, Abby C. King, Christine K. Liu, Todd M. Manini, Mary M. McDermott, Anne B. Newman, W. Jack Rejeski, Jack M. Guralnik, Marco Pahor, Roger A. Fielding
Journal: Annals of Internal Medicine (2018)

Background: Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large long-term randomized trials are lacking. Objective: To determine whether a long-term, structured, moderate-intensity physical activity program is associated with a lower risk for frailty and whether frailty status alters the effect of physical activity on the reduction in major mobility disability (MMD) risk. Design: Multicenter, single-blind, randomized trial. Setting: 8 centers in the United States. Participants: 1635 community-dwelling adults, aged 70 to 89 years, with functional limitations. Intervention: A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises. Measurements: Frailty, as defined by the SOF (Study of Osteoporotic Fractures) index, at baseline and 6, 12, and 24 months, and MMD, defined as the inability to walk 400 m, for up to 3.5 years. Results: Over 24 months of follow-up, the risk for frailty (n = 1623) was not statistically significantly different in the physical activity versus the health education group (adjusted prevalence difference, −0.021 [95% CI, −0.049 to 0.007]). Among the 3 criteria of the SOF index, the physical activity intervention was associated with improvement in the inability to rise from a chair (adjusted prevalence difference, −0.050 [CI, −0.081 to −0.020]). Baseline frailty status did not modify the effect of physical activity on reducing incident MMD (P for interaction = 0.91). Limitation: Frailty status was neither an entry criterion nor a randomization stratum. Conclusion: A structured, moderate-intensity physical activity program was not associated with a reduced risk for frailty over 2 years among sedentary, community-dwelling older adults. The beneficial effect of physical activity on the incidence of MMD did not differ between frail and nonfrail participants. Primary Funding Source: National Institute on Aging, National Institutes of Health.
Zygodactyly (Syndactyly Type A1) Associated With Midfoot Charcot Neuropathy and Diabetes
Authors: Dominic O. McConville, G. Pooler Archbold, Anthony Lewis, Patrick J. Morrison
Journal: Diabetes Care (2018)

Charcot neuropathy (CN) is a known complication of diabetes. Zygodactyly is a congenital malformation causing cutaneous webbing of the second and third toes. We noticed patients with diabetes with CN frequently had zygodactyly. To determine the frequency of this, we examined a prospective series of 25 patients with CN and 29 patients without CN in a podiatry clinic. All had type 2 diabetes and peripheral neuropathy and were referred from diabetes or vascular departments sequentially. The patients with CN (both acute and chronic) had plain foot radiography (lateral, oblique, dorsoplantar weight-bearing views) with Lisfranc dislocation or disorganization or swelling consistent with a Charcot foot and confirmation with MRI. There was no finger syndactyly, facial dysmorphism, or genetic syndrome. Zygodactyly was present (skin webbing occurring from the first metatarsophalangeal joint distally) in 19 case subjects and one control subject (Fig. 1 A – D ). The χ2 statistic where …
STIMULANT ASSOCIATED HEART FAILURE WITH METHAMPHETAMINE AND COCAINE USE: SURVIVAL AND RESOURCE UTILIZATION AT A SAFETY-NET HOSPITAL
Authors: Joseph Ebinger, Brandon Wiley, Ganesh Devendra, Dhruv Kazi, Priscilla Hsue, Courtney Carroll, Robert Pitts, Zian Tseng, Christopher Barnett
Journal: Journal of the American College of Cardiology (2018)
Understanding brain penetrance of anticancer drugs
Authors: Victor A Levin, Benjamin M Ellingson
Journal: Neuro-Oncology (2018)

This paper explicates the impact of tumor capillary permeability for glioma World Health Organization (WHO) grades II to IV on brain-penetrant drug entry and distribution within the tumor and the brain adjacent to tumor (leading edge). In addition, we consider the distribution of non-brain penetrant drugs and how, in some cases, large-molecular-weight drugs might achieve good distribution into tumor and brain adjacent to tumor.
Symptom Burden in the First Year After Cancer Diagnosis: An Analysis of Patient-Reported Outcomes
Authors: Lev D. Bubis, Laura Davis, Alyson Mahar, Lisa Barbera, Qing Li, Lesley Moody, Paul Karanicolas, Rinku Sutradhar, Natalie G. Coburn
Journal: Journal of Clinical Oncology (2018)

Purpose Improvement in the quality of life of patients with cancer requires attention to symptom burden across the continuum of care, with the use of patient-reported outcomes key to achieving optimal care. Yet there have been few studies that have examined symptoms in the early postdiagnosis period during which suboptimal symptom control may be common. A comprehensive analysis of temporal trends and risk factors for symptom burden in newly diagnosed patients with cancer is essential to guide supportive care strategies. Methods A retrospective observational study was performed of patients who were diagnosed with cancer between January 2007 and December 2014 and who survived at least 1 year. Patient-reported Edmonton Symptom Assessment System scores, which are prospectively collected at outpatient visits, were linked to provincial administrative health care data. We described the proportion of patients who reported moderate-to-severe symptom scores by month during the first year after diagnosis according to disease site. Multivariable logistic regression models were constructed to identify risk factors for moderate-to-severe symptom scores. Results Of 120,745 patients, 729,861 symptom assessments were recorded within 12 months of diagnosis. For most symptoms, odds of elevated scores were highest in the first month, whereas nausea had increased odds of elevated scores up to 6 months after diagnosis. On multivariable analysis, cancer site, younger age, higher comorbidity, female sex, lower income, and urban residence were associated with significantly higher odds of elevated symptom burden. Conclusion A high prevalence of moderate-to-severe symptom scores was observed in cancers of all sites. Patients are at risk of experiencing multiple symptoms in the immediate postdiagnosis period, which underscores the need to address supportive care requirements early in the cancer journey. Patient subgroups who are at higher risk of experiencing moderate-to-severe symptoms should be targeted for tailored supportive care interventions.
Erratum. Validation of the Diabetes Prevention Trial–Type 1 Risk Score in the TrialNet Natural History Study. Diabetes Care 2011;34:1785–1787
Authors: Jay M. Sosenko, Jay S. Skyler, Jeffrey Mahon, Jeffrey P. Krischer, Craig A. Beam, David C. Boulware, Carla J. Greenbaum, Lisa E. Rafkin, Catherine Cowie, David Cuthbertson, Jerry P. Palmer
Journal: Diabetes Care (2018)

In the article cited above, the last paragraph of the RESULTS section was corrected to read: The application of the DPTRS is presented in the following hypothetical example. An 8-year-old with a BMI of 18.0 kg/m2 (log …
Loss of the Nuclear Pool of Ubiquitin Ligase CHIP/STUB1 in Breast Cancer Unleashes the MZF1-Cathepsin Pro-oncogenic Program
Authors: Haitao Luan, Bhopal Mohapatra, Timothy A. Bielecki, Insha Mushtaq, Sameer Mirza, Tameka A. Jennings, Robert J. Clubb, Wei An, Dena Ahmed, Rokaya El-Ansari, Matthew D. Storck, Nitish K. Mishra, Chittibabu Guda, Yuri M. Sheinin, Jane L. Meza, Srikumar Raja, Emad A. Rakha, Vimla Band, Hamid Band
Journal: Cancer Research (2018)

CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss of nuclear but not cytoplasmic CHIP to predict more aggressive tumorigenesis and shorter patient survival, with loss of CHIP in two thirds of ErbB2+ and triple-negative breast cancers (TNBC) and in one third of ER+ breast cancers. Reduced CHIP expression was seen in breast cancer patient-derived xenograft tumors and in ErbB2+ and TNBC cell lines. Ectopic CHIP expression in ErbB2+ lines suppressed in vitro oncogenic traits and in vivo xenograft tumor growth. An unbiased screen for CHIP-regulated nuclear transcription factors identified many candidates whose DNA-binding activity was up- or downregulated by CHIP. We characterized myeloid zinc finger 1 (MZF1) as a CHIP target, given its recently identified role as a positive regulator of cathepsin B/L (CTSB/L)-mediated tumor cell invasion downstream of ErbB2. We show that CHIP negatively regulates CTSB/L expression in ErbB2+ and other breast cancer cell lines. CTSB inhibition abrogates invasion and matrix degradation in vitro and halts ErbB2+ breast cancer cell line xenograft growth. We conclude that loss of CHIP remodels the cellular transcriptome to unleash critical pro-oncogenic pathways, such as the matrix-degrading enzymes of the cathepsin family, whose components can provide new therapeutic opportunities in breast and other cancers with loss of CHIP expression.Significance: These findings reveal a novel targetable pathway of breast oncogenesis unleashed by the loss of tumor suppressor ubiquitin ligase CHIP/STUB1. Cancer Res; 78(10); 2524-35. ©2018 AACR.
Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients
Authors: S.T. Kim, K.C. Banks, E. Pectasides, S.Y. Kim, K. Kim, R.B. Lanman, A. Talasaz, J. An, M.G. Choi, J.H. Lee, T.S. Sohn, J.M. Bae, S. Kim, S.H. Park, J.O. Park, Y.S. Park, H.Y. Lim, N.K.D. Kim, W. Park, H. Lee, A.J. Bass, K. Kim, W.K. Kang, J. Lee
Journal: Annals of Oncology (2018)

BackgroundTo identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics.Patients and methodsWe prospectively evaluated the efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples.ResultsComplete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P = 0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P = 0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications.ConclusionsThe present study showed that HER2+ GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.
Membership of the Royal College of General Practitioners (MRCGP)
Authors: David Chao
Journal: BMJ (2005)

MRCGP signifies the achievement of a high professional standard in family practice set by the Royal College of General Practitioners (RCGP). It enables general practitioners not only to enjoy the benefits of the professional organisation of their discipline but also to have an influence in the development and management of the medical profession as a whole through participation in college activities.

During my general practitioner registrar year in the 1990s.

To achieve a high standard of professionalism in general practice and to equip myself for academic practice in family medicine.

My preparation started 12 to 15 months before the exam and included self study, attendance at a weekly half day release course, and a revision course. I studied about 5 to …
Supported Employment for Persons With Posttraumatic Stress Disorder
Authors: Kim T. Mueser
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Mavrilimumab, a Fully Human Granulocyte–Macrophage Colony‐Stimulating Factor Receptor α Monoclonal Antibody
Authors: Gerd R. Burmester, Iain B. McInnes, Joel M. Kremer, Pedro Miranda, Jiří Vencovský, Alex Godwood, Marius Albulescu, M. Alex Michaels, Xiang Guo, David Close, Michael Weinblatt
Journal: Arthritis & Rheumatology (2018)

Objective Mavrilimumab, a human monoclonal antibody, targets granulocyte–macrophage colony‐stimulating factor receptor α. We undertook to determine the long‐term safety and efficacy of mavrilimumab in rheumatoid arthritis patients in 2 phase II b studies (1071 and 1107) and in 1 open‐label extension study (ClinicalTrials.gov identifier: NCT 01712399). Methods In study 1071, patients with an inadequate response to disease‐modifying antirheumatic drugs ( DMARD s) received mavrilimumab (30, 100, or 150 mg) or placebo every other week plus methotrexate. In study 1107, patients with an inadequate response to anti–tumor necrosis factor agents and/or DMARD s received 100 mg mavrilimumab every other week or 50 mg golimumab every 4 weeks plus methotrexate. Patients entering the open‐label extension study received 100 mg mavrilimumab every other week plus methotrexate. Long‐term safety and efficacy of mavrilimumab were assessed. Results A total of 442 patients received mavrilimumab (14 of 245 patients from study 1071, 9 of 70 patients from study 1107, and 52 of 397 patients from the open‐label extension study discontinued mavrilimumab treatment throughout the studies). The cumulative safety exposure was 899 patient‐years; the median duration of mavrilimumab treatment was 2.5 years (range 0.1–3.3 years). The most common treatment‐emergent adverse events ( AE s) were nasopharyngitis (n = 69; 7.68 per 100 patient‐years) and bronchitis (n = 51; 5.68 per 100 patient‐years). At weeks 74 and 104, 3.5% and 6.2% of patients, respectively, demonstrated reduction in forced expiratory volume in 1 second, while 2.9% and 3.4% of patients, respectively, demonstrated reduction in forced vital capacity (&gt;20% reduction from baseline to &lt;80% predicted). Most pulmonary changes were transient and only infrequently associated with AE s. Mavrilimumab at 100 mg every other week demonstrated sustained efficacy; at week 122, 65.0% of patients achieved a Disease Activity Score in 28 joints using the C‐reactive protein level ( DAS 28‐ CRP ) of &lt;3.2, and 40.6% of patients achieved a DAS 28‐ CRP of &lt;2.6. Conclusion Long‐term treatment with mavrilimumab maintained response and was well‐tolerated with no increased incidence of treatment‐emergent AE s. Safety data were comparable with those from both phase II b qualifying studies.
LIMD2 Is Overexpressed in BRAF V600E-Positive Papillary Thyroid Carcinomas and Matched Lymph Node Metastases
Authors: Maria José Carregosa Pinheiro dos Santos, André Uchimura Bastos, Vitor Rodrigues da Costa, Rosana Delcelo, Susan Chow Lindsey, Gabriel Avelar Colozza-Gama, Hongzhuang Peng, Frank J. Rauscher, Gisele Oler, Janete Maria Cerutti
Journal: Endocrine Pathology (2018)
Genome Writing: Current Progress and Related Applications
Authors: Yueqiang Wang, Yue Shen, Ying Gu, Shida Zhu, Ye Yin
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract The ultimate goal of synthetic biology is to build customized cells or organisms to meet specific industrial or medical needs. The most important part of the customized cell is a synthetic genome. Advanced genomic writing technologies are required to build such an artificial genome. Recently, the partially-completed synthetic yeast genome project represents a milestone in this field. In this mini review, we briefly introduce the techniques for de novo genome synthesis and genome editing. Furthermore, we summarize recent research progresses and highlight several applications in the synthetic genome field. Finally, we discuss current challenges and future prospects.
Ethnic minority and non-UK doctors are more likely to fail exams, GMC data show
Authors: Abi Rimmer
Journal: BMJ (2016)

Black and minority ethnic (BME) doctors and international medical graduates (IMGs) are less likely to pass specialty exams than their white UK counterparts, data from the General Medical Council show.

On Thursday 21 July the GMC published research and data on the progression of doctors from different ethnicities and backgrounds through exams and recruitment. The findings showed that white UK medical graduates remained more likely to pass specialty exams than their BME UK counterparts. IMG doctors whose primary qualification was gained outside the UK or European Economic Area (EEA) were even less likely to do well in exams or recruitment, …
The T2-FLAIR mismatch sign as an imaging marker for non-enhancing IDH-mutant, 1p/19q-intact lower-grade glioma: a validation study
Authors: Martinus P G Broen, Marion Smits, Maarten M J Wijnenga, Hendrikus J Dubbink, Monique H M E Anten, Olaf E M G Schijns, Jan Beckervordersandforth, Alida A Postma, Martin J van den Bent
Journal: Neuro-Oncology (2018)

The purpose of this study was to assess the reproducibility of the previously described T2-fluid attenuated inversion recovery (FLAIR) mismatch sign as a specific imaging marker in non-enhancing isocitrate dehydrogenase (IDH) mutant, 1p/19q non-codeleted lower-grade glioma (LGG), encompassing both diffuse and anaplastic astrocytoma.MR scans (n = 154) from 3 separate databases with genotyped LGG were evaluated by 2 independent reviewers to assess (i) presence/absence of "T2-FLAIR mismatch" sign and (ii) presence/absence of homogeneous signal on T2-weighted images. Interrater agreement with Cohen's kappa (κ) was calculated, as well as diagnostic test performance of the T2-FLAIR mismatch sign to identify IDH-mutant astrocytoma.There was substantial interrater agreement for the T2-FLAIR mismatch sign [κ = 0.75 (0.64-0.87)], but only fair agreement for T2 homogeneity [κ = 0.38 (0.25-0.52)]. The T2-FLAIR mismatch sign was present in 38 cases (25%) and had a positive predictive value of 100%, negative predictive value of 68%, a sensitivity of 51%, and a specificity of 100%.With a robust interrater agreement, our study confirms that among non-enhancing LGG the T2-FLAIR mismatch sign represents a highly specific imaging marker for IDH-mutant astrocytoma. This non-invasive marker may enable a more informed patient counsel and can aid in the treatment decision processes in a significant proportion of patients presenting with non-enhancing, LGG-like lesions.
Patient Data Ownership
Authors: Jorge L. Contreras, John Rumbold, Barbara Pierscionek
Journal: JAMA (2018)

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