tbuckley/cabot-search huggingface dataset:
Changes in glucose, insulin, and insulin resistance from presurgery to post adjuvant treatment for breast cancer.
Authors: Emer M. Guinan, Juliette M. Hussey, Laura Healy, Paul A. Carroll, John Kennedy, E. M. Connolly
Journal: Journal of Clinical Oncology (2012)

1511 Background: Elevated fasting insulin levels at breast cancer diagnosis are associated with increased risk of recurrence and reduced survival. (Goodwin PJ, et al. JCO. 2012;30:164-171) Weight gain related to adjuvant treatment coupled with sedentary activity habits may further alter insulin-related measures for breast cancer survivors. We present results from a prospective longitudinal study examining changes in insulin-related markers from pre breast cancer surgery to post adjuvant treatment. Methods: Subjects were recruited from St. James’s hospital, Dublin, Ireland at the time of breast cancer diagnosis (stage I-III). Fasting pre-surgery blood samples were drawn to measure insulin, glucose and glycosylated haemoglobin A1c (HBA1C). Insulin resistance was calculated using the homeostatic model assessment (HOMA). Subjects with no evidence of active cancer completed the same measurements 2-5 years later. Paired sample t-tests were used to measure changes from pre-surgery to post-adjuvant treatment. Statistical significance was set at P = .05. Results: Forty-four subjects (n = 22 postmenopausal) completed both measurements (mean ± SD age 54.1±8.6 years). Mean time since diagnosis to follow-up measures was 3.4±0.8 years. Adjuvant therapy included chemotherapy (n=37), radiotherapy (n=36), biological therapy (n=8) and concurrent hormonal therapy (n=37). There was a statistically significant increase in insulin (mean ± SD change 2.8±4.1mU/L, P=.000), insulin resistance (0.54±1.0, P=.001) and HBA1C (0.1±0.2 %, P= .003). Fasting glucose levels did not change (P = .06). Conclusions: Results indicate that patients with breast cancer experience significant increases in insulin, insulin resistance and HBA1C from pre-surgery to post adjuvant treatment. Elevated post-treatment insulin levels may further contribute to risk of breast cancer recurrence and mortality, while also predisposing to the development of cardiovascular disease and type 2 diabetes mellitus. Exercise and diet interventions are warranted in this population to improve markers of insulin resistance as a surrogate for improving breast cancer and overall health outcomes.
Problem solving strategy can help prevent depression in low income mothers
Authors: Jacqui Wise
Journal: BMJ (2017)

A simple problem solving education intervention shows promise in helping prevent depression in low income mothers, a randomised controlled trial published in JAMA Psychiatry has found.1

Maternal depression disproportionately affects low income and minority women. A cognitive behavioural programme was delivered to mothers who were enrolled in Head Start, an early learning programme that provides services for about a million low income families each year in the United States.

The study included 230 mothers who had depressed …
Elevated factor H–related protein 1 and factor H pathogenic variants decrease complement regulation in IgA nephropathy
Authors: Agustín Tortajada, Eduardo Gutiérrez, Elena Goicoechea de Jorge, Jaouad Anter, Alfons Segarra, Mario Espinosa, Miquel Blasco, Elena Roman, Helena Marco, Luis F. Quintana, Josué Gutiérrez, Sheila Pinto, Margarita Lopez-Trascasa, Manuel Praga, Santiago Rodriguez de Córdoba
Journal: Kidney International (2017)
Abstract 254: Defects in c-kit Receptor Function Affect Myocyte Turnover Resulting in Premature Myocardial Aging in the W/WV Mouse
Authors: Maria-Virginia Caballero, Sergio Signore, Ramaswamy Kannappan, Junghyun Kim, Barbara Ogórek, Ewa Wybieralska, Giulia Borghetti, Fiorenza Valeriani, Antonio Cannata, Laura Graciotti, Annarosa Leri, Marcello Rota, Jan Kajstura, Piero Anversa
Journal: Circulation Research (2013)

The objective of this study was to determine whether attenuation of cardiac stem cell (CSC) growth in the adult heart interferes with physiologic cell turnover leading to premature accumulation of senescent myocytes and myocardial aging. For this purpose, W/W V mice, which carry a mutated non-functional c-kit receptor, were studied. The W/W V mouse is a compound heterozygous mutant mouse. The W mutation corresponds to a large amino acid deletion that includes the transmembrane domain of the c-kit receptor while the W V mutation is a point mutation in the kinase domain of this receptor. These genetic modifications reduce c-kit kinase activity by approximately 80-90% affecting hematopoiesis, gametogenesis and melanogenesis. Echocardiographically, at 2-3 months of age, LV diameters and ejection fraction were similar in controls and W/W V mice. However, at 5-6 months and 8-9 months, diastolic and systolic LVDs were larger in W/W V mice than in WT. Ejection fraction decreased with age in W/W V mice. These various aspects of negative ventricular remodeling typically occur with the development of the aging myopathy in mice 24 month-old and older. Moreover, ventricular dilation is commonly associated with wall thinning, both critical parameters of diastolic and systolic wall stress. Importantly, these anatomical and functional changes in W/W V mice were associated with a marked increase in the percentage of CSCs and myocytes expressing the senescence-associated marker p16 INK4a . At two months of age, wild-type mice and W/W V mice had the same number of LV myocytes which were essentially identical in volume. However, in comparison with wild-type mice, W/W V mice at 4 months of age had a decreased number of LV myocytes which were larger in volume. The magnitude of myocyte proliferation at the time of sacrifice was assessed by two markers of the cell cycle, Ki67 and MCM5. On average, cycling myocytes were 3-4-fold higher in wild type mice than in W/W V mice. In contrast, apoptotic myocytes, evaluated by the TdT assay and hairpin 1 in situ ligation, were significantly more frequent in W/W V mice than in WT mice. In conclusion, mutation of the c-kit receptor in CSCs impairs new myocyte formation and promotes accumulation of senescent myocytes.
Early predictors of outcome after mild traumatic brain injury (UPFRONT): an observational cohort study
Authors: Joukje van der Naalt, Marieke E Timmerman, Myrthe E de Koning, Harm J van der Horn, Myrthe E Scheenen, Bram Jacobs, Gerard Hageman, Tansel Yilmaz, Gerwin Roks, Jacoba M Spikman
Journal: The Lancet Neurology (2017)
Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus
Authors: Caroline E. Dale, Ghazaleh Fatemifar, Tom M. Palmer, Jon White, David Prieto-Merino, Delilah Zabaneh, Jorgen E.L. Engmann, Tina Shah, Andrew Wong, Helen R. Warren, Stela McLachlan, Stella Trompet, Max Moldovan, Richard W. Morris, Reecha Sofat, Meena Kumari, Elina Hyppönen, Barbara J. Jefferis, Tom R. Gaunt, Yoav Ben-Shlomo, Ang Zhou, Aleksandra Gentry-Maharaj, Andy Ryan, Renée de Mutsert, Raymond Noordam, Mark J. Caulfield, J. Wouter Jukema, Bradford B. Worrall, Patricia B. Munroe, Usha Menon, Chris Power, Diana Kuh, Debbie A. Lawlor, Steve E. Humphries, Dennis O. Mook-Kanamori, Naveed Sattar, Mika Kivimaki, Jacqueline F. Price, George Davey Smith, Frank Dudbridge, Aroon D. Hingorani, Michael V. Holmes, Juan P. Casas
Journal: Circulation (2017)

Background: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. Methods: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Results: Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28–1.71), similar to findings for BMI (1 SD≈4.6 kg/m 2 ; OR for CHD, 1.36; 95% CI, 1.22–1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03–1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38–2.42) and OR, 1.98 (95% CI, 1.41–2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%–77% per 1 SD). Conclusions: Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.
The Arginine Transporter ATB(0,+) is Upregulated in Colorectal Cancer
Authors: N Gupta, S Miyauchi, H Hu, A Herdman, R Podolsky, PM Martin, S Mager, RG Martindale, V Ganapathy
Journal: Endoscopy (2004)

Introduction: Excess production of nitric oxide (NO) from arginine by the enzyme iNOS plays a crucial role in colorectal cancer. Recently, a highly efficient arginine transporter ATB0,+ has been described in human tissues. We hypothesize that ATB0,+ is upregulated in colorectal cancer as a means to deliver arginine to iNOS for excess NO production.
Appearance of Mycoplasma pneumoniae in lungs of experimentally infected hamsters and sputum from patients with natural disease
Authors: A. M. Collier, W. A. Clyde
Journal: American Journal of Respiratory and Critical Care Medicine (1974)

tion in graded ethanol and embedding in Epon. Thick (l-,um) sections were stained with Richardson's blue for light microscopy; thin sections were cut in areas where cellular infiltrate was present and were stained with uranyl acetate and lead citrate for electron microscopy. Densely staining Mycoplasma pneumoniae with a filamentous appearance and a specialized terminal structure were found in medium-sized bronchi in areas where peribronchial infiltration was present. The organisms were attached to the lumenal respiratory epithelial surface by their ter­ minal organelles. Sputum samples from 18 patients with natural Mycoplasma pneumoniae disease proved by culture were studied for further insight into disease mechanisms and diagnostic features. Quanti­ tative mycoplasma cultures of 10 samples yielded 102 to 106 colony-forming units per ml of sputum (geometric mean value: 104 . 1). Wright's stain smears for cytologic studies revealed a pre­ dominance of polymorphonuclear leukocytes, with large mononuclear cells and desquamated cili­ ated epithelial cells in some specimens. Portions of the sputum samples were processed for electron microscopy. As in the experimental models, the mycoplasma was identified by its characteristic dense staining, size, and filamentous appearance. Organisms were found attached to epithelial cell lumenal membranes, microvilli, and cilia by their differentiated terminal structures. Interpretation of the diagnostic specificity of the cytologic features awaits comparable studies in other diseases. The degree of infectivity of sputum implies that visualization of organisms may be accomplished readily with appropriate techniques. These studies substantiate the morphol~gy of the mycoplasma's parasitic form, which has been suggested by previous studies in vitro, and reveal the nature of the host-parasite relationship in man.
FGFR gene amplification and response to endocrine therapy in metastatic hormone receptor positive (HR+) breast cancer.
Authors: Joshua Z. Drago, Andrzej Niemierko, Laura Spring, Beverly Moy, Dejan Juric, Steven J. Isakoff, A. John Iafrate, Leif W. Ellisen, Aditya Bardia
Journal: Journal of Clinical Oncology (2017)

1013 Background: Amplification in Fibroblast Growth Factor Receptor (FGFR) genes occurs in 10% of breast cancers, is associated with poor prognosis, and appears to drive resistance to endocrine therapies in vitro. However, the role of FGFR in modulating the clinical response to endocrine therapies is unclear, and could have important implications given that FGFR is a potential therapeutic target. This study aims to evaluate the association between FGFR amplification and clinical response to endocrine therapy in HR+ metastatic breast cancer (MBC). Methods: Primary or metastatic tumor specimens from patients with HR+/HER2 negative MBC underwent dual-color fluorescence in situ hybridization (FISH) of the FGFR1 locus on chromosome 8p. FISH ratios of ≥2 were considered positive for gene amplification (FGFR+). Time to progression (TTP) on first line endocrine therapy was evaluated in FGFR+ versus wild type (WT) patients using actuarial analysis. Results: Between 2012 and 2016, we identified 95 patients with HR+ MBC who underwent FGFR FISH testing. Of these, 24 (25.3%) were FGFR+. FGFR+ and WT patients did not differ in being postmenopausal at initial breast cancer diagnosis (28.6% vs. 31.7%; p = 1.0), having de-novo MBC (16.7% vs. 21.1%; p = 0.773), having received adjuvant chemotherapy (75% vs. 76.8%; p = 1.0) or having received adjuvant endocrine therapy (90% vs. 91.1%; p = 1.0). However, FGFR+ patients tended to be younger than WT patients (54.3 vs. 59.3 years; p = 0.045), and more likely to have PR-negative MBC (50.0% vs. 19.1%; p = 0.011). While there was no difference in TTP on first-line chemotherapy in FGFR+ vs. WT patients (5.0 vs. 6.2 months; p = 0.8), FGFR+ patients had a shorter median TTP on first-line endocrine therapy than WT (8.5 vs. 10.8 months; p = 0.047). These results were similar when stratified by presence of de-novo metastatic disease. Conclusions: In patients with HR+ MBC, FGFR gene amplification is associated with shorter time to progression on first line endocrine therapy. Further studies are needed to confirm these findings, and to investigate potential strategies for endocrine therapy and FGFR-directed combinatorial therapy in FGFR+ breast cancer.
Whole body and intracranial efficacy of ceritinib in ALK-inhibitor (ALKi)-naive patients (pts) with ALK-rearranged (ALK+) NSCLC and baseline (BL) brain metastases (BM): Results from ASCEND-1 and -3.
Authors: Enriqueta Felip, Daniel Shao-Weng Tan, Dong-Wan Kim, Ranee Mehra, Sergey Orlov, Keunchil Park, Chong-Jen Yu, Tony Mok, Makoto Nishio, Giorgio V. Scagliotti, David R. Spigel, Santosh Sutradhar, Dajana Cesic, Alice Tsang Shaw
Journal: Journal of Clinical Oncology (2016)

e20520 Background: Here we present efficacy outcomes in ALK+ NSCLC pts with BL BM treated with the selective oral ALKi ceritinib in the ASCEND-1 (ph1; NCT01283516) and ASCEND-3 (ph2; NCT01685138) trials. Methods: ALKi-naive pts with ALK+ NSCLC and stable BL BM received ceritinib 750 mg/d. Efficacy analyses (by blinded independent review committee [BIRC]) assessed whole body responses for ASCEND-1 and -3 according to RECIST 1.0 and 1.1 criteria, respectively. Pooled intracranial responses were evaluated by BIRC (ASCEND-1, retrospectively; ASCEND-3, prospectively) in pts with measureable BL BM (RECIST 1.1). Results: Of 26 and 50 ALKi-naïve pts with BL BM enrolled in ASCEND-1 and -3, respectively, 88.5% and 100% had prior chemotherapy and 57.7% and 54.0% had prior brain radiotherapy (RT); median times from prior RT to first ceritinib dose were 4.6 and 2.7 mo. Ceritinib showed whole body and intracranial efficacy (Table). The most common AEs (ASCEND-1; ASCEND-3) were nausea (84.6%; 78.0%), diarrhea (92.3%; 76.0%) and vomiting (76.9%; 72.0%); 46 pts (ASCEND-1: 19; ASCEND-3: 27) had dose reductions and 4 pts (ASCEND-1: 3; ASCEND-3: 1) discontinued due to AEs. Conclusions: Clinically meaningful whole body and intracranial activity with an acceptable tolerability profile were observed in ALKi-naïve pts with ALK+ NSCLC and BL BM treated with ceritinib. ASCEND-1 ASCEND-3 Pooled Data cutoff 14 Apr 14 27 Jun 14 - ALK-naive pts with BL BM 26 50 - Median duration of follow-up (range), mo 12.3 (0.6–22.1) 7.5 (0.6–13.8) - Whole body response (BIRC) ORR [CI], % 65.4 [44.3, 82.8] 60.0 [45.2, 73.6] - Disease control rate [CI], % 76.9 [56.4, 91.0] 78.0 [64.0, 88.5] - Median DORa [CI], mo NR [4.2, NR] 9.4 [5.6, NR] - Median PFS [CI], mo 18.4 [4.6, NR] 11.0 [7.2, NR] - Intracranial response (BIRC) Pts with measurable BL BM 8 17 25 Intracranial ORR [CI], % 62.5 [24.5, 91.5] 58.8 [32.9, 81.6] 60.0 [38.7, 78.9] Intracranial disease control rate [CI], % 62.5 [24.5, 91.5] 82.4 [56.6, 96.2] 76.0 [54.9, 90.6] Median intracranial DORa [CI], mo 8.2 [5.6, NR] NR [5.6, NR] 8.2 [5.6, NR] a Calculated for pts with confirmed CR or PR. CI, 95% confidence interval; NR, not reached.
The Old Bromides and Their 21st Century Refreshment
Authors: Thomas Cropley, Zachary Theroux
Journal: JAMA Dermatology (2017)

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
Osteocyte-specific WNT1 regulates osteoblast function during bone homeostasis
Authors: Kyu Sang Joeng, Yi-Chien Lee, Joohyun Lim, Yuqing Chen, Ming-Ming Jiang, Elda Munivez, Catherine Ambrose, Brendan H. Lee
Journal: Journal of Clinical Investigation (2017)

Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with spontaneous fractures similar to that observed in OI patients. Conversely, Wnt1 overexpression from osteocytes stimulated bone formation by increasing osteoblast number and activity, which was due in part to activation of mTORC1 signaling. While antiresorptive therapy is the mainstay of OI treatment, it has limited efficacy in WNT1-related OI. In this study, anti-sclerostin antibody (Scl-Ab) treatment effectively improved bone mass and dramatically decreased fracture rate in swaying mice, a model of global Wnt1 loss. Collectively, our data suggest that WNT1-related OI and osteoporosis are caused in part by decreased mTORC1-dependent osteoblast function resulting from loss of WNT1 signaling in osteocytes. As such, this work identifies an anabolic function of osteocytes as a source of Wnt in bone development and homoeostasis, complementing their known function as targets of Wnt signaling in regulating osteoclastogenesis. Finally, this study suggests that Scl-Ab is an effective genotype-specific treatment option for WNT1-related OI and osteoporosis.
To assess the effects of parathyroidectomy (TPTX versus TPTX+AT) for Secondary Hyperparathyroidism in chronic renal failure: A Systematic Review and Meta-Analysis
Authors: Miao-E. Liu, Nian-Cun Qiu, Si-Luo Zha, Zhi-Peng Du, Yi-Fan Wang, Qiang Wang, Qi Chen, Xiao-Xia Cen, Ying Jiang, Qiong Luo, Cheng-Xiang Shan, Ming Qiu
Journal: International Journal of Surgery (2017)
Alternative Science and Human Reproduction
Authors: R. Alta Charo
Journal: New England Journal of Medicine (2017)

Interview with Prof. R. Alta Charo on recent Trump administration appointees and the implications of alternative science for women’s health. (10:44)Download U.S. executive-branch appointees Valerie Huber, Teresa Manning, Charmaine Yoest, and Katy Talento embrace false claims about contraception, abortion, sex education, and pregnancy. Such “alternative science” leads to bad policy.
The rs7903146 Variant in the <i>TCF7L2</i> Gene Increases the Risk of Prediabetes/Type 2 Diabetes in Obese Adolescents by Impairing β-Cell Function and Hepatic Insulin Sensitivity
Authors: Catrina Cropano, Nicola Santoro, Leif Groop, Chiara Dalla Man, Claudio Cobelli, Alfonso Galderisi, Romy Kursawe, Bridget Pierpont, Martina Goffredo, Sonia Caprio
Journal: Diabetes Care (2017)

OBJECTIVE In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents. RESEARCH DESIGN AND METHODS The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp. In 307 subjects, a follow-up oral glucose tolerance test was repeated after 3.11 ± 2.36 years. RESULTS The TCF7L2 rs7903146 risk allele was associated with higher 2-h glucose levels in Caucasians (P = 0.006) and African Americans (P = 0.009), and a trend was seen also in Hispanics (P = 0.072). Also, the T allele was associated with decreased β-cell responsivity and IGT (P &amp;lt; 0.05). Suppression of endogenous hepatic glucose production was lower in subjects with the risk variant (P = 0.006). Finally, the odds of showing IGT/T2D at follow-up were higher in subjects carrying the minor allele (odds ratio 2.224; 95% CI 1.370–3.612; P = 0.0012). CONCLUSIONS The rs7903146 variant in the TCF7L2 gene increases the risk of IGT/T2D in obese adolescents by impairing β-cell function, and hepatic insulin sensitivity predicts the development of IGT/T2D over time.