tbuckley/cabot-search huggingface dataset:
Phase II feasibility study of a physical activity and dietary change weight loss intervention in a subset analysis of breast cancer survivors (SWOG S1008).
Authors: Heather Greenlee, Danika Lew, Dawn L. Hershman, John P. Pierce, Lisa Kathryn Hansen, Vicky A. Newman, Judith Korner, Antoine Sayegh, Louis Fehrenbacher, Shelly S. Lo, Jennifer R. Klemp, Kristine Rinn, John M. Robertson, Joseph M. Unger, Julie Gralow, Kathy S. Albain, Robert S. Krouse, Carol J. Fabian
Journal: Journal of Clinical Oncology (2015)

9572 Background: Weight loss among overweight and obese breast and colorectal cancer survivors is hypothesized to be associated with improved disease-free survival. Phase III trials are needed to test effective and implementable weight loss interventions in breast and colorectal cancer survivors. Methods: We conducted a feasibility study of a 12-month community-situated physical activity and telephone-based dietary change weight loss intervention in female breast and colorectal cancer survivors. We report the primary outcomes for the breast cancer (BC) cohort. Sedentary postmenopausal women with prior Stage I-III BC and BMI ≥ 25 kg/m2 were eligible. Primary objectives were to assess feasibility and weight loss at 12 months. Target accrual was 25 BC participants (ppts). Ppts were assigned a telephone counselor and given a 12-month membership to a local Curves fitness center, which offers a 30-minute circuit-based exercise program. Ppts were counseled 14 times over 12 months and were instructed to exercise 150 minutes/week, walk 10,000 steps/day, and decrease caloric intake by 500 kcal/day. The intervention would be considered feasible if full accrual was met within 10 months, ≥ 68% of ppts met minimum goals for exercise (attend ≥ 2 exercise sessions/week for ≥ 36 weeks) and diet (reduce caloric intake by ≥ 100 kcal/day and/or increase fruit/vegetable intake by ≥ 1 serving/day) (adherence), and ≥ 68% of ppts provided anthropometric measures at 12 months (retention). Results: Among 25 evaluable ppts, median age was 57.3 years with median BMI 37.5 kg/m2 (range 27.7-54.6), 64% Stage I, and median 2.1 years from diagnosis. Accrual occurred in 10 months, 80% of ppts provided anthropometric measures at 12 months, 96% of ppts met the diet goal, and 28% of ppts met the exercise goal. Thus feasibility goals were met, with the exception of exercise adherence as defined a priori. At 12 months, average weight loss was 7.6% (95% CI -3.9%, 19.2%) with median weight loss of 7.1%. Conclusions: It is feasible to recruit and retain BC survivors in a multicenter weight loss trial using dietary change plus physical activity to achieve clinically meaningful weight loss over 12 months. Clinical trial information: NCT01453452.
68Ga DOTATATE PET/CT Versus 18F-FDG PET/CT for Detecting Intramedullary Hemangioblastoma in a Patient With Von Hippel-Lindau Disease
Authors: Farnaz Banezhad, Zahra Kiamanesh, Farshad Emami, Ramin Sadeghi
Journal: Clinical Nuclear Medicine (2019)

Von Hippel-Lindau disease is an inherited syndrome associated with several benign and malignant tumors such as central nervous system (CNS) hemangioblastoma. Herein, we report a known case of A Von Hippel-Lindau patient with a cerebral hemangioblastoma who was referred for further evaluation because of recent paraparesis. F-FDG PET/CT showed no focal uptake in the thoracic spine, which demonstrated increased Ga DOTATATE activity, owing to overexpression of somatostatin receptors, suggesting spinal cord hemangioblastoma. This case report indicates the significant role of Ga-labeled somatostatin receptor analogs in the diagnosis of hemangioblastoma.
Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial
Authors: Qaiser Bashir, Peter F Thall, Denái R Milton, Patricia S Fox, Jitesh D Kawedia, Partow Kebriaei, Nina Shah, Krina Patel, Borje S Andersson, Yago L Nieto, Ben C Valdez, Simrit Parmar, Gabriela Rondon, Ruby Delgado, Chitra Hosing, Uday R Popat, Betul Oran, Stefan O Ciurea, Pei Lin, Donna M Weber, Sheeba K Thomas, Hans C Lee, Elisabet E Manasanch, Robert Z Orlowski, Loretta A Williams, Richard E Champlin, Muzaffar H Qazilbash
Journal: The Lancet Haematology (2019)
Medical audit in general practice. I: Effects on doctors' clinical behaviour for common childhood conditions. North of England Study of Standards and Performance in General Practice.
Authors: Ian Russell, Julia Addington-Hall, Peter Avery, Claire Bamford, Andrew Barton, Cam Donaldson, Martin Eccles, Christopher Foy, Erica Haimes, Newcastle Upon, Jenny Hewison, Mary Ho, Hong Kong, Robin Humphrey, Allen Hutchinson, Tyne Donald, Elaine Mccoll, Louise Parker, Nicholas Steen, Elizabeth Towner, G Webb
Journal: BMJ (1992)

To estimate the effects of medical audit, particularly setting clinical standards, on general practitioners' clinical behaviour.Before and after study strengthened by a replicated Latin square.62 training general practices in the north of England.92 general practitioner trainers, 84 (91%) of whom completed the study; random sample of 3500 children consulting one of these trainers for any of five conditions--acute cough, acute vomiting, bedwetting, itchy rash, and recurrent wheezy chest--stratified by doctor consulted, condition, and age.Clinical standard set by each of 10 small groups of general practitioner trainers for one randomly selected childhood condition. Each group also experienced a different type of medical audit, randomly selected, for each of the four other study conditions (receiving a clinical standard set by another trainer group, tabulated data comparing clinical performance with that of all other groups, tabulated data from only their own group, and nothing ("control" condition)).Content of initial consultation divided into: history, examination, investigation, diagnosis, and management (abstracted from medical records and "enhancement forms" completed by doctors).There was increased prescribing of bronchodilators for acute cough, oral rehydration fluids for acute vomiting, antibiotics for itchy rash, and bronchodilators and oral steroids for recurrent wheezy chest and reduced prescribing of antibiotics for acute cough and recurrent wheezy chest and tricyclic antidepressants for bedwetting. Fewer children were "discharged." Each change was consistent with the standard and either limited to doctors who set a standard for that condition or significantly greater for them than all other doctors.Setting clinical standards improved prescribing and follow up.
SAT-073-Micronutrient deficiencies in patients with decompensated cirrhosis
Authors: Gemma Llibre Nieto, Alba Lira, Mercedes Vergara, Mireia Miquel, Meritxell Casas, Blai Dalmau, Valentí Puig-Diví, Gemma Solé, Josep Maria Barrades, Nuria Nava, Noemí Martínez, Montse Ortega, Estefanía Martínez, Montserrat García, Antònia Humanes, Laia Grau-López, Jordi Sánchez-Delgado
Journal: Journal of Hepatology (2019)
The Notch signaling pathway promotes basophil responses during helminth-induced type 2 inflammation
Authors: Lauren M. Webb, Oyebola O. Oyesola, Simon P. Früh, Elena Kamynina, Katherine M. Still, Ravi K. Patel, Seth A. Peng, Rebecca L. Cubitt, Andrew Grimson, Jennifer K. Grenier, Tajie H. Harris, Charles G. Danko, Elia D. Tait Wojno
Journal: The Journal of Experimental Medicine (2019)

Type 2 inflammation drives the clearance of gastrointestinal helminth parasites, which infect over two billion people worldwide. Basophils are innate immune cells that support host-protective type 2 inflammation during murine infection with the helminth Trichuris muris. However, the mechanisms required for basophil function and gene expression regulation in this context remain unclear. We show that during T. muris infection, basophils localized to the intestine and up-regulated Notch receptor expression, rendering them sensitive to Notch signals that rapidly regulate gene expression programs. In vitro, Notch inhibition limited basophil cytokine production in response to cytokine stimulation. Basophil-intrinsic Notch signaling was required for T. muris–elicited changes in genome-wide basophil transcriptional programs. Mice lacking basophil-intrinsic functional Notch signaling had impaired worm clearance, decreased intestinal type 2 inflammation, altered basophil localization in the intestine, and decreased CD4+ T helper 2 cell responses following infection. These findings demonstrate that Notch is required for basophil gene expression and effector function associated with helminth expulsion during type 2 inflammation.
FRI-086-Stem cell treatment on acute liver failure model using semipermeable Poly Lactic-co-Glycolic Acid membrane pouch
Authors: Bo-Kyeong Kang, Mi Mi Kim, Dae Won JUN, Jinhwa Park, Jaeyoon Jeong, Joo Hyun Sohn, Hyunwoo Oh, Hyo Young Lee, Sang Bong Ahn, Yong Kyun Cho, Dong Hee Koh
Journal: Journal of Hepatology (2019)
Review: Rapid-acting analogues do not differ from regular human insulin for mortality or HbA<sub>1c</sub>in type 2 diabetes
Authors: Mayer B. Davidson
Journal: Annals of Internal Medicine (2019)

Source Citation Fullerton B, Siebenhofer A, Jeitler K, et al. Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2018;12:CD013228. 30556900
PS-055-The markers of HBV transcriptional activity-HBcrAg and pre-genomic HBV DNA during antiviral therapy with nucleos (t)ide analogue help to predict optimal timing of therapy withdrawal
Authors: Ivana Carey, Jeffrey Gersch, Matthew Bruce, Christiana Moigboi, Bo Wang, Mary Kuhns, Gavin Cloherty, Geoffrey Dusheiko, Kosh Agarwal
Journal: Journal of Hepatology (2019)
pERK as a new prognostic factor in resected, early-staged, non-small cell lung cancer (NSCLC).
Authors: Maria Dolores Mediano, Jesus Corral Jaime, Sonia Molina-Pinelo, Miriam Alonso, Irene Ferrer, Maria Atienza, Nicolas Moreno, Amancio Carnero Moya, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2015)

e18501 Background: Only the 23% of NSCLC patients (pts) are discovered in potential curable disease. Even radical surgery, the 50% of pts will develop metastases, so adjuvant chemotherapy is recommended in stage IB-IIIA NSCLC, improving the overall survival (OS) rate from 4 to 15% in 5 years. Some clinico-pathological factors have already demonstrated a prognostic value as the tobacco use, the lymphatic involvement, the tumor size and the histological subgroup. Indeed, EGFR and p53 expression have been proposed as new prognostic factors. We analyze here our experience searching new prognostic biomarkers to optimize the maximum benefit from adjuvant therapy. Methods: All NSCLC pts who underwent radical surgery for their primary tumor (stages IB-IIIA without neoadjuvant) in our institution from 2000 to 2006 were reviewed retrospectively. Clinical variables and the expression of pEGFR, pAKT, pERK and p53 by immunohistochemistry were analyzed as possible prognostic factors. Results: 248 pts were included in the study; 94% were men, 96.3% were had a performance status of 0-1, 48.4% smokers, and 49.6% had squamous cell tumor versus 39.9% had an adenocarcinoma. 56.9% pts had a stage I, 27.8% stage II and 14.9% stage IIIA. Only 17.3% received adjuvant chemotherapy and 14.1% radiotherapy. With a follow-up of 47.7 months, 48% relapsed and 61.7% passed away, 41.2% related to the progression. Patients with PS 0, stages I-II and radiotherapy naive had better progression free survival (PFS) and OS (p < 0.001 in all subgroups). Moreover, pts without expression or low intensity of pERK had an OS of 55.3 months (35.2-75.3) (p = 0.037) versus 20.3 months (11.8-28.8) in pts with mild and high intensity. In the subsequent multivariate analysis, only the PS, stage TNM and pERK expression reminded significant independent value. Conclusions: Our retrospective study reveals the absence or low immunohistochemistry pERK expression as a new potential prognostic factor in resected stage IB-IIIA NSCLC. New prospective studies are further needed to confirm our hypothesis.
WHO pulls support from initiative promoting global move to plant based foods
Authors: Ingrid Torjesen
Journal: BMJ (2019)

The World Health Organization pulled out of sponsoring a global initiative promoting healthier and sustainable diets across the world after pressure from an Italian official who raised concerns about the impact of the diet on people’s health and livelihoods.

The event—the launch of the EAT-Lancet Commission on Food, Planet, Health in Geneva, Switzerland on 28 March—still went ahead, sponsored by the government of Norway.

WHO dropped its planned sponsorship after Gian Lorenzo Cornado, Italy’s ambassador and permanent representative of Italy to the international organizations in Geneva, questioned the scientific basis for the diet which is focused on promoting predominantly plant based foods, and excluding foods deemed unhealthy, including meat and other animal based foods.

Cornado warned that a global move to such a diet could lead to the loss of millions of jobs linked to animal husbandry and the production of “unhealthy” foods, and destroy traditional diets which are part of cultural heritage.

The initiative “urging for a centralised control of our dietary choices” risked “the total elimination of consumers’ freedom of choice,” …
FRI-033-Long-term obeticholic acid treatment is associated with improvements in collagen morphometry in patients with primary biliary cholangitis
Authors: Andreas E Kremer, Christopher Bowlus, Pierre Bedossa, Albert Parés, Lisa Forman, Joost Ph Drenth, Stephen Ryder, Luigi Maria Terracciano, Yuying Jin, Alexander Liberman, Richard Pencek, Leigh Macconell, Paul Pockros
Journal: Journal of Hepatology (2019)
Correction to: A decade of progress in critical care echocardiography: a narrative review
Authors: Antoine Vieillard-Baron, S. J. Millington, F. Sanfilippo, M. Chew, J. Diaz-Gomez, A. McLean, M. R. Pinsky, J. Pulido, P. Mayo, N. Fletcher
Journal: Intensive Care Medicine (2019)
Abstract 11417: Obstructive Sleep Apnea and Progression of Coronary Artery Calcium: The MESA Study
Authors: Younghoon Kwon, Daniel Duprez, David R Jacobs, Mako Nagayoshi, Robyn L McClelland, Eyal Shahar, Matthew Budoff, Susan Redline, Steven Shea, John J Carr, Pamela L Lutsey
Journal: Circulation (2014)

Background: Obstructive sleep apnea (OSA) is a common condition associated with cardiovascular disease. Its potential effect on progression of subclinical atherosclerosis is not well understood. We...
Neuroendocrine breast cancer: A single center experience.
Authors: Vildan Tasdemir, Neyran Kertmen, Alma Cenoli, Özge Keskin, Yusuf Karakas, Omer Diker, Omer Dizdar, Sercan Aksoy, Yavuz Ozisik, Kadri Altundag
Journal: Journal of Clinical Oncology (2015)

e12037 Background: Neuroendocrine cancer of the breast is rarely seen and grouped into small cell, large cell and carsinoid like carcinoma variants. In our study demographic features of neuroendocrine breast cancer and the treatment modalities were investigated. Methods: We reviewed the records of all patients treated for neuroendocrine breast cancer at our institution from May 2007 through October 2014. Medical records were employed to extract patient characteristics such as age, menopausal status, clinical stage, nuclear grade, estrogen receptor (ER) and progesterone receptor (PR) status. Patients were staged according to 2010 AJGG guideline. Results: Eighteen patients were included, of all66.7% (n = 12) was postmenopausal and, 33.3% (n = 6) premenopausal. Mean age at diagnosis was 56 (28-80). Three patients had previous cancer diagnosis (lung, endometrium and cervix ca). Modified radical mastectomy (MRM) was performed on 33% (n = 6) and breast conserving surgery (BCS) on 61.2% (n = 11) of patients undergoing surgery. At the time of diagnosis 11.1% (n = 2) of patients were stage I, 44.4% (n = 8) stage II, 27.8% (n = 5) stage III and 16.7% (n = 3) stage IV disease. Nine of eighteen patients (50%) had nuclear grade III disease. Hormone receptor status was determined as 77.8% ( n = 14) ER (+) and 83.3 %(n = 15) PR (+). In terms of medical tratments 50% (n = 9) of patients received adriamycin and cyclophosphamide-based chemotherapy. Aromatase inhibitor and tamoxifen therapy were given to 61% (n = 11) and 27% (n = 5) of hormone receptor positive patients respectively. During the follow up, 16.8 % (n = 3) of the patients had lung, bone and mediastine metastasis. Median disease free survival (DFS) was 20 months and overall survival (OS) was 43 months. Conclusions: In conclusion,the other subtypes of neuroendocrine breast cancer except the small cell group have ER and PR expression. Treatment of neuroendocrine breast canser is generally similar to ductal infiltrative cancers.
Selective Sexual Dimorphisms in Musculoskeletal and Cardiopulmonary Pathologic Manifestations and Mortality Incidence in the Tumor Necrosis Factor–Transgenic Mouse Model of Rheumatoid Arthritis
Authors: Richard D. Bell, Emily K. Wu, Christopher A. Rudmann, Megan Forney, Claire R. W. Kaiser, Ronald W. Wood, Joe V. Chakkalakal, Nicole D. Paris, Alanna Klose, Guang‐Qian Xiao, Javier Rangel‐Moreno, Maria L. Garcia‐Hernandez, Christopher T. Ritchlin, Edward M. Schwarz, Homaira Rahimi
Journal: Arthritis & Rheumatology (2019)

Objective To examine and quantify the sexual dimorphism in pathologic features manifested in the musculoskeletal and cardiopulmonary systems and incidence of mortality in the tumor necrosis factor–transgenic ( TNF ‐Tg; Tg3647 strain) mouse model of inflammatory erosive arthritis. Methods Kaplan‐Meier survival estimates were determined in male and female Tg3647 mice and sex‐matched wild‐type ( WT ) littermate mice. Longitudinal and cross‐sectional pathologic outcomes in the musculoskeletal and cardiopulmonary systems were assessed via ultrasound, micro–computed tomography, grip strength measurements, histologic and serologic analyses, flow cytometry, and skeletal muscle physiologic measures. Results Compared to male Tg3647 mice (n = 30), female Tg3647 mice (n = 34) had significantly shorter lifespans ( P &lt; 0.001) and exhibited the following pathologic features (n = 4–6 per group; P &lt; 0.05 versus male Tg3647 littermates): gross deficits in body mass and muscle weight, early‐onset inflammatory arthritis with severity of end‐stage arthritis that was as severe as that seen in male transgenic mice, and early onset and increased severity of inflammatory interstitial lung disease ( ILD ). Histologically, the ILD observed in Tg3647 mice was characterized by inflammatory cell accumulation and pulmonary arteriole thickening, which was concomitant with the presence of right ventricular hypertrophy, a feature that was also more severe in the female compared to male Tg3647 mice ( P &lt; 0.05). No sexual dimorphisms in TNF ‐induced deficient grip strength, axial skeletal growth, or bone loss were found. Globally, the extent of the pathologic changes observed in female Tg3647 mice was greater than that observed in male Tg3647 mice when each group was compared to their sex‐matched WT littermates. Conclusion These findings indicate that TNF selectively drives the early onset of arthritis and progression of pathologic changes in the cardiopulmonary system in female Tg3647 mice. These results in the Tg3647 mouse identify it as a suitable model to better understand the mechanisms underlying sexual dimorphism and cardiopulmonary disease in the setting of inflammatory arthritis and other connective tissue diseases.
Severe Arterial Hypertension from Cullin 3 Mutations Is Caused by Both Renal and Vascular Effects
Authors: Waed Abdel Khalek, Chloé Rafael, Irmine Loisel-Ferreira, Ilektra Kouranti, Eric Clauser, Juliette Hadchouel, Xavier Jeunemaitre
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement In a rare Mendelian form of arterial hypertension, familial hyperkalemic hypertension, scientists have identified relevant mutations in WNK lysine deficient protein kinases 1 and 4 (WNK1 and WNK4) and in two proteins involved in the ubiquitin-dependent proteasome degradation of WNK1 and WNK4, including Cullin 3 (CUL3). To investigate why CUL3 mutations lead to a more severe phenotype, the authors developed cell models that overexpress mutant CUL3 and mouse models that express it ubiquitously or specifically in vascular smooth muscles cells. They provide evidence that CUL3-related hypertension is caused by alteration of both renal and vascular functions, the latter associated with activation of the RhoA signaling pathway. This dual influence helps explain the phenotype severity, but further investigation is needed to identify specific vascular CUL3 substrates. Background Mutations in four genes, WNK lysine deficient protein kinase 1 and 4 ( WNK1 and WNK4 ), kelch like family member 3 ( KLHL3 ), or Cullin 3 ( CUL3 ), can result in familial hyperkalemic hypertension (FHHt), a rare Mendelian form of human arterial hypertension. Although all mutations result in an increased abundance of WNK1 or WNK4, all FHHt-causing CUL3 mutations, resulting in the skipping of exon 9, lead to a more severe phenotype. Methods We created and compared two mouse models, one expressing the mutant Cul3 protein ubiquitously ( pgk-Cul3∆9 ) and the other specifically in vascular smooth muscle cells ( SM22-Cul3∆9 ). We conducted pharmacologic investigations on isolated aortas and generated stable and inducible HEK293 cell lines that overexpress the wild-type Cul3 or mutant Cul3 (Cul3 ∆ 9) protein. Results As expected, pgk-Cul3∆9 mice showed marked hypertension with significant hyperkalemia, hyperchloremia and low renin. BP increased significantly in SM22-Cul3∆9 mice, independent of any measurable effect on renal transport. Only pgk-Cul3∆9 mice displayed increased expression of the sodium chloride cotransporter and phosphorylation by the WNK-SPAK kinases. Both models showed altered reactivity of isolated aortas to phenylephrine and acetylcholine, as well as marked acute BP sensitivity to the calcium channel blocker amlodipine. Aortas from SM22-Cul3∆9 mice showed increased expression of RhoA, a key molecule involved in regulation of vascular tone, compared with aortas from control mice. We also observed increased RhoA abundance and t 1/2 in Cul3 ∆ 9-expressing cells, caused by decreased ubiquitination. Conclusions Mutations in Cul3 cause severe hypertension by affecting both renal and vascular function, the latter being associated with activation of RhoA.