tbuckley/cabot-search huggingface dataset:
Very Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiological Changes in Responders and Nonresponders
Authors: Sarah Steven, Kieren G. Hollingsworth, Ahmad Al-Mrabeh, Leah Avery, Benjamin Aribisala, Muriel Caslake, Roy Taylor
Journal: Diabetes Care (2016)

Type 2 diabetes mellitus (T2DM) is generally regarded as an irreversible chronic condition. Because a very low-calorie diet (VLCD) can bring about acute return to normal glucose control in some people with T2DM, this study tested the potential durability of this normalization. The underlying mechanisms were defined.People with a T2DM duration of 0.5-23 years (n = 30) followed a VLCD for 8 weeks. All oral agents or insulins were stopped at baseline. Following a stepped return to isocaloric diet, a structured, individualized program of weight maintenance was provided. Glucose control, insulin sensitivity, insulin secretion, and hepatic and pancreas fat content were quantified at baseline, after return to isocaloric diet, and after 6 months to permit the primary comparison of change between post-weight loss and 6 months in responders. Responders were defined as achieving fasting blood glucose <7 mmol/L after return to isocaloric diet.Weight fell (98.0 ± 2.6 to 83.8 ± 2.4 kg) and remained stable over 6 months (84.7 ± 2.5 kg). Twelve of 30 participants achieved fasting plasma glucose <7 mmol/L after return to isocaloric diet (responders), and 13 of 30 after 6 months. Responders had a shorter duration of diabetes and a higher initial fasting plasma insulin level. HbA1c fell from 7.1 ± 0.3 to 5.8 ± 0.2% (55 ± 4 to 40 ± 2 mmol/mol) in responders (P < 0.001) and from 8.4 ± 0.3 to 8.0 ± 0.5% (68 ± 3 to 64 ± 5 mmol/mol) in nonresponders, remaining constant at 6 months (5.9 ± 0.2 and 7.8 ± 0.3% [41 ± 2 and 62 ± 3 mmol/mol], respectively). The responders were characterized by return of first-phase insulin response.A robust and sustainable weight loss program achieved continuing remission of diabetes for at least 6 months in the 40% who responded to a VLCD by achieving fasting plasma glucose of <7 mmol/L. T2DM is a potentially reversible condition.
MHPG as a predictor of antidepressant response to imipramine and maprotiline
Authors: A H Rosenbaum, A F Schatzberg, T Maruta, P J Orsulak, J O Cole, E L Grab, J J Schildkraut
Journal: American Journal of Psychiatry (1980)

To explore the hypothesis that depressed patients with low pretreatment levels of urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) respond more favorably to antidepressant drugs which act on noradrenergic neuronal systems than do patients with high MHPG levels, the authors administered 150--200 mg/day of imipramine or maprotiline to 13 depressed patients. All of the 5 patients with low pretreatment MHPG levels responded to treatment compared with 1 of the 14 patients with high MHPG levels; 4 patients dropped out of the study.
Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals
Authors: Jelena S Bezbradica, Rebecca C Coll, Kate Schroder
Journal: Cellular and Molecular Immunology (2016)

Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination.
Pharmacokinetic results of a phase I trial of sorafenib (S) in combination with dacarbazine (DTIC) in patients with advanced metastatic melanoma or other solid tumors
Authors: E. Brendel, E. Zafarana, C. Figuerola, M. Ludwig, C. Lathia, K. Burk, C. Robert, J. C. Soria, J. P. Armand
Journal: Journal of Clinical Oncology (2007)

2563 Background: Sorafenib (S) is a multikinase inhibitor that prevents tumor cell proliferation and angiogenesis via receptor tyrosine kinases, VEGFR-1, -2, -3 and PDGFR-a and -β, and the Raf/MEK/ERK pathway at the level of Raf kinase. Single-agent studies show S is well tolerated with manageable and reversible side effects, most commonly, diarrhea, rash, fatigue, and hand-foot skin (HFS) reaction. This phase I study assessed the safety and pharmacokinetics (PK) of the combination of S and DTIC. Methods: 23 patients (pts) received a fixed dose of DTIC (1,000 mg/m 2 given every 3 wks) starting on Day 1 of cycle 1 (C1). S (400 mg bid) was given on days 2–21 in C1 and continuously thereafter. PK profiles of DTIC and 5-aminoimidazole-4-carboxamide (AIC; an inactive D metabolite that is formed in an equal proportion to the active moiety, diazomethane, that cannot be analytically measured) were obtained from day 1 of both C1 and C2 and PK profiles of S from Day 1 of C2. Results: 23 pts (M:F, 11:12; mean age 57±9 yrs) were treated with S and DTIC. Of these pts, 15 were valid for PK analysis. Following simultaneous administration of S, mean AUC and C max of DTIC were moderately reduced by 23% and 16%, while mean AUC and C max of AIC were increased by 41% and 45%, respectively. Mean AUC (0–12) ss and C max,ss of S were 28.3 mg*h/L (84%) and 3.67 mg/L (77%), respectively, upon concomitant dosing of S and DTIC. These sorafenib exposures are within the range of exposures observed in phase I studies. Six pts had an increase of either C max or AUC of AIC of at least 70%, and in 4 of the 6 pts, this increase was correlated with grade 4 thrombocytopenia. Conclusions: The combination of S and DTIC resulted in moderate decreases of DTIC exposure; however, more pronounced increases in AIC exposure were observed. In patients with a distinct increase (=70%) in AIC, a correlation between exposure and toxicity cannot be excluded, however, all toxicities were manageable. No significant financial relationships to disclose.
Evolution of Mitral Valve Prolapse
Authors: Francesca N. Delling, Jian Rong, Martin G. Larson, Birgitta Lehman, Deborah Fuller, Ewa Osypiuk, Plamen Stantchev, Brianne Hackman, Warren J. Manning, Emelia J. Benjamin, Robert A. Levine, Ramachandran S. Vasan
Journal: Circulation (2016)

Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking.We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 57±11 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all P<0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height ≥5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all P<0.05).NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression.
Lung cancer tissue diagnosis in poor lung function: addressing the ongoing percutaneous lung biopsy FEV<sub>1</sub>paradox using Heimlich valve
Authors: R Abdullah, A N Tavare, A Creamer, D Creer, R Vancheeswaran, S S Hare
Journal: Thorax (2016)

Many centres continue to decline percutaneous lung biopsy (PLB) in patients with poor lung function (particularly FEV<sub>1</sub> &lt;1 L) due to the theoretically increased risk of pneumothorax. This practice limits access to novel lung cancer therapies and minimally invasive surgical techniques. Our retrospective single-centre analysis of 212 patients undergoing PLB, all performed prospectively and blinded to lung function, demonstrates that using ambulatory Heimlich valve chest drain (HVCD) to treat significant postbiopsy pneumothorax facilitates safe, diagnostic, early discharge lung biopsy irrespective of lung function with neither FEV<sub>1</sub> &lt;1 L nor transfer coefficient for carbon monoxide (TLCO) &lt;40% predicted shown to be independent predictors of HVCD insertion or pneumothorax outcomes. Incorporating ambulatory HVCD into standard PLB practice thereby elegantly bridges the gap that currently exists between tissue diagnosis in patients with poor lung function and the advanced therapeutic options available for this cohort.
Abstract 16619: The Role of Capillary Disorder in Coronary Ischemic Congestive Heart Failure in Rats
Authors: Jiqiu Chen
Journal: Circulation (2014)

The aim of present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). Methods: CHF was induced in rats by aortic banding plus ischemia/reperfusion followed by aortic de-banding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were conducted to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Results: Stenosis was found in all levels of coronary artery in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in micro-vessels with diameter ≤ 3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, likely indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart has lower functional reserve; this is likely associated with congestion in coronary microcirculation. Conclusions: Ischemic coronary vascular disorder is not limited to main arteries, but also occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation and roughened surfaces, and is perhaps a primary contributor to the energy starvation which leads to reduction of myocyte intrinsic contractility.
Optimal Strategy with Multi-Targeted Therapies in Egfr-Dependent “Quadruple Wild Type (Wt) for Kras, Braf, Nras and Pik3Ca Genes” Colorectal Cancer (Crc) Xenografts After Combined Treatment of Irinotecan Plus Cetuximab
Authors: T. Troiani, S. Napolitano, E. Martinelli, D. Vitagliano, G. Martini, F. Morgillo, C. Cardone, A. Capasso, V. Gambardella, F. Venturini, F. Ciardiello
Journal: Annals of Oncology (2014)
Human Papillomavirus Genotype Association With Survival in Head and Neck Squamous Cell Carcinoma
Authors: Scott V. Bratman, Jeffrey P. Bruce, Brian O’Sullivan, Trevor J. Pugh, Wei Xu, Kenneth W. Yip, Fei-Fei Liu
Journal: JAMA Oncology (2016)

trial tweets, 78.6% (144 of 183) concerned immunotherapy and 86.3% (158 of 183) had embedded links directing users to news articles.Only 1 tweet linked to a patient recruitment website (Table 2).Discussion | Our investigation shows that the use of Twitter for support (28%) and prevention (28%) dialogues is common.Although some tweets are about clinical trials (18%), virtually none are used for recruitment or provide links to enrollment websites.Social media is a rich and promising avenue for exploring how patients conceptualize and communicate about their specific health issues, but its potential to promote cancer clinical trial accrual remains unknown. 5 This is a pilot study with a relatively small sample size, and findings are therefore exploratory.Enrollment into clinical trials is often the best treatment option for patients, but only 2% to 7% of adult cancer patients participate in clinical trials. 2 Social media may provide an infrastructure that allows investigators to interact with the public in new ways, including stimulating interest in new clinical trials with targeted messages to connect patients, caregivers, and families with potential trial enrollment websites.Social media could become a very useful tool for clinical researchers but may also pose some challenges with respect to both noncoercive content and the assurance of privacy, both of which the IRBs will need to consider carefully.Future efforts are needed to explore whether Twitter can emerge as a viable medium for promoting accrual to clinical trials.
Activation Of p53 By MDM2-Inhibition Sensitizes Quiescent Blast Crisis CML Stem/Progenitor Cells To Bcl-2 Inhibitor- and Tyrosine Kinase Inhibitor-Induced Cell Death
Authors: Bing Z Carter, Po Yee Mak, Duncan H Mak, Marina Konopleva, Jorge Cortes, Michael Andreeff
Journal: Blood (2013)
Multicenter Phase Ii Trial of Neoadjuvant Chemotherapy with Mfolfox6 for Stage Ii/Iii Rectal Cancer with a T3/T4 Tumor Fact Trial
Authors: H. Yokomizo, K. Yoshimatsu, J. Koike, K. Funahashi, H. Kan, T. Yamada, H. Ishida, K. Ishibashi, Y. Saida, T. Enomoto, K. Katsumata, H. Hasegawa, K. Koda, T. Ochiai, K. Sakamoto, M. Nakayama, Y. Naritaka, S. Ogawa, M. Itabashi, S. Kameoka
Journal: Annals of Oncology (2014)
Phase III Trial Of Bortezomib, Melphalan, and Prednisone (VMP) Versus Bortezomib, Thalidomide, and Prednisone (VTP) In Elderly Multiple Myeloma (MM) Patients: Update Follow-Up, Patterns Management Of First Relapse/Progression
Authors: Aurelio Lopez, Marta Valero, Jose Ignacio Lorenzo, Maria-Victoria Mateos, Albert Oriol, Martínez Joaquin, Montserrat Perez, Rafael Martinez, Raquel de Paz, Miguel Granell, Felipe De Arriba, M. Jesús Blanchard, Francisco Javier Peñalver, Jose Luis Bello, Maria Luisa Martin, Joan Bargay, Joan Blade, Juan Jose Lahuerta, Jesús F. San Miguel, Javier De La Rubia
Journal: Blood (2013)
Chromosomes of Some Heterotransplanted Human Tumors. I. H. Emb. Rh. #1, H. S. #1, and ME 1
Authors: Charles P. Miles
Journal: JNCI Journal of the National Cancer Institute (1965)

A variety of human tumors has been carried exclusively in rodent heterotransplant passage for periods ranging from 7 to 11 years. They have preserved human karyotypes and in general have continued to show the microscopic pattern of the original tumors. H. Emb. Rh. #1 has a morphologically normal male karyotype. H. S. #1 has 47 chromosomes with the same stemline karyotype in almost all analyzable cells, but many chromosomes are distinctly abnormal, with 5 of the metacentrics possessing satellites. ME 1 has a probable stemline of 123 chromosomes and can be interpreted as having the same karyotype in most stemline cells.
Homozygous calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency
Authors: Alexandre P. A. Theocharides, Pontus Lundberg, Asvin K. K. Lakkaraju, Veronika Lysenko, Renier Myburgh, Adriano Aguzzi, Radek C. Skoda, Markus G. Manz
Journal: Blood (2016)
Raf kinase inhibitor protein mediates intestinal epithelial cell apoptosis and promotes IBDs in humans and mice
Authors: Wenlong Lin, Chunmei Ma, Fasheng Su, Yu Jiang, Rongrong Lai, Ting Zhang, Kai Sun, Liping Fan, Zijian Cai, Zhongqi Li, He Huang, Jun Li, Xiaojian Wang
Journal: Gut (2016)

<h3>Objective</h3> Raf kinase inhibitor protein (RKIP) appears to control cancer cell metastasis and its expression in colonic tissue is related to colonic cancer development. We sought to identify the roles of RKIP in maintaining homeostasis of GI tract. <h3>Design</h3> The expression of RKIP was determined by immunohistochemistry and western blot analysis. RKIP knockout and wild-type mice were administered dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis, and the mice were assessed based on colitis symptoms and biochemical approaches. The mechanism was analysed using immunoprecipitation and pull-down experiments. <h3>Results</h3> The RKIP expression is positively correlated with the severity of IBD. RKIP deficiency protects mice from DSS-induced or TNBS-induced colitis and accelerated recovery from colitis. RKIP deficiency inhibits DSS-induced infiltration of acute-phase immune cells and reduces production of proinflammatory cytokines and chemokines in colon. RKIP deficiency inhibits DSS-induced or TNBS-induced colonic epithelial barrier damage and intestinal epithelial cell (IEC) apoptosis. RKIP deficiency also inhibits tumour necrosis factor-alpha-induced IEC apoptosis and colitis. Mechanistically, RKIP enhances the induction of P53-upregulated modulator of apoptosis by interacting with TGF-β-activated kinase 1 (TAK1) and promoting TAK1-mediated NF-κB activation. This is supported by the observation that TAK1 activation is positively correlated with the expression of RKIP in human clinical samples and the development of IBD. <h3>Conclusions</h3> RKIP contributes to colitis development by promoting inflammation and mediating IEC apoptosis and might represent a therapeutic target of IBD.
Foetus Papyraceus
Authors: E. M. Southern
Journal: BMJ (1956)

A Case of Foetus Papyraceus m Foetus papyraceus is a rare but interesting condition in which there is intrauterine death of one foetus of a twin pregnancy which is retained in utero and compressed within the membranes and the uterine wall.The condition was recognized by Pliny (A.D. 23), who made mention of it in early writings.Smellie (1752) wrote: "At times, the child that lies next to the fundus is the smallest and follows after the birth of the other in a dead and petrified state."Kindred (1944) obtained references to 150 cases from a search of the literature.
Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer
Authors: Nan Hu, Mitsutaka Kadota, Huaitian Liu, Christian C. Abnet, Hua Su, Hailong Wu, Neal D. Freedman, Howard H. Yang, Chaoyu Wang, Chunhua Yan, Lemin Wang, Sheryl Gere, Amy Hutchinson, Guohong Song, Yuan Wang, Ti Ding, You-Lin Qiao, Jill Koshiol, Sanford M. Dawsey, Carol Giffen, Alisa M. Goldstein, Philip R. Taylor, Maxwell P. Lee
Journal: Cancer Research (2016)

Abstract Gastric cancer and esophageal cancer are the second and sixth leading causes of cancer-related death worldwide. Multiple genomic alterations underlying gastric cancer and esophageal squamous cell carcinoma (ESCC) have been identified, but the full spectrum of genomic structural variations and mutations have yet to be uncovered. Here, we report the results of whole-genome sequencing of 30 samples comprising tumor and blood from 15 patients, four of whom presented with ESCC, seven with gastric cardia adenocarcinoma (GCA), and four with gastric noncardia adenocarcinoma. Analyses revealed that an A&amp;gt;C mutation was common in GCA, and in addition to the preferential nucleotide sequence of A located 5 prime to the mutation as noted in previous studies, we found enrichment of T in the 5 prime base. The A&amp;gt;C mutations in GCA suggested that oxidation of guanine may be a potential mechanism underlying cancer mutagenesis. Furthermore, we identified genes with mutations in gastric cancer and ESCC, including well-known cancer genes, TP53, JAK3, BRCA2, FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR. Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including MACROD2, FHIT, and PARK2 that were often intragenic deletions. These structural alterations were validated using the The Cancer Genome Atlas dataset. Our studies provide new insights into understanding the genomic landscape, genome instability, and mutation profile underlying gastric cancer and ESCC development. Cancer Res; 76(7); 1714–23. ©2016 AACR.
Malignancies masquarading as psoas abscesses: An unusual presentation in a developing country
Authors: H. Singh, S. Chawla, A. J. Joshi, D. Marwaha, R. R. Saggar, M. A. Joshi
Journal: Journal of Clinical Oncology (2007)

19675 Background: Psoas abscess is regarded as a rare disease in medical literature, more so as primary presentation of malignancy or its recurrence. We describe a series of 10 cancer patients who presented with psoas abscess seen in a 18 month period at a large tertiary care cancer hospital in northern India. They were subsequently diagnosed as having malignancy or recurrence of a past malignancy. Methods: A retrospective study of cancer patients who presented with psoas abscess was undertaken. We reviewed clinical data from patients who presented in the period from April 2005 to December 2006 at the Patel Cancer &amp; Superspeciality hospital, Jalandhar, India. Results: In this period 10 cases of cancer met the diagnosis of psoas abscess at presentation. The average age was 51 years (range 20 to 85) with a male female ratio of 4:1. In 7 patients psoas abscess was the presentation at initial diagnosis while in 3 patients it was the presentation of recurrence/relapse. None of the patients had any predisposing conditions like IV drug use, diabetes mellitus, hematoma or HIV positivity.. Majority (7/10) of primary tumors were genito- urinary cancers (Renal - 2, Ureter - 1, Cervix - 1, Prostate - 1, Dysgerminoma - 1, Penis-1) while 3 were of unknown origin. Squamous cell carcinoma was the commonest histology (4/10), followed by metastatic adenocarcinoma (3/10). Majority of the abscess were left sided (7/10) corresponding to the side of primary lesion. Under lying destruction of iliac bone with metastasis was found in only 2 patients. Most of the patients (9/10) responded poorly to treatment ie chemotherapy and radiotherapy, all of them dying of disease progression within a year. Conclusions: Psoas abscess can be a rare presentation of intra abdominal malignancy. Pre disposing factors may not necessarily be present. Genito-urinary malignancies should be kept in the differential diagnosis of unexplained psoas abscesses. Development of psoas abscess does not always signify metastatic disease but portends a poor prognosis to treatment. No significant financial relationships to disclose.