tbuckley/cabot-search huggingface dataset:
Maternal Serum Prolactin and Prediction of Postpartum β-Cell Function and Risk of Prediabetes/Diabetes
Authors: Ravi Retnakaran, Chang Ye, Caroline K. Kramer, Philip W. Connelly, Anthony J. Hanley, Mathew Sermer, Bernard Zinman
Journal: Diabetes Care (2016)

OBJECTIVE The insulin resistance of mid- to late pregnancy poses a physiologic stress test for the pancreatic β-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of β-cell mass induced by the hormones prolactin and human placental lactogen (HPL). Conversely, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a negative regulator of β-cell function in pregnancy. Given their respective roles in the β-cell response to the stress test of gestation, we hypothesized that antepartum prolactin, HPL, and CMPF may relate to a woman’s underlying glucoregulatory physiology and hence to her metabolic status after pregnancy. RESEARCH DESIGN AND METHODS Three hundred and sixty-seven women underwent measurement of fasting serum prolactin, HPL, and CMPF in the late-2nd/early-3rd trimester, followed by an oral glucose tolerance test (OGTT) at 3 months postpartum that enabled assessment of glucose tolerance, insulin sensitivity/resistance, and β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]). RESULTS The postpartum OGTT identified 301 women with normal glucose tolerance (NGT) and 66 with prediabetes or diabetes. Serum prolactin in pregnancy was higher in women with postpartum NGT compared with those with postpartum prediabetes/diabetes (mean 98.2 vs. 80.2 ng/mL, P = 0.0003), whereas HPL and CMPF did not differ between the groups. On multiple linear regression analyses, antepartum prolactin was an independent determinant of postpartum ISSI-2 (β = 0.0016, t = 2.96, P = 0.003). Furthermore, higher serum prolactin in pregnancy independently predicted a lower risk of postpartum prediabetes/diabetes (odds ratio 0.50, 95% CI 0.35–0.72, P = 0.0002). CONCLUSIONS Serum prolactin in pregnancy predicts postpartum β-cell function and risk of prediabetes/diabetes.
Case 34-1972
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Walter T. St. Goar, Benjamin Castleman
Journal: New England Journal of Medicine (1972)

Presentation of CaseA 64-year-old man was admitted to the hospital because of a renal tumor.Twenty years earlier he had a peptic ulcer; there was no recurrence. Eight years before admission he was reported to have hypertension and a myocardial infarct. During the year before entry he experienced nocturia. Six months before admission hydrochlorothiazide was prescribed. Three months later nausea developed, followed by epigastric distress. He was admitted to another hospital, where laparotomy disclosed chronic pancreatitis; a mass was observed in the right kidney, and a biopsy revealed a renal-cell carcinoma. He was transferred to this hospital.There was . . .
Negative association between autoantibodies against IL-17, IL-17/anti-IL-17 antibody immune complexes and destruction in rheumatoid arthritis
Authors: Ndieme Ndongo-Thiam, Alice Clement, Jean-Jacques Pin, Diane Razanajaona-Doll, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2016)

Autoantibodies against proinflammatory cytokines1 such as interleukin (IL)-1α are protective and a marker of good prognosis in rheumatoid arthritis (RA).2 ,3 They bind their antigen, that is, the cytokine, forming immune complexes (ICs). IL-17 is a new therapeutic target for a growing number of disorders,4 and levels of circulating bioactive IL-17 are associated with RA severity.5 Our objective was to define the contribution of anti-IL-17 autoantibodies and IL-17-anti-IL-17 ICs.

A competitive ELISA was developed to measure anti-IL-17 autoantibodies. A positive control with added anti-IL-17 antibodies showed an inverse dose–response curve reflecting the competition, with no variation with irrelevant antibodies (figure 1A). Plasma of 30 healthy donors were first tested to determine the threshold (absorbance=0.9±0.1 at 1/2 dilution) with no variation between 1/4 and 1/8 dilutions, indicating an absence of anti-IL-17 autoantibodies. In contrast, they were detected in 36.6% of the 60 patients with RA (p<0.05 vs controls, figure 1B). To study the relationship with severity, 30 destructive RA (wrist Larsen score: 2 and over) versus 30 non-destructive RA (Larsen score: 0 or 1) were tested. The two groups had similar mean age (71.3±9.3 vs 66.1±10.8 years), disease duration (23.0±9.8 vs 18.6±9.6 years), DAS28 (4.0±1.4 vs 3.9±1.2) but a different level of bone destruction (Larsen score: 0.5±0.5 vs 3.3±1.0, p<0.0001). Anti-IL-17 autoantibodies were detected in 46.6% of …
High-Throughput Blood- and Lymph-Capillaries with Open-Ended Pores Which Allow the Transport of Drugs and Cells
Authors: Daichi Hikimoto, Akihiro Nishiguchi, Michiya Matsusaki, Mitsuru Akashi
Journal: Advanced Healthcare Materials (2016)

High-throughput screening of drug diffusion and cell transports from the blood-/lymph-capillary (BC/LC) networks to the peripheral cells in 3D engineered tissues using a microplate would make a powerful tool for in vitro pharmacokinetic assessments. Here, perfusable BC/LC networks embedded in 3D-tissues inside a 24-microplate using a cell-coating technology are reported which allows location control of cell layers. Arrangement of an endothelial cell layer at the top, middle, and bottom of dermal fibroblast tissues provides an interconnected BC/LC networks possessing open pores on both surfaces. When fluorescently labeled dextran, microparticles, and red blood cells are applied to the top surfaces, diffusion and penetration through the networks are observed depending on the size of the substances. Moreover, BC networks mimick a series of in vivo processes of cancer metastasis, extravasation, growth, and growth suppression with drug treatment. The perfusable networks existing in 3D-tissues show great potential for in vitro pharmacokinetic studies.
High levels of neurological involvement but low mortality in miliary tuberculosis: a 6-year case-series from the UK
Authors: Navin Venkatraman, Thomas King, David Bell, Gerrit Woltmann, Martin Wiselka, Ibrahim Abubakar, Manish Pareek
Journal: European Respiratory Journal (2016)

Tuberculosis (TB) remains one of the biggest global health challenges. Whilst the greatest burden of active disease is seen in Asia and Africa [1], TB remains a significant issue in the UK. Miliary TB is one of the severest manifestations of TB disease [2–4]. Up-to-date clinicopathological data on miliary TB from the developed world are lacking. We undertook a comprehensive 6-year review (2007–2012) of cases presenting to a single UK centre with an ethnically diverse population with high levels of population exchange with the Indian Subcontinent and Africa. Miliary TB was defined as the presence of miliary nodules on thoracic imaging in patients who presented with symptoms compatible with the diagnosis and either culture of Mycobacterium tuberculosis complex or culture-negative patients with clinical and/or histological features compatible with TB who were commenced on a course of antituberculous therapy (ATT). Miliary TB: high level of CNS involvement best investigated by head MRI which suggests re-evaluation of NICE guidance <http://ow.ly/X3CDK>
Animal Models of Thrombosis From Zebrafish to Nonhuman Primates
Authors: Pudur Jagadeeswaran, Brian C. Cooley, Peter L. Gross, Nigel Mackman
Journal: Circulation Research (2016)

Thrombosis is a leading cause of morbidity and mortality worldwide. Animal models are used to understand the pathological pathways involved in thrombosis and to test the efficacy and safety of new antithrombotic drugs. In this review, we will first describe the central role a variety of animal models of thrombosis and hemostasis has played in the development of new antiplatelet and anticoagulant drugs. These include the widely used P2Y 12 antagonists and the recently developed orally available anticoagulants that directly target factor Xa or thrombin. Next, we will describe the new players, such as polyphosphate, neutrophil extracellular traps, and microparticles, which have been shown to contribute to thrombosis in mouse models, particularly venous thrombosis models. Other mouse studies have demonstrated roles for the factor XIIa and factor XIa in thrombosis. This has spurred the development of strategies to reduce their levels or activities as a new approach for preventing thrombosis. Finally, we will discuss the emergence of zebrafish as a model to study thrombosis and its potential use in the discovery of novel factors involved in thrombosis and hemostasis. Animal models of thrombosis from zebrafish to nonhuman primates are vital in identifying pathological pathways of thrombosis that can be safely targeted with a minimal effect on hemostasis. Future studies should focus on understanding the different triggers of thrombosis and the best drugs to prevent each type of thrombotic event.
Case 4-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Martin J. Wohl, Benjamin Castleman
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 21-year-old woman was admitted to the hospital for cardiac catheterization.She had had multiple arthralgias most of her life. Ten years previously there was the onset of Raynaud's phenomenon, complicated by the development of ulceration and infection of the fingertips. Six years before entry she was admitted to another hospital because of arthralgias, fever, pleuritic pain and a malar rash. A diagnosis of rheumatic fever was made; she was given penicillin and prednisone and was placed on limited activity for one year. Four years before admission she began to experience progressive exertional dyspnea accompanied by occasional . . .
A new clinical sign or just fancy apparel? Determining the significance of a skirt
Authors: Nicholas Burgess, Michael Bourke
Journal: Endoscopy (2016)

As endoscopic technology advances, the mucosal pathology that can be seen in real time has expanded. High-definition endoscopes, magnification, manipulation of light wavelengths, and image processing techniques have allowed us to interrogate the surface patterns, morphology, and vascular patterns of the gastrointestinal mucosa in ever greater detail. Many of these technologies have been available for some time, yet new endoscopic findings are still regularly encountered. Many features must have been in plain sight for several years. Some of these findings were likely to have been disregarded by endoscopists, either consciously or unconsciously, as “noise” as the features did not yet fit into the contemporary framework of understanding for interpretation of mucosal pathology.
Gender Differences in Homicide of Neonates, Infants, and Children under 5 y in South Africa: Results from the Cross-Sectional 2009 National Child Homicide Study
Authors: Naeemah Abrahams, Shanaaz Mathews, Lorna J. Martin, Carl Lombard, Nadine Nannan, Rachel Jewkes
Journal: PLoS Medicine (2016)

Background Homicide of children is a global problem. The under-5-y age group is the second largest homicide age group after 15–19 y olds, but has received little research attention. Understanding age and gender patterns is important for assisting with developing prevention interventions. Here we present an age and gender analysis of homicides among children under 5 y in South Africa from a national study that included a focus on neonaticide and infanticide. Methods and Findings A retrospective national cross-sectional study was conducted using a random sample of 38 medico-legal laboratories operating in 2009 to identify homicides of children under 5 y. Child data were abstracted from the mortuary files and autopsy reports, and both child and perpetrator data data were collected from police interviews. We erred towards applying a conservative definition of homicide and excluded sudden infant death syndrome cases. We estimated that 454 (95% CI 366, 541) children under the age of 5 y were killed in South Africa in 2009. More than half (53.2%; 95% CI 46.7%, 59.5%) were neonates (0–28 d), and 74.4% (95% CI 69.3%, 78.9%) were infants (under 1 y), giving a neonaticide rate of 19.6 per 100,000 live births and an infanticide rate of 28.4 per 100,000 live births. The majority of the neonates died in the early neonatal period (0–6 d), and abandonment accounted for 84.9% (95% CI 81.5%, 87.8%) of all the neonates killed. Distinct age and gender patterns were found, with significantly fewer boy children killed in rural settings compared to urban settings (odds ratio 0.6; 95% CI 0.4, 0.9; p = 0.015). Abuse-related killings and evidence of sexual assault were more common among older girls than in all other age and gender groups. Mothers were identified as the perpetrators in all of the neonaticides and were the most common perpetrators overall (71.0%; 95% CI 63.9%, 77.2%). Abandoned neonates were mainly term babies, with a mean gestational age of 38 wk. We did not have information on abandonment motives for all newborns and did not know if babies were abandoned with the intention that they would die or with the hope that they would be found alive. We therefore considered all abandoned babies as homicides. Conclusions Homicide of children is an extreme form or consequence of violence against children. This national study provides one of the first analyses of neonaticide and infanticide by age and gender and shows the failure of reproductive and mental health and social services to identify and help vulnerable mothers. Multi-sectoral prevention strategies are needed.
A phase II, randomized, double-blinded, placebo-controlled study of simtuzumab or placebo in combination with FOLFIRI for the second line treatment of metastatic KRAS mutant colorectal adenocarcinoma.
Authors: J. Randolph Hecht, Johanna C. Bendell, Dmitry Vyushkov, Katia Bencardino, Udit N. Verma, Yingsi Yang, Dung Luong Thai
Journal: Journal of Clinical Oncology (2015)

3537 Background: Simtuzumab (SIM) is a humanized antibody that inhibits lysyl oxidase-like molecule 2 (LOXL2), a matrix enzyme that catalyzes the cross-linking of collagen and is widely expressed across desmoplastic tumors. Inhibiting LOXL2 is expected to block formation of desmoplasia, which is thought to play an important role in tumor progression and metastasis. In Phase I, SIM was safe in patients (pts) with advanced solid tumors and showed early evidence of efficacy. Based on these results, a randomized, double-blind, placebo-controlled phase II study of SIM+5-fluorouracil, leucovorin and irinotecan (FOLFIRI) vs. placebo (pbo)+FOLFIRI as second line therapy in pts with metastatic KRAS mutant colorectal adenocarcinoma (CRC) was conducted. Methods: Enrolled pts had advanced KRAS mutated CRC that had progressed on first-line oxaliplatin-based chemotherapy. Pts were ECOG performance status (PS) ≤ 2. Subjects were randomized in a 1:1:1 ratio to receive SIM 200 mg, SIM 700 mg, or pbo in combination with FOLFIRI every 2 weeks, and the randomization was stratified according to ECOG PS (0 or > 0). The primary endpoint was progression free survival (PFS) and the secondary endpoints were overall survival (OS) and objective response rate (ORR). Results: Between April, 2012 and December, 2014, 249 pts were randomized and treated; 85 pts (200 mg SIM/FOLFIRI), 84 pts (700 mg SIM/FOLFIRI), and 80 pts (pbo/FOLFIRI). Median PFS was 5.4 months (HR 1.45; 95% CI 1.01 to 2.06; p = 0.04 vs pbo), 5.5 months (HR 1.32; 95% CI 0.92 to 1.89; p = 0.10 vs pbo), and 5.8 months for the 200 mg SIM/FOLFIRI, 700 mg SIM/FOLFIRI, and pbo/FOLFIRI arms, respectively. Median OS was 10.5 (HR 1.50; 95% CI 0.98 to 2.30; p = 0.06 vs pbo), 11.4 (HR 1.23; 95% CI 0.80 to 1.91; p = 0.25 vs pbo), and 16.3 months, respectively. ORR was 5.9%, 11.9%, and 10%, respectively. There were no differences in the safety profile of the SIM/FOLFIRI groups versus pbo/FOLFIRI group. Conclusions: The addition of SIM to FOLFIRI does not improve PFS or OS in advanced KRAS mutant CRC pts. Exploratory analyses to investigate the potential prognostic factors influencing PFS or OS are being conducted. Clinical trial information: NCT01479465.
Clinical significance of fibrinogen and albumin score for postoperative recurrence in esophageal cancer patients.
Authors: Satoru Matsuda, Hiroya Takeuchi, Kazumasa Fukuda, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Hirofumi Kawakubo, Yoshiro Saikawa, Tai Omori, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2014)

14 Background: In order to predict the postoperative recurrence in esophageal cancer patients, we previously reported that esophageal cancer patients who had preoperative hyperfibrinogenemia (&gt;350 mg/dl) showed high recurrence rate. Currently, combining the preoperative plasma fibrinogen level and serum albumin level, we established a new scoring system. In this study, we aim to clarify the validity of the fibrinogen and albumin score (FA score) in esophageal cancer patients. Methods: We retrospectively reviewed 215 patients who underwent curative transthoracic esophagectomy in our institution between January 2004 and August 2012. Preoperative plasma fibrinogen level and serum albumin level were confirmed in 204 patients. We investigated patient characteristics, clinicopathological factors, preoperative plasma fibrinogen level and plasma albumin level. Based on our previous reports, we defined a cutoff value of fibrinogen as 350 mg/dl. The cut off value of albumin was determined after the analysis of the albumin distribution in the present study. Prognostic score was constructed by assigning one point for hyperfibrinogenemia or hypoalbuminemia. Cumulative FA score was obtained by combining them. Results: Based on the result that preoperative serum albumin level was 4.1 ± 0.34 g/dl (mean ± SD), we defined a cutoff value of albumin as 4.0 g/dl. Approximately, 33% had hyperfibrinogenemia and 34% had hypoalbuminemia. The number of each FA score 0/1/2 was 98(48%)/75(37%)/31(15%) cases. The patients with advanced stage showed significantly high score. In survival univariate analysis, neoadjuvant treatment, depth of tumor invasion, lymph node metastasis, pretreatment stage, preoperative fibrinogen level and FA score were significantly correlated with postoperative disease free survival. In multivariate analysis, pretreatment stage and FA score were shown to predict postoperative DFS significantly. Conclusions: FA score was shown to predict postoperative recurrence in esophageal cancer patients. Both fibrinogen and albumin are popular indicators routinely measured in daily clinical practice, FA score may be highly validate and feasible.
TCTAP A-014 Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction: A Propensity Score Matched Analysis from the Korea Acute Myocardial Infarction Registry
Authors: Doo Sun Sim, Myung-Ho Jeong, Youngkeun Ahn, Young Jo Kim, Shung Chull Chae, Taek Jong Hong, In-Whan Seong, Jei Keon Chae, Chong-Jin Kim, Myeong-Chan Cho, Seung-Woon Rha, Jang-Ho Bae, Ki-Bae Seung, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2016)
<i>TP53</i>Gene and Cancer Resistance in Elephants
Authors: Allan P. Pessier, Jere K. Stern, Carmel L. Witte
Journal: JAMA (2016)

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Abstract 1122: Personalized oncogenomics in advanced stage breast cancer
Authors: Sophie Sun, Karen A. Gelmon, Stephen Chia, Caroline Lohrisch, Tamara Shenkier, Diego Villa, Yaoqing Shen, Martin Jones, Erin Pleasance, Katayoon Kasaian, Peter Eirew, Sreeja Leelakumari, Yusanne Ma, Tony Ng, Stephen Yip, Steven JM Jones, Marco A. Marra, Janessa J. Laskin
Journal: Cancer Research (2015)

Abstract Background Breast cancer is a complex disease with clinical, pathological, and molecular heterogeneity. Recent studies have identified several subtypes of breast cancers driven by specific molecular pathways that can be inhibited by targeted drugs. We studied the feasibility of using molecular data from whole genome and transcriptome sequencing of breast cancers to guide treatment. Methods Patients were consented as part of the Personalized Onco-Genomics (POG) study at the British Columbia Cancer Agency. Fresh tumor, blood for normal DNA, and archival tumor were collected. Tissue and blood samples were sequenced using the Ion Torrent AmpliSeq panel, followed by comprehensive DNA and RNA sequencing. In-depth bioinformatic analyses were performed. Somatic mutations, copy number changes, structural variants and gene expression were characterized. Results from genomic analyses were reviewed in a multi-disciplinary team. Results From August 2012 to October 2014, tissue samples from 30 patients with advanced stage breast cancer were analyzed. The median age at diagnosis was 53 years (range 32-75). The median number of lines of cytotoxic therapy prior to sequencing was 2 (range 0-10). All cases were invasive ductal carcinoma; 63% were ER+ and HER2-; 27% triple negative; 7% ER+ and HER2+; and 3% ER- and HER2+. The most frequently mutated genes were TP53 (67%), PI3KCA (23%), ESR1 (20%), ATM (10%), ARID1A (10%), and BRCA1/2 (10%). Somatic mutations in other genes of interest including HER2, PARP1, NF1, BAP1, PTEN, NOTCH1, were also identified. Molecular data were informative for patient care and/or actionable to guide treatment in 57% (17/30) of cases. Conclusion The use of whole genome sequencing technology to identify valuable molecular information to guide personalized breast cancer treatment is feasible. Further studies are warranted to evaluate the usefulness of genome-wide sequencing of breast cancers in clinical practice. Citation Format: Sophie Sun, Karen A. Gelmon, Stephen Chia, Caroline Lohrisch, Tamara Shenkier, Diego Villa, Yaoqing Shen, Martin Jones, Erin Pleasance, Katayoon Kasaian, Peter Eirew, Sreeja Leelakumari, Yusanne Ma, Tony Ng, Stephen Yip, Steven JM Jones, Marco A. Marra, Janessa J. Laskin. Personalized oncogenomics in advanced stage breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1122. doi:10.1158/1538-7445.AM2015-1122