tbuckley/cabot-search huggingface dataset:
A New Hantavirus Infection in North America
Authors: Richard P. Wenzel
Journal: New England Journal of Medicine (1994)

Like wars and natural disasters, new epidemics of infections occur regularly. Sometimes they skip generations and are perceived as novel and improbable, when in fact they are ageless and routine. Thus, we should not be astonished to read in this issue of the Journal of the emergence of yet another infectious disease, initially involving 17 patients in the southwestern United States1. The patients were all previously healthy, yet 13 died from an apparent adult respiratory distress syndrome and myocardial depression leading to irreversible hypotension. After four to five days of an influenza-like prodrome, virtually all the patients had fever . . .
Development of TG101348 for the treatment of JAK2-driven malignancies
Authors: J. Hood, J. Cao, C. Chow, J. Doukas, E. Hanna, D. Lohse, C. Mak, M. Martin, S. Stoughton, B. Tam, R. Soll
Journal: Journal of Clinical Oncology (2008)

7083 Background: The molecular pathogenesis of the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocytosis, and myelofibrosis with myeloid metaplasia has been conclusively linked to an activating mutation of JAK2 (Janus Associated Kinase 2). In addition, aberrant activation of the JAK-STAT pathway has been implicated in the etiology of other human cancers due to activation of JAK2 by excessive cytokines and silencing of SOCs, a negative regulator of JAK-STAT signaling. In order to address this unmet clinical need TG101348 was designed and synthesized as a potent inhibitor of JAK2 that is highly selectivity against undesirable off-target kinases, including 332X, 135X and 35 selectivity versus JAK3, Tyk2 and JAK1, respectively as well as potently inhibiting less than 2% of the kinases evaluated in a commercially available, phylogenetically diverse panel of 223 kinases. Methods: TG101348 was evaluated for its capacity to block aberrant cell proliferation and reverse JAK2-induced clinical symptoms in vitro and in vivo in models utilizing primary and cultured cells in which JAK2 is activated. Results: TG101348 blocked proliferation and colony formation in vitro against cultured and patient-derived cells bearing the JAK2V617F mutations. In contrast, activity was much less against hematopoietic cells in which the JAK-STAT pathway is not activated by mutations. Similarly, TG101348 blocked STAT5 phosphorylation and cellular proliferation of hepatocellular carcinoma (HCC) cells in which SOCs, a negative regulator of JAK2 signaling, was silenced, but not in HCC cells in which SOCs function was normal. In vivo, oral administration of TG101348 reversed the polycythemia, leukocytosis, extramedullary hematopoiesis and splenomegaly in a statistically significant, dose-dependent manner in a bone marrow transplant model emulating JAK2V617F-driven myeloproliferative disease. Based on these promising efficacy results as well as equally promising pharmaceutical properties and preliminary toxicity TG101348 has been progressed to clinical evaluations. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration TargeGen TargeGen
Survival in colorectal cancer with Asian ethnicity
Authors: H. Le, A. Ziogas, J. A. Zell
Journal: Journal of Clinical Oncology (2008)

4042 Background: It has been reported that Asian ethnicity confers a survival benefit in colorectal cancer (CRC) when compared to the other major ethnic groups. The reasons for this have not yet been clearly elucidated. We set out to determine differences in CRC clinical characteristics at presentation and survival, among Asian subsets using data from the large, population-based California Cancer Registry (CCR). Methods: The authors conducted a case-only analysis of CCR data (1994–2004), including descriptive analysis of relevant clinical variables and Asian subsets. Overall survival (OS) univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. Results: 61,494 incident cases of colon and 24,350 incident cases of rectal cancer were analyzed, including 1,905 Chinese, 1,162 Filipino, 414 Vietnamese, 391 Korean, 1,091 Japanese, 148 Asian Indian, and 77,554 Caucasians. Sigmoid colon tumors were most common among Filipinos (32%) and least common among Caucasians (22%). After adjustment for age, sex, grade, histology, site within the colon, stage, insurance status, socioeconomic status (SES), and therapy, Filipino (Colon: HR, 0.85; 95% CI, 0.76–0.95; Table 1) (Rectum: HR, 0.82; 95% CI, 0.71–0.94) and Chinese ethnicity (Colon: HR, 0.90; 95% CI, 0.92- 0.98) had significantly decreased risk of death compared with Caucasians. Sigmoid lesions were independently associated with improved survival among all cases (HR, 0.93; 95% CI, 0.89–0.96) (Reference=prox and transverse lesions), and among Asian-only cases in separate analysis (HR, 0.78; 95% CI, 0.70–0.87). Conclusion: Although survival after CRC diagnosis is improved for Asians in general, significant survival differences are observed only in specific Asian subsets. These differences are not well understood but our data suggest survival among Asians is less affected by SES or treatment disparities, and may be due to biologic factors. Multivariate colorectal cancer-specific survival analysis for colon and rectum by ethnicity Race Colon HR (95% CI) Rectum HR (95% CI) White 1.00 (Reference) 1.00 (Reference) Chinese 0.90 (0.92–0.98) 1.00 (0.87–1.16) Filipino 0.85 (0.76–0.95) 0.82 (0.71–0.94) Vietnamese 0.90 (0.75-1.09) 0.96 (0.73–1.25) Korean Japanese 1.10 (0.91–1.32) 0.92 (0.82–1.03) 0.84 (0.67–1.06) 0.84 (0.70–1.00) Other Southeast Asian 1.22 (0.88–1.67) 1.02 (0.67-1.55) Other Asian Asian Indian 0.87 (0.72–1.06) 0.87 (0.61-1.24) 1.07 (0.82–1.40) 0.98 (0.61–1.55) Adjustment made for age, gender, histologic grade, AJCC stage, insurance status, socioeconomic status, colon site, surgery, radiation, and chemotherapy No significant financial relationships to disclose.
TCTAP A-089 Reduction of In-Stent Thrombus Immediately After Percutaneous Coronary Intervention by Pretreatment with a Lower Dosage of Prasugrel Compared to a Standard Dosage of Clopidogrel: An Optical Coherence Tomography Study in Asian Populations
Authors: Yosuke Katayama, Takashi Kubo, Yasushi Ino, Yoshiki Matsuo, Takashi Yamano, Takeyoshi Kameyama, Tsuyoshi Nishiguchi, Keisuke Satogami, Makoto Orii, Tomoyuki Yamaguchi, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2016)
Toward better management of rare and orphan pulmonary diseases
Authors: Sergio Harari, Marc Humbert
Journal: European Respiratory Journal (2016)

Following the publication of the last article of the European Respiratory Journal ( ERJ )/ European Respiratory Review ( ERR ) series on rare diseases and orphan drugs [1–9], we would like to take the opportunity to highlight that there are several very good reasons for pulmonologists to take rare pulmonary diseases and orphan drugs into due consideration. Efforts deployed by the ERS and its publications to promote rare disease and orphan drug research <http://ow.ly/YNbNN>
GP admits to falsifying clinical trial of insomnia drug
Authors: Clare Dyer
Journal: BMJ (2016)

A GP from Northern Ireland has pleaded guilty at Belfast Crown Court to falsifying a clinical trial of a sleeping pill for the drug company Sanofi Aventis. Hugh McGoldrick was due to go to trial on eight charges but pleaded guilty on two of the charges after the jury was sworn in.

He admitted two counts of conducting a clinical trial of the efficacy and safety of M100907 in sleep maintenance insomnia, in breach of the Medicines for Human Use (Clinical Trials) Regulations 2004, on dates from November 2007 to June 2008. The …
Abstract P004: Estimating the Mortality Benefits of Ideal Cardiovascular Health: A Dose-response Meta-analysis
Authors: Ehimen C Aneni, Alessio Crippa, Adnan Younus, Chukwuemeka U Osondu, Emir Veledar, Khurram Nasir
Journal: Circulation (2016)

Background: Studies have shown that individuals with higher levels of Ideal Cardiovascular Health (ICVH) metrics have favorable health outcomes. However, none of these studies quantify the reduction in the risk of death per unit increase in ICVH. In this study, we estimated the reduction in CVD and all-cause mortality attributable to per unit improvement in ICVH. Methods: Five studies identified through a literature search were included. Major differences in the re-categorization of the 7 ICVH metrics were noted, with studies having between 3-6 groups. Reference groups also ranged from 0 to ≤2 ideal CVH metrics. Because of these differences, risk reduction per unit increase in ICVH was not comparable across studies. To overcome these challenges, we quantified association between ICVH metrics and all-cause/CVD mortality using a dose-response meta-analysis, so all exposure categories contribute to a defined pooled association and heterogeneity is reduced by accounting for values assigned to these qualitative metrics. Results: Original data and meta-analysis model of studies assessing CVD mortality are shown in the figure. There was a significant linear trend ( p &lt; 0.001) with moderate heterogeneity (Q test = 12, p = 0.02 and I2 = 66 %). Each unit increase in ICVH metric was associated with 18% (95% CI: 12, 23) reduction in HR. In all-cause mortality analysis (graph not shown), there was also a significant linear trend (p &lt; 0.001) with moderate heterogeneity (Q test = 18, p = 0.003, and I2 = 72 %). Each unit increase in ICVH metric was associated with a 10% (95% CI: 6, 13) reduction in HR for all cause mortality. Conclusion: Our study is the first meta-analysis to demonstrate a dose-response impact of ICVH on mortality. The novel dose-response design allowed us to investigate strength, direction and type of association as well as overcomes challenges posed by heterogeneity ICVH metrics categorization while preserving the statistical control for confounding variables that was conducted in the individual studies.
Expanding Role of Positron Emission Tomography in Cancer of the Uterine Cervix
Authors: Joseph G. Rajendran, Benjamin E. Greer
Journal: Journal of the National Comprehensive Cancer Network (2006)

Molecular imaging through positron emission tomography (PET) is playing a very important role in the management of several different cancers. Its noninvasive nature and ability to study biologic function are ideal for oncology practice. PET is establishing itself in staging, guiding therapy, and follow-up of patients with cervical cancer. The emergence and widespread availability of combined PET/computed tomography technology has further consolidated the role of molecular scanning in managing these patients. This technology is now accessible to every cancer center in the United States and is also available in most countries. Although it is approved for staging patients with cervical cancer, its use in other clinical management situations is being evaluated. The real power of molecular imaging will be to predict treatment response and guide therapy and applications of novel PET tracers for studying complex cellular functions that characterize the tumor for individualized treatment approaches. Although PET technology is beyond the reach of many developing countries, the experience gained in major centers would help devise more effective and simpler treatments that can be introduced.
Nipple Aspirate Cytology for the Study of Breast Cancer Precursors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E B King, K L Chew, N L Petrakis, V L Ernster
Journal: JNCI Journal of the National Cancer Institute (1983)

The association of abnormal nonmalignant cells in nipple aspirate fluid (NAF) and atypical proliferative disease (APD) of breast ducts was examined in the presence and absence of breast cancer in 134 patients. A high frequency of NAF samples with cellular abnormalities (atypical hyperplasia) was found when APD occurred with either breast cancer (70%) or benign breast biopsy specimens (54%). APD was present in 27 malignant cases (80%) and in 39 benign cases (39%). Inasmuch as APD may represent an intermediate step in the malignant transformation of duct epithelium, the cytologic examination of NAF offers a new approach with which to study the spectrum of breast cancer precursors and to assist in identifying women at risk for breast cancer.
Glomerular expression of tissue inhibitor of metalloproteinase (TIMP-1) in normal and diabetic rats.
Authors: S J Shankland, H Ly, K Thai, J W Scholey
Journal: Journal of the American Society of Nephrology (1996)

Recent studies suggest that decreased extracellular matrix (ECM)-protein degradation may contribute to the progressive mesangial matrix expansion that characterizes diabetic glomerular injury. Tissue inhibitors of metalloproteinases (TIMP) constitute a family of proteins that bind to and inactivate extracellular proteases and thus may serve to lower ECM protein degradation. Accordingly, the aim of this study was to determine whether there was an increase in TIMP-1 protein in the glomeruli of diabetic rats. Studies were performed in age-matched normal rats (C) and rats that received Streptozotocin (60 mg/kg IV) (Sigma Chemical Co., St. Louis, MO). A first group of diabetic rats (D) received daily injections of insulin to maintain moderate hyperglycemia (15 to 22 mmol/L). A second group of diabetic rats (D-Rx) received insulin injections twice daily to normalize blood glucose (3 to 7 mmol/L). Western blot analysis of glomerular proteins showed that there was an early increase in TIMP-1 expression during the rapid phase of glomerular hypertrophy that follows the onset of hyperglycemia. The increase in TIMP-1 expression was ameliorated by insulin treatment that normalized blood glucose levels. Six wk after the onset of hyperglycemia, the increase in TIMP-1 expression in glomeruli was sustained. These studies suggest that an early increase in TIMP-1, a protein that decreases extracellular metalloproteinase activity, may contribute to a decrease in ECM protein degradation in the diabetic glomerulus.
Abstract P304: The Association of Sleep Duration and Severe Obesity in a Working Population: The Baptist Health South Florida Employee Study
Authors: Chukwuemeka U Osondu, Ehimen C Aneni, Maribeth Rouseff, Sankalp Das, Don Parris, Henry Guzman, Thinh Tran, Adnan Younus, Rameez Ahmad, Shozab Ali, Muhammad A Latif, Theodore Feldman, Emir Veledar, Khurram Nasir
Journal: Circulation (2016)

Background: Although studies have described an inverse relationship between sleep duration and obesity, there is limited knowledge about the association between sleep duration and severe obesity in the work place. In this study, we evaluated the relationship between self-reported sleep duration and severe obesity in a large, healthcare employee population. Methods: Employees of Baptist Health South Florida (BHSF), a large nonprofit healthcare organization participated in an annual Health Risk Assessment in 2014, from which data for this study was obtained. Average sleep duration was self-reported while weight, height and other biometric measures were captured in person. Obesity status was categorized as BMI &lt;30, 30 - 34.9 and ≥35kg/m2, while average sleep duration was also categorized (as &lt; 6 hours, 6 - 8 hours and &gt; 8 hours). Results: A total of 10363 participants (mean age 42.8 ± 12.1 years, 75% females, 57% Hispanic) had complete information on the variables of interest. Almost one-quarter (24%) of employees who slept less than 6 hours a day were severely obese, compared to about 13% and 14% of employees who sleep between 6-8 hours and 8 or more hours of sleep respectively. Compared to those who slept for 6 - 8 hours, persons who slept for less than 6 hours had almost a 2-fold increase in odds of severe obesity (OR= 1.9; 1.6 - 2.2). Conclusion: In this large diverse employee population, short sleep duration is associated with a significantly increased risk of severe forms of obesity. Workplace-based programs should be encouraged to place more emphasis on adequate sleep as an important factor associated with weight control and cardiovascular health. Further studies are needed to define a temporal relationship between sleep duration and obesity severity.
TCTAP C-111 Stent Edge Dissection Caused by Hinge Motion in Tortuous Vessels
Authors: Takatoyo Kiko, Yoshifumi Kashima, Daitarou Kanno, Tomohiko Watanabe, Yutaka Tadano, Takuro Sugie, Ken Kobayashi, Tsutomu Fujita
Journal: Journal of the American College of Cardiology (2016)
PICC line–associated thrombosis in cancer patients (pts).
Authors: D. H. Ahn, H. B. Illum, D. H. Wang, A. Sharma, J. Dowell
Journal: Journal of Clinical Oncology (2011)

e19574 Background: Peripheral inserted central catheters (PICC) are often used in place of medi-port catheters due to cost, the lack of operating room time, and to prevent delays in therapy. One common complication with the use of long-term venous catheters is upper extremity venous thrombosis (UEVT). The purpose of this study is to ascertain which factors are associated with an increased risk of PICC associated UEVT in cancer pts. Methods: A retrospective study looking at 237 cancer pts, who received a PICC at the Dallas Veterans Affairs Medical Center from 2006 to 2009. Risk factors analyzed included age, white blood cell and platelet count, ethnicity, catheter diameter, number of lumens, catheter tip location, chemotherapy regimen, PICC infection (PI), prior central venous catheter, use of erythrocyte stimulating agent (ESA), use of anti-platelet agent (APA), solid versus hematologic malignancy, stage of cancer, radiotherapy treatment, hospitalization, use of prophylactic dose (PDA) or treatment dose anticoagulation (TDA), and use of bevacizumab. Results: 36 out of 237 pts (15%) were found to have UEVT. In multivariate analysis, risk factors positively associated with UEVT were use of ESAs, hospitalization, PI and TDA while pts on APAs had a lower risk of UEVT. Conclusions: Specific factors (use of ESAs, hospitalization, TDA, PI) significantly increase the risk of UEVT in cancer pts with a PICC while the use of APA’s appears to have a protective effect against UEVT. It is unclear why pts already on TDA have a higher risk of UEVT. Conceivably, these pts are hypercoagulable and are sub-therapeutically anticoagulated. The association between UEVT and PI may be due to a correlation between duration of PICC placement and increased risk of both PI and UEVT. These results may aid in the development of a predictive model for identifying pts at high risk of UEVT who may benefit from APA, as well as in the development of preventative strategies for reducing the risk of PICC associated UEVT. Parameter Odds ratio for UEVT 95% CI P value ESA 10.657 (2.249, 50.49) 0.003 APA 0.248 (0.067, 0.920) 0.037 Hospitalization 2.376 (1.047, 5.390) 0.038 TDA 8.341 (2.982, 23.33) <0.0001 PI 2.458 (1.034, 5.848) 0.037
Advancing global programmatic management of latent tuberculosis infection for at risk populations
Authors: Haileyesus Getahun, Alberto Matteelli, Ibrahim Abubakar, Barbara Hauer, Emanuele Pontali, Giovanni Battista Migliori
Journal: European Respiratory Journal (2016)

In this issue of the European Respiratory Journal , Erkens et al. [1] present experience and results of long-term data (1993–2013) in the recording and reporting of latent tuberculosis (TB) infection (LTBI) management from the Netherlands. The authors report a high rate of initiation (77%) among the 37 729 eligible persons and a high rate of treatment completion (82%). Valid and complete data were available on almost all (96%) persons who started treatment, due to the use of a technically sound notification system supported by a legal framework and standardised indicators [1]. These findings are important additions to the renewed focus and call to address LTBI, which is considered as the reservoir for virtually all TB cases [2, 3]. Other renewed efforts include the establishment of a World Health Organization (WHO) global task force to raise the profile of programmatic management of LTBI, including monitoring and evaluation of implemented activities, as well as promoting research. UNITAID has also identified LTBI as one of its areas of intervention. Intensification of #LTBI treatment for child #TB contacts and people living with #HIV and other at risk populations <http://ow.ly/ZfzAv>
Epigenome-wide association study links site-specific DNA methylation changes with cow's milk allergy
Authors: Xiumei Hong, Christine Ladd-Acosta, Ke Hao, Ben Sherwood, Hongkai Ji, Corinne A. Keet, Rajesh Kumar, Deanna Caruso, Xin Liu, Guoying Wang, Zhu Chen, Yuelong Ji, Guanyun Mao, Sheila Ohlsson Walker, Tami R. Bartell, Zhicheng Ji, Yifei Sun, Hui-Ju Tsai, Jacqueline A. Pongracic, Daniel E. Weeks, Xiaobin Wang
Journal: Journal of Allergy and Clinical Immunology (2016)
Clinical Management of the Osteoporoses.
Journal: Annals of Internal Medicine (1977)

Book Reviews1 March 1977Clinical Management of the Osteoporoses.https://doi.org/10.7326/0003-4819-86-3-374_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail AbstractGordan and Vaughn provide an up-to-date clinical review of a common problem in medical practice. In the first few chapters they deal with the definition of osteoporosis and with its relation to physical activity, aging, and hormone and endocrine function. Bone physiology and pathology is presented comprehensibly. Middle chapters carry a discussion of diagnostic tests and a rather lengthy review of quantitative measures of bone density. After discussing the main differential diagnosis of osteoporosis, the authors take up the major types of osteoporosis: postmenopausal osteoporosis, immobilization osteoporosis, and corticoid osteoporosis. Emphasis is on pathophysiology, diagnosis, and treatment. Various therapeutic regimens This content is PDF only. To continue reading please click on the PDF icon. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1977Volume 86, Issue 3 Page: 374-374 Keywords Aging Bone Bone density Exercise Hormones Osteoporosis ePublished: 1 December 2008 Issue Published: 1 March 1977 PDF downloadLoading ...
TCTAP A-141 Procedural Safety and Intermediate Term Efficacy of Zotarolimus Eluting Resolute Integrity Stent in the Management of Native Very Long Segment Coronary Artery Lesion: A Prospective Observational Real World Study with 12-Month Follow-up
Authors: Soumya Patra, Rabindranath Chakraborty, Praskas Chandra Mandal
Journal: Journal of the American College of Cardiology (2016)