tbuckley/cabot-search huggingface dataset:
The effect of text messaging on latent tuberculosis treatment adherence: a randomised controlled trial
Authors: James C. Johnston, Mia L. van der Kop, Kirsten Smillie, Gina Ogilvie, Fawziah Marra, Mohsen Sadatsafavi, Kamila Romanowski, Matthew A. Budd, Jan Hajek, Victoria Cook, Richard T. Lester
Journal: European Respiratory Journal (2018)

There is limited high-quality evidence available to inform the use of text messaging to improve latent tuberculosis infection (LTBI) treatment adherence. We performed a parallel, randomised controlled trial at two sites to assess the effect of a two-way short message service on LTBI adherence. We enrolled adults initiating LTBI therapy from June 2012 to September 2015 in British Columbia, Canada. Participants were randomised in a 1:1 ratio to standard LTBI treatment (control) or standard LTBI treatment plus two-way weekly text messaging (intervention). The primary outcome was treatment completion, defined as taking ≥80% prescribed doses within 12 months (isoniazid) or 6 months (rifampin) of enrolment. The trial was unblinded except for the data analyst. A total of 358 participants were assigned to the intervention (n=170) and control (n=188) arms. In intention-to-treat analysis, the proportion of participants completing LTBI therapy in the intervention and control arms was 79.4% and 81.9%, respectively (RR 0.97, 95% CI 0.88–1.07; p=0.550). Results were similar for pre-specified secondary end-points, including time-to-completion of LTBI therapy, completion of &gt;90% of prescribed LTBI doses and health-related quality of life. Weekly two-way text messaging did not improve LTBI completion rates compared to standard LTBI care; however, completion rates were high in both treatment arms.
p16INK4A silencing augments DNA damage-induced apoptosis in cervical cancer cells
Authors: Wen-Min Lau, Tew Ho, Kam Hui
Journal: Cancer Research (2007)

3690  Cancer of the cervix is the second most common cancer among women worldwide, with a higher prevalence in the developing countries. The p16INK4A tumor suppressor gene has been reported to be frequently inactivated in human cancer. However, for cervical cancer cells, the accumulation of p16 was observed, possibly resulting from the inactivation of Rb by E7. Consequently, p16 has been suggested to be a potential early diagnostic bio-marker for cervical cancer. Despite this, the functional impact of p16 over-expression in cervical cancer has not been thoroughly investigated. In this study, we have demonstrated the consistent and significant up-regulation of p16 in cervical cancer tissues when compared to both matched non-tumourous tissues of the same patient and normal cervical tissues from non-cancerous patients. To gain further insights into the over-expression of p16 in cervical carcinogenesis, we employed p16-specific siRNA to down-regulate the expression of p16. Although the silencing of p16 was accompanied by the up-regulation of p53, p21 and Rb protein expression, no significant effect on cell cycle progression was observed. However, when the p16 siRNA-silenced cells were subjected to DNA damage stress including UV-irradiation and cisplatin treatments, a significantly higher percentage of apoptotic cells could be detected in the p16-siRNA silenced cells compared to control siRNA-treated cells. The induction of apoptosis was associated with the activation of p53 through phosphorylation, and this process, when analyzed by gene profiling experiments, demonstrated the involvement of both the intrinsic mitochondrial and extrinsic death-receptor apoptotic pathways. Of particular interest, it was noted that target genes related to p53-mediated DNA damage, including p21, PCNA, and GADD45A were up-regulated, while the anti-apoptotic genes BAG1, TIMP3, AKT1, MCL1 and FAIM were down-regulated. Similarly, apoptotic genes belonging to both the mitochondrial and death receptor pathways, such as caspase 8, Bcl family-related genes, APAF1, FAS, FADD and TNFR-family genes were also up-regulated in UV-irradiated, p16-silenced cervical cancer cells. In summary, the observation that p16-silencing could augment DNA damage-induced apoptosis in cervical cancer cells offers alternative strategies for anti-cancer therapies for human cervical cancer.
Abstract 21144: Gene-Based Risk Stratification for Cardiac Disorders in <i>LMNA</i> Mutation Carriers in Japan
Authors: Suguru Nishiuchi, Takeshi Aiba, Takeru Makiyama, Kenzaburo Nakajima, Nobue Yagihara, Taisuke Ishikawa, Kenji Onoue, Nobuyuki Murakoshi, Ichiro Watanabe, Kimie Ohkubo, Hiroshi Watanabe, Seiko Ohno, Takahiro Doi, Satoshi Shizuta, Tohru Minamino, Yoshihiko Saito, Yasushi Oginosawa, Akihiko Nogami, Kazutaka Aonuma, Kengo Kusano, Naomasa Makita, Wataru Shimizu, Minoru Horie, Takeshi Kimura
Journal: Circulation (2017)

Introduction: Mutations in LMNA, which encodes lamin A and C, typically cause age-dependent cardiac phenotypes, including dilated cardiomyopathy, cardiac conduction disturbance (CCD), atrial fibrillation, and malignant ventricular arrhythmias (MVAs). Although the type of LMNA mutations have been reported to be associated with susceptibility to MVAs, the gene-based risk stratification for cardiac complications remains unexplored. Hypothesis: We hypothesized that truncation mutations might be associated with poor prognosis in LMNA mutation carriers, due to CCD, MVAs, and heart failure. Methods: The multicenter cohort included 77 LMNA mutation carriers (49 male, mean age: 45+/-17 yrs old) in 45 families from 7 institutions in Japan. All cause mortality and cardiac disorders were retrospectively analyzed. Results: Genetic analysis showed truncation mutations in 58 patients from 31 families and missense mutations in 19 patients from 14 families, in which 71 (92%) were phenotypically affected, and showed CCD (81%), lower left ventricular ejection fraction (LVEF&lt;50%; 45%), atrial arrhythmias (AAs: 58%), and MVAs (26%). During the follow-up period (median 47 months), 9 (12%) patients died due to end-stage heart failure (n=7) or suddenly (n=2), but not differ between the the type of mutations. On the other hand, the onset of cardiac disorders indicated that subjects with truncation mutations had an earlier occurrence of CCD (41+/-12 vs. 51+/-10 yrs old; p=0.004) and LVEF&lt;50% (47+/-12 vs. 56+/-7 yrs old; p=0.07) compared to those with missense mutations. In addition, the truncation mutation was found to be at risk for the early onset of CCD (Odds ratio [OR]=3.55, 95%CI:1.1-12.3, p=0.04) and the occurrence of AAs (OR=5.18 [1.4-20.4], p=0.01), LVEF&lt;50% (OR=3.92 [1.0-16.6], p=0.04), and MVAs (OR=12.8 [1.9-259], p=0.006), as estimated using multivable analyses. However, no significant difference was observed in each cardiac phenotype between probands vs. relatives and male vs. female. Conclusions: The truncation mutations were associated with earlier manifestation of cardiac phenotypes in LMNA -related cardiomyopathy, suggesting that genetic analysis might be useful for diagnosis and risk stratification in LMNA mutation carriers.
Rapamycin for lymphangioleiomyomatosis: optimal timing and optimal dosage
Authors: Kai-Feng Xu, Xinlun Tian, Yanli Yang, Hongbing Zhang
Journal: Thorax (2018)

Lymphangioleiomyomatosis (LAM) occurs predominantly in women in one of two forms: sporadic LAM and LAM associated with the autosomal dominant genetic disease tuberous sclerosis complex (TSC). Its clinical presentation includes dyspnoea, pneumothorax, chylothorax and renal angiomyolipoma. Many patients exhibit mild symptoms at the time of diagnosis, and their lung function then gradually declines. In the end-stage of LAM, lung transplantation is the only option. Due to mutations of either TSC1 or TSC2 gene, aberrant activation of mammalian/mechanistic target of rapamycin (mTOR) causes TSC and/or LAM.1 2 There were no effective therapeutics for LAM until the mTOR inhibitor rapamycin (sirolimus) exhibited efficacy in an open-label study published in 20083. The efficacy of this drug was confirmed in the randomised, double-blinded Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial.4 Primarily based on findings from the MILES study, sirolimus has been approved for the treatment of LAM in Japan and USA. In recent guidelines for LAM issued by the American Thoracic Society and the Japanese Respiratory Society, rapamycin is recommended for patients with reduced lung function.5

A real-world observational study by Bee and colleagues that appears in Thorax expanded our knowledge regarding two important questions: when and how much rapamycin could be used to treat LAM.6 In a prospective cohort comprising 47 patients during a 3-year follow-up, the authors found that (1) patients with LAM with a shorter duration of disease and less severely impaired lung function responded better to rapamycin; (2) different dosages of rapamycin produced similar benefits and (3) lower doses had fewer side effects. Therefore, early treatment with low-dose rapamycin may better preserve lung function …
BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange–like syndrome
Authors: Gabrielle Olley, Morad Ansari, Hemant Bengani, Graeme R. Grimes, James Rhodes, Alex von Kriegsheim, Ana Blatnik, Fiona J. Stewart, Emma Wakeling, Nicola Carroll, Alison Ross, Soo-Mi Park, Wendy A. Bickmore, Madapura M. Pradeepa, David R. FitzPatrick
Journal: Nature Genetics (2018)
Postoperative chemotherapy as effective as preoperative for N2-positive stage III non-small cell lung cancer.
Authors: Daniel J Boffa, Jacquelyn Hancock, Amy Moreno, Joshua Rosen, Anthony W. Kim, Frank C. Detterbeck
Journal: Journal of Clinical Oncology (2014)

7533 Background: Neoadjuvant chemotherapy followed by surgery is superior to surgery alone for stage III non-small cell lung cancer (NSCLC) with mediastinal (N2) lymph node involvement. It is unclear, however, if postoperative (adjuvant) chemotherapy is as effective as preoperative (neoadjuvant) chemotherapy in this setting. The objective of this study was to determine the survival of resected stage III NSCLC according to the timing of chemotherapy. Methods: The National Cancer Database (NCDB) was queried for patients with clinical T1-4N2M0 NSCLC (clinical Stage III - N2) undergoing resection via lobectomy or pneumonectomy between 2003 and 2006. Results: The efficacy of post-operative (adjuvant) therapy in clinical Stage III - N2 NSCLC was evaluated in two ways. First we examined a cohort of 698 treatment-naïve (no preoperative treatment) clinical N2 patients confirmed to be pathologic N2 by the surgical resection of primary tumor (cN2pN2). We compared surgery “alone” to surgery followed by adjuvant chemotherapy. The 5-year survival of cN2pN2 patients was significantly higher with adjuvant chemotherapy (36%, n= 212) or chemoradiation (33%, n= 230) than surgery alone (21%, n= 256, p<.0001). In a multivariable analysis adjusting for patient demographics, tumor attributes, a modified Charlson comorbidity index and type of resection, the use of postoperative chemotherapy (HR, 0.66 95%CI [0.52-0.84], p=.0005) and chemoradiation (HR 0.75, 95%CI [0.59-0.95], p=.016) were both superior to surgery alone. There was no significant difference between chemotherapy and chemoradiation. We next directly compared postoperative chemotherapy (adjuvant) to preoperative therapy (neoadjuvant) in clinically staged III – clinical N2 NSCLC. A multivariable Cox model including variables noted above indicated that adjuvant therapy (n = 649) was associated with a similar outcome to neoadjuvant therapy (n = 1,356) HR 1.05, 95% CI [.92 – 1.18], p = .475). Conclusions: Chemotherapy appears to be similarly effective in stage III NSCLC patients with N2 disease when given before or after resection in the NCDB. This finding, could impact the role preoperative mediastinal staging in operable stage III lung cancer.
Doctors are cleared to prescribe cheaper drug for wet AMD
Authors: Deborah Cohen
Journal: BMJ (2018)

Doctors who prescribe bevacizumab (Avastin) for age related macular degeneration (AMD) will “not raise fitness to practise concerns,” the UK medical regulator has said, after the National Institute for Health and Care Excellence judged that the drug was as safe and effective as licensed treatments.

The General Medical Council’s chief executive, Charlie Massey, said, “Where doctors are working in partnership with patients, following clinical guidance, and making prescribing decisions in good faith on the basis of evidence and experience, the use of Avastin would not cause us any concerns.”

In its long awaited clinical guideline on AMD, NICE recommended that people with suspected late form of the disease (wet active) be referred to a macula service quickly for prompt diagnosis and fast access to effective treatments.1

For patients with confirmed late AMD, an antivascular endothelial growth factor (anti-VEGF) drug should be …
Just one cigarette a day seriously elevates cardiovascular risk
Authors: Kenneth C Johnson
Journal: BMJ (2018)

Pancreatic cystic lesions (PCLs) can present complex diagnostic and management challenges with uncertainty as to the most appropriate investigations, interventions and surveillance. Guidelines have been developed to aid decision making, including the European Study Group, American College of Gastroenterology and International Study Group guidelines. This paper presents issues relating to risk stratification and the appropriate management of patients with PCLs, reviewing these recently published guidelines. While there are similarities across these expert guidelines, there are notable differences in terms of features associated with increased risk of malignant transformation, the most appropriate imaging modality and timing of interval imaging. Where variations exist, this reflects differing interpretations of a limited evidence base, and decision making will likely evolve further as experience with these guidelines develops.
Overall Survival of Transplant Eligible Patients with Newly Diagnosed Multiple Myeloma: Comparative Effectiveness Analysis of Modern Induction Regimens on Outcome
Authors: Ashley Paquin, Shaji K Kumar, Francis K Buadi, Morie A. Gertz, Martha Q Lacy, Angela Dispenzieri, David Dingli, Lisa Hwa, Amie Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S Go, Yi Lin, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A Kyle, S. Vincent Rajkumar
Journal: Blood (2017)
Vhl deletion in osteoblasts boosts cellular glycolysis and improves global glucose metabolism
Authors: Naomi Dirckx, Robert J. Tower, Evi M. Mercken, Roman Vangoitsenhoven, Caroline Moreau-Triby, Tom Breugelmans, Elena Nefyodova, Ruben Cardoen, Chantal Mathieu, Bart Van der Schueren, Cyrille B. Confavreux, Thomas L. Clemens, Christa Maes
Journal: Journal of Clinical Investigation (2018)

The skeleton has emerged as an important regulator of systemic glucose homeostasis, with osteocalcin and insulin representing prime mediators of the interplay between bone and energy metabolism. However, genetic evidence indicates that osteoblasts can influence global energy metabolism through additional, as yet unknown, mechanisms. Here, we report that constitutive or postnatally induced deletion of the hypoxia signaling pathway component von Hippel–Lindau (VHL) in skeletal osteolineage cells of mice led to high bone mass as well as hypoglycemia and increased glucose tolerance, not accounted for by osteocalcin or insulin. In vitro and in vivo data indicated that Vhl-deficient osteoblasts displayed massively increased glucose uptake and glycolysis associated with upregulated HIF-target gene expression, resembling the Warburg effect that typifies cancer cells. Overall, the glucose consumption by the skeleton was increased in the mutant mice, as revealed by 18F-FDG radioactive tracer experiments. Moreover, the glycemia levels correlated inversely with the level of skeletal glucose uptake, and pharmacological treatment with the glycolysis inhibitor dichloroacetate (DCA), which restored glucose metabolism in Vhl-deficient osteogenic cells in vitro, prevented the development of the systemic metabolic phenotype in the mutant mice. Altogether, these findings reveal a novel link between cellular glucose metabolism in osteoblasts and whole-body glucose homeostasis, controlled by local hypoxia signaling in the skeleton.
Inequalities in the use of secondary prevention of cardiovascular disease by socioeconomic status: evidence from the PURE observational study
Authors: Adrianna Murphy, Benjamin Palafox, Owen O'Donnell, David Stuckler, Pablo Perel, Khalid F AlHabib, Alvaro Avezum, Xiulin Bai, Jephat Chifamba, Clara K Chow, Daniel J Corsi, Gilles R Dagenais, Antonio L Dans, Rafael Diaz, Ayse N Erbakan, Noorhassim Ismail, Romaina Iqbal, Roya Kelishadi, Rasha Khatib, Fernando Lanas, Scott A Lear, Wei Li, Jia Liu, Patricio Lopez-Jaramillo, Viswanathan Mohan, Nahed Monsef, Prem K Mony, Thandi Puoane, Sumathy Rangarajan, Annika Rosengren, Aletta E Schutte, Mariz Sintaha, Koon K Teo, Andreas Wielgosz, Karen Yeates, Lu Yin, Khalid Yusoff, Katarzyna Zatońska, Salim Yusuf, Martin McKee
Journal: The Lancet Global Health (2018)

There is little evidence on the use of secondary prevention medicines for cardiovascular disease by socioeconomic groups in countries at different levels of economic development.
UKPDS 28: A Randomized Trial of Efficacy of Early Addition of Metformin in Sulfonylurea-Treated Type 2 Diabetes
Journal: Diabetes Care (1998)

To assess the efficacy over 3 years of the addition of metformin to maximum sulfonylurea therapy in type 2 diabetes.This multicenter randomized open-controlled trial was conducted in outpatient diabetes clinics in 15 U.K. hospitals. A total of 591 subjects who had already been randomly allocated to sulfonylurea therapy were taking maximum doses with suboptimal glycemic control, i.e., raised fasting plasma glucose (FPG) concentrations of 6-15 mmol/l but no significant hyperglycemic symptoms. The main outcome measures included FPG, glycated hemoglobin, protocol-defined marked hyperglycemia, body weight, blood pressure, fasting plasma lipids, compliance, and hypoglycemia and other side effects.After the addition of metformin, FPG concentrations decreased by mean (95% CI) -0.47 (-0.82 to -0.13) mmol/l over 3 years compared with an increase of 0.44 (0.07-0.81) mmol/l in subjects on sulfonylurea alone (P < 0.00001). Median FPG concentrations at 3 years were 8.6 vs. 9.9 mmol/l, respectively (P < 0.00001), and HbA1c values were 7.5 and 8.1%, respectively (P = 0.006). Adjustment for baseline BMI or FPG concentration did not affect response to therapy. Only 7% of those allocated to sulfonylurea plus metformin developed protocol-defined marked hyperglycemia compared with 36% of those allocated to sulfonylurea alone (P < 0.0001). Fasting plasma lipids, body weight, and blood pressure did not change significantly. The incidence of hypoglycemic episodes did not differ between groups: 4% on sulfonylurea plus metformin and 2% on sulfonylurea alone (NS).Early addition of metformin improved glycemic control in patients with suboptimal glycemic control while taking maximum sulfonylurea therapy, irrespective of obesity or baseline FPG concentrations.
Blunt Trauma during Pregnancy
Authors: Jane F. Desforges, Mark D. Pearlman, Judith E. Tintinalli, Robert P. Lorenz
Journal: New England Journal of Medicine (1990)

THE most common causes of blunt maternal injury during pregnancy are motor vehicle accidents, falls, and assaults.1 2 3 4 5 Although trauma is the leading cause of nonobstetrical death in pregnant women in at least one state,6 it causes the death of the fetus much more often than the death of the mother.7 8 9 10 11 The management of trauma during pregnancy requires special considerations, because pregnancy alters maternal physiology and because the fetus is a second potential victim.Fetal PhysiologyThe effect of trauma on pregnancy depends on the gestational age of the fetus, the type and severity of the trauma, and the extent of . . .
Detection of Helicobacter pylori-associated chronic gastritis using NIR Raman spectroscopy
Authors: Seng Khoon Teh, Wei Zheng, Khek Yu Ho, Ming Teh, Khay Guan Yeoh, Manuel Salto-tellez, Zhiwei Huang
Journal: Cancer Research (2008)

5157   Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically probing the biomolecular changes associated with diseased tissues. The purpose of this study was to investigate the use of near-infrared (NIR) Raman spectroscopy for distinguishing  Helicobacter pylori (Hp)- associated chronic gastritis from normal and  non-Hp associated  chronic gastritis gastric mucosa tissues. A total of 34 gastric tissue samples obtained from 26 patients who underwent endoscopy or gastrectomy without prior antibiotic treatment were used in this study, and a rapid-acquisition dispersive-type NIR Raman system was utilized for tissue Raman spectroscopic measurements at 785 nm laser excitation. Histopathogical examinations showed that 16 tissue specimens were normal, and 11 were chronic gastritis not associated with Hp, and 7 were  Hp- associated chronic gastritis. Multivariate statistical techniques, including principal component analysis (PCA), linear discriminant analysis (LDA) were employed to develop effective diagnostic algorithms for classification of NIR Raman spectra among different types of gastric tissues. High-quality Raman spectra in the range of 800-1800 cm -1  can be acquired from gastric tissue within 5 seconds. Raman spectral shapes were significantly different among normal, non- Hp- associated chronic gastritis and  Hp- associated chronic gastritis, particularly in the spectral ranges of 850-900 cm -1 , 1200-1250 cm -1  and 1600-1800 cm -1  which contain signals related to hydroxyproline for collagen, amide III, amide I and C=C stretching of lipids. Raman spectra from  Hp- associated chronic gastritis showed higher intensities at 1450 cm -1  for CH 2  bending of proteins and lipids, while lower at 875 cm -1  for hydroxyproline of collagen, compared to normal and non- Hp- associated chronic gastritis tissues. PCA-LDA classifications of Raman spectra from the three groups gave the sensitivity and specificity for differentiation between normal and non- Hp- associated chronic gastritis tissue,  Hp- associated chronic gastritis and non- Hp- associated chronic gastritis tissue, and  Hp- associated chronic gastritis tissues from normal gastric tissue of 72.7% and 81.2%, 85.7% and 93.8%, and 71.4% and 100.0%, respectively. NIR Raman spectroscopy in conjunction with multivariate technique is capable of differentiating  Hp- associated chronic gastritis from normal and non- Hp- associated chronic gastritis gastric mucosal tissues. The technology may potentially be useful for rapid, in vivo diagnosis of  Hp  infections in the human stomach.
Models to Predict Hepatitis B Virus Infection Among Patients With Cancer Undergoing Systemic Anticancer Therapy: A Prospective Cohort Study
Authors: Jessica P. Hwang, Anna S. Lok, Michael J. Fisch, Scott B. Cantor, Andrea Barbo, Heather Y. Lin, Jessica T. Foreman, John M. Vierling, Harrys A. Torres, Bruno P. Granwehr, Ethan Miller, Cathy Eng, George R. Simon, Sairah Ahmed, Alessandra Ferrajoli, Jorge Romaguera, Maria E. Suarez-Almazor
Journal: Journal of Clinical Oncology (2018)

Most patients with cancer are not screened for hepatitis B virus (HBV) infection before undergoing anticancer therapy, and optimal screening strategies are unknown. We sought to develop selective HBV screening strategies for patients who require systemic anticancer therapy.
Mesh versus suture repair of umbilical hernia in adults: a randomised, double-blind, controlled, multicentre trial
Authors: Ruth Kaufmann, Jens A Halm, Hasan H Eker, Pieter J Klitsie, Jeroen Nieuwenhuizen, Dick van Geldere, Maarten P Simons, Erwin van der Harst, Martijne van 't Riet, Bronno van der Holt, Gert Jan Kleinrensink, Johannes Jeekel, Johan F Lange
Journal: The Lancet (2018)