snu-aidas/HVMap-dataset huggingface dataset:
Long term pharmacotherapy for obesity and overweight: updated meta-analysis.

OBJECTIVE To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status. DESIGN Updated meta-analysis of randomised trials. DATA SOURCES Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006. STUDIES REVIEWED Double blind randomised placebo controlled trials of approved anti-obesity drugs used in adults (age over 18) for one year or longer. RESULTS 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine improved [corrected] concentrations of high density lipoprotein cholesterol and triglycerides [corrected] Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders. CONCLUSIONS Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.
The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries

Centrosomes are microtubule-organizing centres of animal cells. They influence the morphology of the microtubule cytoskeleton, function as the base for the primary cilium and serve as a nexus for important signalling pathways. At the core of a typical centrosome are two cylindrical microtubule-based structures termed centrioles, which recruit a matrix of associated pericentriolar material. Cells begin the cell cycle with exactly one centrosome, and the duplication of centrioles is constrained such that it occurs only once per cell cycle and at a specific site in the cell. As a result of this duplication mechanism, the two centrioles differ in age and maturity, and thus have different functions; for example, the older of the two centrioles can initiate the formation of a ciliary axoneme. We discuss spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of centrioles and centrosomes.
Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche

Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and repopulate the tumour. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and reactivation. In this study, we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state that is switched 'on' by engagement with bone-lining cells or osteoblasts, and switched 'off' by osteoclasts remodelling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy that targets dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
IDEAL in meshes for prolapse, urinary incontinence, and hernia repair.

PURPOSE Mesh surgeries are counted among the most frequently applied surgical procedures. Despite global spread of mesh applying surgeries, there is no current systematic analysis of incidence and possible prevention of adverse events after mesh implantation. MATERIALS AND METHODS Based on the recommendations of IDEAL an in vitro test system for biocompatibility of surgical meshes has been generated (Innovation). Coating strategies for biocompatibility optimization have been developed (Development). The native and modified alloplastic materials have been tested in an animal model over 2 years (Exploration and Assessment and Long-term study). RESULTS In 3 meshes, implanted in sheep and explanted at 4 different time points (a, 3 months; b, 6 months; c, 12 months; and d, 24 months) over 24 months, thickness of inflammatory tissue (TVT a, 35 µm; b, 32 µm; c, 33 µm; d, 28 µm; UltraPro, a, 25 µm; b, 24 µm; c, 21 µm; d, 22 µm; PVDF a, 20 µm; b, 21 µm; c, 14 µm; d, 15µm), connective tissue (TVT a, 37 µm; b, 36 µm; c, 43 µm; d, 41 µm; UltraPro a, 33 µm; b, 32 µm; c, 40 µm; d, 38 µm; PVDF a, 25 µm; b, 22 µm; c, 22 µm; d, 24 µm), and macrophage infiltration (TVT a, 36%; b, 33%; c, 23%; d, 20%; UltraPro a, 34%; b, 28%; c, 25%; d, 22%; PVDF a, 24%; b, 18%; c, 18%; d, 16%) revealed comparable ranking characteristics at every time point after explantation. The in vivo performance of these meshes in a sheep model was predictable with a previously developed in vitro test system. Coating of meshes with autologous plasma prior to implantation seems to have a positive effect on the meshes biocompatibility. CONCLUSION We have applied IDEAL criteria on a new innovation for surgical meshes. The results permit the generation of a ranking of currently available meshes with potential to optimize future meshes.
Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues.

In semisyngeneic heterotopic bone marrow transplants the donor or recipient origin of cells of osteogenic and hematopoietic tissues was identified by chromosome markers (T6) and by reverse transplantation into the initial donor line. In syngeneic and semisyngeneic grafts of bone marrow under the renal capsule bone and bone marrow are formed. In allogeneic grafts only bone is formed; this bone is subsequently resorbed. In 14-month semisyngeneic transplants the bone marrow consists of recipient cells. This is true for both the proliferating pool and the stem cells of hematopoietic tissue. At the same time, osteogenic precursor cells and bone tissue in these transplants are of donor origin. A discussion is presented of the interrelationship between determinated osteogenic precursor cells (preosteoblasts) and hematopoietic stem cells (or their descendants) in which osteogenesis is inducible.
Progression of preclinical diastolic dysfunction to the development of symptoms.

BACKGROUND Preclinical diastolic dysfunction (PDD) has been defined as subjects with normal systolic function, diastolic dysfunction but no symptoms of heart failure (HF). The clinical phenotype and natural history of the syndrome remains poorly defined. This study's objective was to determine the clinical phenotype and progression to HF in a group of patients with normal systolic function and moderate or severe diastolic dysfunction as determinate by Doppler criteria without any clinical diagnosis of HF according to the Framingham criteria or any symptoms of HF, specifically dyspnoea, oedema or fatigue at the time of echocardiography. METHODS The authors used resources of the Mayo Clinic echocardiography database to consecutively select among patients who had an echocardiogram in 2005, a cohort with moderate or severe diastolic dysfunction by Doppler criteria and EF >or=50%. Patients could not have a diagnosis of HF, or any HF symptoms-specifically dyspnoea, oedema or fatigue-at the time of echocardiography; nor grade 3 or greater valvular dysfunction (except tricuspid valve). A total of 82 patients had their medical chart reviewed. Primary endpoint was the time to the development of (1) HF according to the Framingham criteria or (2) any symptoms of dyspnoea, oedema or fatigue. RESULTS The mean age of the cohort of PDD subjects was 69+/-10 years with a female (67%) preponderance. Presence of hypertension was 76%, coronary artery disease was 29%, paroxysmal atrial fibrillation was 26%, estimated creatinine clearance <60 ml/min was 51%. The 2-year cumulative probability of development of HF according to the Framingham criteria was 1.9%; however, the 2-year cumulative probability of development of any symptoms was 31.1%. The 2-year cumulative probability for cardiac hospitalisation was 21.2%. Peripheral vascular disease and hypertension were independently associated with increased likelihood for the development of symptoms. CONCLUSION The study demonstrates that hypertension, hyperlipidaemia, CAD and renal dysfunction are prevalent in patients with PDD. More importantly, although the progression to the development of clinical HF over 2 years was low, there was a moderate degree of progression to development of symptoms and cardiac hospitalisations over 2 years. Based on the finding that only PVD and hypertension were independently associated with the progression to the development of symptoms in subject with PDD, the authors speculate that ventricular-arterial interaction may be important to the progression of diastolic dysfunction to the development of symptoms.
Aspirin in the chemoprevention of colorectal neoplasia: an overview.

Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50% or more reduction in the risk of CRC commencing five years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation.
Brief, four-session group CBT reduces binge eating behaviors among bariatric surgery candidates.

BACKGROUND The objective of this study was to evaluate the effectiveness of a brief, 4-session cognitive behavioral, group psychotherapy for binge eating among bariatric surgery candidates at an academic medical center. Binge eating behaviors have been linked to poorer outcomes among bariatric surgery patients, and binge eating disorder have be considered a contraindication in surgery programs, some of which have mandated preoperative binge eating treatment. However, no previous studies have examined whether a preoperative binge eating intervention could successfully reduce binge eating behaviors among severely obese bariatric surgery candidates. METHODS A total of 243 bariatric surgery candidates completed a brief cognitive behavioral group treatment for binge eating behaviors and were administered the Binge Eating Scale and reported the number of weekly binge eating episodes at the initial psychological evaluation and again after the group sessions. The study used a pre-post intervention design. RESULTS The results suggested significant reductions in both binge eating behaviors and cognitions and binge eating episodes after the group intervention. The intervention's effectiveness did not differ according to gender or ethnicity (black versus white). CONCLUSION A brief cognitive behavioral intervention can reduce binge eating behaviors among bariatric surgery candidates. Given the potential influence of binge eating on outcomes, bariatric surgery programs could benefit by treating binge eating before surgery.
Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis

OBJECTIVE To systematically review the evidence that smoking cessation after diagnosis of a primary lung tumour affects prognosis. DESIGN Systematic review with meta-analysis. DATA SOURCES CINAHL (from 1981), Embase (from 1980), Medline (from 1966), Web of Science (from 1966), CENTRAL (from 1977) to December 2008, and reference lists of included studies. STUDY SELECTION Randomised controlled trials or observational longitudinal studies that measured the effect of quitting smoking after diagnosis of lung cancer on prognostic outcomes, regardless of stage at presentation or tumour histology, were included. DATA EXTRACTION Two researchers independently identified studies for inclusion and extracted data. Estimates were combined by using a random effects model, and the I(2) statistic was used to examine heterogeneity. Life tables were used to model five year survival for early stage non-small cell lung cancer and limited stage small cell lung cancer, using death rates for continuing smokers and quitters obtained from this review. RESULTS In 9/10 included studies, most patients studied were diagnosed as having an early stage lung tumour. Continued smoking was associated with a significantly increased risk of all cause mortality (hazard ratio 2.94, 95% confidence interval 1.15 to 7.54) and recurrence (1.86, 1.01 to 3.41) in early stage non-small cell lung cancer and of all cause mortality (1.86, 1.33 to 2.59), development of a second primary tumour (4.31, 1.09 to 16.98), and recurrence (1.26, 1.06 to 1.50) in limited stage small cell lung cancer. No study contained data on the effect of quitting smoking on cancer specific mortality or on development of a second primary tumour in non-small cell lung cancer. Life table modelling on the basis of these data estimated 33% five year survival in 65 year old patients with early stage non-small cell lung cancer who continued to smoke compared with 70% in those who quit smoking. In limited stage small cell lung cancer, an estimated 29% of continuing smokers would survive for five years compared with 63% of quitters on the basis of the data from this review. CONCLUSIONS This review provides preliminary evidence that smoking cessation after diagnosis of early stage lung cancer improves prognostic outcomes. From life table modelling, the estimated number of deaths prevented is larger than would be expected from reduction of cardiorespiratory deaths after smoking cessation, so most of the mortality gain is likely to be due to reduced cancer progression. These findings indicate that offering smoking cessation treatment to patients presenting with early stage lung cancer may be beneficial.
Sex differences in mortality following acute coronary syndromes.

CONTEXT Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS). OBJECTIVES To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates. DESIGN, SETTING, AND PARTICIPANTS A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina. MAIN OUTCOME MEASURE Thirty-day mortality following ACS. RESULTS Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70). CONCLUSIONS Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease.
Identifying and Characterizing Interplay between Hepatitis B Virus X Protein and Smc5/6

Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).
Hepatitis C Virus (HCV) Vertical Transmission in 12-Month-Old Infants Born to HCV-Infected Women and Assessment of Maternal Risk Factors

Background. Hepatitis C virus (HCV) is an underappreciated cause of pediatric liver disease, most frequently acquired by vertical transmission (VT). Current guidelines that include the option of screening infants for HCV RNA at 1-2 months are based on data prior to current real-time polymerase chain reaction (PCR)-based testing. Previous studies have demonstrated VT rates of 4%-15% and an association with high maternal viral load. We evaluated HCV RNA in infants with HCV VT and assessed maternal risk factors in a prospective cohort in Cairo, Egypt. Methods. Pregnant women were screened for HCV from December 2012 to March 2014. For those with HCV viremia, their infants were tested at 12 months for HCV RNA using real-time PCR. Maternal risk factors assessed for HCV VT association included HCV RNA levels, mode of delivery, and maternal IL28B genotype. Results. Of 2514 women screened, a total of 54 women were viremic (2.1%) and delivered 56 infants. Of those, 51 infants of 49 women were tested at 12 months of age. Only 7 infants were viremic, with an HCV VT rate of 14.3% (7 of 49). Median HCV RNA in the infants was 2100 IU/mL. None of the maternal risk factors analyzed were associated with transmission. Conclusions. In Egypt where HCV is highly endemic, we observed an overall 12-month HCV VT rate of 14.3%. Further studies should focus on better identification of pregnant women more likely to vertically transmit HCV and earlier testing of infants to identify those likely to develop chronicity.
Long-term follow-up of cervical disease in women screened by cytology and HPV testing: results from the HART study

BACKGROUND Several studies have shown that testing for high-risk human papillomavirus (HPV) types results in an improved sensitivity for CIN2+, compared with cytology, although with a somewhat lower specificity. METHODS We obtained follow-up results, with at least one smear after participation in the HART study, which compared HPV testing (HC-II) with cytology as a primary screening modality. RESULTS With a median follow-up of 6 years, 42 additional cases of CIN2+ were identified; women who were HPV positive at baseline were more likely to develop CIN2+ than those who were HPV negative (hazard ratio (HR) 17.2; 95% confidence interval (CI) (9.3-31.6)) and the risk increased with increasing viral load. Compared with HPV-negative women (relative light unit (RLU) <1), the HR (95% CI) was 5.4 (1.6, 18.2) for 1-10 RLU and 25.5 (13.6, 47.9) for RLU > or = 10. Positive cytology (borderline or worse compared with negative) was also predictive of developing CIN2, although to a lesser extent (HR 8.7; 95% CI (4.5-17.1)). Only one case of CIN3 and three cases of CIN2 were found in women who showed a positive cytology result but were HPV negative at baseline. CONCLUSION After 5 years of follow-up, CIN2+ occurred in 0.23% of women who were HPV negative at baseline compared with 0.48% of women who showed a negative cytology result, indicating a much longer low-risk interval for CIN2+ after HPV testing.