snu-aidas/HVMap-dataset huggingface dataset:
Time from finding abnormality on mass-screening to final diagnosis of lung cancer.

Mass-screening for lung cancer is rather a unique system in Japan. This study illustrates time from finding abnormality on mass-screening to final diagnosis of lung cancer. Among the 517 patients with lung cancer who were admitted to our hospital over a 10-year period up to December 2001, 83 (16.1%) were detected by mass-screening. We reviewed medical records of the 83 patients and determined the intervals from the mass-screening to the pathological diagnosis with clinical staging. Time from the mass-screening to the date of hospital visit was <2 months in 62 (74.7%) cases. Five (6.0%) patients visited hospital more than 6 months after the mass-screening. With respect to the interval, there was no statistical difference in gender (p=0.0680) and age (p=0.1532). Among 60 patients who were referred from outside, on average, patients visited our hospital 0.5 month after they first sought medical attention at nearby clinic, and at our hospital 0.5 month was required to make a pathological diagnosis of lung cancer with TNM staging. There was a statistical difference in survival between the patients who were diagnosed <4 months and the patients who were diagnosed >4 months from the screening (p=0.0487). The interval in most cases was acceptable. However, further improvements are still needed to minimize the delay and to maximize the benefits of early cancer detection.
Antibiotics and risk of subsequent first-time acute myocardial infarction.

CONTEXT Increasing evidence supports the hypothesis of a causal association between certain bacterial infections and increased risk of developing acute myocardial infarction. If such a causal association exists, subjects who used antibiotics active against the bacteria, regardless of indication, might be at lower risk of developing acute myocardial infarction than nonusers. OBJECTIVE To determine whether previous use of antibiotics decreases the risk of developing a first-time acute myocardial infarction. DESIGN Population-based case-control analysis. SETTING The United Kingdom-based General Practice Research Database comprising 350 general practices. PATIENTS A total of 3315 case patients aged 75 years or younger with a diagnosis of first-time acute myocardial infarction between 1992 and 1997 and 13139 controls without myocardial infarction matched to cases for age, sex, general practice attended, and calendar time. MAIN OUTCOME MEASURES Use of antibiotics among those who did or did not have a first-time acute myocardial infarction. RESULTS Cases were significantly less likely to have used tetracycline antibiotics (adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.55-0.90) or quinolones (adjusted OR, 0.45; 95% CI, 0.21-0.95). No effect was found for previous use of macrolides (primarily erythromycin), sulfonamides, penicillins, or cephalosporins. CONCLUSIONS The findings from this large case-control analysis provide further, albeit indirect, evidence for an association between bacterial infections with organisms susceptible to tetracycline or quinolone antibiotics and the risk of acute myocardial infarction. These results of preliminary nature should stimulate more research to further explore the role of infections in the etiology of acute myocardial infarction.
Competition between target sites of regulators shapes post-transcriptional gene regulation

Post-transcriptional gene regulation (PTGR) of mRNA turnover, localization and translation is mediated by microRNAs (miRNAs) and RNA-binding proteins (RBPs). These regulators exert their effects by binding to specific sequences within their target mRNAs. Increasing evidence suggests that competition for binding is a fundamental principle of PTGR. Not only can miRNAs be sequestered and neutralized by the targets with which they interact through a process termed 'sponging', but competition between binding sites on different RNAs may also lead to regulatory crosstalk between transcripts. Here, we quantitatively model competition effects under physiological conditions and review the role of endogenous sponges for PTGR in light of the key features that emerge.
Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association.

Stroke ranks as the third leading cause of death in the United States. It is now estimated that there are more than 700 000 incident strokes annually and 4.4 million stroke survivors.1 2 The economic burden of stroke was estimated by the American Heart Association to be $51 billion (direct and indirect costs) in 1999.3 Despite the advent of treatment of selected patients with acute ischemic stroke with tissue plasminogen activator and the promise of other experimental therapies, the best approach to reducing the burden of stroke remains prevention.4 5 High-risk or stroke-prone individuals can be identified and targeted for specific interventions.6 This is important because epidemiological data suggest a substantial leveling off of prior declines in stroke-related mortality and a possible increase in stroke incidence.7 8   The Stroke Council of the American Heart Association formed an ad hoc writing group to provide a clear and concise overview of the evidence regarding various established and potential stroke risk factors. The writing group was chosen based on expertise in specific subject areas, and it used literature review, reference to previously published guidelines, and expert opinion to summarize existing evidence and formulate recommendations (Table 1⇓). View this table:   Table 1. Levels of Evidence and Grading of Recommendations    As given in Tables 2 through 4⇓⇓⇓, risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented, less well documented).5 The tables give the estimated prevalence, population attributable risk, relative risk, and risk reduction with treatment for each factor when known. Population attributable risk reflects the proportion of ischemic strokes in the population that can be attributed to a particular risk factor and is given by the formula 100×[prevalence(relative risk−1)/prevalence(relative risk−1)+1]). …
Global prevalence of anxiety disorders: a systematic review and meta-regression.

BACKGROUND The literature describing the global prevalence of anxiety disorders is highly variable. A systematic review and meta-regression were undertaken to estimate the prevalence of anxiety disorders and to identify factors that may influence these estimates. The findings will inform the new Global Burden of Disease study. Method A systematic review identified prevalence studies of anxiety disorders published between 1980 and 2009. Electronic databases, reference lists, review articles and monographs were searched and experts then contacted to identify missing studies. Substantive and methodological factors associated with inter-study variability were identified through meta-regression analyses and the global prevalence of anxiety disorders was calculated adjusting for study methodology. RESULTS The prevalence of anxiety disorders was obtained from 87 studies across 44 countries. Estimates of current prevalence ranged between 0.9% and 28.3% and past-year prevalence between 2.4% and 29.8%. Substantive factors including gender, age, culture, conflict and economic status, and urbanicity accounted for the greatest proportion of variability. Methodological factors in the final multivariate model (prevalence period, number of disorders and diagnostic instrument) explained an additional 13% of variance between studies. The global current prevalence of anxiety disorders adjusted for methodological differences was 7.3% (4.8-10.9%) and ranged from 5.3% (3.5-8.1%) in African cultures to 10.4% (7.0-15.5%) in Euro/Anglo cultures. CONCLUSIONS Anxiety disorders are common and the substantive and methodological factors identified here explain much of the variability in prevalence estimates. Specific attention should be paid to cultural differences in responses to survey instruments for anxiety disorders.
Prevention of malaria in long-term travelers.

CONTEXT Long-term travelers, defined here as those traveling for periods of 6 months or longer, face particular challenges regarding malaria prevention. Current guidelines for malaria prevention primarily address prevention of Plasmodium falciparum infections in short-term travelers. OBJECTIVES To examine the risk of malaria in long-term travelers, recent developments in personal protective measures, and the safety and tolerability of malaria chemoprophylaxis during long-term use and to consider prevention strategies including continuous chemoprophylaxis, stand-by emergency self-treatment, seasonal prophylaxis, and strategies to prevent primary infection and relapses from P vivax malaria. EVIDENCE ACQUISITION Comprehensive search of scientific publications including MEDLINE via both OVID and PubMED for relevant studies and articles with a cutoff date of July 2006, using the search terms long-term travel and malaria prevention, long-term malaria chemoprophylaxis, and insect repellent and malaria. Additional references were obtained from searching the bibliographies of the selected articles, from dissertations, and from the proceedings of relevant conferences on travel medicine. There were no language restrictions. EVIDENCE SYNTHESIS Long-term travelers have a higher risk of malaria than short-term travelers. Long-term travelers underuse personal protective measures and adhere poorly to continuous chemoprophylaxis regimens. A number of strategies are used during long-term stays: discontinuation of chemoprophylaxis after the initial period, sequential regimens with different medications for chemoprophylaxis, stand-by emergency self-treatment, and seasonal chemoprophylaxis targeting high-incidence periods or locations. All strategies have advantages and drawbacks. Counterfeit drugs sold in countries endemic for malaria pose serious concern for long-term travelers who purchase their medications overseas. Vivax malaria causes significant illness in travelers, but relapses of vivax malaria are not prevented with the current first-line chemoprophylaxis regimens. Consensus guidelines are needed for prevention of malaria in long-term travelers. CONCLUSIONS Prevention of malaria in long-term travelers is a complex issue and requires expert advice from travel medicine specialists. Recommendations for prevention of malaria in long-term travelers must be individualized.
Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo

Cigarette smoking promotes body weight reduction in humans while paradoxically also promoting insulin resistance (IR) and hyperinsulinemia. However, the mechanisms behind these effects are unclear. Here we show that nicotine, a major constituent of cigarette smoke, selectively activates AMP-activated protein kinase α2 (AMPKα2) in adipocytes, which in turn phosphorylates MAP kinase phosphatase-1 (MKP1) at serine 334, initiating its proteasome-dependent degradation. The nicotine-dependent reduction of MKP1 induces the aberrant activation of both p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, leading to increased phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307. Phosphorylation of IRS1 leads to its degradation, protein kinase B inhibition, and the loss of insulin-mediated inhibition of lipolysis. Consequently, nicotine increases lipolysis, which results in body weight reduction, but this increase also elevates the levels of circulating free fatty acids and thus causes IR in insulin-sensitive tissues. These results establish AMPKα2 as an essential mediator of nicotine-induced whole-body IR in spite of reductions in adiposity.
Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.
Evidence for energy-dependent accumulation of paraquat into rat lung

THE herbicide paraquat (N,N′-dimethyl 4,4′-bipyridilium) can produce widespread oedema and fibrosis in the human lung after accidental ingestion1–3. In those cases where death occurs after several weeks, there are no apparent pulmonary changes during the first few days following ingestion. Animal experiments in a variety of species have shown the lung to be the major target organ4–6. After administration of paraquat to animals, the lung has a high initial concentration and retains paraquat7–9. This retention appears to be related to the development of lung damage7 (L. L. Smith and M. S. Rose, unpublished work). The mechanism of retention of paraquat by the lung is at present not understood.
Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence.

OBJECTIVE To determine the incidence of surgically managed pelvic organ prolapse and urinary incontinence in a population-based cohort, and to describe their clinical characteristics. METHODS Our retrospective cohort study included all patients undergoing surgical treatment for prolapse and incontinence during 1995; all were members of Kaiser Permanente Northwest, which included 149,554 women age 20 or older. A standardized data-collection form was used to review all inpatient and outpatient charts of the 395 women identified. Variables examined included age, ethnicity, height, weight, vaginal parity, smoking history, medical history, and surgical history, including the preoperative evaluation, procedure performed, and details of all prior procedures. Analysis included calculation of age-specific and cumulative incidences and determination of the number of primary operations compared with repeat operations performed for prolapse or incontinence. RESULTS The age-specific incidence increased with advancing age. The lifetime risk of undergoing a single operation for prolapse or incontinence by age 80 was 11.1%. Most patients were older, postmenopausal, parous, and overweight. Nearly half were current or former smokers and one-fifth had chronic lung disease. Reoperation was common (29.2% of cases), and the time intervals between repeat procedures decreased with each successive repair. CONCLUSION Pelvic floor dysfunction is a major health issue for older women, as shown by the 11.1% lifetime risk of undergoing a single operation for pelvic organ prolapse and urinary incontinence, as well as the large proportion of reoperations. Our results warrant further epidemiologic research in order to determine the etiology, natural history, and long-term treatment outcomes of these conditions.
Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis.

OBJECTIVES Prevention of cognitive decline and dementia with blood pressure lowering treatments has shown inconsistent results. We compared the effects of different classes of antihypertensive drugs on the incidence of dementia, and on cognitive function. METHODS We conducted a systematic review and included 19 randomized trials (18 515 individuals) and 11 studies (831 674 individuals) analysing the effects of antihypertensive treatment on cognition and on the incidence of dementia, respectively, in hypertensive patients without prior cerebrovascular disorders. Network meta-analysis was used for the comparison of antihypertensive classes. RESULTS Antihypertensive treatment, regardless of the drug class, had benefits on overall cognition [effect size 0.05, 95% confidence interval (CI) 0.02-0.07] and all cognitive functions except language. Antihypertensive treatment reduced the risk of all-cause dementia by 9%, with reference to the control group (hazard ratio 0.91, 95% CI 0.89-0.94), when randomized trials and observationnal studies were combined (n = 15). Result was not significant with randomized trials alone (n = 4). Angiotensin II receptor blockers (ARBs) had larger benefits than placebo on overall cognition (adjusted effect size 0.60 ± 0.18, P = 0.02). ARBs were more effective than β-blockers (0.67 ± 0.18, P = 0.01), diuretics (0.54 ± 0.19, P = 0.04) and angiotensin-converting enzyme inhibitors (0.47 ± 0.17, P = 0.04) in rank. The mean change in blood pressure did not differ significantly between the different antihypertensive drug classes. CONCLUSION Our results support the notion that antihypertensive treatment has beneficial effects on cognitive decline and prevention of dementia, and indicate that these effects may differ between drug classes with ARBs possibly being the most effective.
Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to regulate insulin production and secretion

Endoplasmic reticulum (ER) stress causes pancreatic β-cell dysfunction and contributes to β-cell loss and the progression of type 2 diabetes. Wolfram syndrome 1 (WFS1) has been shown to be an important regulator of the ER stress signalling pathway; however, its role in β-cell function remains unclear. Here we provide evidence that WFS1 is essential for glucose- and glucagon-like peptide 1 (GLP-1)-stimulated cyclic AMP production and regulation of insulin biosynthesis and secretion. Stimulation with glucose causes WFS1 translocation from the ER to the plasma membrane, where it forms a complex with adenylyl cyclase 8 (AC8), an essential cAMP-generating enzyme in the β-cell that integrates glucose and GLP-1 signalling. ER stress and mutant WFS1 inhibit complex formation and activation of AC8, reducing cAMP synthesis and insulin secretion. These findings reveal that an ER-stress-related protein has a distinct role outside the ER regulating both insulin biosynthesis and secretion. The reduction of WFS1 protein on the plasma membrane during ER stress is a contributing factor for β-cell dysfunction and progression of type 2 diabetes.
Two Rice GRAS Family Genes Responsive to N-Acetylchitooligosaccharide Elicitor are Induced by Phytoactive Gibberellins: Evidence for Cross-Talk Between Elicitor and Gibberellin Signaling in Rice Cells

In this study, we present data showing that two members of the GRAS family of genes from rice, CIGR1 and CIGR2(chitin-inducible gibberellin-responsive), inducible by the potent elicitor N-acetylchitooligosaccharide (GN), are rapidly induced by exogenous gibberellins. The pattern of mRNA accumulation was dependent on the dose and biological activity of the gibberellins, suggesting that the induction of the genes by gibberellin is mediated by a biological receptor capable of specific recognition and signal transduction upon perception of the phytoactive compounds. Further pharmacological analysis revealed that the CIGR1 and CIGR2 mRNA accumulation by treatment with gibberellin is dependent upon protein phosphorylation/dephosphorylation events. In rice calli derived from slender rice 1, a constitutive gibberellin-responsive mutant, or d1, a mutant deficient in the α-subunit of the heterotrimeric G-protein, CIGR1 and CIGR2 were induced by a GN elicitor, yet not by gibberellin. Neither gibberellin nor GN showed related activities in defense or development, respectively. These results strongly suggested that the signal transduction cascade from gibberellin is independent of that from GN, and further implied that CIGR1 and CIGR2 have dual, distinct roles in defense and development.
Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component.

BACKGROUND In systemic amyloidosis the distribution and progression of disease have been difficult to monitor, because they can be demonstrated only by biopsy. Serum amyloid P component (SAP) is a normal circulating plasma protein that is deposited on amyloid fibrils because of its specific binding affinity for them. We investigated whether labeled SAP could be used to locate amyloid deposits. METHODS Purified human SAP labeled with iodine-123 was given intravenously to 50 patients with biopsy-proved systemic amyloidosis--25 with the AL (primary) type and 25 with the AA (secondary) type--and to 26 control patients with disease and 10 healthy subjects. Whole-body images and regional views were obtained after 24 hours and read in a blinded fashion. RESULTS In the patients with amyloidosis the 123I-SAP was localized rapidly and specifically in amyloid deposits. The scintigraphic images obtained were characteristic and appeared to identify the extent of amyloid deposition in all 50 patients. There was no uptake of the 123I-SAP by the control patients and the healthy subjects. In all patients with AA amyloidosis the spleen was affected, whereas the scans showed uptake in the heart, skin, carpal region, and bone marrow only in patients with the AL type. Positive images were seen in six patients in whom biopsies had been negative or unsuccessful; in all six, amyloid was subsequently found on biopsy or at autopsy. Progressive amyloid deposition was observed in 9 of 11 patients studied serially. CONCLUSIONS Scintigraphy after the injection of 123I-SAP can be used for diagnosing, locating, and monitoring the extent of systemic amyloidosis.