Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved survival in patients obtaining remission of nephrotic range albuminuria in diabetic nephropathy.

BACKGROUND The level of albuminuria is related to progression of diabetic nephropathy, and patients with nephrotic range albuminuria have advanced renal structural changes and the fastest decline in glomerular filtration rate (GFR). We have previously demonstrated that the rate of decline in GFR is diminished in patients obtaining remission of nephrotic range albuminuria, but information is scarce concerning the impact of remission of nephrotic range albuminuria on the long-term prognosis. METHODS At the Steno Diabetes Center, we performed a prospective cohort study of all type 1 diabetic patients with nephrotic range albuminuria (N= 125), who had annual measurement of GFR [(51)chromium-ethylenediaminetetraacetic acid ((51)Cr-EDTA) plasma clearance] carried out for at least 3 years. Patients were followed from onset of nephrotic range albuminuria until death or the end of year 2003. Nephrotic range albuminuria was defined as persistent albuminuria above 2.5 g/24 hours, remission of nephrotic range albuminuria was defined as sustained albuminuria <0.6 g/24 hours for at least 1 year. RESULTS Nephrotic range albuminuria occurred in 90 men and 35 women, age [mean (SD)] 34 (8) years, duration of diabetes 22 (8) years, and follow-up time from onset of nephrotic range albuminuria [median (range)] 12.4 (3.0 to 24.9) years. Remission was induced in 32 patients (26%), 25 predominantly treated with angiotensin-converting enzyme (ACE) inhibitors, seven with non-ACE inhibitors. The remission lasted 5.5 (1.0 to 22.4) years. At the end of follow-up, 25% in the remission group and 74% in the no remission group had reached the composite end point of end-stage renal disease (ESRD) (dialysis, transplantation) or death. A Cox proportional hazard regression analysis with gender and age as fixed covariates and remission as time-dependent covariate revealed that obtaining remission was associated with a lower risk of dialysis, transplantation, or death, relative risk (95% CI) 0.28 (0.13 to 0.59), P= 0.001, whereas older age at onset of nephrotic range albuminuria (per 10-year increase) was associated with higher risk of reaching the end point, 1.42 (1.08 to 1.87), P= 0.01. CONCLUSION Our prospective study suggests that remission of nephrotic range albuminuria in type 1 diabetic patients, induced by aggressive antihypertensive treatment with and without ACE inhibitors, is associated with a slower progression in diabetic nephropathy and a substantially improved survival.
Medication Errors Related to Computerized Order Entry for Children

OBJECTIVE. The objective of this study was to determine the frequency and types of pediatric medication errors attributable to design features of a computerized order entry system. METHODS. A total of 352 randomly selected, inpatient, pediatric admissions were reviewed retrospectively for identification of medication errors, 3 to 12 months after implementation of computerized order entry. Errors were identified and classified by using an established, comprehensive, active surveillance method. Errors attributable to the computer system were classified according to type. RESULTS. Among 6916 medication orders in 1930 patient-days, there were 104 pediatric medication errors, of which 71 were serious (37 serious medication errors per 1000 patient-days). Of all pediatric medication errors detected, 19% (7 serious and 13 with little potential for harm) were computer related. The rate of computer-related pediatric errors was 10 errors per 1000 patient-days, and the rate of serious computer-related pediatric errors was 3.6 errors per 1000 patient-days. The following 4 types of computer-related errors were identified: duplicate medication orders (same medication ordered twice in different concentrations of syrup, to work around computer constraints; 2 errors), drop-down menu selection errors (wrong selection from a drop-down box; 9 errors), keypad entry error (5 typed instead of 50; 1 error), and order set errors (orders selected from a pediatric order set that were not appropriate for the patient; 8 errors). In addition, 4 preventable adverse drug events in drug ordering occurred that were not considered computer-related but were not prevented by the computerized physician order entry system. CONCLUSIONS. Serious pediatric computer-related errors are uncommon (3.6 errors per 1000 patient-days), but computer systems can introduce some new pediatric medication errors that are not typically seen in a paper ordering system.
Performance Trade-Offs in Wild White-Footed Mice (Peromyscus Leucopus)

Various aspects of performance (e.g., sprint speed, grip strength) are thought to be important determinants of the success of animals in natural activities such as foraging, mating, and escaping from predators. However, it is generally known that morphological properties enhancing one type of performance (e.g., speed) can lead to a reduction in another (e.g., strength). Such performance trade-offs have been quantified at the inter-specific level, but evidence at the inter-individual level remains equivocal. To test for the presence of a performance trade-off, I initiated a study on wild white-footed mice ( Peromyscus leucopus ). In summer 2016, I captured a total of 186 individuals, 87 of which were repeatedly phenotyped for grip strength and sprint speed. A significant positive relationship was found between body mass and grip strength (but not for sprint speed). Individual differences in performance were repeatable through time for both grip strength and sprint speed. Using a bivariate mixed model, I detected a significant negative correlation between grip strength and sprint speed at the among individual level. By contrast, the within -individual correlation between grip strength and sprint speed tended to be positive, suggesting that some unquantified aspects of the mouse phenotype (e.g., body condition, age) may have a positive effect on both performance traits. Given the relatively low repeatability of grip strength and sprint speed, a failure to properly partition the correlation at the among- and within-individual level generates a counter-intuitive, positive correlation. This study is one the first to detect a performance trade-off at the among-individual level in a wild animal population.
Debt Retirement at IPO and Firm Growth

Abstract This paper examines whether debt retirement at the time of initial public offering (IPO) can stimulate firm growth. Our findings demonstrate that highly leveraged firms tend to use the proceeds of IPOs to repay more existing debt. Then, increased debt capacity and reduced interest burden enable firms to expand their businesses. Firms that retire more debt also present better performance in the long-term. These results indicate that firms that have previously been labeled low-growth firms can achieve high growth in the post-IPO period by conducting debt retirement.
Cost-effectiveness analysis of using antiretroviral drug resistance testing

Human immunodeficiency virus (HIV)-infected patients failing highly active antiretroviral therapy (HAART) have a substantially lower chance of clinical success than naive patients given their first antiretroviral therapy. This suggests that HAART failure is a determinant for an increase in the cost of treatment. A review of the literature regarding cost and impact of antiretroviral drug-resistance testing was performed. Examination of existing methods to execute a cost-effectiveness analysis on the use of these tests in clinical practice was also undertaken. The cost of treatment failure in HIV-infected patients has been quantified in several retrospective studies. The cost of care for patients with virological suppression was significantly lower than those with a single virological failure. Moreover, the latter group had lower costs than patients with multiple failures. The result of the cost-effective analysis based on a specific model application using genotypic resistance assays to guide the choice of a subsequent therapy in HIV disease, is cost-effective under a wide range of assumptions regarding effectiveness and costs. The available studies on the cost-effective evaluation of genotypic tests are limited, and the respective studies supply important indications on cost-effective evaluations. Despite its demonstrated benefits, antiretroviral drug resistance testing presents features and limitations that also restrict the cost-effectiveness analysis.
Effect of initial biopsy procedure on prognosis in Stage 1 invasive cutaneous malignant melanoma: Review of 1086 patients

After treatment for primary clinical Stage 1 invasive cutaneous malignant melanoma, 1086 patients were followed for a minimum of 5 years from initial operation. Patient data were retrieved from the unit's melanoma registry; 96 (8.8 per cent) were treated initially by incisional biopsy, 292 (26.9 per cent) by narrow margin excision biopsy and 698 (64.3 per cent) by wide margin excision. Logistic regression analysis was performed to assess the statistical significance of the association between the various factors. The method of initial biopsy was related to maximal tumour thickness, age, and sex. Incisional biopsy rendered 38 out of 96 (40 per cent) lesions not fully assessable on current histopathological criteria, significantly higher than for the other biopsy techniques (P<0.0001). Incisional biopsy did not adversely affect prognosis in terms of local recurrence and mortality. Prognosis was related to tumour thickness, age and sex of the patient, and not to biopsy technique. We recommend that all suspicious lesions should be submitted to excisional rather than incisional biopsy to avoid compromising the histological assessment, given the importance of maximal tumour thickness in determining treatment and prognosis.
Outcome of idiopathic thrombocytopenic purpura in pregnancy in King Chulalongkorn Memorial Hospital.

OBJECTIVE To study the maternal and fetal outcome of idiopathic thrombocytopenic purpura (ITP) in pregnancy. MATERIAL AND METHOD The medical records of women who were diagnosed to be idiopathic thrombocytopenic purpura during and before pregnancy from January 1995 to December 2004 were reviewed. RESULTS There were 33pregnancies from 29 ITP women as four women had two pregnancies each and one was twins. Nine cases (27.3%) were active ITP, five cases (15.2%) were relapsing ITP and eight cases (24.2%) were inactive ITP. Eleven cases (33.3%) had severe thrombocytopenia during delivery and five neonates (23.8%) had severe thrombocytopenia. There was no statistical correlation between maternal and neonatal platelet concentration (r = -0.0601). None of the mothers and fetuses had serious hemorrhagic complication such as intracranial hemorrhage. CONCLUSION There were low hemorrhagic risks in both mothers and infants because of the constant monitoring of multidisciplinary groups of experienced physicians, including obstetricians, hematologists, anesthesiologists and neonatologist.
Matrix metalloproteinase‐1 is associated with poor prognosis in oesophageal cancer

The matrix metalloproteinases (MMPs) are a family of closely related proteolytic enzymes which are involved in the degradation of different components of the extracellular matrix. There is increasing evidence to indicate that individual MMPs have an important role in tumour invasion and tumour spread. Monoclonal antibodies specific for MMP‐1, MMP‐2, or MMP‐9 have been produced, using as immunogens peptides selected from the amino acid sequences of individual MMPs. The presence of MMP‐1, MMP‐2, and MMP‐9 in oesophageal cancer was investigated by immunohistochemistry on formalin‐fixed, wax‐embedded sections of oesophageal cancers. The relationship of individual MMPs to prognosis and survival was determined. MMP‐1 was present in 24 per cent of oesophageal cancers, while MMP‐2 and MMP‐9 were present in 78 and 70 per cent of tumours, respectively. The presence of MMP‐1 was associated with a particularly poor prognosis (log rank test 8·46, P<0·004) and was an independent prognostic factor (P=0·02). The identification of individual MMPs in oesophageal cancer provides a rational basis for use in the treatment of oesophageal cancer of MMP inhibitors which are currently undergoing clinical trial. © 1998 John Wiley & Sons, Ltd.
Progress on outbound tourism expenditure research: A review

ABSTRACT This study aims to identify how the paradigm of outbound tourism expenditure (OTE) research transforms from economic to social concern. It also explicates the evolution of OTE from an advocacy platform to a sustainability platform. This study adopts a hybrid of narrative and systematic reviews to study OTE as a complex social phenomenon. This hybrid review is complemented by a thematic review and semantic network analysis on gaps and future directions of relevant studies. The results reveal that the paradigm of OTE research is directed from economic toward social thinking. This study proposes an application of socially related antecedent configurations, social theories, pragmatic methods, and various scales of study contexts as promising solutions to address the complexity and heterogeneity of OTE. The study concludes that the conceptual structure of OTE is premised on a sustainability platform, which is influenced by socio-cultural, environmental, economic, and political issues. This study provides a road map that enlightens the current state of OTE, prevailing topics, and pathways for further research.
Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans

In Caenorhabditis elegans, longevity is increased by a partial loss‐of‐function mutation in the mitochondrial complex III subunit gene isp‐1. Longevity is also increased by RNAi against the expression of a variety of mitochondrial respiratory chain genes, including isp‐1, but it is unknown whether the isp‐1(qm150) mutation and the RNAi treatments trigger the same underlying mechanisms of longevity. We have identified nuo‐6(qm200), a mutation in a conserved subunit of mitochondrial complex I (NUDFB4). The mutation reduces the function of complex I and, like isp‐1(qm150), results in low oxygen consumption, slow growth, slow behavior, and increased lifespan. We have compared the phenotypes of nuo‐6(qm200) to those of nuo‐6(RNAi) and found them to be distinct in crucial ways, including patterns of growth and fertility, behavioral rates, oxygen consumption, ATP levels, autophagy, and resistance to paraquat, as well as expression of superoxide dismutases, mitochondrial heat‐shock proteins, and other gene expression markers. RNAi treatments appear to generate a stress and autophagy response, while the genomic mutation alters electron transport and reactive oxygen species metabolism. For many phenotypes, we also compared isp‐1(qm150) to isp‐1(RNAi) and found the same pattern of differences. Most importantly, we found that, while the lifespan of nuo‐6, isp‐1 double mutants is not greater than that of the single mutants, the lifespan increase induced by nuo‐6(RNAi) is fully additive to that induced by isp‐1(qm150), and the increase induced by isp‐1(RNAi) is fully additive to that induced by nuo‐6(qm200). Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently.
Implementation and Operational Research: Convenient HIV Testing Service Models Are Attracting Previously Untested Gay and Bisexual Men: A Cross-sectional Study

Introduction:HIV testing is a cornerstone of the treatment as prevention approach. We assessed which HIV testing service delivery models were more likely to attract untested or infrequent tested gay, bisexual and other men who have sex with men (GBM). Methods:We compared demographics, risk behavior, and HIV testing history among new GBM clients attending 3 different HIV testing service models (fast-track Xpress clinic, fixed-site community-based service, and time-limited community-based shopfront) between August 2013 and May 2014. We used bivariate and multivariate regression to assess factors (including service model) associated with being untested or infrequent testers (not tested within the past 12 months). Results:Overall, 1704 new GBM attended the services; 19% were untested and 41% were infrequent testers. Across the services, there were significant differences in demographics, risk behavior, and HIV testing history. The overall HIV seropositivity was 1.2% (95% confidence interval: 0.8% to 1.9%) and sexually transmitted infection positivity was 12.4% (95% confidence interval: 11.6 to 17.2) with no significant differences across services. Factors independently associated with being untested were attendance at the 2 community sites, younger age, being born in Asia, living in North Sydney, being bisexual and reporting fewer male sexual partners. Factors independently associated with infrequent testers were attending the fast track Xpress clinic, being older, being born in Asia, and reporting fewer male partners. Conclusions:The findings suggest both community and fast track testing service models are important to increase HIV testing among GBM with a similar yield of HIV diagnoses at the 3 services. The community models reached more untested men and the fast track model more infrequent testers.
Salvage therapy with pegylated liposomal doxorubicin, bortezomib, cyclophosphamide, and dexamethasone in relapsed/refractory myeloma patients

In vitro studies have shown synergistic anti‐myeloma effects of bortezomib combined with alkylating agents or anthracycline. We tested safety and efficacy of the combination of bortezomib, doxorubicin cyclophosphamide, and dexamethasone (ABCD) in the treatment of relapsed/refractory myeloma.
Destabilization of the Retinoblastoma Tumor Suppressor by Human Papillomavirus Type 16 E7 Is Not Sufficient To Overcome Cell Cycle Arrest in Human Keratinocytes

ABSTRACT The E7 oncoprotein of human papillomavirus type 16 promotes cell proliferation in the presence of antiproliferative signals. Mutagenesis of E7 has revealed that this activity requires three regions, conserved regions 1 and 2 and a C-terminal zinc finger. Binding to the retinoblastoma tumor repressor (Rb) through an LxCxE motif in conserved region 2 is necessary, but not sufficient, for E7 to induce proliferation. We tested the hypothesis that binding to Rb is not sufficient because conserved region 1 and/or the C terminus are required for E7 to functionally inactivate Rb and thus induce proliferation. One mechanism proposed for how E7 inactivates Rb is by blocking Rb-E2F binding. Either conserved region 1 or the C terminus was necessary, in combination with the LxCxE motif, for E7 to block Rb-E2F binding in vitro. While all full-length E7 proteins with mutations outside of the LxCxE motif inhibited Rb-E2F binding, some failed to abrogate cell cycle arrest, demonstrating that blocking Rb-E2F binding is not sufficient for abrogating antiproliferative signals. Another mechanism proposed for how E7 inactivates Rb is by promoting the destabilization of Rb protein. Mutations in conserved region 1 or the LxCxE motif prevented E7 from reducing the half-life of Rb. Though no specific C-terminal residues of E7 were essential for destabilizing Rb, a novel class of mutations that uncouple the destabilization of Rb from the deregulation of keratinocyte proliferation was discovered. Destabilization of Rb correlated with the abrogation of Rb-induced quiescence but was not sufficient for overriding DNA damage-induced cell cycle arrest or for increasing keratinocyte life span. Finally, the same regions of E7 required for destabilizing Rb were required for reducing p107 and p130 levels. Together, these results suggest that inactivation of all three Rb family members is not sufficient to deregulate keratinocyte cell cycle control.
Where diseases and networks collide: lessons to be learnt from a study of the 2001 foot-and-mouth disease epidemic

This paper uses a graph-theoretical approach to investigate the properties of the observed network of disease transmission in the 2001 foot-and-mouth epidemic in the United Kingdom. This analysis revealed both global and local heterogeneity in the contact pattern between the infected premises in the first 3 weeks of the disease. In particular, the global heterogeneity contributed to the failure of the culling strategy imposed by the UK government. However, a more effective strategy targeting selective deletion of key premises in the network was not available once the epidemic had begun. We recommend that post-hoc analyses of this sort should become part of preventative and proactive policy rather than part of a reaction to an ongoing crisis.
Normal and High-Normal Blood Pressures, but Not Body Mass Index, Are Risk Factors for the Subsequent Occurrence of Both Preeclampsia and Gestational Hypertension: A Retrospective Cohort Study

Blood pressure (BP) levels and body mass index (BMI) are known as risk factors for preeclampsia and gestational hypertension. However, there have been few investigations regarding the effects of BP and BMI levels on preeclampsia and gestational hypertension in the same cohort. In the present study, we conducted a retrospective cohort study using multiple logistic regression analysis. The cohort included 1,518 patients without nephritis. The unadjusted odds ratios (ORs) of preeclampsia and gestational hypertension were increased in pregnant women with normal BP (120–129 mmHg systolic or 80–84 mmHg diastolic), high-normal BP and hypertension in the second trimester compared to those with optimal BP. The unadjusted ORs of preeclampsia and gestational hypertension were also increased in obese women in the pre-pregnancy period compared to women with normal range BMI. When adjustment was made for both the BP levels and pre-pregnancy BMI levels, the ORs (95% confidence intervals) of normal BP, high-normal BP, hypertension and obesity for the subsequent occurrence of preeclampsia were 5.1 (2.2–12), 8.3 (3.1–22), 16 (5.0–50) and 2.0 (0.67–5.9), and those for the subsequent occurrence of gestational hypertension were 7.0 (2.6–19), 7.4 (2.1–25), 22 (6.1–83) and 1.3 (0.33–4.8), respectively. For the subsequent occurrence of preeclampsia or gestational hypertension, normal BP, high-normal BP and hypertension in the second trimester may be independent risk factors. Obesity in the pre-pregnancy period, however, may not be an independent risk factor.