Miracle-dz/UniFAR-FTUs huggingface dataset:
Long QT syndrome: beyond the causal mutation

Abstract Congenital long QT syndrome (LQTS) is caused by single autosomal‐dominant mutations in a gene encoding for a cardiac ion channel or an accessory ion channel subunit. These single mutations can cause life‐threatening arrhythmias and sudden death in heterozygous mutation carriers. This recognition has been the basis for world‐wide staggering numbers of subjects and families counselled for LQTS and treated based on finding (putative) disease‐causing mutations. However, prophylactic treatment of patients is greatly hampered by the growing awareness that simple carriership of a mutation often fails to predict clinical outcome: many carriers never develop clinically relevant disease while others are severely affected at a young age. It is still largely elusive what determines this large variability in disease severity, where even within one pedigree, an identical mutation can cause life‐threatening arrhythmias in some carriers while in other carriers no disease becomes clinically manifested. This suggests that additional factors modify the clinical manifestations of a particular disease‐causing mutation. In this article, potential demographic, environmental and genetic factors are reviewed, which, in conjunction with a mutation, may modify the phenotype in LQTS, and thereby determine, at least partially, the large variability in disease severity.
Submillimeter-wave atmospheric transmission at El Leoncito, Argentina Andes

We present the results of one year of daytime atmosphere transmission measurements obtained at 212 and 405 GHz by a 1.5 m solar radio telescope located at El Leoncito site, 2550 m altitude in Argentina Andes. We used three different methods: 1) absolute derivation from strong solar signal at different elevation angles; 2) direct derivation from observed known solar brightness times the antenna coupling factor; and 3) fitting the observed sky emission plots as a function of elevation angle, also known as "tipping. " Some differences were found for the transmission determined by the three methods, the most important is that methods 1) and 2) are restricted to smaller values of opacity. Method 1) is restricted to measurements at low elevation angles. Method 2) has the advantage to extend measurements to considerably higher values of attenuation. For the El Leoncito site the correlation of optical depth at 405 and 212 GHz was found (/spl tau//sub 405///spl tau//sub 212/)=4.43, smaller than model predictions (/spl ap/5.0). Measurements at both frequencies obtained for 319 days in one year indicate that 50% of time /spl tau//sub 212/<0.3 (or >74% zenithal transmission) and /spl tau//sub 405/<1.5 (or >22% transmission), with small seasonal dependence compared to other sites. The opacity related precipitable water vapor is smaller compared to model estimates, suggesting an upper atmosphere water vapor depression, characteristic to the region.
Contractures of the upper extremities in spinal muscular atrophy type II. Descriptive clinical study with retrospective data collection.

BACKGROUND The most significant orthopaedic problem for patients with the intermediate form of spinal muscular atrophy, SMA type II, is the appearance of contractures in addition to progressive scoliosis and pelvic obliquity with increasing loss of sitting stability. This study deals with restrictions of the passive range of motion and the development of contractures in the joints of the upper extremities in these patients. MATERIAL AND METHODS We followed up 143 patients, 74 female and 69 male, with SMA type II for an average of 5.3 years (± 4.0, 0.2 - 18.7). Their average age at the first examination was 8.4 years (± 6.6, 0.1 - 34.1) and at the last examination 12.3 years (± 6.5, 0.7 - 37.1). The passive range of joint motion was determined using a goniometer. According to Johnson et al. (1992), we calculated the relative contracture index (CI). RESULTS The loss of range of motion and the contractures of the joints of the upper extremities (shoulder, elbow and wrist) increased progressively with age. The most marked restriction of motion was in the elbow joint with severe flexion contractures in some cases. CONCLUSION The findings of this study give us more information about the development of contractures of the upper extremities and aim to help to improve the quality of orthopaedic care of patients with SMA type II.
The use of pornographic materials by adolescent male cancer patients when banking sperm in the UK: Legal and ethical dilemmas

Increased awareness of the importance of fertility concerns to teenage cancer survivors is leading to growing numbers of male teenagers being offered sperm banking at the time of diagnosis. This is now extending to males diagnosed with other conditions where gonadotoxic agents are used in treatment. The storage of sperm in these circumstances is a challenging aspect of health care, given the complex issues and timescale involved. UK law has been enacted to protect legal minors from the potentially harmful effects of exposure to pornographic materials, yet there is reason to suppose that their use in this context could have therapeutic benefit in aiding successful masturbation. This paper uses material gained through consultation with the eleven largest UK sperm banks and 94 male teenage cancer survivors, to discuss the associated legal and ethical dilemmas, including those around the role of parents/carers. Findings suggest that there is variable practice in sperm banks, that almost a quarter of teenage males wanted access to soft porn when banking sperm, and half wanted to bring in their own materials. It concludes that there is an urgent need for any legal barriers to the therapeutic use of pornographic materials to be understood and examined.
Is European NATO really free-riding? Patterns of material and non-material burden-sharing after the Cold War

ABSTRACT Does European NATO free-ride on America? This article uses a mixed-methods approach to explore developments after the Cold War. I investigate both “material” measures, such as military expenditure and troop numbers, and a “non-material” indicator that draws on survey data of the public’s willingness to fight for their country. Results and conclusions are not univocal. On the one hand, European NATO members have generally reduced their military spending (relative to GDP), abolished conscription and downsized their military forces. Their citizens’ self-reported willingness to fight has also been quite low after the Cold War, in particular in states that host US military bases. On the other hand, some of these developments can surely be explained by a decrease in threat perceptions in Europe. Trends changed markedly after Russia’s 2014 annexation of Crimea, which moved many allies – in particular new NATO member states – to increase their defence efforts.
Low oxygen tension stimulates collagen synthesis and COL1A1 transcription through the action of TGF‐β1

Recent findings point to low oxygen tension (hypoxia) as an important mechanism for the expression of several eukaryotic genes. We have previously shown that hypoxia (2% O2), when compared to standard oxygen tension (20% O2), upregulates the mRNA levels of the human α1(I) (COL1A1) procollagen gene and transforming growth factor‐beta1 (TGF‐β1) in human dermal fibroblasts. In this report, we determined the effect of hypoxia on collagen synthesis and transcription. Exposure of human dermal fibroblasts to hypoxia for 24–72 h led to a threefold, dose‐dependent increase in collagenous protein (P < 0.0001; r = 0.9794) and to enhanced type I procollagen deposition, as shown by direct immunofluorescence. Transient transfections with a series of luciferase‐ and CAT‐promoter constructs of the human COL1A1 gene (spanning from − 2.5 kb to + 113 bp) showed that hypoxia increases the transcriptional activity of constructs having 5′ endpoints between − 804 bp and − 107 bp, with loss of stimulation at − 84 bp. Maximal increase in promoter activity in hypoxia was observed between − 190 and − 174 bp of the proximal promoter, once a cKrox repressor site (− 199 to − 224 bp) was deleted. Upregulation of COL1A1 mRNA levels in hypoxia was blocked by a TGF‐β1 anti‐sense oligonucleotide, and failed to occur in fibroblasts from TGF‐β1 knock‐out mice. Co‐transfection and overexpression with a Smad7 construct abrogated the increase in COL1A1 promoter activity observed in hypoxia. Upregulated transcriptional activity of the TGF‐β1 promoter in hypoxia was found to be maximal between − 453 and − 175 bp from the transcriptional start site. Since hypoxia is a critical feature of the early phases of wound repair, we conclude that it may act as a potent physiologic stimulus for collagen synthesis. TGF‐β1 appears to be a critical component of this response. J. Cell. Physiol. 191: 42–50, 2002. © 2002 Wiley‐Liss, Inc.
Nighttime procedures are not associated with adverse outcomes in kidney transplantation

Surgeries performed during the night are associated with higher complication rates. The aim of this study was to determine the impact of nighttime surgery on the outcome after kidney transplantation. In all, 873 deceased donor kidney transplants were retrospectively analyzed and grouped according to the time of surgery: daytime (8 am to 8 pm, n = 610) versus nighttime (8 pm to 8 am, n = 263). Statistical analysis compared patient/graft survival, rate of delayed graft function (DGF), acute rejection rate, and surgical complications. One and 5‐year patient and graft survival did not differ between daytime and nighttime transplants. DGF occurred in 31.1% of daytime compared to 37.6% of nighttime procedures (P = 0.06). Acute allograft rejection was observed in 22.6% of daytime compared to 18.3% in nighttime graft recipients (P = 0.15). Nighttime procedures were associated with 22.4% complications compared to 22.1% in daytime procedures (P = 0.92). Most importantly, if transplantations were postponed until the next morning, cold ischemia time (CIT) would have increased from 16.6 h to 24.6 h (P < 0.0001) which would have resulted in decreased long‐term survival (P < 0.02). Nighttime kidney transplants are neither associated with a higher surgical complication rate nor worse 5‐year outcomes than daytime procedures, thus are justified to keep CIT short.
Fatty acid pattern of human prostasome lipid.

Prostasomes are organelles of prostatic origin found in human semen. Their average diameter is about 150 nm and they appear as a lipoprotein membrane surrounding less organized material. Their lipid composition is peculiar, having much cholesterol and sphingomyelin. On the other hand, many of their proteins possess catalytic activity and are involved in the immune response. In previous work, we have shown that prostasomes may fuse to sperm at slightly acidic pH values, thereby modifying the composition of the sperm plasma membrane. In this paper, we examine the fatty acid pattern of prostasome lipid and find that it is completely different from that of sperm membrane lipid. Polyunsaturated phosphatidylcholines, common in sperm membrane, are rare in prostasome. Therefore, the fusion between prostasomes and sperm should stabilize sperm plasma membrane by enriching it in cholesterol, sphingomyelin, and saturated glycerophospholipid. This would prevent the untimely occurrence of the acrosome reaction.
Evaluation of naltrexone for dissociative symptoms in borderline personality disorder

Data from a pilot study suggest that naltrexone might reduce dissociative symptoms in patients with borderline personality disorder. However, the interpretation of these data is limited by the lack of a control group and by the nonblind nature of this study. Hence, we examined the effects of naltrexone using a more rigorous design that controlled for major confounders such as spontaneous reduction of dissociation over time and placebo effects. Unmedicated patients with BPD [according to Diagnostic and Statistical Manual of Mental Disorders-IVth edition (DSM-IV)] were included in two small double-blind placebo-controlled randomized trials (total n=29). Patients received both 3 weeks of naltrexone (50 or 200 mg/day) and 3 weeks of placebo in a randomized order. Twenty-five patients completed the study according to protocol. Dissociation under naltrexone and placebo, respectively, was compared by repeated-measures analyses of variance. In either trial, both the intensity and duration of dissociative symptoms were numerically lower under naltrexone than under placebo. However, the effects were too small to reach statistical significance. Our data provide the first estimate of the pure pharmacological antidissociative efficacy of naltrexone from a rigorously designed trial.
Investigating Ministry Names for Comparative Policy Analysis: Lessons from Energy Governance

ABSTRACT This commentary contends that ministry names offer a valuable construct for furthering the state of comparative policy analysis. Using energy governance as an example, this study shows that ministries’ names are stable in some countries but subject to changes in others. Furthermore, there is variation in the ministries’ names over time. Creating or maintaining a ministry that explicitly mentions “energy” is interpreted as signaling enhanced political attention to this issue, whereas removing the referral to “energy” signals the opposite. The names of ministries responsible for energy matters also affect energy policy outputs. Drawing on 43 OECD and BRICS countries, the empirical analysis shows that countries which have ministries in place that mention “energy” together with “economy” in their names are swifter in adopting renewable energy targets. Ministries that mention “economy” along with “climate” and/or “environment” also have an inclination to be faster in adopting such targets, but the coefficients fail to reach conventional levels of statistical significance. Given this finding, it appears worth pursuing this line of research further.
Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome.

The purpose of the study was to examine the relationship between the endothelin-1 (ET-1) concentration and the metabolic variables characteristic of the insulin resistance syndrome ([IRS] hyperinsulinemia, insulin resistance, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, visceral obesity, and glycemic abnormalities). The measurement of circulating ET-1 is a well-recognized marker of endothelial atherosclerotic and cardiovascular disease. Two hundred subjects were divided into 3 groups. Group 1 included 50 subjects with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) with IRS. Group 2 included 50 subjects with IGT or NIDDM without IRS. Group 3 included 100 normal subjects as controls. ET-1 levels were higher in group 1 versus groups 2 and 3 in women (11.2 +/- 0.7 v 7.9 +/- 0.5 and 6.6 +/- 0.4 pg/mL, P < .01) and men (10.1 +/- 0.6 v 6.5 +/- 0.8 and 7.2 +/- 0.3 pg/mL, P < .01). No differences were found between groups 2 and 3. With simple regression analysis, ET-1 levels significantly correlated with insulin, glycosylated hemoglobin, body weight, waist to hip ratio, and triglyceride values. However, with multiple regression analysis, only triglycerides (P < .009) and glycosylated hemoglobin (P < .001) remained independently correlated with ET-1. In conclusion, this cross-sectional study indicates that glycosylated hemoglobin and triglycerides are independently correlated with ET-1 levels in patients with IRS.
Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection.

AIM Previous studies suggest that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis B or C. Therefore, it was the aim of this study to evaluate this particular population for BMD and bone turnover markers. METHODS Biochemical markers of bone turnover and BMD were measured in 43 consecutive patients with HCV (n = 30) or HBV (n = 13) infection without histological evidence for liver cirrhosis. Mean age was 49 years (range 26-77 years). BMD was measured by dual X-ray absorptiometry in the femoral neck (FN) and the lumbar spine (LS) region. In addition, bone metabolism markers were measured. RESULTS BMD was lowered in 25 (58%) of the patients with chronic hepatitis B or C (FN: 0.76 (0.53-0.99); LS: 0.96 (0.62-1.23) g/cm(2)). Eight (32%) osteopenic patients were diagnosed with osteoporosis. Bone-specific alkaline phosphatase (P = 0.005) and intact parathyroid hormone (iPTH) (P = 0.001) were significantly elevated in the more advanced stages of fibrosis. Mean T-score value was lower in patients with chronic hepatitis C as compared to patients suffering from chronic hepatitis B; however, the difference was not statistically significant (P = 0.09). CONCLUSION There was a significantly reduced BMD in non-cirrhotic patients with chronic hepatitis B or C infection. Alterations of bone metabolism already occurred in advanced liver fibrosis without cirrhosis. According to our results, these secondary effects of chronic viral hepatitis should be further investigated.
Environmental Policy, Environmental Performance, and Financial Distress in China: Do Top Management Team Characteristics Matter?

This study investigates the effect of environmental performance that is driven by good environmental policies, regulations, and management on firm's financial distress and, consequently, ascertains the extent to which top management teams' (TMTs') characteristics can moderate the environmental performance–financial distress nexus in China using 749 firms over the 2009–2014 period (i.e., generating over 3,000 individual observations). Our findings are twofold. First, our results indicate that increased environmental performance that is driven by good environmental policies tends to strategically reduce the extent of firm financial distress. Second, this nexus is moderated by TMT gender diversity, foreign exposure, and political connection. We interpret our findings within neo‐institutional, upper echelons, and risk management theoretical perspectives. The findings are robust to the use of alternative measures of financial distress, estimation techniques, and endogeneity problems.
The drivers and value of enterprise risk management: evidence from ERM ratings

ABSTRACT In the course of recent regulatory developments, holistic enterprise-wide risk management (ERM) frameworks have become increasingly relevant for insurance companies. The aim of this paper is to contribute to the literature by analyzing determinants (firm characteristics) as well as the impact of ERM on the shareholder value of European insurers using the Standard & Poor’s ERM rating to identify ERM activities. This has not been done so far, even though it is of high relevance against the background of the introduction of Solvency II, which requires a holistic approach to risk management. Results show a significant positive impact of ERM on firm value for the case of European insurers. In particular, we find that insurers with a high quality risk management (RM) system exhibit a Tobin’s Q that on average is about 6.5% higher than for insurers with less high quality RM after controlling for covariates and endogeneity bias.
The negative consequences of other students' drinking: Inventory development and assessment of differences by student characteristics and risk behaviors

UNLABELLED College students continue to report being disrupted by other students' alcohol use. OBJECTIVE This study was designed to develop measures to document the consequences resulting from other students' drinking and identify differences in experiencing these consequences by student characteristics and drinking behaviors. STUDY GROUP A stratified random sample of undergraduate students (N = 3,908) from ten universities in North Carolina, USA, completed a web-based assessment. METHODS Exploratory factor analysis (EFA) was performed on the random first split-half sample (n = 1,954) to identify factor structure. Confirmatory factor analysis (CFA) was performed on the remaining half sample (n = 1,954) using structural equation modeling. RESULTS EFA revealed two inventories: interpersonal and community consequences of others' drinking inventories. CFA on the second split-half sample identified model fits for the two factor structure suggested by EFA. Of 3,908 participants, 78% reported experiencing one or more consequences due to others' drinking during the past 30 days. Multivariable generalized linear mixed modeling further validated the inventories and resulted in several associations. Male students who reported getting drunk experienced significantly more interpersonal consequences from others' drinking (p < .001). Minority students, students who lived on campus and students who reported getting drunk experienced significantly more community consequences from others' drinking (p < .01). CONCLUSIONS These findings demonstrate that 4 out of 5 college students experience consequences from others' drinking, and consequences vary for different subgroups of students. Although these inventories should be tested further, these findings propose standardized measures that may be useful to assess the consequences of others' drinking among college students.
Ranibizumab for exudative age-related macular degeneration: 24-month outcomes from a single-centre institutional setting

Background To analyse the 24-month outcomes of intravitreal ranibizumab injections for choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). Methods The authors reviewed the charts of all consecutive eyes with CNV secondary to AMD, who underwent one intravitreal ranibizumab injection (followed by a pro re nata (1+PRN) decision to retreat or to not retreat) at least 24 months before. Best-corrected visual acuity (BCVA) changes and central macular thickness (CMT) were retrospectively assessed, from baseline (m0) to month 12 (m12), and 24 (m24). Results Ninety-six eyes of 79 patients (23 male, 56 female, aged 63–90 years) were included for analysis. The number of intravitreal injections administered ranged from 1 to 16. The mean BCVA significantly improved from m0 (0.78±0.33) to m12 (0.61±0.39, p<0.001), and m24 (0.65±0.38, p<0.001). The mean CMT significantly decreased from m0 (323.7±118.1) to m12 (254.6±92.3, p<0.001), and m24 (259.0±89.9, p<0.001). At m24, subretinal fluid, cystoid macular oedema and pigment epithelium detachment were present in fewer eyes (13, 31 and 31 eyes respectively), compared with m0 (33, 61 and 72 eyes, respectively). Overall, at m12 and m24, 91 eyes (94.8%) and 84 eyes (87.5%) lost fewer than 15 letters, and 25 (26%) eyes and 24 eyes (25%) improved by 15 letters or more, respectively; five eyes (5.2%) and 12 eyes (12.5%) lost more than 15 letters, at m12 and m24, respectively. Conclusion In this study, similarly to other studies of variable dosing regimen over 24 months, intravitreal ranibizumab was effective in significantly increasing BCVA and reducing CMT.