Miracle-dz/UniFAR-FTUs huggingface dataset:
Id1 Expression Promotes T Regulatory Cell Differentiation by Facilitating TCR Costimulation

T regulatory (Treg) cells play crucial roles in the regulation of cellular immunity. The development of Treg cells depends on signals from TCRs and IL-2Rs and is influenced by a variety of transcription factors. The basic helix-loop-helix proteins are known to influence TCR signaling thresholds. Whether this property impacts Treg differentiation is not understood. In this study, we interrogated the role of basic helix-loop-helix proteins in the production of Treg cells using the CD4 promoter-driven Id1 transgene. We found that Treg cells continued to accumulate as Id1 transgenic mice aged, resulting in a significant increase in Treg cell counts in the thymus as well as in the periphery compared with wild-type controls. Data from mixed bone marrow assays suggest that Id1 acts intrinsically on developing Treg cells. We made a connection between Id1 expression and CD28 costimulatory signaling because Id1 transgene expression facilitated the formation of Treg precursors in CD28−/− mice and the in vitro differentiation of Treg cells on thymic dendritic cells despite the blockade of costimulation by anti-CD80/CD86. Id1 expression also allowed in vitro Treg differentiation without anti-CD28 costimulation, which was at least in part due to enhanced production of IL-2. Notably, with full strength of costimulatory signals, however, Id1 expression caused modest but significant suppression of Treg induction. Finally, we demonstrate that Id1 transgenic mice were less susceptible to the induction of experimental autoimmune encephalomyelitis, thus illustrating the impact of Id1-mediated augmentation of Treg cell levels on cellular immunity.
[Anastomotic stricture following radical retropubic prostatectomy: insights into incidence, management and factors predisposing for occurrence].

PURPOSE Anastomotic stricture (AS) following radical prostatectomy (RP) decreases patients' quality of life. It occurs in 0.5% to 32% of men after open radical retropubic prostatectomy (RRP), although its etiology is poorly understood. In a series of patients who received RRP, we analyzed the incidence, possible predisposing factors, and management of AS after RP. MATERIALS & METHODS Between April 1997 and March 2006, 129 consecutive patients underwent RRP in our hospital. Anastomosis between the bladder neck and urethra was performed with interrupted anastomosis using four 2-0 absorbable sutures. AS was diagnosed when a 16Fr. panendoscope could not be passed. We assessed the relationship between the management method for AS and time interval between the surgical procedure and diagnosis of the stricture. The relationships between comorbidities identified preoperatively (hypertension [HT], diabetes mellitus [DM], cardiovascular disease [CVD], cerebral infarction [CI] and smoking history) and the incidence of AS were determined. Risk factors, including age, body mass index [BMI], preoperative PSA, total prostate volume, operative time, blood loss, Foley duration, amount of stress urinary incontinence (SUI) per day, amount of drain output, pathological T stage, Gleason sum and surgical margin status were also assessed. RESULTS The rate of AS after RRP was 10.9% (14/129). In 10 patients (72%), AS occurred within 3 months of surgery, in 2 (14%) it occurred at 4-12 months after surgery and in 2 (14%) more than 12 months after surgery. In univariate and multivariate analyses, intraoperative bleeding of 1,800 ml or more was independently the strongest predictor of AS. In two patients a urethral bougie was used and 11 underwent internal urethrotomy. Only 1 patient underwent transurethral resection. Of the 8 patients whose strictures were diagnosed within 3 months after surgery and underwent internal urethrotomy, 6 had recurrent anastomotic strictures. CONCLUSIONS Risk factors for AS are thought to be multifactorial. Intraoperative blood loss was significantly associated with the development of anastomotic stricture. We should understand that anastomotic stricture following radical retropubic prostatectomy is not a rare morbidity and should inform patients about the possibility of postoperative AS.
Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus

Reduced brain levels of long chain polyunsaturated fatty acids [arachidonic acid and docosahexanoic acid (DHA)] are observed in elderly subjects and patients with Alzheimer's disease. To determine the effects of n-3 fatty acids on aged rat brain, 2-year-old rats were fed fish oil (27% DHA content) for 1 month, and gene expression analysis and fatty acid and molecular species composition of the major phospholipid species were assessed. No significant alteration could be observed in the fatty acid composition of ethanolamine phosphoglycerides and phosphatidylserines with the exception of DHA, which was slightly higher in brains of rats receiving fish oil. However, a drastic reduction in arachidonic acid in phosphatidylinositoles was observed. The expression of 23 genes was altered in response to fish oil feeding in the hippocampus. The transcription of transthyretin (TTR) was induced by 10-fold as evidenced by microarray analysis and confirmed by real-time quantitative RT-PCR. Expression of IL-1 and NO synthase, which has been implicated in the prevention of neurological diseases, was unaltered. TTR is an amyloid β protein scavenger, so an increase in its expression could prevent amyloid aggregate formation. We believe the beneficial effects of fish oil might be common to other agents, i.e., induce TTR expression, like nicotine and Ginkgo biloba extract.
Cognitive Functioning after Surgery in Middle-aged and Elderly Danish Twins

Background:Postoperative cognitive dysfunction is common, but it remains unclear whether there are long-term adverse cognitive effects of surgery combined with anesthesia. The authors examined the association between exposure to surgery and level of cognitive functioning in a sample of 8,503 middle-aged and elderly twins. Methods:Results from five cognitive tests were compared in twins exposed to surgery, classified as major, minor, hip and knee replacement, or other, with those of a reference group without surgery using linear regression adjusted for sex and age. Genetic and shared environmental confounding was addressed in intrapair analyses of 87 monozygotic and 124 dizygotic same-sexed twin pairs in whom one had a history of major surgery and the other did not. Results:Statistically significantly lower composite cognitive score was found in twins with at least one major surgery compared with the reference group (mean difference, −0.27; 95% CI, −0.48 to −0.06), corresponding to one tenth of an SD, that is, a negligible effect size. In the intrapair analysis, the surgery-exposed co-twin had the lower cognitive score in 49% (95% CI, 42 to 56%) of the pairs. None of the other groups differed from the reference group except the knee and hip replacement group that tended to have higher cognitive scores (mean difference, 0.35; 95% CI, −0.18 to 0.87). Conclusions:A history of major surgery was associated with a negligibly lower level of cognitive functioning. The supplementary analyses suggest that preoperative cognitive functioning and underlying diseases were more important for cognitive functioning in mid- and late life than surgery and anesthesia.
Effect of government regulations on the severity of injuries in fisheries

ABSTRACT This study analyses the severity of commercial fishing accidents in the Gulf of Mexico using data from the USCG. Estimates from ordered probit models find no statistically significant effect for either the IFQGT program or the Coast Guard Authorization Act of 2010. However, the presence of an NOAA observer on fishing vessels appears to have reduced the severity of injuries during the study period, which can be partially attributed to the success of the USCG vessel safety certification program. Poor weather conditions increase the likelihood of fatality, particularly when a person falls overboard. Information from the interaction effects between poor weather conditions and vessel attributes can be used in designing new commercial fishing vessels to enhance safety.
End-stage renal disease and survival in people with diabetes: a national database linkage study

Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. Results: Point prevalence of chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM. Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.
Ubiquitous transgene expression and Cre-based recombination driven by the ubiquitin promoter in zebrafish

Molecular genetics approaches in zebrafish research are hampered by the lack of a ubiquitous transgene driver element that is active at all developmental stages. Here, we report the isolation and characterization of the zebrafish ubiquitin (ubi) promoter, which drives constitutive transgene expression during all developmental stages and analyzed adult organs. Notably, ubi expresses in all blood cell lineages, and we demonstrate the application of ubi-driven fluorophore transgenics in hematopoietic transplantation experiments to assess true multilineage potential of engrafted cells. We further generated transgenic zebrafish that express ubiquitous 4-hydroxytamoxifen-controlled Cre recombinase activity from a ubi:creERt2 transgene, as well as ubi:loxP-EGFP-loxP-mCherry (ubi:Switch) transgenics and show their use as a constitutive fluorescent lineage tracing reagent. The ubi promoter and the transgenic lines presented here thus provide a broad resource and important advancement for transgenic applications in zebrafish.
Ten evidence-based policy accelerators for transforming primary health care in the WHO European Region

In this special issue, the evidence and experiences captured have been reviewed, summarized and translated into 10 evidence-based policy accelerators for advancing a primary health care approach in the WHO European Region (Box 1). The accelerators were presented and discussed at two recent events in Kazakhstan: a scientific conference in Almaty, in October 2018, which was a pre-event to the global conference in Astana (3). These accelerators – policy options, must-dos, or leapfrogging opportunities for primary health care – signify high-impact entry-points for implementing bold reforms. While not exhaustive, they are among the “best buys” for allocating time and resources to transforming services delivery through tried and tested research and practice. Furthermore, they are the agenda for a minister of health when further prioritized, based on the needs of a country.
NoC router using STT-MRAM based hybrid buffers with error correction and limited flit retransmission

In this paper, we present a unique methodology to implement deep IO buffers for Network-on-Chip (NoC) platform, based on a hybrid design involving conventional SRAM and emerging Spin-Transfer-Torque Magnetic Random Access Memory (STT-MRAM) technology. We focus on the system-level impact of probabilistic switching of STT-MRAM devices, arising when write latency of STT-MRAM is reduced through conservative programming and aggressive scaling. We incorporate STT-MRAM specific error detection and correction schemes at the input buffers, and propose a new limited flit retransmission scheme to reduce flit errors due to the probabilistic switching. Our hybrid STT-MRAM buffers along with additional logic consume less than 80% of the area of SRAM-only FIFOs of the same depth. We demonstrate optimum NoC throughput at moderate injection rates on a mesh NoC.
An Assay Method for Herpes Simplex Virus Type 1 Seroprevalence Survey—Detection of Antibody in Saliva by Avidin‐Biotin Complex Enzyme‐Linked Immunosorbent Assay (ABC‐ELISA)

To determine whether the avidin‐biotin complex enzyme‐linked immunosorbent assay (ABC‐E) is a potentially useful method for detection of herpes simplex virus type 1 (HSV‐1) antibody in saliva, paired serum and saliva samples from 129 healthy individuals aged 18 to 25 years were collected simultaneously and subjected to a neutralization test (NT) for neutralizing antibody and also to an indirect ELISA (IE) and ABC‐E for HSV‐1 specific IgG detection. Compared with the results of NT, the sensitivities of the IE and ABC‐E for serum were both 100% (45/45), and for saliva 82.2% (37/45) and 93.3% (42/45), respectively. The specificity of all these methods was 100% (84/84). With the same ABC‐E method, a significant correlation (r=0.66, P < 0.001) between the OD‐difference (d‐OD) values of positive serum and saliva samples was observed. Furthermore, the consistency of ABC‐E for salivary antibody detection was confirmed with the paired serum and saliva samples which were collected from four individuals followed up for eight months. It was clear that the ABC‐E method for saliva can be used in place of the NT and ABC‐E method for serum for seroprevalence studying of HSV‐1 infection.
Review of four publications on the Danish cohort study on mobile phone subscribers and risk of brain tumors

Abstract Background: Since the International Agency for Research on Cancer recently classified radiofrequency electromagnetic fields, such as those emanating from mobile and cordless phones, as possibly carcinogenic to humans (group 2B), two additional reports relevant to the topic have been published. Both articles were new updates of a Danish cohort on mobile phone subscribers and concern the possible association between assumed use of mobile phones and risk of brain tumors. The aim of the present review is to reexamine all four publications on this cohort. Methods: In brief, publications were scrutinized, and in particular, if the authors made explicit claims to have either proved or disproved their hypothesis, such claims were reviewed in light of applied methods and study design, and in principle, the stronger the claims, the more careful our review. Results: The nationwide Danish cohort study on mobile phone subscribers and risk of brain tumors, including at best 420,095 persons (58% of the initial cohort), is the only one of its kind. In comparison with previous investigations, i.e., case-control studies, its strength lies in the possibility to eliminate non-response, selection, and recall bias. Although at least non-response and recall bias can be excluded, the study has serious limitations related to exposure assessment. In fact, these limitations cloud the findings of the four reports to such an extent that render them uninformative at best. At worst, they may be used in a seemingly solid argument against an increased risk – as reassuring results from a large nationwide cohort study, which rules out not only non-response and recall bias but also an increased risk as indicated by tight confidence intervals. Conclusion: Although two of the most comprehensive case-control studies on the matter both have methodological limitations that need to be carefully considered, type I errors are not the only threats to the validity of studies on this topic – the Danish cohort study is a textbook example of that.
Schmallenberg virus, a novel orthobunyavirus infection in ruminants in Europe: Potential global impact and preventive measures

Abstract In autumn 2011, Schmallenberg virus was the first orthobunyavirus detected in Europe. The virus belongs to the Simbu serogroup. Like other orthobunyaviruses, it is apparently transmitted by arthropod vectors, primarily by biting midges (Culicoides spp.). Ruminants and new-world camelids (alpacas) are susceptible to infection. Adult animals may develop mild disease, if any. However, transplacental infection can lead to severe congenital malformations such asarthrogryposis, malformation of the vertebral column (kyphosis, lordosis, scoliosis, torticollis) and of the skull (macrocephaly, brachygnathia inferior) as well as variable malformations of the brain (hydranencephaly, porencephaly, cerebellar hypoplasia, hypoplasia of the brain stem) and of the spinal cord in lambs, goat kids and calves. The infection spread rapidly over large parts of North-Western Europe. Belgium, Denmark, Germany, France, Italy, Luxembourg, the Netherlands, Spain and the United Kingdom were affected in the transmission season 2011/2012. The disease has re-emerged, at least in France, Germany and the United Kingdom during the vector-active season in 2012 and recently spread to Austria, Finland, Poland, Switzerland and Sweden. It remains to be seen whether the infection will establish permanently in the affected area. Measures have been proposed by the World Organisation for Animal Health (OIE) to help countries free from Schmallenberg virus to avoid the introduction of the infection without imposing inappropriate trade barriers. The aim of this article is to provide a state-of-the-art review on Schmallenberg virus 1 year after its first detection.
The male factor.

The use of a specific radiolabeled antiglobulin test to detect antisperm antibodies has given positive results in 7% of infertile men and 13% of infertile women, and may be a reliable means of identifying and possibly treating patients whose infertility is caused by immune mechanisms. The importance of studying the infertile couple rather than the women only has been emphasized; the sparse data available suggest that deficiencies may occur in the man in as many as 1/2 of the estimated 10-15% of couples who are infertile. Most infertile men are still classified as having idiopathic oligospermia, implying sperm counts below those associated with ready fertility, without apparent cause. It is now clear that the fertility potential of both partners must be evaluated in assessing the importance of oligospermia, making assessment of the response to therapy more difficult. The diagnosis of oligospermia itself is beset by such difficulties as the variability of the sperm count at both normal and low levels and the overlap between presumed fertile and infertile levels of sperm. The maximum number of sperm necessary to define oligospermia has declined over recent years to 10 million sperm/ml. Oligospermia appears to represent a common response of the male reproductive system to a variety of insults. Most patients have abnormal pituitary responsiveness related to decreased feedback control of hypothalamus and pituitary by the testis. Altered testicular function is most likely when the sperm count is below 5 million/ml. Environmental factors, intrinsic testicular defects, and androgen insensitivity due to a decreased number of androgen receptors are other possible causes. The probable diversity of pathogenesis and the difficulty of obtaining properly controlled studies are reasons for the inconclusive results of most therapeutic efforts. However, significant progress in the understanding of testicular disorders in the past few years has led to an outburst of scientific and collegial activities related to andrology, and there is reasonable hope for a more definite understanding of male fertility in the near future.
A Novel Technique For Mapping the Lipid Composition of Atherosclerotic Fatty Streaks by En Face Fluorescence Microscopy

We introduce here a new fluorescence microscopy technique for en face analysis of the atherosclerotic fatty streaks (FS). This technique is semiquantitative and has the sensitivity and resolution to map lipids to individual cells in FS less than 100 μm in diameter. New Zealand White rabbits were fed an atherogenic diet for up to 26 weeks. Aortas were fixed in formalin and stained en bloc with the fluorescent dyes Nile red and filipin. Fluorescent staining was validated by correlating microfluorimetric and biochemical measurements of the lipid content in FS. To determine the cell types associated with the different staining patterns, FS were also evaluated by transmission electron microscopy (TEM) and immunohistochemistry (IH). Correlation of microfluorimetry, TEM, IH, and biochemical data indicated that regions rich in non-esterified cholesterol stained with filipin and fluoresced blue owing to accumulations of lipid vessicles and/or cholesterol crystals. Regions rich in neutral and polar lipids stained with Nile red and fluoresced yellow or orange, respectively, owing to accumulations of lipids in both macrophages and smooth muscle cells (SMC). Digital overlays of the filipin and Nile red images revealed that larger lesions (>0.5 mm diameter) had a “nested” distribution of lipids, with a blue (filipin) fringe surrounding an orange (Nile red) fringe surrounding a yellow (Nile red) center.
Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413.

PURPOSE This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%. MATERIALS AND METHODS Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) < or = 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause. RESULTS With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P =.022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT (P =.56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively; P =.008). No survival advantage has yet been seen. CONCLUSION WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.