Miracle-dz/UniFAR-FTUs huggingface dataset:
Automated Measurement of Microvascular Function Reveals Dysfunction in Systemic Sclerosis: A Cross-sectional Study

Objective. The aim of our study was to determine whether an automated capture and analysis system could detect differences in structure and function of sublingual microvessels in patients with systemic sclerosis (SSc) compared to healthy controls. Methods. Intravital microscopy of the sublingual microcirculation was automatically captured and analyzed in 40 patients with SSc and 10 age-matched healthy controls. Results. Total and perfused microvascular density were lower in patients with SSc compared with controls (total microvascular density: 2471 ± 134 µm/mm2 vs 3067 ± 197 µm/mm2, p = 0.020; perfused microvascular density: 1708 ± 92 µm/mm2 vs 2192 ± 144 µm/mm2, p = 0.009). However, the relative percentage of perfused to total microvascular density was similar between SSc and controls (72 ± 2% vs 71 ± 2%, respectively, p = 0.429). Mean red blood cell (RBC) fraction, which indicates the longitudinal tube hematocrit of microvessel segments, was lower in patients with SSc compared with controls (69 ± 1% vs 77 ± 1%, respectively, p < 0.001). Perfused boundary region (PBR), a marker of endothelial glycocalyx barrier properties, was higher in patients with SSc compared with controls (2.1 ± 0.0 µm vs 1.9 ± 0.0 µm, respectively, p = 0.012), suggestive of a dysfunctional glycocalyx. There was an inverse association of PBR with perfused microvascular density (r = −0.40, p = 0.004) and RBC fraction (r = −0.80, p < 0.001). Conclusion. Our results indicate that automated capture and analysis of sublingual microvessel segments produces detailed, objective microvascular structural and functional data that have allowed us to distinguish patients with SSc from controls. These data suggest that microvascular structural and functional abnormalities present in patients with SSc could be at least partly due to a dysfunctional glycocalyx.
Effectiveness of a Binocular Video Game vs Placebo Video Game for Improving Visual Functions in Older Children, Teenagers, and Adults With Amblyopia: A Randomized Clinical Trial

Importance Binocular amblyopia treatment using contrast-rebalanced stimuli showed promise in laboratory studies and requires clinical trial investigation in a home-based setting. Objective To compare the effectiveness of a binocular video game with a placebo video game for improving visual functions in older children and adults. Design, Setting, and Participants The Binocular Treatment of Amblyopia Using Videogames clinical trial was a multicenter, double-masked, randomized clinical trial. Between March 2014 and June 2016, 115 participants 7 years and older with unilateral amblyopia (amblyopic eye visual acuity, 0.30-1.00 logMAR; Snellen equivalent, 20/40-20/200) due to anisometropia, strabismus, or both were recruited. Eligible participants were allocated with equal chance to receive either the active or the placebo video game, with minimization stratified by age group (child, age 7 to 12 years; teenager, age 13 to 17 years; and adult, 18 years and older). Interventions Falling-blocks video games played at home on an iPod Touch for 1 hour per day for 6 weeks. The active video game had game elements split between eyes with a dichoptic contrast offset (mean [SD] initial fellow eye contrast, 0.23 [0.14]). The placebo video game presented identical images to both eyes. Main Outcomes and Measures Change in amblyopic eye visual acuity at 6 weeks. Secondary outcomes included compliance, stereoacuity, and interocular suppression. Participants and clinicians who measured outcomes were masked to treatment allocation. Results Of the 115 included participants, 65 (56.5%) were male and 83 (72.2%) were white, and the mean (SD) age at randomization was 21.5 (13.6) years. There were 89 participants (77.4%) who had prior occlusion. The mean (SD) amblyopic eye visual acuity improved 0.06 (0.12) logMAR from baseline in the active group (n = 56) and 0.07 (0.10) logMAR in the placebo group (n = 59). The mean treatment difference between groups, adjusted for baseline visual acuity and age group, was −0.02 logMAR (95% CI, −0.06 to 0.02; P = .25). Compliance with more than 25% of prescribed game play was achieved by 36 participants (64%) in the active group and by 49 (83%) in the placebo group. At 6 weeks, 36 participants (64%) in the active group achieved fellow eye contrast greater than 0.9 in the binocular video game. No group differences were observed for any secondary outcomes. Adverse effects included 3 reports of transient asthenopia. Conclusions and Relevance The specific home-based binocular falling-blocks video game used in this clinical trial did not improve visual outcomes more than the placebo video game despite increases in fellow eye contrast during game play. More engaging video games with considerations for compliance may improve effectiveness. Trial Registration anzctr.org. au Identifier: ACTRN12613001004752
A comparative analysis of RAPD and ISSR markers for assessing genetic diversity in Iranian populations of Nigella sativa L.

The genetic diversity of 18 Iranian populations of Nigella sativa L. was tested using RAPD (10 primers) and ISSR (12 primers) molecular markers. RAPD primers produced 103 acceptable bands and out of them, 42 bands were polymorphic and the total percentage of polymorphism was estimated 40.5%. Out of the 12 ISSR primers, only 5 of them produced acceptable bands. Five ISSR primers generated 39 amplified products and out of them, 19 bands were polymorphic and the total percentage of polymorphism was estimated 57.4%. As a result, the level of polymorphism obtained from the ISSR markers was higher than of the RAPD markers. Mean of marker index (MI) (0.822 for RAPD and 0.74 for ISSR) and Polymorphic information content (PIC) (0.402 for RAPD and 0.35 for ISSR) for each of the marker systems indicated that both markers were effective for evaluating genetic diversity. Cluster analysis classified the populations into 5 groups for both DNA markers. By integration and analyzing of the two marker systems, the populations were classified into 4 groups. The results of this research showed that RAPD and ISSR molecular markers can be useful for identifying and classifying the Iranian Nigella sativa L. POPULATIONS
Arthroplasty in cervical degenerative disc disease: fulfilling its long-term promise?

There has been an increasing interest in anterior cervical discectomy with arthroplasty (ACDA) over the past decade. The presumed benefit of ACDA over the more common anterior cervical discectomy with fusion (ACDF) approach is reducing rates of adjacent segment disease, by maintaining mobility in the operated motion segment. Several authors have questioned the role of arthroplasty in actually preventing adjacent segment disease (1,2). In a recent meta-analysis, the authors found a 5.1% incidence of adjacent segment disease 12–24 months after ACDA (3). This is roughly consistent with the yearly incidence of adjacent segment disease after ACDF, which has been reported to be 2.9% (4). If there is indeed a lower yearly incidence of adjacent segment disease in ACDA compared to ACDF, this should become increasingly apparent over time.
Lateral Transperitoneal Adrenalectomy Versus Posterior Retroperitoneoscopic Adrenalectomy for Benign Adrenal Gland Disease: Randomized Controlled Trial at a Single Tertiary Medical Center

Objective: The aim of this study was to compare the surgical outcomes of lateral transperitoneal adrenalectomy (LTA) and posterior retroperitoneoscopic adrenalectomy (PRA) for benign adrenal tumor. Background: Although LTA is the standard treatment for benign adrenal gland tumor, PRA has recently gained popularity. Studies comparing the surgical outcomes of the 2 approaches have reported conflicting findings and thus it remains unclear which approach is superior. Methods: This trial was conducted between September 2012 and February 2016. Patients were randomized to either LTA or PRA groups in a 1:1 ratio using web-based randomization. The primary outcome was operative time, and the secondary outcomes were blood loss, intraoperative hemodynamic stability, postoperative pain, recovery of bowel movement, and complication rates. This trial was registered with ClincalTrials.gov, number NCT01676025. Results: A total of 83 patients were randomly assigned to the LTA group (n = 42) or the PRA group (n = 41). Median follow-up was 31.3 months. The mean operative times of LTA and PRA were comparable (59.7 ± 18.6 vs 67.6 ± 28.7 minutes, P = 0.139). Logistic regression analysis showed that male sex [odds ratio (OR) = 4.20] and pheochromocytoma (OR = 5.06) were associated with an operative time ≥60 minutes. There were no differences in the secondary outcomes between the groups. One patient in the PRA group required open conversion. Conclusion: Both LTA and PRA were performed safely with similar operative outcomes, and thus are comparable options for the treatment of benign adrenal gland tumor.
Reducing the time until psychotherapy initiation reduces sick leave duration in participants diagnosed with anxiety and mood disorders.

BACKGROUND Sick leave in patients with a mental disorder is characterized by having a long duration. Studies suggest that the time until a patient on sick leave for a common mental health disorder initiates evaluation and treatment by a healthcare professional is an important factor in the duration of the sick leave. However, in these studies, the intervention was not performed by a mental health specialist. The aim of this study was to find out whether the length of sick leave was associated with the time before initiating psychotherapy, age, time until returning to work after psychotherapy ends, and duration of psychotherapy. In a further analysis, we examined whether the model composed of age, duration of psychotherapy, and time before initiating psychotherapy predicted the length of sick leave. METHOD The sample consisted of 2,423 participants, 64.1% (n = 1,554) women and 35.9% (n = 869) men, who were on sick leave for anxiety disorders or depressive disorder. RESULTS The total duration of the sick leave of participants diagnosed with depression and anxiety was positively associated with the time before beginning psychotherapy. Time before beginning psychotherapy predicted the length of sick leave when the variables age and duration of psychotherapy were controlled. CONCLUSION It is necessary to reduce the time until beginning psychotherapy in people on sick leave for common mental disorders.
Pharmacokinetics and Exposure-Response Analysis of RG7667, a Combination of Two Anticytomegalovirus Monoclonal Antibodies, in a Phase 2a Randomized Trial To Prevent Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients

ABSTRACT RG7667, a novel combination of two anticytomegalovirus (anti-CMV) monoclonal IgG1 antibodies (MCMV5322A and MCMV3068A), was designed to block CMV entry into host cells. It was developed as a potential therapy for preventing CMV infection and disease in transplant recipients. RG7667 was assessed for preventing CMV infection in a phase 2a trial with CMV-seronegative recipients of kidney transplants from CMV-seropositive donors. The patients received 4 intravenous doses of RG7667 (10 mg/kg of body weight of each antibody, n = 60) or placebo (n = 60) at the time of the transplant and at 1, 4, and 8 weeks after the transplant. Serum samples were collected for pharmacokinetic (PK) analysis and antidrug antibody (ADA) evaluation. To guide future dose selection, the relationships between RG7667 exposure and pharmacological activity were evaluated. MCMV5322A and MCMV3068A exposures were confirmed in all RG7667-treated patients. Mean clearances for MCMV5322A and MCMV3068A were 2.97 and 2.65 ml/day/kg, respectively, and the terminal half-lives of MCMV5322A and MCMV3068A were 26.9 and 27.4 days, respectively. The ADA incidence was low and was not associated with lower drug exposure. Patients with RG7667 or component antibody exposures greater than the respective median values had a lower incidence of viremia at 12 weeks and 24 weeks after transplantation and a longer delayed time to detectable CMV viremia than patients with exposures less than the median values. MCMV5322A and MCMV3068A exhibited expected IgG1 PK profiles in high-risk kidney transplant recipients, consistent with the earlier PK behavior of RG7667 in healthy subjects. Higher drug exposure was associated with better anti-CMV pharmacological activity. (This study has been registered at ClinicalTrials.gov under identifier NCT01753167.)
Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat.

We have recently reported oral and parenteral bioactivity for a new GH-releasing peptide, hexarelin. In the present study, we have examined the neuroendocrine mechanism by which hexarelin and GHRP-6, two GH-releasing peptides, mediate their actions. Although previous studies have looked at the role of growth hormone-releasing hormone (GHRH) and somatostatin in regulating the action of GHRP-6 in culture and in stressed animals, our study looked at the role of both somatostatin and GHRH in regulating the action of hexarelin as well as GHRP-6 in conscious and freely-moving, nonstressed rats. Adult male rats, prepared with indwelling jugular catheters, were pretreated i.v. with either control antiserum (CTLas), growth hormone-releasing hormone antiserum (GHRHas), somatostatin antiserum (SSas), or both GHRHas and SSas. Animals were then treated i.v. with 25 micrograms/kg of either hexarelin or GHRP-6 4 h after i.v. antisera pretreatment. Blood samples were collected every 20 min for the 3 h prior to peptide treatment and at 5, 10, 15, 20, 40 and 60 min following hexarelin or GHRP-6 injection. The peak plasma GH responses in rats pretreated with CTLas were 552 +/- 125 ng/ml following hexarelin administration and 386 +/- 132 ng/ml following GHRP-6 administration. Rats pretreated with SSas exhibited peak GH responses following hexarelin or GHRP-6 of 702 +/- 115 and 312 +/- 42 ng/ml, respectively. These plasma GH responses were similar to those observed in the CTLas-pretreated animals. (ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced Wort Fermentation with De Novo Lager Hybrids Adapted to High-Ethanol Environments

ABSTRACT Interspecific hybridization is a valuable tool for developing and improving brewing yeast in a number of industry-relevant aspects. However, the genomes of newly formed hybrids can be unstable. Here, we exploited this trait by adapting four brewing yeast strains, three of which were de novo interspecific lager hybrids with different ploidy levels, to high ethanol concentrations in an attempt to generate variant strains with improved fermentation performance in high-gravity wort. Through a batch fermentation-based adaptation process and selection based on a two-step screening process, we obtained eight variant strains which we compared to the wild-type strains in 2-liter-scale wort fermentations replicating industrial conditions. The results revealed that the adapted variants outperformed the strains from which they were derived, and the majority also possessed several desirable brewing-relevant traits, such as increased ester formation and ethanol tolerance, as well as decreased diacetyl formation. The variants obtained from the polyploid hybrids appeared to show greater improvements in fermentation performance than those derived from diploid strains. Interestingly, it was not only the hybrid strains, but also the Saccharomyces cerevisiae parent strain, that appeared to adapt and showed considerable changes in genome size. Genome sequencing and ploidy analysis revealed that changes had occurred at both the chromosome and single nucleotide levels in all variants. Our study demonstrates the possibility of improving de novo lager yeast hybrids through adaptive evolution by generating stable and superior variants that possess traits relevant to industrial lager beer fermentation. IMPORTANCE Recent studies have shown that hybridization is a valuable tool for creating new and diverse strains of lager yeast. Adaptive evolution is another strain development tool that can be applied in order to improve upon desirable traits. Here, we apply adaptive evolution to newly created lager yeast hybrids by subjecting them to environments containing high ethanol levels. We isolated and characterized a number of adapted variants which possess improved fermentation properties and ethanol tolerance. Genome analysis revealed substantial changes in the variants compared to the original strains. These improved variant strains were produced without any genetic modification and are suitable for industrial lager beer fermentations.
Accuracy analysis of range detection for SFCW portable through-wall radar

This paper discusses the accuracy of range detection for stepped-frequency continuous-wave (SFCW) portable through-wall radar (TWR) and its analysis through simulation software. The radar which is portably constructed of some modular devices has operating frequency range between 1600MHz and 2500MHz. Here, the use of simulation software aims to do modelling to investigate information contained in transmitted and received signals. The simulation of SFCW radar for range detection in the designated frequency was able to range some targets located at the distance of 2.6m and 5.2m. From the result, it shows that the SFCW method was suitable for designing the portable TWR which could range some targets at the distance more than 5m from the radar.
Warming combined with more extreme precipitation regimes modifies the water sources used by trees.

The persistence of vegetation under climate change will depend on a plant's capacity to exploit water resources. We analyzed water source dynamics in piñon pine and juniper trees subjected to precipitation reduction, atmospheric warming, and to both simultaneously. Piñon and juniper exhibited different and opposite shifts in water uptake depth in response to experimental stress and background climate over 3 yr. During a dry summer, juniper responded to warming with a shift to shallow water sources, whereas piñon pine responded to precipitation reduction with a shift to deeper sources in autumn. In normal and wet summers, both species responded to precipitation reduction, but juniper increased deep water uptake and piñon increased shallow water uptake. Shifts in the utilization of water sources were associated with reduced stomatal conductance and photosynthesis, suggesting that belowground compensation in response to warming and water reduction did not alleviate stress impacts for gas exchange. We have demonstrated that predicted climate change could modify water sources of trees. Warming impairs juniper uptake of deep sources during extended dry periods. Precipitation reduction alters the uptake of shallow sources following extended droughts for piñon. Shifts in water sources may not compensate for climate change impacts on tree physiology.
Profiles of Plasma Serpins in Patients with Advanced Malignant Melanoma, Gastric Cancer and Breast Cancer

Blood coagulation and fibrinolysis are activated systemically in patients with malignancy. The precarious balance between coagulation and fibrinolysis is modulated by serine proteinase inhibitors (serpins). Levels of selected serpins (α1-antichymotrypsin, α1-antitrypsin, α2-macroglobulin, antithrombin III, C1 inhibitor, α2-antiplasmin), substrates (factor XIIIa, fibrinogen, fibronectin) and endproducts (fibrin/fibrinogen degradation products) of coagulation reactions were measured in the plasma of 61 patients with common malignancies associated with a tendency to thrombosis (i.e. malignant melanoma, gastric cancer and breast cancer). The data revealed a heterogeneity in plasma levels of serpins between tumor types. The most profound differences between cancer and healthy subject groups were found in breast cancer patients. Levels of α1-antitrypsin were significantly higher and levels of α2-antiplasmin were significantly lower in all cancer groups, whereas there were no differences in antithrombin III levels.
Histamine Receptor 2 is Required to Suppress Innate Immune Responses to Bacterial Ligands in Patients with Inflammatory Bowel Disease

Background:Histamine is a key immunoregulatory mediator in immediate-type hypersensitivity reactions and chronic inflammatory responses, in particular histamine suppresses proinflammatory responses to bacterial ligands, through histamine receptor 2 (H2R). The aim of this study was to investigate the effects of histamine and H2R on bacteria-induced inflammatory responses in patients with IBD. Methods:Peripheral blood mononuclear cells (PBMCs) were obtained from patients with Crohn's disease, patients with ulcerative colitis, and healthy controls. PBMC histamine receptor expression was evaluated by flow cytometry. Cytokine secretion following Toll-like receptor (TLR)-2, TLR-4, TLR-5, or TLR-9 stimulation in the presence or absence of histamine or famotidine (H2R antagonist) was quantified. Biopsy histamine receptor gene expression was evaluated using reverse transcription–polymerase chain reaction. The in vivo role of H2R was evaluated in the T-cell transfer murine colitis model. Results:The percentage of circulating H2R+ monocytes was significantly reduced in patients with IBD. Histamine effectively suppressed TLR-induced cytokine secretion from healthy volunteer PBMCs but not for PBMCs from patients with IBD. Famotidine reversed this suppressive effect. H1R, H2R, and H4R gene expression was increased in inflamed gastrointestinal mucosa compared with noninflamed mucosa from the same patient and expression levels correlated with proinflammatory cytokine gene expression. Mice receiving lymphocytes from H2R−/− donors, or treated with famotidine, displayed more severe weight loss, higher disease scores and increased numbers of mucosal IFN-&ggr;+ and IL-17+ T cells. Conclusion:Patients with IBD display dysregulated expression of histamine receptors, with diminished anti-inflammatory effects associated with H2R signaling. Deliberate manipulation of H2R signaling may suppress excessive TLR responses to bacteria within the gut.
Wavelet Analysis of Resultant Velocity Belonging to Genuine and Forged Signatures

This study presents a wavelet analysis of resultant velocity features belonging to genuine and forged groups of signature sample. Signatures of individuals were initially classified based on visual human perceptions of their relative sizes, complexities, and legibilities of the genuine counterparts. Then, the resultant velocity was extracted and modeled through wavelet analysis from each sample. The wavelet signal was decomposed into several layers based on maximum overlap discrete wavelet transform (MODWT). Next, the zero crossing rate features were calculated from all the high wavelet sub‐bands. A total of seven hypotheses were then tested using a two‐way ANOVA testing methodology. Of these, four hypotheses were conducted to test for significance differences between distributions. In addition, three hypotheses were run to provide test for interaction between two factors of signature authentication versus perceived classification. The results demonstrated that both feature distributions belonging to genuine and forged groups of samples cannot be distinguished by themselves. Instead, they were significantly different under the influence of two other inherent factors, namely perceived size and legibility. Such new findings are useful information particularly in providing bases for forensic justifications in establishing the authenticity of handwritten signature specimens.