Miracle-dz/UniFAR-FTUs huggingface dataset:
A comparative study on the use of fractional CO2 laser with tacrolimus or calcipotriol or narrow band ultraviolet‐B in treatment of stable nonsegmental vitiligo

Conventional methods of treatment for vitiligo are often unsatisfactory to the patients and time consuming, new treatment modalities are needed. This study was conducted to evaluate the efficacy and safety of fractional carbon dioxide (CO2) laser therapy followed by narrow band ultraviolet‐B (NB‐UVB) phototherapy, topical tacrolimus or topical calcipotriol on stable nonsegmental vitiligo. Thirty patients with stable nonsegmental vitiligo were evaluated. All patients were subjected to three sessions of fractional CO2 laser 1 month apart. Patients were divided into three groups (each group 10 patients). Group (A) treated with tacrolimus ointment twice daily for 3 months, group (B) treated with calcipotriol ointment twice daily for 3 months, and group (C) treated with NB‐UVB twice weekly for 3 months. Outcomes were evaluated by calculating vitiligo area scoring index (VASI) score change, percentage of repigmentation, patient satisfaction, and adverse effects. There was a statistical significant decrease in VASI score after treatment in the three groups. The VASI change and % of regimentation was higher in group (C) treated by laser and NB‐UVB and this was significantly higher than group (B) treated with laser and calcipotriol. Otherwise, there was no statistical significant difference between other treatment groups. In concluion, NB‐UVB phototherapy, topical tacrolimus, or topical calcipotriol in combination with fractional CO2 laser could be used effectively and safely as an alternative modality for treatment of vitiligo. The combination of fractional CO2 laser and NB‐UVB was found to be more effective.
A novel method for calculating relative free energy of similar molecules in two environments

Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy, simple implementation, robustness and efficiency, which prevent the calculations from being automated and limit their use in computational drug discovery. Here we present an exact and complete decoupling analysis in which the partition functions of the compared systems decompose into the partition functions of the common and different subsystems. This decoupling analysis is applicable to submolecules with coupled degrees of freedom and to any potential function, enabling to remove less terms in the transformation. Then we show mathematically, in the context of partition function decoupling, that the two compared systems can be simulated separately, eliminating the need to design a composite system. We demonstrate the decoupling analysis and the separate transformations in an MD calculation of relative free energy for a general force field which is in agreement with experiments. We present a unified soft core technique that will ensure the monotonicity of the numerically integrated function. Finally, we show that when the systems have rugged energy landscape they can be equilibrated without introducing another sampling dimension. The concepts presented in the article have implications in accuracy, efficiency, simplicity and robustness of free energy calculations.
Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study

Abstract Background Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. Methods We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. Results At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. Conclusions The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. Trial registration ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials. gov. Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr. org.cn/enindex.aspx
A fluidized immunoadsorption device for removing beta-2-microglobulin from whole blood : a potential treatment for dialysis-related amyloidosis

Dialysis-related amyloidosis (DRA) is a frequent complication of end-stage renal disease that has been associated with the accumulation of β2-microglobulin (β2m). Excluding transplantation, existing kidney replacement technologies are believed to remove insufficient quantities of β2m for the prevention of DRA, as they are non-specific and based on size-exclusion. A proposed DRA therapy is to use immunoadsorptive particles within an extracorporeal Vortex Flow Plasmapheretic Reactor (VFPR) to specifically remove β2m from blood. The compartmental design of the VFPR allows for the use of small adsorbent particles (~100 μm) that possess inherent mass-transfer advantages over the larger ones (>400 μm) that are required for safe contact with whole blood for this application. Demonstrating the efficacy of this technology as a therapy for DRA would support its tailored application for treating other pathologies that are caused by circulating compounds such as sepsis, liver failure, autoimmune disease, drug overdoses, and genetic disorders. Whole anti-β2m antibodies (BBM.1) were immobilized onto agarose beads and used within a VFPR to remove donor baseline and defined quantities of recombinant β2m from whole human blood, in vitro. A dynamic immunoadsorption model was developed for the VFPR that was based upon the independent characterization of the mass-transfer processes within the VFPR and the thermodynamics of the immunoadsorbent. The experimentallyobserved and model-predicted dynamics of β2m clearance from the blood indicate that the process controlling the rate of β2m removal was the hemofiltration rate (50 mL-plasma/min),
Cerebrospinal fluid features in COVID-19 patients with neurologic manifestations: correlation with brain MRI findings in 58 patients

Abstract Background Neurological manifestations are common in patients with COVID-19, but little is known about pathophysiological mechanisms. In this single-center study, we describe neurological manifestations of 58 patients, regarding cerebrospinal fluid (CSF) analysis and neuroimaging findings. Methods 58 COVID-19 patients with neurologic manifestations and SARS-CoV-2 RT-PCR screening on CSF analysis were included. Clinical, laboratory, and brain MRI data were retrospectively collected and analyzed. Results Patients were mostly men (66%) with a median age of 62 years. Encephalopathy was frequent (81%), followed by a pyramidal dysfunction (16%), seizures (10%), and headaches (5%). Protein and albumin levels in CSF were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient suggesting impaired blood‐brain barrier integrity. CSF-specific IgG oligoclonal band was found in five (11%) cases, suggesting an intrathecal synthesis of IgG, and 26 (55%) patients presented identical oligoclonal bands in serum and CSF. Four (7%) patients harbored a positive SARS-CoV-2 RT-PCR in CSF. Regarding brain MRI, 20 (38%) patients presented leptomeningeal enhancement. Conclusions Brain MRI abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV 2 detection in CSF remained scanty.
BOILING WATER HEAT TRANSFER BURNOUT IN UNIFORMLY HEATED ROUND TUBES: A COMPILATION OF WORLD DATA WITH ACCURATE CORRELATIONS

All available World burn-out data for vertical, uniformly heated round tubes, with liquid water inlet, have been compiled and are presented in systematic order. A total of 4,389 experimental results is recorded, covering a very extensive range of parameters. Detailed examination of these data over the years has indicated a number of inconsistencies and these are discussed. The majority of the data fall into four main pressure groups: 560, 1000, 1550, and 2000 p.s. i.a. , and accurate correlations of these data are presented together with error distribution histograms and graphical aids to rapid calculation of burn-out flux.
Systemic supplemental oxygen therapy during accelerated corneal crosslinking for progressive keratoconus: randomized clinical trial

Addition of systemic oxygen supplementation during accelerated corneal crosslinking demonstrated greater improvement in maximum keratometry and corneal biomechanics compared with the accelerated crosslinking protocol and the Dresden protocol. Purpose: To investigate the potential additive effect of systemic supplemental oxygen administered during accelerated corneal crosslinking (CXL) for progressive keratoconus (KC). Setting: Academic center. Design: Randomized clinical trial. Methods: Eyes with progressive KC randomized to 3 different CXL protocols were included. The first group (OA-CXL) included 19 eyes that underwent an accelerated CXL protocol (9 mW/cm2 for 10 minutes) while receiving systemic oxygen at a rate of 5 L/min for 10 minutes. The second group consisted of 14 eyes undergoing the same accelerated CXL protocol without supplemental oxygen therapy (A-CXL). The third group (C-CXL) comprised 14 eyes undergoing conventional CXL according to the Dresden protocol. All subjects were followed up for at least 6 months. Visual acuity, keratometry and corneal biomechanical parameters including corneal hysteresis and corneal resistance factor (CRF) were measured preoperatively and 6 months postoperatively. Results: Reduction in maximum keratometry (Kmax) was significantly greater in the OA-CXL group (P = .01). At baseline, the mean Kmax was 54.31 ± 3.64 diopters (D) in the OA-CXL group, 54.66 ± 4.99 D in the A-CXL group, and 56.03 ± 5.28 D in the C-CXL group (P = .58), which reached 53.58 ± 3.24 D, 54.59 ± 4.65 D, and 55.87 ± 4.73 D at 6 months in the 3 study groups, respectively (P = .115). The mean CRF increased significantly only in the OA-CXL group from a baseline value of 6.32 ± 2.12 mm Hg to 7.38 ± 1.88 mm Hg at 6 months (P = .009). Conclusions: This study suggests superior efficacy of an accelerated CXL protocol coupled with systemic oxygen supplementation when compared with the accelerated CXL protocol and the conventional protocol in eyes with progressive KC. In addition to greater reduction in Kmax as the primary outcome, improvement in corneal biomechanics was also observed at 6 months.
DNA methylation dynamics of sperm cell lineage development in tomato.

During the sexual reproduction of higher plants, DNA methylation and transcription are broadly changed to reshape a microspore into two sperm cells and a vegetative cell. However, when and how the DNA methylation of sperm cells is established remains not fully understood. Here we investigate the DNA methylation (5mC) dynamics of sperm cell lineage and the vegetative cell in tomato using whole-genome bisulfite sequencing. We find the asymmetric division of the microspore gives its two daughter cells differential methylome. Compared with the generative cell, the vegetative cell is hypomethylated at CG sites while hypermethylated at CHG and CHH sites with the majority of differentially methylation regions (DMRs) targeted to transposable elements (TEs). Sperm cells have a nearly identical DNA methylome to the generative cell, suggesting that the methylation landscape in sperm cells may be pre-established following the asymmetric division or inherited from the generative cell. The random forest classifier for predicting gene and TE expression shows that methylation within the gene body is a more powerful predictor for gene expression. Among all tested samples, gene and TE expression in the microspore may be more predictable by DNA methylation. Our results depict an intact DNA methylome landscape of sperm cell lineage in higher plants and reveal that the impact of DNA methylation on transcription is variant in different cell types. SUPPORTING INFORMATION.
Climate, urbanization, and species traits interactively drive flowering duration

A wave of green leaves and multi‐colored flowers advances from low to high latitudes each spring. However, little is known about how flowering offset (i.e., ending of flowering) and duration of populations of the same species vary along environmental gradients. Understanding these patterns is critical for predicting the effects of future climate and land‐use change on plants, pollinators, and herbivores. Here, we investigated potential climatic and landscape drivers of flowering onset, offset, and duration of 52 plant species with varying key traits. We generated phenology estimates using >270,000 community‐science photographs and a novel presence‐only phenometric estimation method. We found longer flowering durations in warmer areas, which is more obvious for summer‐blooming species compared to spring‐bloomers driven by their strongly differing offset dynamics. We also found that higher human population density and higher annual precipitation are associated with delayed flowering offset and extended flowering duration. Finally, offset of woody perennials was more sensitive than herbaceous species to both climate and urbanization drivers. Empirical forecast models suggested that flowering durations will be longer in 2030 and 2050 under representative concentration pathway (RCP) 8.5, especially for summer‐blooming species. Our study provides critical insight into drivers of key flowering phenophases and confirms that Hopkins’ Bioclimatic Law also applies to flowering durations for summer‐blooming species and herbaceous spring‐blooming species.
Clinical Characteristics and Treatment Response With Checkpoint Inhibitors in Malignant Melanoma of the Vulva and Vagina

Objectives The aims of the study were to assess the clinical and histopathological characteristics of a comprehensive cohort of women with vulvovaginal melanoma (VVM) treated at our institution and to study the treatment response of checkpoint inhibitors in this patient cohort. Materials and Methods This is a retrospective study of women with invasive VVM treated at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, over a period of 15 years. Clinical and histopathological characteristics, treatment, as well as treatment-related outcome were analyzed in 32 women. Treatment response was evaluated retrospectively using the “response criteria for use in trials testing immunotherapeutics” (iRECIST). The objective response rate was defined as the proportion of patients with complete or partial response based on the best overall response. Results At a median follow-up of 37.8 months (5.8–110.4), 26 women (81.3%) had disease progression and 16 (50%) died. Thirteen patients with locally unresectable or metastatic melanoma were treated with immune checkpoint inhibitors. Ten additional cases were identified from previously published reports. The best objective response rate for immune checkpoint inhibitors was 30.4% (95% CI = 11.6%–49.2%) and the clinical benefit rate was 52.2% (95% CI = 31.8%–72.6%). The clinical benefit rate was significantly better for programmed cell death protein 1 inhibitors (or a combination) compared with ipilimumab alone (Fisher exact, p = .023). Grade 3/4 adverse events were observed in 3 (13.0%) of the 23 patients. Conclusions Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.
Prediction of Individual Basal Rate Profiles From Patient Characteristics in Type 1 Diabetes on Insulin Pump Therapy

Background: Basal rate profiles in patients with type 1 diabetes on insulin pump therapy are subject to enormous inter-individual heterogeneity. Tools to predict basal rates based on clinical characteristics may facilitate insulin pump therapy. Methods: Data from 339 consecutive in-patients with adult type 1 diabetes on insulin pump therapy were collected. Basal rate tests were performed over 24 hours. A mathematical algorithm to predict individual basal rate profiles was generated by relating the individual insulin demand to selected clinical characteristics in an exploratory cohort of 170 patients. The predicted insulin pump profiles were validated in a confirmatory cohort of 169 patients. Findings: Basal rates (0.27 ± 0.01 IU.d−1.kg−1) showed circadian variations with peaks corresponding to the “dawn” and “dusk” phenomena. Age, gender, duration of pump treatment, body-mass-index, HbA1c, and triacylglycerol concentrations largely predicted the individual basal insulin demand per day (IU/d; exploratory vs prospective cohorts: r2 = 0.518, P < .0001). Model-predicted and actual basal insulin rates were not different (exploratory cohort: Δ 0.1 (95% CI −0.9; 1.0 U/d; P = .95; prospective cohort: Δ −0.5 (95% CI −1.5; 0.6 IU/d; P = .46). Similarly, precise predictions were possible for each hour of the day. Actual and predicted “dawn” index correlated significantly in the exploratory but not in the confirmatory cohort. Interpretation: Clinical characteristics predict 52% of the variation in individual basal rate profiles, including their diurnal fluctuations. The multivariate regression model can be used to initiate or optimize insulin pump treatment in patients with type 1 diabetes.
Role of pre‐transplant MRD level detected by flow cytometry in recipients of allogeneic stem cell transplantation with AML

We analyzed the impact of pretransplant MRD level in bone marrow measured by flow cytometry using “different from normal” method on outcomes for 189 AML patients (108 males; median age, 58 (21‐80) years). All patients were subdivided into negative (n = 96), “low” (0.1%‐0.5%, n = 32), and “high” MRD (>0.5%, n = 61) groups.
Antileishmanial activity of neo-clerodane diterpenes from Croton echioides

Abstract Nowadays, new leishmanicidal drugs are needed and natural products arise as a promising alternative source. Therefore, bioguided fractionation of a hydroethanolic extract from the stem bark of Croton echioides Baill. were conducted based on its antileishmanial activity. Two novel neo-clerodane diterpenoids methyl-15,16-epoxy-3,13(16),14-neo-clerodatrien-17,18-dicarboxylate (1) and dimethyl-3-oxo-15,16-epoxy-13(16),14-neo-clerodadien-17,18-dicarboxylate (2) were isolated, as well as four known compounds (3–6) and lupeol, from the hexane fraction. Their structures were established by NMR analysis. The crude extract, fractions and the compounds (1 and 3–6) were evaluated for their in vitro antileishmanial activity and cytotoxicity against macrophages J774A.1. The selectivity index (SI) were calculated. The most active compound against promastigote forms of L. amazonensis was the clerodane diterpene 4, with IC50 values of 8.3 µM and SI value of 80.9. Our results highlighted stem bark of Croton echioides Baill. as a promising source for the development of a new chemotherapeutic agent to combat leishmaniasis. Graphical Abstract
Needle-based Confocal Laser Endomicroscopy (nCLE) for Evaluation of Pancreatic Cystic Lesions

Supplemental Digital Content is available in the text. Background and Aims: Given the variable diagnostic yield of endoscopic ultrasound and endoscopic ultrasound–guided fine-needle aspiration for pancreatic cystic lesions (PCLs), novel imaging techniques including needle-based confocal laser endomicroscopy (nCLE) have been devised. The aim of this study was to perform a structured systematic review and meta-analysis to evaluate the diagnostic performance and safety of nCLE for the diagnosis of PCLs. Methods: Individualized search strategies were developed in accordance with PRISMA and MOOSE guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. Measured outcomes included diagnostic characteristics and procedure-associated adverse events. A bivariate model was used to compute combined weighted sensitivity, specificity, positive/negative likelihood ratio (LR), diagnostic odds ratio, and summary receiver operating characteristic curve with corresponding 95% confidence intervals (CIs). Results: Seven studies (n=324; mean age: 63.99±5.36 y; 52.47% female) were included. The pooled sensitivity, specificity, positive LR, and negative LR of nCLE was 85% (95% CI, 71-93; I 2=74.20%), 99% (95% CI, 90-100; I 2=72.60%), 78.66 (95% CI, 7.99-774.68; I 2=26.86%), and 0.15 (95% CI, 0.07-0.31; I 2=75.84%), respectively. Diagnostic accuracy as measured by summary receiver operating characteristic curve was 99% (95% CI, 98-100). The pooled diagnostic odds ratio was 534 (95% CI, 50-5664; I 2=58.00%). Postprocedure pancreatitis developed in 1% (95% CI, 0-3; I 2=5.64%) of cases. Conclusions: On the basis of this meta-analysis, nCLE appears to be an effective and safe technique for the diagnostic evaluation of PCLs. Although moderate-to-high amounts of heterogeneity were present, our results demonstrated that nCLE has a diagnostic accuracy of 99% with a low rate of adverse events.