Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel chromobox 2 inhibitory peptide decreases tumor progression

ABSTRACT Background The Polycomb Repressor Complex 1 (PRC1) is an epigenetic regulator of differentiation and development, consisting of multiple subunits including RING1, BMI1, and Chromobox. The composition of PRC1 dictates its function and aberrant expression of specific subunits contributes to several diseases including cancer. Specifically, the reader protein Chromobox2 (CBX2) recognizes the repressive modifications including histone H3 lysine 27 tri-methylation (H3K27me3) and H3 lysine 9 dimethylation (H3K9me2). CBX2 is overexpressed in several cancers compared to the non-transformed cell counterparts, it promotes both cancer progression and chemotherapy resistance. Thus, inhibiting the reader function of CBX2 is an attractive and unique anti-cancer approach. Research design & methods Compared with other CBX family members, CBX2 has a unique A/T-hook DNA binding domain that is juxtaposed to the chromodomain (CD). Using a computational approach, we constructed a homology model of CBX2 encompassing the CD and A/T hook domain. We used the model as a basis for peptide design and identified blocking peptides that are predicted to directly bind the CD and A/T-hook regions of CBX2. These peptides were tested in vitro and in vivo models. Conclusion The CBX2 blocking peptide significantly inhibited both 2D and 3D growth of ovarian cancer cells, downregulated a CBX2 target gene, and blunted tumor growth in vivo.
Automated Detection of Optic Nerve Boundary Based on L~*a~*b~* Color Space

The parameters of optic nerve,such as shape,area, depth and so on,are the important indices to estimate the retinal health.Extraction of the optic nerve boundary is the precon- dition for quantifying these parameters.To accurately identify the boundary,a new method to detect the exact optic nerve boundary is proposed based on the L*a*b* color space in this paper.Using morphology and region-aided geometric snake in the L*a*b* color space,the method applies the automatic optic nerve localization base on cross-network to realize the automatic extraction of optic nerve boundary.The feasibility of the new method has been successfully tested for the DRIVE fundus im- age databases and our clinic images.
An Experiment on the Sensitivity of a Global Circulation Model

Abstract The growth of small errors in numerical models of the atmospheric circulation destroys the detailed predictive capability of those models within a few days. Despite the failure of the models to produce accurate local predictions, it was hypothesized that a change in the equator-to-pole temperature gradient would produce discernible effects in average conditions. This paper presents the results of an experiment to test this hypothesis. The Mintz-Arakawa model was started with a standard set of initial conditions and was run 60 days. The experiment was then replicated twice, with two independent sets of random temperature variations superposed on the temperatures at the σ = 0.25 and σ = 0.75 levels. At this point, the ice of the Arctic Ocean was replaced with water at the freezing temperature. Again the model was run, starting once with the standard initial conditions (other than the ice removal) and once each with the two sets of temperature “errors” added. For the four replications with temperatu.
Molecular recognition requires dimerization of a VHH antibody

ABSTRACT Camelid heavy-chain-only antibodies are a unique class of antibody that possesses only a single variable domain (termed VHH) for antigen recognition. Despite their apparent canonical mechanism of target recognition, where a single VHH domain binds a single target, an anti-caffeine VHH has been observed to possess 2:1 stoichiometry. Here, the structure of the anti-caffeine VHH/caffeine complex enabled the generation and biophysical analysis of variants that were used to better understand the role of VHH homodimerization in caffeine recognition. VHH interface mutants and caffeine analogs, which were examined to probe the mechanism of caffeine binding, suggested caffeine recognition is only possible with the VHH dimer species. Correspondingly, in the absence of caffeine, the anti-caffeine VHH was found to form a dimer with a dimerization constant comparable to that observed with VH:VL domains in conventional antibody systems, which was most stable near physiological temperature. While the VHH:VHH dimer structure (at 1.13 Å resolution) is reminiscent of conventional VH:VL heterodimers, the homodimeric VHH possesses a smaller angle of domain interaction, as well as a larger amount of apolar surface area burial. To test the general hypothesis that the short complementarity-determining region-3 (CDR3) may help drive VHH:VHH homodimerization, an anti-picloram VHH domain containing a short CDR3 was generated and characterized, which revealed it also existed as dimer species in solution. These results suggest homodimer-driven recognition may represent a more common method of VHH ligand recognition, opening opportunities for novel VHH homodimer affinity reagents and helping to guide their use in chemically induced dimerization applications.
Topical roflumilast for the treatment of psoriasis

ABSTRACT Introduction New non-steroidal topical agents are needed for the treatment of psoriasis. Roflumilast cream 0.3% is a once daily phosphodiesterase-4 inhibitor that was recently approved by the FDA for the treatment of plaque psoriasis in adolescents and adults. It is indicated for use on all body surfaces including intertriginous areas. Areas covered In this review, we summarize the current knowledge about roflumilast cream for the treatment of psoriasis, highlighting its efficacy and safety profile from published clinical trials. Roflumilast’s mechanism of action and pharmacokinetic profile are also discussed. Expert opinion Positive results were reported across trials with 48% of patients treated with roflumilast achieving an Investigator Global Assessment score of clear or almost clear at 8 weeks in phase III studies. Most adverse events were mild or moderate in severity and few application-site reactions were reported among participants. Unique advantages of the cream are its success in treating intertriginous areas and its ability to reduce symptoms of itch, results of which may significantly improve quality of life for patients. In the future, real-world data and active comparator trials with existing non-steroidal agents are needed to better understand roflumilast’s place in the current treatment landscape.
Transgenic modifications of silkworms as a means to obtain therapeutic biomolecules and protein fibers with exceptional properties

Transgenic modification of Bombyx mori silkworms is a benign approach for the production of silk fibers with extraordinary properties and also to generate therapeutic proteins and other biomolecules for various applications. Silk fibers with fluorescence lasting more than a year, natural protein fibers with strength and toughness exceeding that of spider silk, proteins and therapeutic biomolecules with exceptional properties have been developed using transgenic technology. The transgenic modifications have been done primarily by modifying the silk sericin and fibroin genes and also the silk producing glands. Although the genetic modifications were typically performed using the sericin 1 and other genes, newer techniques such as CRISPR/Cas9 have enabled successful modifications of both the fibroin H‐chain and L‐chain. Such modifications have led to the production of therapeutic proteins and other biomolecules in reasonable quantities at affordable costs for tissue engineering and other medical applications. Transgenically modified silkworms also have distinct and long‐lasting fluorescence useful for bioimaging applications. This review presents an overview of the transgenic techniques for modifications of B. mori silkworms and the properties obtained due to such modifications with particular focus on production of growth factors, fluorescent proteins, and high performance protein fibers.
Dynamic Output Feedback Controller Design for a Class of Takagi-Sugeno Descriptor Systems

This paper considers the design problem of dynamic output feedback controller for a class of nonlinear descriptor systems described by Takagi-Sugeno (T-S) fuzzy models with measurable premise variables. The approach is based on the separation between dynamic and static relations in the descriptor model. The convergence of the closed-loop state system is studied by using the Lyapunov theory and the stability conditions are given in terms of linear matrix inequalities (LMIs). In practice, the computation of solutions of descriptor systems requires the combination of an ordinary differential equation (ODE) routine together with an optimization algorithm. The main result of this paper consists in showing that the dynamic output feedback controller problem for a class of T-S descriptor systems can be achieved by using a fuzzy controller based on an ODE structure only. Finally, simulation results are provided in order to show the validity of the proposed method.
Diagnostic Tests for Innovations of ARMA Models Using Empirical Processes of Residuals

In view of applications to diagnostic tests of ARMA models, the asymptotic behavior of multivariate empirical and copula processes based on residuals of ARMA models is investigated. Multivariate empirical processes based on squared residuals and other functions of the residuals are also investigated. It is shown how these processes can be used to develop distribution free tests of change-point analysis and serial independence. It is also demonstrated that these empirical processes provide an easy mechanism for developing goodness-of-fit tests for the distribution of the innovations, and that the well-known Lilliefors test can be applied to the residuals of ARMA models without any change.
A CXCR4 inhibitor (balixafortide) enhances docetaxel‐mediated antitumor activity in a murine model of prostate cancer bone metastasis

Prostate cancer (PCa) bone metastases have been shown to be more resistant to docetaxel than soft tissue metastases. The proinflammatory chemokine receptor CXCR4 has been shown to confer resistance to docetaxel (DOC) in PCa cells. Balixafortide (BLX) is a protein epitope mimetic inhibitor of CXCR4. Accordingly, we hypothesized that BLX would enhance DOC‐mediated antitumor activity in PCa bone metastases.
Trends in prostate cancer incidence among Black men in the Caribbean and the United States

Prostate cancer incidence is highest for Black men of the African diaspora in the United States and Caribbean. Recent changes in recommendations for prostate cancer screening have been shown to decrease overall prostate cancer incidence and increase the likelihood of late stage disease. However, it is unclear how trends in prostate cancer characteristics among high risk Black men differ by geographic region during the changes in screening recommendations.
Mechanical Dispersion Discriminates between Arrhythmic and Non-Arrhythmic Sudden Death: From the POST SCD Study

Background: Global longitudinal strain (GLS) and mechanical dispersion (MD) by speckle-tracking echocardiography can predict sudden cardiac death (SCD) beyond left ventricular ejection fraction (LVEF) alone. However, prior studies have presumed cardiac cause from EMS records or death certificates rather than gold-standard autopsies. Objectives: We sought to investigate whether abnormal GLS and MD, reflective of underlying myocardial fibrosis, are associated with autopsy-defined sudden arrhythmic death (SAD) in a comprehensive postmortem study. Methods: We identified and autopsied all World Health Organization-defined (presumed) SCDs ages 18-90 via active surveillance of out of hospital deaths in the ongoing San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study to refine presumed SCDs to true cardiac causes. We retrieved all available pre-mortem echocardiograms and assessed LVEF, LV-GLS, and MD. The extent of LV myocardial fibrosis was assessed and quantified histologically. Results: Of 652 autopsied subjects, 65 (10%) had echocardiograms available for primary review, obtained at a mean 1.5 years before SCD. Of these, 37 (56%) were SADs and 29 (44%) were non-SADs; fibrosis was quantified in 38 (58%). SADs were predominantly male, but had similar age, race, baseline comorbidities, and LVEF compared to non-SADs (all p>0.05). SADs had significantly reduced LV-GLS (median: -11.4% versus -18.5%, p=0.008) and increased MD (median: 14.8 ms versus 9.4 ms, p=0.006) compared to non-SADs. MD was associated with total LV fibrosis by linear regression in SADs (r=0.58, p=0.002). Conclusion: In this countywide postmortem study of all sudden deaths, autopsy-confirmed arrhythmic deaths had significantly lower LV-GLS and increased MD than non-arrhythmic sudden deaths. Increased MD correlated with higher histologic levels of LV fibrosis in SADs. These findings suggest that increased MD, which is a surrogate for the extent of myocardial fibrosis, may improve risk stratification and specification for SAD beyond LVEF.
Glyoxal Acid-Free (GAF) histological fixative is a suitable alternative to formalin: results from an open label comparative non-inferiority study.

Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, Glyoxal Acid-Free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard Phosphate Buffered Formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local centre reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7+/-0.5 vs 3.9+/-0.3 for the central reviewer and 3.8+/-0.5 vs 4.0+/-0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organ tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both, structural preservation and diagnostic value of the preparations.
DNA repair biomarkers to guide usage of combined PARP inhibitors and chemotherapy: a meta-analysis and systematic review

Purpose The addition of PARP inhibitors to chemotherapy has been assessed in ~80 clinical trials across multiple malignancies, on the premise that PARP inhibitors will increase chemotherapy effectiveness regardless of whether cancers have underlying disruption of DNA repair pathways. Consequently, the majority of combination therapy trials have been performed on patients without biomarker selection, despite the use of homologous recombination deficiency to dictate use of PARP inhibitors in the maintenance setting. An unresolved question is whether biomarkers are needed to identify patients who respond to combination PARP inhibitors and chemotherapy. Methods A systematic literature review identified studies using PARP inhibitors in combination with chemotherapy versus chemotherapy alone, where the study included a biomarker of DNA repair function (BRCA1, BRCA2, BRCAPRO, ATM, ERCC1, SFLN11). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance and fixed or random effects modelling. Subgroup analyses were conducted on biomarker selection and type of malignancy. Results Nine studies comprising 2,084 patients met the inclusion criteria. Progression-free survival (PFS) was significantly better in patients with a DNA repair biomarker (HR 0.52, 95% confidence interval (CI) 0.43 to 0.63; p < 0.00001), but there was no benefit in patients who lacked a biomarker (HR 0.94, 95% CI 0.82 to 1.08; p = 0.38). Subgroup analysis showed that BRCA mutation and SFLN11 biomarkers could predict benefit, and biomarker-driven benefit occurred in ovarian, breast and small cell lung cancers. The addition of PARP inhibitors was associated with increased grade 3/4 side effects, and particularly neutropenia. Conclusions Combination therapy only increases PFS in patients with identifiable DNA repair biomarkers. This indicates that PARP inhibitors do not sensitise patients to chemotherapy treatment, except where their cancer has a homologous recombination defect, or an alternative biomarker of altered DNA repair. While effective in patients with DNA repair biomarkers, there is a risk of high-grade haematological side-effects with the use of combination therapy. Thus, the benefit in PFS from combination therapy must be weighed against potential adverse effects, as individual arms of treatment can also confer benefit.
Nurses' perceptions of videoconferencing telenursing: comparing frontal learning vs. online learning before and after the COVID-19 pandemic

Introduction: During the COVID-19 pandemic, a digital transformation led to an expansion in telenursing practices and a shift in training to online learning. The aim of this study was to explore the impact of behavioral-related factors, based on both TAM and TPB variables, on the intention to use telenursing through videoconferencing and to compare the effect of frontal (before COVID-19) vs. online (during and after COVID-19) training in post-basic nursing courses on nursing attitudes to telenursing. Methods: A cross-sectional online survey was conducted in December 2022 among nurses working mainly at hospitals in Israel who underwent post-basic education training between January 2017 and December 2022. A multivariate ordinary least squares (OLS) regression analysis was used to investigate determinants of intention to use telenursing through videoconferencing Results: Nurses have a positive attitude towards telenursing technology via videoconferencing for remote patient care, regardless of whether they learned about it through face-to-face or online training. The ease of use and the perception of the technology's importance by colleagues and supervisors were found to have the most significant impact on the attitude of both research groups towards the use of telelearning. Discussion: Successful implementation of new technology in healthcare requires organizational and collegial support. Therefore, managers should encourage the use of telenursing by providing appropriate training for nurses and the necessary resources and support.
Continuous renal replacement therapy in patients receiving extracorporeal membrane oxygenation therapy

Methods of continuous renal replacement therapy (CRRT) in extracorporeal membrane oxygenation (ECMO) patients include dedicated central venous cannula (CVC) (vCRRT), in-series with filter connected to ECMO circuit (eCRRT) or in-line with haemodiafilter incorporated within ECMO circuit. We assessed the efficacy and safety of eCRRT versus vCRRT in 20 ECMO-CRRT patients. Average filter lifespan was 42 vs 28 hours and filter runs completing 72hours were 40% vs 13.8% (eCRRT vs vCRRT, respectively). One incidence of ECMO circuit air embolus occurred (vCRRT). eCRRT achieved adequate filtration and increased filter lifespan, and has become our default for ECMO-CRRT if a pre-existing dialysis CVC is not present.
Fingerprint Image Segmentation Based on Support Vector Machines

We present a fingerprint image segmentation algorithm based on support vector machines(SVM). The algorithm uses the features of the gray variance and contrast to train the SVM for image segmentation,and fits the segmentation result of the SVM to convex hull.The experimental results show the algorithm is robust,especially for training segmentation algorithm with a small quantity of samples.
Increased abundance of bacteria of the family Muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats

Background The incidence of nephrolithiasis is increasing rapidly worldwide. Calcium oxalate is the most common constituent, contributing to approximately 80% of all kidney stones. The gut microbiome, through its oxalate-degrading ability, may play a role in decreasing morbidity due to urinary calculus. Fecal microbiome transplantation (FMT) has been reported to be effective in restoring the gastrointestinal microbial community in different conditions. The transplantation of whole communities that have oxalate-degrading function may be a more effective strategy than the transplantation of isolated strains. Methods FMT was carried out in male guinea pigs and male Sprague–Dawley laboratory rats (SDRs). Fresh feces were collected from guinea pigs housed in metabolic cages. SDRs were divided into four groups: two groups received standard rat chow (SC) (groups SC and SC + FMT), and two groups were fed a 5% potassium oxalate diet (OD) (groups OD + phosphate-buffered saline (PBS) and OD + FMT). On day 14, groups OD + PBS, OD + FMT, and SC + FMT received either PBS or guinea pig feces by esophageal gavage. The composition of the microbiota of guinea pigs and SDRs was analyzed using a 16S rRNA gene sequencing approach. Biochemical analysis of urine samples from SDRs revealed the presence of calcium oxalate (CaOx) crystals, which were presumed to originate from kidney stones. Renal function was examined using real-time PCR analysis and immunohistochemical staining for renin, angiotensin-converting enzyme, and osteopontin (OPN) expression. Results FMT resulted in a gut microbiota that was a mixture of guinea pig and SDR bacteria. A microbial network involving Muribaculaceae, Lactobacillus, and Bifidobacterium was activated by FMT in group OD + FMT. As a result, urinary oxalate, calcium, uric acid, creatinine and urea in urine samples were reduced significantly. Similarly, significant reduction of uric acid and blood urea nitrogen to creatinine ratio in serum samples was observed (p < 0.05). Microscopic observations revealed a high CaOx crystal score (4+) in the kidneys of rats in group OD + PBS, whereas a lower score (2+) was observed in the rats in group OD + FMT. Up-regulation of OPN and down-regulation of renin were also associated with FMT. Conclusion A microbial network involving Muribaculaceae and other oxalate-degrading bacteria achieved by FMT was capable of reducing urinary oxalate excretion and CaOx crystal deposition in the kidney through increasing intestinal oxalate degradation. FMT may exert a renoprotective function in oxalate-related kidney stones.