Miracle-dz/UniFAR-FTUs huggingface dataset:
Presumed neuroprotective therapies prescribed by veterinary ophthalmologists for canine degenerative retinal and optic nerve diseases.

OBJECTIVE To investigate veterinary ophthalmologists' use of presumed neuroprotective therapies for degenerative retinal and optic nerve diseases in dogs. PROCEDURES An online survey was sent to 663 board-certified veterinary ophthalmologists who were Diplomates of the American College of Veterinary Ophthalmologists (ACVO), Asian College of Veterinary Ophthalmologists (AiCVO), Latin American College of Veterinary Ophthalmologists (Colegio Latinoamericano de Oftalmólogos Veterinarios, CLOVE), or European College of Veterinary Ophthalmologists (ECVO). The survey was created using Qualtrics® software and focused on the prescription of presumed neuroprotective treatments for canine glaucoma, sudden acquired retinal degeneration syndrome (SARDS), progressive retinal atrophy (PRA), and retinal detachment (RD). RESULTS A total of 165 completed surveys were received, representing an overall response rate of 25%, which was comparable across the four specialty colleges. Of all respondents, 140/165 (85%) prescribed some form of presumed neuroprotective therapies at least once in the last five years: 114/165 (69%) for glaucoma, 51/165 (31%) for SARDS, 116/165 (70%) for PRA, and 50/165 (30%) for RD. The three most recommended neuroprotective reagents were the commercial Ocu-GLO™ Vision Supplement for animals, amlodipine, and human eye supplements. CONCLUSIONS Despite lack of published clinical efficacy data, the majority of surveyed board-certified veterinary ophthalmologists previously prescribed a presumed neuroprotective therapy at least once in the last five years in dogs with degenerative retinal and optic nerve diseases.
HIR V2: a human interactome resource for the biological interpretation of differentially expressed genes via gene set linkage analysis

Abstract To facilitate biomedical studies of disease mechanisms, a high-quality interactome that connects functionally related genes is needed to help investigators formulate pathway hypotheses and to interpret the biological logic of a phenotype at the biological process level. Interactions in the updated version of the human interactome resource (HIR V2) were inferred from 36 mathematical characterizations of six types of data that suggest functional associations between genes. This update of the HIR consists of 88 069 pairs of genes (23.2% functional interactions of HIR V2 are in common with the previous version of HIR), representing functional associations that are of strengths similar to those between well-studied protein interactions. Among these functional interactions, 57% may represent protein interactions, which are expected to cover 32% of the true human protein interactome. The gene set linkage analysis (GSLA) tool is developed based on the high-quality HIR V2 to identify the potential functional impacts of the observed transcriptomic changes, helping to elucidate their biological significance and complementing the currently widely used enrichment-based gene set interpretation tools. A case study shows that the annotations reported by the HIR V2/GSLA system are more comprehensive and concise compared to those obtained by the widely used gene set annotation tools such as PANTHER and DAVID. The HIR V2 and GSLA are available at http://human.biomedtzc. cn.
Meiobenthic biodiversity in areas of the Gulf of Taranto (Italy) exposed to high environmental impact

Biological and chemical parameters (meiofauna density and diversity, redox profiles) were investigated in relation to the environmental conditions of sediments in the Gulf of Taranto. Sediment cores were collected from 42 stations from −5 to −20 m depth, in 1995, 2000 and 2001. Meiofauna abundance and diversity were significantly lower in the Mar Piccolo, the area most heavily polluted by organic loads; in Mar Grande and Chiatona areas the same parameters showed slightly higher values. Eh profiles revealed anoxic conditions in coastal sediments impacted by industrial and sewage discharges. Meiofauna density ranged from 186 to 1370 individuals × 10 cm−2. Generally, over 80% of total meiofauna was composed of nematodes; the contribution of other taxa is much less important. The widespread presence of the lessepsian Chlorophyte Caulerpa racemosa since 1996, seemed to enhance the abundance of meiofauna, and increased microhabitat complexity, but reduced diversity of some taxa, such as the meiobenthic crustaceans. Comparing 2001–2002 data with 1995 (before C. racemosa invasion), the recent decrease of some groups (ostracods, amphipods, isopods, tanaids and cumaceans) was markedly evident. In conclusion, our findings confirm the chronically degraded environmental conditions in the Gulf of Taranto, and draw attention to the further contribution of C. racemosa invasion.
Associations of Serum Nonesterified Fatty Acids With Coronary Heart Disease Mortality and Nonfatal Myocardial Infarction: The CHS (Cardiovascular Health Study) Cohort

Background Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n‐6 and n‐3], and trans fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. Methods and Results CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996–1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow‐up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P=0.0328) and dihomo‐γ‐linolenic acid (20:3n‐6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02–1.76; P=0.0351). Elaidic acid (18:1n‐7t) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01–2.12; P=0.0445). No significant associations were observed for NEFA subclass and any outcomes. Conclusions In CHS participants, 2 NEFAs, dihomo‐γ‐linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.
Structural insight into the binding interactions of NTPs and nucleotide analogues to RNA dependent RNA polymerase of SARS-CoV-2

Abstract RNA dependent RNA polymerase (RdRP) from positive-stranded RNA viruses has always been a hot target for designing of new drugs. Major class of drugs that are targeted against RdRP are nucleotide analogues. Extensive docking and molecular dynamics study describing the binding of natural nucleotides (NTPs) and its analogues leading to significant structural variation in the RdRP has been presented here. RdRP simulations in its apo, NTP-bound, and analogue-bound form have been performed. Nucleotide analogues included in this study were, favipiravir, galidesivir, lamivudine, ribavirin, remdesivir and sofosbuvir. The conformational flexibility of the RdRP molecule has been explored using principal component (PCA) and Markov state modeling (MSM) analysis. PCA inferred the presence of correlated motions among the conserved motifs of RdRP. Inter-domain distances between the finger and thumb subdomain flanking the nascent RNA template entry site sampled open and closed conformations. The ligand and template binding motifs F and G showed negatively correlated motions. K551, R553, and R555, a part of motif F appear to form strong interactions with the ligand molecules. R836, a primer binding residue was observed to strongly bind to the analogues. MSM analysis helped to extract statistically distinct conformations explored by the RdRP. Ensemble docking of the ligands on the Markov states also suggested the involvement of the above residues in ligand interactions. Markov states obtained clearly demarcated the open/closed conformations of the template entry site. These observations on residues from the conserved motifs involved in binding to the ligands may provide an insight into designing new inhibitors. Communicated by Ramaswamy H. Sarma
COLORECTAL SURGERY Computed tomography-measured body composition parameters do not influence survival in non-metastatic colorectal cancer

Background: There is an increasing interest in studying the impact of altered body composition parameters and colorectal cancer (CRC) treatment outcomes. The aim of this study is to explore the impact of computed tomography (CT)-measured visceral obesity, sarcopenia and myosteatosis on survival of non-metastatic CRC. Methods: Consecutive patients with stage I–III CRC who underwent curative-intent treatment between January 2010 and December 2015 were included. By measuring the visceral fat area, and the skeletal muscle index and radiodensity in the pre-operative staging CT, patients were classified as visceral obese, sarcopenic or myosteatotic. The associations between CT-based body composition parameters and survival were assessed using log-rank tests and a Cox regression analysis. Results: Of 359 patients, 263 (73.3%) were visceral obese, 85 (23.7%) sarcopenic and 80 (22.3%) myosteatotic. Overall (OS), cancer-specific (CSS) and disease-free survivals (DFS) at 5 years were 78.8%, 84.7% and 75%, respectively. Myosteatosis and the combination of myosteatosis and visceral obesity were associated with a reduced DFS (hazard ratio 1.67; 95% confidence interval 1.06–2.61 and hazard ratio 1.85; 95% confidence interval 1.15–2.96, respectively). However, after performing a multivariate analysis including other relevant clinicopathological factors, none of the body composition parameters were associated with any long-term outcome measures, even after stratifying by cancer stage. Conclusions: CT-measured body composition parameters do not independently influence survival in non-metastatic CRC. There is a need for larger cohort studies with standardized patient selection and methodology to confirm these findings.
Comparative pharmacokinetic analysis of the blood-brain barrier penetration of dasatinib and ponatinib in mice

Karthik Ravi , Andrea Franson , Morgan J. Homan, Holly Roberts, Manjunath P. Pai, Zachary Miklja, Miao He, Bo Wen, Lydia L. Benitez, Anthony J. Perissinotti, Dale L. Bixby, Carl Koschmann and Bernard L. Marini Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; University of Michigan College of Pharmacy, Ann Arbor, MI, USA; Medical College of Wisconsin, Wauwatosa, WI, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
Classification of distinct endotypes in human skin scarring: S. C. A. R. - A novel perspective on dermal fibrosis.

SIGNIFICANCE Skin scarring is a permanent, irreversible end point of cutaneous injury and is recognized as complex with significant variability in individuals' scar type and response to treatment. Despite these tangible differences in treatment response, to date there has been no simplified approach in defining spectrum of skin scarring in relation to prediction and outcome post-treatment. Thus, we here propose that scarring consists of distinct endotypes which is characterised by their specific pathology. Four distinct scar endotypes can be observed: (1) Stretched (flat), (2) Contracted, (3) Atrophic (depressed) and (4) Raised scarring, which can be abbreviated to S.C. A.R. endotypes. We also present a structured approach in assessment of all parameters in scar evaluation including: clinical (symptoms, & signs) & non-clinical parameters (device measurements of structural, mechanical and physiological properties of scars as well as gene/protein laboratory studies). Recent Advances: Scars can be phenotypically characterised based on a multitude of parameters assessed, however, not all scar types will share all of the same characteristics. This leads to the question of whether skin scarring is a single disease entity with varying phenotypic characteristics or should be classed as several disease entities which have certain similar parameters. We suggest the latter and propose distinct scarring phenotypes arise mainly due to genetic, and environmental susceptibilities associated with the development of each specific scar endotype. CRITICAL ISSUES The concept of identifying different endotypes is key in formulating personalised treatments with improved outcomes beyond what is achieved with current non-specific approaches in scar management. This approach has gained interest and significant traction in several other medical conditions including asthma, rheumatoid arthritis and atopic dermatitis. FUTURE DIRECTIONS By identifying distinct endotypic features in skin scarring, this approach may lead to improved theranostic outcomes and further understanding of the pathophysiology of the complex nature of human skin scarring.
Family Matters in Ontario: Understanding and Addressing Homelessness Among Newcomer Families in Canada

Background Canada, a key player in global humanitarian affairs is faced with enormous challenges in relation to housing and homelessness. As international migration continues to occur, homelessness among immigrant families is increasing worldwide; a situation that needs urgent attention and action. Purpose We designed this study to explore the needs of homeless families, identify risk factors associated with family homelessness, and to find strategies that could assist in mitigating and preventing homelessness among families in Canada. Methods This paper reports qualitative findings from a focused ethnographic study embedded in participatory action research that explored the experiences of 11 immigrant families with housing challenges in Ontario Canada. Results Thematic analysis yielded five (5) major themes: life challenges; lack of understanding of the system; difficulty with conflict resolution; escaping as a solution for hardship; and reducing immigrant family homelessness. Conclusion Findings from the study highlight the urgent need for advocacy and a well-tailored supportive housing policy to address family homelessness in Ontario.
Advances in In Situ Ultra-High Vacuum Electron Microscopy: Growth of SiGe on Si

▪ Abstract In situ Ultra-High Vacuum (UHV) electron microscopy, including Transmission Electron Microscopy (TEM) at 300 keV electron energy and Low-Energy Electron Microscopy (LEEM) at 0-30 eV electron energy, has advanced enormously over the last decade. Growth of thin films such as epitaxial Si1−xGex alloy thin films on Si substrates has become routine, allowing high-resolution video-rate studies of processes such as misfit dislocation injection and interaction, surface roughening and faceting, self-assembly of quantum dots, and shape transitions in such quantum dots. We review results obtained in the SiGe/Si system in the last five years. In addition we discuss new directions in in situ electron microscopy as they apply to thin film formation in a range of materials and environments. [Erratum]
An in vitro reconstituted U1 snRNP allows the study of the disordered regions of the particle and the interactions with proteins and ligands

Abstract U1 small nuclear ribonucleoparticle (U1 snRNP) plays a central role during RNA processing. Previous structures of U1 snRNP revealed how the ribonucleoparticle is organized and recognizes the pre-mRNA substrate at the exon–intron junction. As with many other ribonucleoparticles involved in RNA metabolism, U1 snRNP contains extensions made of low complexity sequences. Here, we developed a protocol to reconstitute U1 snRNP in vitro using mostly full-length components in order to perform liquid-state NMR spectroscopy. The accuracy of the reconstitution was validated by probing the shape and structure of the particle by SANS and cryo-EM. Using an NMR spectroscopy-based approach, we probed, for the first time, the U1 snRNP tails at atomic detail and our results confirm their high degree of flexibility. We also monitored the labile interaction between the splicing factor PTBP1 and U1 snRNP and validated the U1 snRNA stem loop 4 as a binding site for the splicing regulator on the ribonucleoparticle. Altogether, we developed a method to probe the intrinsically disordered regions of U1 snRNP and map the interactions controlling splicing regulation. This approach could be used to get insights into the molecular mechanisms of alternative splicing and screen for potential RNA therapeutics.
Bioinformatics analysis of Myelin Transcription Factor 1

BACKGROUND AND OBJECTIVE: We aimed to further study the role of Myelin Transcription Factor 1(MyT1) in tumor and other diseases and epigenetic regulation, and better understand the regulatory mechanism of MyT1. METHODS: Using bioinformatics analysis, the structure and function of MyT1sequence were predicted and analyzed using bioinformatics analysis, and providing a theoretical basis for further experimental verification and understanding the regulatory mechanism of MyT1. The first, second and third-level structures of MyT1 were predicted and analyzed by bioinformatics analysis tools. RESULTS: MyT1 is found to be an unstable hydrophilic protein, rather than a secretory protein, with no signal peptide or trans-membrane domain; total amino acids located on the surface of the cell membrane. It contains seven zinc finger domains structurally. At sub-cellular level, MyT1 is localized in the nucleus. The phosphorylation site mainly exists in serine, and its secondary structure is mainly composed of random coils and alpha helices; the three-dimensional structure is analyzed by modeling. CONCLUSIONS: In this study, the structure and function of MyT1 protein were predicted, thereby providing a basis for subsequent expression analysis and functional research; it laid the foundation for further investigation of the molecular mechanism involved in the development of diseases.
Crosstalk of low density lipoprotein and liposome as a paradigm for targeting of 5-fluorouracil into hepatic cells: cytotoxicity and liver deposition

ABSTRACT This study aimed to utilize cholesterol conjugation of 5-fluorouracil (5-FUC) and liposomal formulas to enhance the partitioning of 5-FU into low density lipoprotein (LDL) to target hepatocellular carcinoma (HCC). Thus, 5-FU and 5-FUCwere loaded into liposomes. Later, the direct loading and transfer of 5-FU, and 5-FUC from liposomes into LDL were attained. The preparations were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and cytotoxicity using the HepG2 cell line. Moreover, the drug deposition into the LDL and liver tissues was investigated. The present results revealed that liposomal preparations have a nanosize range (155 − 194 nm), negative zeta potential (- 0.82 to – 16 mV), entrapment efficiency of 69% for 5-FU, and 66% for 5-FUC. Moreover, LDL particles have a nanosize range (28–49 nm), negative zeta potential (- 17 to −27 mV), and the entrapment efficiency is 11% for 5-FU and 85% for 5-FUC. Furthermore, 5-FUC loaded liposomes displayed a sustained release profile (57%) at 24 h compared to fast release (92%) of 5-FU loaded liposomes. 5-FUC and liposomal formulas enhanced the transfer of 5-FUC into LDL compared to 5-FU. 5-FUC loaded liposomes and LDL have greater cytotoxicity against HepG2 cell lines compared to 5-FU and 5-FUC solutions. Moreover, the deposition of 5-FUC in LDL (26.87ng/mg) and liver tissues (534 ng/gm tissue) was significantly increased 5-FUC liposomes compared to 5-FU (11.7 ng/g tissue) liposomal formulation. In conclusion, 5-FUC is a promising strategy for hepatic targeting of 5-FU through LDL-mediated gateway. Graphical abstract
A method using an on‐line digital computer for the improvement of resolution of backscattered electron images

In principle, the resolution of backscattered electron (BSE) images can be little improved, even though an infinitely small beam size is achieved by various improvements in the intrinsic instrument. In order to circumvent this problem, a method is proposed which utilizes an on‐line digital computer for the image recording and processing. The major image‐processing tools are reduction, expansion, super‐imposition with matching of the images, and high‐emphasis filtering in the Fourier domain. By using various combinations of these techniques, the resolution of BSE images has been significantly improved. The validity of these improved images has been confirmed. In the case of a BSE image with too wide a dynamic range, both the present method and digital homomorphic filtering provide successful results.
Implementation of computational approaches to explore the deleterious effects of non-synonymous SNPs on pRB protein

Abstract Retinoblastoma 1 (RB1) is the first discovered tumor suppressor gene and recognized as the simple model system whose encoded defective protein can cause a pediatric cancer retinoblastoma. It functions as a negative regulator of the cell cycle through the interactions with members of the E2F transcription factors family. The protein of the RB1 gene (pRB) is engaged in various cell cycle processes including apoptosis, cell cycle arrest and chromatin remodeling. Recent studies on Retinoblastoma also exhibited multiple sets of point mutation in the associated protein due to its large polymorphic information in the local database. In this study, we identified the list of disease associated non-synonymous single nucleotide polymorphisms (nsSNPs) in RB1 by incorporating different computational algorithms, web servers, modeling of the mutants and finally superimposing it. Out of 826 nsSNPs, W516G and W563G were predicted to be highly deleterious variants in the conserved regions and found to have an impact on protein structure and protein-protein interaction. Moreover, our study concludes the effect of W516G variant was more detrimental in destabilizing protein’s nature as compared to W563G variant. We also found defective binding of pRB having W516G mutation with E2F2 protein. Findings of this study will aid in shortening of the expensive experimental cost of identifying disease associated SNPs in retinoblastoma for which specialized personalized treatment or therapy can be formulated. Communicated by Ramaswamy H. Sarma
An analysis on the risk of being injured and killed in road travel injuries in Namibia

Abstract Road traffic injuries (RTIs) are a major, global problem. Few studies on RTIs have been conducted in Namibia, despite having one of the highest RTI rates globally. We conducted multinomial logistic regression on national Namibian datasets on RTIs 2012–2014. Being a motorcyclist was associated with the greatest risk of being injured (adjusted Relative Risk Ratio (aRRR) 82.1 (95% CI 47.2–142.9)) or killed (aRRR 202.1 (112.7–362.7)). Risks were also elevated for cyclists (57.3 (23.6–139.5)), pedestrians (15.8 (13.2–18.9), passengers (6.1 (5.2–7.2)), relative to drivers. Among those admitted to hospital, the method of transportation to hospital had the largest association with the risk of dying. To our knowledge this study presents new information on vulnerability of different road users, which can be of use to policymakers to develop specific and targeted interventions to protect the most vulnerable road users.