Miracle-dz/UniFAR-FTUs huggingface dataset:
Transforming Growth Factor Induced Protein Promotes NF-Kappa-B Mediated Angiogenesis During Postnatal Lung Development.

Pulmonary angiogenesis is a key driver of alveolarization. Our prior studies showed that nuclear factor kappa-B (NFκB) promotes pulmonary angiogenesis during early alveolarization. However, the mechanisms regulating temporal-specific NFκB activation in the pulmonary vasculature are unknown. To identify mechanisms that activate pro-angiogenic NFκB signaling in the developing pulmonary vasculature. Proteomic analysis of the lung secretome was performed using two-dimensional difference gel electrophoresis (2D-DIGE). NFκB activation and angiogenic function was assessed in primary pulmonary endothelial cells (PEC) and TGFBI-regulated genes identified using RNA-sequencing. Alveolarization and pulmonary angiogenesis was assessed in WT and Tgfbi null mice exposed to normoxia or hyperoxia. Lung TGFBI expression was determined in premature lambs supported by invasive and noninvasive respiratory support. Secreted factors from the early alveolar, but not the late alveolar or adult lung, promoted proliferation and migration in quiescent, adult PEC. Proteomic analysis identified transforming growth factor beta-induced protein (TGFBI) as one protein highly expressed by the early alveolar lung that promoted PEC migration by activating NFκB via αvβ3 integrins. RNA-sequencing identified Csf3 as a TGFBI-regulated gene that enhances nitric oxide production in PEC. Loss of TGFBI in mice exaggerated the impaired pulmonary angiogenesis induced by chronic hyperoxia, and TGFBI expression was disrupted in premature lambs with impaired alveolarization. Our studies identify TGFBI as a developmentally-regulated protein that promotes NFκB-mediated angiogenesis during early alveolarization by enhancing nitric oxide production. We speculate that dysregulation of TGFBI expression may contribute to diseases marked by impaired alveolar and vascular growth.
Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. Results: Recruitment was stopped prematurely due to slow inclusions (n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) (p = 0.79)). Conclusion: POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.
Aquarium Tank Design Is Integral to the Elimination of Mantle Abrasion in the Captive Curled Octopus (Eledone cirrhosa): A Case Study at Macduff Marine Aquarium

ABSTRACT Macduff Marine Aquarium is a native species aquarium situated on the Moray Firth coastline and houses the curled octopus, Eledone cirrhosa, for public display. Historically, the designated octopus display tank has been in-keeping with the overall theme of the aquarium, consisting of artificially created rock work mimicking the local rocky coastline, within an angular glass tank. This tank was not originally designed for housing octopus and as a consequence, if individuals on display exhibited jetting behavior mantle abrasion occurred. In 2016, a new bespoke octopus tank was designed and installed. Since then 14 different octopuses have been individually housed and maintained within the tank, with none having experienced mantle abrasion. This paper highlights the importance of aquarium design for the ethical maintenance of an intelligent and challenging species.
Micellar Nanocarriers from Dendritic Macromolecules Containing Fluorescent Coumarin Moieties

The design of efficient drug-delivery vehicles remains a big challenge in materials science. Herein, we describe a novel class of amphiphilic hybrid dendrimers that consist of a poly(amidoamine) (PAMAM) dendritic core functionalized with bisMPA dendrons bearing cholesterol and coumarin moieties. Their self-assembly behavior both in bulk and in water was investigated. All dendrimers exhibited smectic A or hexagonal columnar liquid crystal organizations, depending on the generation of the dendrimer. In water, these dendrimers self-assembled to form stable spherical micelles that could encapsulate Nile Red, a hydrophobic model compound. The cell viability in vitro of the micelles was studied in HeLa cell line, and proved to be non-toxic up to 72 h of incubation. Therefore, these spherical micelles allow the encapsulation of hydrophobic molecules, and at the same time provided fluorescent traceability due to the presence of coumarin units in their chemical structure, demonstrating the potential of these dendrimers as nanocarriers for drug-delivery applications.
Deep Learning in LncRNAome: Contribution, Challenges, and Perspectives

Long non-coding RNAs (lncRNA), the pervasively transcribed part of the mammalian genome, have played a significant role in changing our protein-centric view of genomes. The abundance of lncRNAs and their diverse roles across cell types have opened numerous avenues for the research community regarding lncRNAome. To discover and understand lncRNAome, many sophisticated computational techniques have been leveraged. Recently, deep learning (DL)-based modeling techniques have been successfully used in genomics due to their capacity to handle large amounts of data and produce relatively better results than traditional machine learning (ML) models. DL-based modeling techniques have now become a choice for many modeling tasks in the field of lncRNAome as well. In this review article, we summarized the contribution of DL-based methods in nine different lncRNAome research areas. We also outlined DL-based techniques leveraged in lncRNAome, highlighting the challenges computational scientists face while developing DL-based models for lncRNAome. To the best of our knowledge, this is the first review article that summarizes the role of DL-based techniques in multiple areas of lncRNAome.
Management of Ocular Surface Disease in Glaucoma: A Survey of Canadian Glaucoma Specialists

Supplemental Digital Content is available in the text. Précis: Ocular surface disease (OSD) in glaucoma is an area for improvement in the management of patients with glaucoma. This study explores the knowledge of glaucoma subspecialists toward OSD in glaucoma, then provides a suggested treatment algorithm. Purpose: To assess the attitudes, knowledge, and level of comfort of Canadian glaucoma specialists with respect to the assessment and management of OSD among patients with glaucoma. Methods: Ophthalmologist members of the Canadian Glaucoma Society with fellowship training in glaucoma were contacted to participate in this cross-sectional survey study. Responses were recorded to statements regarding attitudes toward OSD in glaucoma, and assessment and management modalities. These were recorded primarily in the form of a Likert scale rated 1 to 7 from “strongly disagree” to “strongly agree. ” Descriptive statistics were generated, and mean and SD for responses on Likert scales. Results: Thirty-six responses were included. All respondents agreed that comprehensive management of OSD could improve quality of life, 97% agreed it could lead to better glaucoma outcomes, whereas only 22% agreed it is presently being adequately managed in glaucoma practices. Respondents were asked to list all treatment modalities they felt knowledgeable about, ranging from 100% for optimizing topical glaucoma therapies to 31% for serum tears. Nearly all respondents (92%) agreed that a suggested algorithm for the treatment of OSD in glaucoma could improve their approach to management. Conclusion: OSD is a common comorbidity of glaucoma. Although respondents overwhelmingly agreed that comprehensive management of OSD may lead to improved quality of life and glaucoma-related outcomes, only a small percentage felt it was presently adequately managed. Increasing knowledge related to the assessment and management of OSD in glaucoma may in the future improve patient care.
The Role of APOBECs in Viral Replication

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) proteins are a diverse and evolutionarily conserved family of cytidine deaminases that provide a variety of functions from tissue-specific gene expression and immunoglobulin diversity to control of viruses and retrotransposons. APOBEC family expansion has been documented among mammalian species, suggesting a powerful selection for their activity. Enzymes with a duplicated zinc-binding domain often have catalytically active and inactive domains, yet both have antiviral function. Although APOBEC antiviral function was discovered through hypermutation of HIV-1 genomes lacking an active Vif protein, much evidence indicates that APOBECs also inhibit virus replication through mechanisms other than mutagenesis. Multiple steps of the viral replication cycle may be affected, although nucleic acid replication is a primary target. Packaging of APOBECs into virions was first noted with HIV-1, yet is not a prerequisite for viral inhibition. APOBEC antagonism may occur in viral producer and recipient cells. Signatures of APOBEC activity include G-to-A and C-to-T mutations in a particular sequence context. The importance of APOBEC activity for viral inhibition is reflected in the identification of numerous viral factors, including HIV-1 Vif, which are dedicated to antagonism of these deaminases. Such viral antagonists often are only partially successful, leading to APOBEC selection for viral variants that enhance replication or avoid immune elimination.
Megacystis Microcolon Intestinal Hypoperistalsis Syndrome: A Case Series with Long Term Follow up and Prolonged Survival.

OBJECTIVES Describe clinical characteristics, management and outcome in a cohort of Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS) patients. METHODS We conducted a retrospective chart review of MMIHS patients followed at a large transplant and intestinal rehabilitation center over a period of 17 years. RESULTS We identified 25 patients with MMIHS (68% females, 13 transplanted). One transplanted and one non-transplanted patient were lost to follow-up. We estimated 100%, 100%, and 86% for 5-,10-, and 20-year survival respectively with only one death. Of the 22 patients alive at the time of study (11 transplanted, 11 non-transplanted), median age was 9.2 years (range 2.7-22.9 years). Longest post-transplant follow-up was 16 years. 17 patients had available prenatal imaging reports, all showed distended bladder. Eight had genetic testing (5-ACTG2, 2-MYH11, 1-MYL9). Almost all patients had normal growth with median weight z-score -0.77 (interquartile range -1.39, 0.26), height z-score -1.2 (-2.04, -0.48) and Body-Mass-Index z-score 0.23 (-0.37, 0.93) with no statistical difference between transplanted and non-transplanted patients. All non-transplanted patients were on parenteral nutrition with minimal/no feeds, and all except one of the transplanted patients were on full enteral feeds. Recent average bilirubin, INR, albumin and creatinine fell within the reference ranges. CONCLUSIONS This is the largest single center case series with the longest duration of follow-up for MMIHS patients. In the current era of improved intestinal rehabilitation and transplantation, MMIHS patients have excellent outcomes in survival, growth, and liver function. This observation contradicts previous reports and should alter counselling and management decisions in these patients at diagnosis.
Simultaneous needle catheter selection and dwell time optimization for preplanning of high-dose-rate brachytherapy of prostate cancer

Purpose. Needle catheter positions critically affect the quality of treatment plans in prostate cancer high-dose-rate (HDR) brachytherapy. The current standard needle positioning approach is based on human intuition, which cannot guarantee a high-quality plan. This study proposed a method to simultaneously select needle catheter positions and determine dwell time for preplanning of HDR brachytherapy of prostate cancer. Methods. We formulated the needle catheter selection problem and inverse dwell time optimization problem in a unified framework. In addition to the dose objectives of the planning target volume (PTV) and organs at risk (OARs), the objective function incorporated a group-sparsity term with a needle-specific adaptive weighting scheme to generate high-quality plans with the minimal number of needle catheters. The optimization problem was solved by a fast-iterative shrinkage-thresholding algorithm. For validation purposes, we tested the proposed algorithm on 10 patient cases previously treated at our institution and compared the resulting plans with plans generated using needle catheters selected manually. Results. Compared to the plan with manually selected needle catheters, when normalizing both plans to the same PTV coverage V 100% = 95%, the plans generated by the proposed algorithm reduced median V 125% from 65% to 64%, but increased median V 150% from 35% to 38%, and V 200% from 14% to 16%. All planning objectives were met. All clinically important dosimetric parameters of OARs were reduced. D 1cc of bladder and rectum were reduced from 8.57 Gy to 8.50 Gy and from 7.24 Gy to 6.80 Gy, respectively. D max of urethra was reduced from 15.85 Gy to 15.77 Gy. The median number of selected needle catheters was reduced by two. The computational time for solving the proposed optimization problem was ∼90 s using MATLAB. Conclusion. The proposed algorithm was able to generate plans for prostate cancer HDR brachytherapy preplanning with increased median conformity index (0.73–0.77) and slightly lower median homogeneity index (0.64–0.62) with the number of selected needles reduced by two compared to the manual needle selection approach.
Does body mass index predict response to intravenous ketamine treatment in adults with major depressive and bipolar disorder? Results from the Canadian Rapid Treatment Center of Excellence

Abstract Background Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD). Methods Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith–Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35). Results Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups. Conclusions The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.
Endophilin recruitment drives membrane curvature generation through coincidence detection of GPCR loop interactions and negative lipid charge

Endophilin plays key roles during endocytosis of cellular receptors, including generating membrane curvature to drive internalization. Electrostatic interactions between endophilin’s BIN/Amphiphysin/Rvs domain and anionic membrane lipids have been considered the major driving force in curvature generation. However, the SH3 domain of endophilin also interacts with the proline-rich third intracellular loop (TIL) of various G-protein-coupled receptors (GPCRs), and it is unclear whether this interaction has a direct role in generating membrane curvature during endocytosis. To examine this, we designed model membranes with a membrane density of 1400 receptors per μm2 represented by a covalently conjugated TIL region from the β1-adrenergic receptor. We observed that TIL recruits endophilin to membranes composed of 95 mol% of zwitterionic lipids via the SH3 domain. More importantly, endophilin recruited via TIL tubulates vesicles and gets sorted onto highly curved membrane tubules. These observations indicate that the cellular membrane bending and curvature sensing activities of endophilin can be facilitated through detection of the TIL of activated GPCRs in addition to binding to anionic lipids. Furthermore, we show that TIL electrostatically interacts with membranes composed of anionic lipids. Therefore, anionic lipids can modulate TIL/SH3 domain binding. Overall, our findings imply that an interplay between TIL, charged membrane lipids, BAR domain, and SH3 domain could exist in the biological system and that these components may act in coordination to regulate the internalization of cellular receptors.
Sequential Colocalization of ERa, PR, and AR Hormone Receptors Using Confocal Microscopy Enables New Insights into Normal Breast and Prostate Tissue and Cancers

Simple Summary At present, platforms for multiplex immunohistochemistry (e.g., Opal) identify markers in distinct cell populations within a tissue section using multispectral fluorescence and optic microscopy. However, the optic resolution is not enough to colocalize markers at the subcellular level in the main epithelial or cancer population. We use confocal microscopy in multiplex detection of nuclear hormone receptors since they are an important part of the diagnosis and treatment of breast and prostate cancer. Moreover, we increased the quantitative dynamic range and resolution through increasing the signal/noise ration through reducing autofluorescence and increased longer antibody incubations. ColNu mIHCF identified distinct patterns of nuclear receptor colocalization in breast cancers. Furthermore, in prostate cancer all cancer epithelium was positive for ERa at the plasma membrane; and in normal prostate a small ERa+/p63+/AR− basal population suggest stem cell commitment to differentiation. ColNu mIHCF could be used for improving diagnosis and treatment in cancer. Abstract Multiplex immunohistochemistry (mIHC) use markers staining different cell populations applying widefield optical microscopy. Resolution is low not resolving subcellular co-localization. We sought to colocalize markers at subcellular level with antibodies validated for clinical diagnosis, including the single secondary antibody (combination of anti-rabbit/mouse-antibodies) used for diagnostic IHC with any primary antibody, and confocal microscopy. We explore colocalization in the nucleus (ColNu) of nuclear hormone receptors (ERa, PR, and AR) along with the baseline marker p63 in paired samples of breast and prostate tissues. We established ColNu mIHCF as a reliable technique easily implemented in a hospital setting. In ERa+ breast cancer, we identified different colocalization patterns (nuclear or cytoplasmatic) with PR and AR on the luminal epithelium. A triple-negative breast-cancer case expressed membrane-only ERa. A PR-only case was double positive PR/p63. In normal prostate, we identified an ERa+/p63+/AR-negative distinct population. All prostate cancer cases characteristically expressed ERa on the apical membrane of the AR+ epithelium. We confirmed this using ERa IHC and needle-core biopsies. ColNu mIHCF is feasible and already revealed a new marker for prostate cancer and identified sub-patterns in breast cancer. It could be useful for pathology as well as for functional studies in normal prostate and breast tissues.
To Provide a Double Feeder in Growing Pigs Housed under High Environmental Temperatures Reduces Social Interactions but Does Not Improve Weight Gains

Simple Summary Competition for food can increase if pigs concentrate feeding times in the cool hours of the day during the warmest seasons. The present study addresses whether providing the animals with a double feeder would benefit the performance of pigs when subjected to high environmental temperatures. The results showed that high environmental temperatures reduced the final body weight of pigs and increased the percentage of fat in the carcass of the animals. When provided with two feeders instead of one, the animals reduced the number of social interactions, so less competition for food was achieved. However, an unexpected result was a decrease in the body weight of the animals with two feeders when compared to the animals with one, so in terms of performance, the strategy failed in providing the expected results. Abstract Heat stress and competition for food are two major challenges in pigs reared in intensive conditions. The aim of the present work was to study the effect of providing a double feeder for pigs reared under two different environmental temperatures. In addition, two types of flooring, of 100% slat and 30% slat 70% concrete, were also considered. A total of 256 pigs in the growing-finishing period (from 27 kg to 110 kg) were housed using two environmental temperatures: control (from 18 °C to 25 °C) and heat stress (above 30 °C six hours a day). They were housed in 32 pens of 8 pigs each, distributed into 4 rooms (16 with one feeder and 16 with two). Pigs subjected to temperatures above 30 °C up to six hours had lower body weight gains than pigs subjected to a maximum temperature of 25 °C, confirming that thermal stress negatively affects performance in pigs. In addition, heat stress affected the final product by decreasing the lean percentage of carcasses by 2.6%. A double feeder reduced the presence of negative social behavior, especially in the feeding area, but body weight was lower than when one single feeder was used. A 30% slat 70% concrete floor showed better results in the pig stress indicators and body weights than 100% slat. It is concluded that providing a double feeder in the pens, although reducing the presence of negative social interactions, negatively affected body weight, in comparison to pigs fed with just one feeder.