Miracle-dz/UniFAR-FTUs huggingface dataset:
Upregulation of miR-1266-5p serves as a prognostic biomarker of hepatocellular carcinoma and facilitates tumor cell proliferation, migration and invasion.

OBJECTIVE Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. This study aimed to analyze the prognostic value of microRNA-1266-5p (miR-1266-5p) in HCC patients and investigate its biological function in HCC progression. METHODS The expression of miR-1266-5p in tissues and cells was measured by quantitative real-time PCR (qRT-PCR). Cell counting kit-8 (CCK-8) assay was used to detect HCC cell proliferation. Transwell assay was performed to evaluate the migration and invasion of HCC cells. Kaplan-Meier methods and Cox regression analysis were used to assess the prognostic value of miR-1266-5p in HCC patients. The relationship between miR-1266-5p and DAB2IP was evaluated by luciferase reporter assay. RESULTS Relative expression of miR-1266-5p in tumor tissues, tissues from patients with advanced TNM stage (III-IV) and HCC cells was increased compared with that in corresponding control group. MiR-1266-5p expression was significantly associated with tumor size and TNM stage in HCC patients. Elevated expression of miR-1266-5p was associated with poor prognosis of HCC patients and served as an independent prognostic factor for HCC patients. Overexpression of miR-1266-5p significantly promoted, while miR-1266-5p knockdown significantly inhibited the proliferation, migration and invasion of HCC cells. DAB2IP could directly bind to the miR-1266-5p. CONCLUSION Our findings indicated that elevated expression of miR-1266-5p can predict the poor prognosis of HCC patients, and promotes the proliferation, migration and invasion of HCC cells. Therefore, we predict that miR-1266-5p may be a novel biomarker and therapeutic target for the treatment of HCC.
Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed “trained immunity. ” An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to “bend the pandemic curve,” averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.
Survival without Bronchopulmonary Dysplasia of Extremely Preterm Infants: A Predictive Model at Birth

Introduction: Early prediction of survival without bronchopulmonary dysplasia (BPD) at 36 weeks of postmenstrual age remains challenging for infants born extremely preterm. We aimed to provide a new predictive model including variables available only at or soon after birth based on the literature and existing models. Methods: We conducted a systematic review to identify all variables considered to be significant predictors of BPD and survival at birth in extremely preterm infants. We then assessed the external validity of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network BPD estimator on the PREMILOC cohort, a recent French study with a large sample of extremely preterm infants and a vast number of variables at baseline. Finally, we attempted to improve this model by testing the added value of other early predictors reported in previous studies. Results: Restricted to baseline predictors, the NICHD Neonatal Research Network BPD estimator confirmed its calibration and fair discrimination (area under the receiver operating characteristic [auROC] [95% CI] = 0.73 [0.68–0.77] when used with a published model and auROC [95% CI] = 0.77 [0.73–0.81] when fitted to the PREMILOC dataset). We were able to improve the discriminatory power by adding candidate variables at birth associated with BPD in previous studies. The modified best predicting model included gestational age at birth, birthweight, respiratory support at baseline, gender, center effect, and multiple pregnancy as baseline predictors. This model showed significantly better discrimination (auROC [95% CI] = 0.85 [0.82–0.88]) and better confirmed calibration (Hosmer-Lemeshow test, p = 0.45). Conclusion: This new model, based on 6 early predictors, appears to improve the prediction soon after birth of BPD-free survival in extremely preterm infants.
Assessment of glomerular and tubular function to guide fluid management in a pre-eclamptic critical patient with oliguria and volume overload: case report

Oliguria in the setting of critically ill patients is usually treated by admini-stering fluids and furosemide [1]. Invasive therapies, namely renal replacement therapies (RRT), are reserved for patients in whom less invasive measures have failed [2], especially if acute pulmonary oedema complicates the clinical picture [1]. Intravascular volume depletion elicits a kidney response consisting of augmented sodium retention at Henle's loop and water at the collecting tubules. In such conditions, loop diuretics such as furosemide would be less effective to improve diuresis and water loss than osmotic diuretics such as mannitol [3, 4]. This case report aims to highlight the utility of the assessment of the glomerular and tubular functions to identify an ineffective diuretic strategy and to select a successful one, which prevented the use of invasive RRT. A 33-year-old female patient suffering from preeclampsia (gestational age was 35 + 6 weeks) was admitted to our Post-surgical Intensive Care Unit (PICU) after an urgent caesarean section performed under spinal anaesthesia, without further incidents.
United Kingdom British association for sexual health and HIV national guideline for the management of epididymo-orchitis, 2020

The British Association for Sexual Health and HIV (BASHH) UK guideline for the management of epididymo-orchitis has been updated in 2020. It offers advice on diagnostic tests, treatment and health promotion principles in the effective management of epididymo-orchitis. Empirical treatment should be started in patients with objective swelling and tenderness on testicular examination. First-line empirical treatment for sexually acquired epididymo-orchitis has changed to ceftriaxone 1g intramuscularly and doxycycline. Higher dose of ceftriaxone in line with the BASHH 2018 gonorrhoea guideline ensures effective treatment of strains with reduced susceptibility. Ofloxacin or doxycycline is recommended in patients with epididymo-orchitis probably due to non-gonococcal organisms (e.g. negative microscopy for gram-negative intracellular diplococci or no risk factors for gonorrhoea identified). Where Mycoplasma genitalium is tested and identified, treatment should include an appropriate antibiotic (e.g. moxifloxacin). If enteric pathogens are a likely cause (e.g. older patient, not sexually active, recent instrumentation, men who practice insertive anal intercourse, men with known abnormalities of the urinary tract or a positive urine dipstick for leucocytes and nitrites), ofloxacin and levofloxacin are recommended. A clinical care pathway has been produced to simplify the management of epididymo-orchitis. A patient information leaflet has been developed.
Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells

Significance Although immune checkpoint blockade therapies have achieved long-term responses in several malignancies, in colorectal cancer (CRC) patients clinical benefit is observed only in heavily mutated tumors that are mismatch-repair–deficient or have high microsatellite instability. This limitation urges the identification of novel immune escape mechanisms and the design of additional immunotherapeutic modalities. We show that Galectin-1 (Gal-1) confers immune privilege to CRC by increasing the frequency of CD8+CD122+PD-1+ regulatory T cells (Tregs) and accentuating their immunosuppressive activity in experimental models. Accordingly, analysis of CRC patient datasets revealed a “poor prognosis signature” characterized by high Gal-1 expression and elevated CD8+ Treg score. Thus, targeting Gal-1/glycan interactions may represent a potential immunotherapeutic modality for treating CRC by recalibrating the CD8+ Treg compartment. Colorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8+ regulatory T cell (Treg) compartment. Mice lacking Gal-1 (Lgals1−/−) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8+CD122+PD-1+ Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8+CD122+PD-1+ Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8+ Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8+ Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8+CD122+PD-1+ Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC.
Comparison of Superior and Inferior Visual Field Asymmetry Between Normal-tension and High-tension Glaucoma

Precis: Increased severity of glaucoma heightened the hemispherical asymmetry in normal-tension and high-tension glaucoma (NTG/HTG), especially NTG. NTG showed localized superior defects in the central and paracentral areas whereas HTG showed mild asymmetry with diffuse defects. Purpose: The purpose of this study was to compare the patterns of visual field (VF) defects according to glaucoma severity in NTG and HTG. Materials and Methods: A total of 1458 eyes with NTG (936) and HTG (522) were classified by mean deviation values into mild, moderate, and severe. The mean total deviation (mTD) values for each nasal, central, paracentral, arcuate 1, and arcuate 2 region of the Glaucoma Hemifield Test (GHT) were calculated. The differences in mTD between the superior and inferior hemifields of NTG and HTG were compared, and the degree of hemifield asymmetry was plotted. Results: In NTG and HTG, the mTDs of the 5 regions of the superior GHT were significantly worse than those of the corresponding regions of the inferior GHT at all severity levels except for mild HTG. However, NTG showed significantly greater asymmetry than HTG in 2 regions at mild, 3 at moderate, and all 5 at severe. Moderate and severe NTG showed severe asymmetry with localized superior field defects concentrated at the central and paracentral areas with >8 dB asymmetry. However, in all HTG groups showed mild asymmetry with diffuse defects. Conclusions: The superior hemifield was more severely affected than the inferior hemifield in NTG and HTG. As the severity of glaucoma increased, so did the asymmetry in both groups, with NTG showing more profound asymmetric VF defects in the central and paracentral areas whereas HTG did not. Different VF patterns suggest differing pathologic mechanisms and possible need for different therapeutic strategies in NTG and HTG.
Cochlear Implantation Hearing Outcome in Ménière’s Disease

Objective The aim of this study was to evaluate the hearing outcome of cochlear implantation in patients deafened by Ménière’s disease. Study Design Retrospective single-institution study. Setting Tertiary medical center. Methods Our institutional database of 1400 patients with cochlear implants was reviewed to identify cases with deafness due to Ménière’s disease. Twenty-nine patients were identified: 24 with unilateral and 5 with sequential bilateral cochlear implants. Pre- and postoperative speech recognition scores and medical data were extracted from the medical record and analyzed. Results Overall the mean difference between pre- and postoperative speech recognition after >1 year was 56% (95% CI, 47.08%-64.92%). The mean preoperative monosyllabic word score was 9.5%, and the mean postoperative scores at 1 month, 3 months, 6 months, 1 year, and >1 year were 37.1%, 46.1%, 54.1%, 59.1%, and 66.8%, respectively. Cochlear implantation resulted in improved word scores in all patients regardless of prior medical or surgical treatment (endolymphatic sac, labyrinthectomy). The mean postoperative hearing improvement in patients aged <70 and ≥70 years was 65.26% (95% CI, 54.79%-75.73%) and 40.00% (95% CI, 27.22%-52.77%). Postoperative word scores in patients with bilateral cochlear implants were not significantly different between the first and second implanted ears or between the monoaural and binaural testing conditions. Conclusion Cochlear implant in patients deafened by Ménière’s disease significantly improves word recognition scores regardless of whether medical or surgical treatment is used prior to implantation. The potential improvement in word recognition scores decreases after age 70 years.
The effects of crop attributes, selection, and recombination on Canadian bread wheat molecular variation

Cultivated germplasm provides an opportunity to investigate how crop agronomic traits, selection for major genes, and differences in crossing‐over rates drive patterns of allelic variation. To identify how these factors correlated with allelic variation within a collection of cultivated bread wheat (Triticum aestivum L.), we generated genotypes for 388 accessions grown in Canada over the past 170 yr using filtered single nucleotide polymorphism (SNP) calls from an Illumina Wheat iSelect 90K SNP‐array. Entries’ breeding program, era of release, grain texture, kernel color, and growth habit contributed to allelic differentiation. Allelic diversity and linkage disequilibrium (LD) of markers flanking some major loci known to affect traits such as gluten strength, growth habit, and grain color were consistent with selective sweeps. Nonetheless, some flanking markers of major loci had low LD and high allelic diversity. Positive selection may have acted upon homoeologous genes that had significant enrichment for the gene ontology terms ‘response‐to‐auxin’ and ‘response‐to‐wounding. ’ Long regions of LD, spanning approximately one‐third the length of entire chromosomes, were associated with many pericentromeric regions. These regions were also characterized by low diversity. Enhancing recombination across these regions could generate novel allele combinations to accelerate Canadian wheat improvement.
Myofibroblast progeny in wound biology and wound healing studies

Fibroblasts and myofibroblasts play a myriad of important roles in human tissue function, especially in wound repair and healing. Among all cells, fibroblasts are group of cells that decide the status of wound as they maintain tissue homeostasis. Currently, the increase in the deleterious effects of chronic wound and their morbidity rate has necessitated the need to understand the influence of fibroblasts and myofibroblasts, which chiefly originate locally from tissue‐resident fibroblasts to address the same. Wound pathophysiology is complex, herein, we have discussed fibroblast and myofibroblast heterogeneity in skin and different organs by understanding the phenotypical and functional properties of each of its sub‐populations in the process of wound healing. Recent advancements in fibroblast activation, differentiation to myofibroblasts, proliferation and migration are discussed in detail. Fibroblasts and myofibroblasts are key players in wound healing and wound remodelling, respectively, and their significance in wound repair is discussed. An increased understanding of their biology during wound healing also gives an opportunity to explore more of fibroblast and myofibroblast focused therapies to treat chronic wounds which are clinical challenges. In this regard, in the current review, we have described the different methods for isolation of primary fibroblasts and myofibroblasts from both animal models and humans, and their characterization. Additionally, we have also provided details on possible molecular targets for better understanding of prognosis, diagnosis and treatment of chronic wounds. Information will help both researchers and clinicians in providing molecular insight that enable them for effective chronic wound management. The knowledge of intimate dialogue between the fibroblast, sub‐populations like, myofibroblast and their microenvironment, will serve useful in determining novel, efficient and specific therapeutic targets to treat pathological wound conditions.
Solutions for Purification of Fc-fusion Proteins : When platform processes are applied to fusion molecules, innovation and flexibility are needed

Platform processes are valuable tools in process development. Applying them to complex fusion molecules made up of different structures, however, can lead to unexpected results. EA2 is a unique engineered molecule, and it did not fit well into a platform process. It does, however, have three potential affinity and pseudo-affinity sites, each target site having a platform purification unit operation. One site is the antibody Fc region for Protein A binding, but the product was too sensitive to low pHs for typical Protein A elution conditions, so a high pH elution process was developed instead. The other two pseudo-affinity sites proved to be unusable, as did ion exchange chromatography. The final process that was developed added hydrophobic interaction and mixed mode (HIC and AEX) chromatography polishing, with a solvent and detergent (S/D) treatment instead of the typical low pH virus inactivation. This product points out the need for innovation and flexibility in cases where platforms do not work.
Metabolic activation of deferiprone mediated by CYP2A6

Abstract Deferiprone (DFP) is a metal chelating agent generally used to treat patients with thalassaemia, due to iron overload in clinical settings. Studies have revealed that long-term use of DFP can induce hepatotoxicity, however, mechanisms of its toxic action remain unclear. The present studies are aimed to characterize the reactive metabolite of DFP, to define the metabolic pathway, and to determine the P450 enzymes participating in the bioactivation. A demethylation metabolite (M1) was observed in rat liver microsomal incubations. Additionally, a glutathione (GSH) conjugate (M2) and an N-acetylcysteine (NAC) conjugate (M3) were detected in microsomal incubations fortified with DFP and GSH/NAC. Biliary M2 and urinary M3 were respectively found in animals administered DFP. CYP2A6 enzyme dominated the catalysis to bioactivate DFP.
[10]-Gingerol-Loaded Nanoemulsion and its Biological Effects on Triple-Negative Breast Cancer Cells

The apoptotic, cytotoxic, and cytostatic activities for [10]-gingerol in triple-negative breast cancer cells (TNBCs) were already reported. However, despite these important antitumor activities, the compound has the disadvantage to have a hydrophobic characteristic, hindering in vivo administration. To surpass this issue, in this study we have created a [10]-gingerol-loaded nanoemulsion (10GNE) in order to increase the stability and solubility of the compound. The nanoemulsion was characterized and tested for its cytotoxic, cytostatic, and apoptotic effects on a panel of murine and human TNBC cell lines, as well as non-tumor cells, and compared with a [10]-gingerol-free nanoemulsion (NE) and with [10]-gingerol itself. Except for the murine 4T1.13 cell line, the IC50 of the free 10G molecule, after 72 h of incubation, was higher in all cell lines tested, both murine and human, demonstrating therefore the efficacy of the 10GNE regarding cytotoxicity. In murine tumor cells, 60 μM 10GNE was able to arrest cell cycle at sub-G0 phase and induce apoptosis, leading to 48% and 78% of total cell death in 4T1.13 and 4T1Br4 murine tumor cells, respectively. This represents an improvement compared to 10G-free molecule that only induced 74% of total apoptosis at 100 μM in 4T1Br4 cells. Taken together, our results show that nanoformulation preserved the [10]-gingerol cytotoxic and cytostatic properties and improved its apoptotic function on murine TNBC cell lines. These data open new perspectives to a more suitable drug-delivery approach for [10]-gingerol for TNBC treatment that should be further demonstrated using in vivo assays.
Diagnostic accuracy of fine‐needle aspiration cytology for lymphoma: A systematic review and meta‐analysis

Fine‐needle aspiration cytology (FNAC) has become one of the most useful modalities for diagnosis and staging of lymphoma. However, diagnostic accuracy of this technique has been reported with varying results across several studies around the world. Hence, this meta‐analysis was done to assess the accuracy of FNAC for lymphoma diagnosis.
On The Biogeography of Habitat Islands: The Importance of Matrix Effects, Noncore Species, and Source-Sink Dynamics

Habitat islands can be defined as distinct patches of habitat surrounded by less contrasting matrix types. In contrast to true island biogeography (traditionally the study of islands surrounded by water), there have been less efforts to synthesize the myriad habitat island biogeography studies that have been published, particularly syntheses that cover the full range of habitat island types. By building on previous work, I aim to provide a review of habitat island biogeography in order to provide a blueprint for future research on habitat islands, including both naturally and anthropogenically fragmented systems. The review is organized into three main parts. First, the differences between habitat and true islands are summarized. Second, the main theoretical frameworks currently used to analyze habitat island systems are reviewed. Third, the findings of habitat island studies focused on various biological patterns are synthesized. Drawing on this synthesis, I put forward two main points regarding improving our understanding of habitat island biogeography: first, increasing the integration of matrix properties (including matrix variation across space and time) into habitat island biogeographic models and, second, testing for, and understanding the implications of, the potential prevalence of mass effects and source-sink dynamics in habitat island systems.