Miracle-dz/UniFAR-FTUs huggingface dataset:
Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits

Through forward genetic screening for mutations affecting visual system development, we identified prominent coloboma and cell-autonomous retinal neuron differentiation, lamination and retinal axon projection defects in eisspalte (ele) mutant zebrafish. Additional axonal deficits were present, most notably at midline axon commissures. Genetic mapping and cloning of the ele mutation showed that the affected gene is slbp, which encodes a conserved RNA stem-loop binding protein involved in replication dependent histone mRNA metabolism. Cells throughout the central nervous system remained in the cell cycle in ele mutant embryos at stages when, and locations where, post-mitotic cells have differentiated in wild-type siblings. Indeed, RNAseq analysis showed down-regulation of many genes associated with neuronal differentiation. This was coincident with changes in the levels and spatial localisation of expression of various genes implicated, for instance, in axon guidance, that likely underlie specific ele phenotypes. These results suggest that many of the cell and tissue specific phenotypes in ele mutant embryos are secondary to altered expression of modules of developmental regulatory genes that characterise, or promote transitions in, cell state and require the correct function of Slbp-dependent histone and chromatin regulatory genes. Author Summary Congenital deficits of eye formation are common in humans and to help understand the genetic basic of such conditions, we are studying zebrafish with comparable eye defects. We identified defects in both the shaping of the eye and in its connections to the brain in eisspalte mutant fish. Further analyses revealed additional deficits in the brain, most notably a severe reduction in neurons and their connections. We find that this is due to an inability of the cells that generate neurons to transition from proliferation to neuronal differentiation. By using a sequencing approach to compare mutant embryos to their normal siblings, we identified the affected gene as slbp, which encodes a protein that binds the mRNAs of other genes important for cell proliferation. This sequencing approach revealed the full extent of changes in gene expression in the mutant, helping us to better understand why the nervous system defects occur. Our study suggests that in the absence of Slbp function, cells lose the ability to transition from the proliferative to the differentiated state and this leads to additional defects in the eyes and brain.
Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease

BACKGROUND In non-alcoholic fatty liver disease (NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis. We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD. AIM To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet. METHODS The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing (51Cr-EDTA). RESULTS Twenty Caucasian patients, 90% male, median age 43 years, body mass index (BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight (-5.3 ± 4.1 kg, P = 0.003), mean waist circumference (-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase (ALT) -28.3 ± 11.9 IU/L, P = 0.0001; aspartate aminotransferase (AST) -6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after 16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline (mean percentage retention of 51Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet. CONCLUSION Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.
Prevalence and Factors Associated with Undernutrition among Exclusively Breastfeeding Women in Arba Minch Zuria District, Southern Ethiopia: A Cross-sectional Community-Based Study

Background In developing countries, women are generally vulnerable to undernutrition especially during lactation because of inadequate nutrient intake. The purpose of this study was to assess the prevalence of underweight, associated factors and mean dietary intake of selected nutrients among lactating women in Arba Minch Zuriya districts, Gamo Gofa, Ethiopia Methods Multistage cluster sampling technique was used to select 478 exclusively breastfeeding women. Data was collected by using structured questionnaire, and weight and height measurements. Mean intake of calories, calcium, iron, zinc and vitamin A was assessed by using 24-hour recall method on subsample of 73 subjects and compared against the Ethiopian and African food composition tables. Logistic regression analysis was used to evaluate the association between various independent variables and maternal underweight. Results The prevalence of underweight was 17.4%. Maternal underweight significantly associated with short birth to pregnancy interval, high workload burden, household food insecurity, less access to nutrition information and low level of women educational status. Conclusions A significant proportion of women suffered from undernutrition and the mean intake of calories, calcium and zinc were below the recommended level for lactating women. Hence, to improve nutritional status of lactating women, strategies should focus on nutrition counseling, improvement in women's access to labour saving technologies and effective household food security interventions
Factors Influencing the Results in Matrix-Associated Autologous Chondrocyte Implantation: A 2 - 5 Year Follow-Up Study

Background This study aimed to investigate the outcomes of matrix-associated autologous chondrocyte implantation (MACI) on the treatment of osteochondral lesions in the knee joint and to determine the factors affecting the functional results. Methods The study included 34 patients with a cartilage defect in the knee joint who were applied MACI® (GenzymeBiosurgery, Cambridge, Massachusetts, USA) technique between the years 2010 - 2015. The defect localizations and sizes, past surgeries were recorded. The clinical results were measured with Cincinnati and Lysholm scores. Results As a result of the repeated measures at postoperatively, it was found that the patients had increased Lysholm and Cincinnati functional scores in all follow-up periods (P = 0.0001). When the mean value of Lysholm and Cincinnati functional scores were assessed according to BMI group, no statistically significant difference was determined (P = 0.941 and P = 0.779). The measurements at 6 and 12 months of the follow-up indicated that the mean scores of the group with no concomitant pathologies were significantly higher than those of the group with concomitant pathologies. Conclusions The MACI application provides good and stable outcomes for focal cartilage damage in young patients. In order to obtain significant results after autologous chondrocyte implantation, the selection of appropriate patients without concomitant pathologies is required.
Human immunodeficiency virus and hepatotropic viruses co-morbidities as the inducers of liver injury progression

Hepatotropic viruses induced hepatitis progresses much faster and causes more liver- related health problems in people co-infected with human immunodeficiency virus (HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus (HBV) and hepatitis C virus (HCV) causes significant numbers of non-acquired immune deficiency syndrome (AIDS)-related deaths in co-infected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals (DAA) and antiretroviral therapy (ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV co-infected individuals.
Draft Genome Sequence of Staphylococcus sciuri Strain LCHXa, a Lithium-Tolerant Bacterium Isolated from Laguna Chaxa, Salar de Atacama, Chile

A Gram-positive, coagulase-negative, novobiocin resistant, and lithium-tolerant bacterium was isolated from Salar de Atacama. Strain LCHXa is closely related to Staphylococcus sciuri. ABSTRACT A Gram-positive, coagulase-negative, novobiocin resistant, and lithium-tolerant bacterium was isolated from Salar de Atacama. Strain LCHXa is closely related to Staphylococcus sciuri. Its genome is 3,013,090 bp long and contains 2,551 predicted protein genes. We observed 58 genes associated with stress response and 17 genes linked to osmoregulation, mainly related to glycine betaine metabolism.
Magnitude of Intestinal Parasitosis and Associated Factors in Rural School Children, Northwest Ethiopia

Background Intestinal parasitoses are among the most commonly encountered infections among school children in poor regions of the world. Up to 600 million school children are living in areas where there is high transmission of parasitic worms. Intestinal parasitic infection has been found to have a great effect on nutritional and cognitive status, school absenteeism and dropouts among school age children. This study aimed at determining the prevalence of intestinal parasites infections and associated factors among children in a rural primary school, Northwest Ethiopia. Methods A cross-sectional study was conducted in May 2016 among Gob Gob Primary School children. The study participants were provided with labeled stool cups to give stool specimen. The stool samples were processed via direct wet mount and formal-ether concentration techniques. A structured questionnaire was used to collect demographic data and data on factors associated with intestinal parasitic infection through face-to-face interview. Results Out of the 273 school children, 84(30.8%) were infected with at least one parasite species. Higher proportion of intestinal parasitic infection was recorded for boys (38.9%), the age group 6–10 years (38.9%), children with untrimmed finger nails (36.4%) and among those whose drinking water was from a stream (56.1%). The predominant species identified were A. lumburicoides 28(33.3%), H. nana 12(14%), E. histolytica/dispar 11(13%), G. lamblia 9(11%), hookworms 7(8.3%), Taenia spp 6(7%), E. vermicularis 6(7%), T. trichuria 4(4.8%) and S. stericoralis 1(1.2%). Conclusion This study showed that intestinal parasites were prevalent among the school children in focus. Ascaris lumbricoides was the predominant species.
Feasibility of gastric endoscopic submucosal dissection with continuous low-dose aspirin for patients receiving dual antiplatelet therapy

BACKGROUND Endoscopic submucosal dissection (ESD) for gastric neoplasms during continuous low-dose aspirin (LDA) administration is generally acceptable according to recent guidelines. This retrospective study aimed to investigate the effect of continuous LDA on the postoperative bleeding after gastric ESD in patients receiving dual antiplatelet therapy (DAPT). AIM To investigate the feasibility of gastric ESD with continuous LDA in patients with DAPT. METHODS A total of 597 patients with gastric neoplasms treated with ESD between January 2010 and June 2017 were enrolled. The patients were categorized according to type of antiplatelet therapy (APT). RESULTS The postoperative bleeding rate was 6.9% (41/597) in all patients. Patients were divided into the following two groups: no APT (n = 443) and APT (n = 154). APT included single-LDA (n = 95) and DAPT (LDA plus clopidogrel, n = 59) subgroups. In the single-LDA and DAPT subgroups, 56 and 39 patients were received continuous LDA, respectively. The bleeding rate with continuous single-LDA (10.7%) was similar to that with discontinuous single-LDA (10.3%) (P > 0.99). Although the bleeding rate with continuous LDA in patients receiving DAPT (23.1%) was higher than that with discontinuous LDA in patients receiving DAPT (5.0%), no significant difference was observed (P = 0.141). CONCLUSION The bleeding rate with continuous LDA in patients receiving DAPT was not statistically different from that with discontinuous LDA in patients receiving DAPT. Therefore, continuous LDA administration may be acceptable for ESD in patients receiving DAPT, although patients should be carefully monitored for possible bleeding.
TNFα mediated ceramide generation triggers cisplatin induced apoptosis in B16F10 melanoma in a PKCδ independent manner

Ceramide is one of the important cellular components involved in cancer regulation and exerts its pleiotropic role in the protective immune response without exhibiting any adverse effects during malignant neoplasm. Although, the PKCδ-ceramide axis in cancer cells has been an effective target in reduction of cancer, involvement of PKCδ in inducing nephrotoxicity have become a major questionnaire. In the present study, we have elucidated the mechanism by which cisplatin exploits the ceramide to render cancer cell apoptosis leading to the abrogation of malignancy in a PKCδ independent pathway with lesser toxicity. Our study revealed that cisplatin treatment in PKCδ silenced melanoma cells induces ceramide mediated apoptosis. Moreover, cisplatin induced upregulation of the transcription factor IRF1 leading to the induction of the transcriptional activity of the TNFα promoter was evident from the pharmacological inhibition and RNA interference studies. Increased cellular expression of TNFα resulted in an elevated ceramide generation by stimulating acid-sphingomyelinase and cPLA2. Furthermore, reciprocity in the regulation of sphingosine kinase 1 (Sphk1) and sphingosine kinase 2 (Sphk2) during PKCδ independent ceramide generation was also observed during cisplatin treatment. PKCδ inhibited murine melanoma model showed reduction in nephrotoxicity along with tumor regression by ceramide generation. Altogether, the current study emphasized the unexplored signaling cascade of ceramide generation by cisplatin during PKCδ silenced condition, which is associated with increased TNFα generation. Our findings enlightened the detailed mechanistic insight of ceramide mediated signaling by chemotherapeutic drugs in cancer therapy exploring a new range of targets for cancer treatment strategies.
Liver cancer incidence and mortality in China: Temporal trends and projections to 2030

Objective Liver cancer is one of the most common cancers and major cause of cancer deaths in China, which accounts for over 50% of new cases and deaths worldwide. The systematic liver cancer statistics including of projection through 2030 could provide valuable information for prevention and control strategies in China, and experience for other countries. Methods The burden of liver cancer in China in 2014 was estimated using 339 cancer registries’ data selected from Chinese National Cancer Center (NCC). Incident cases of 22 cancer registries were applied for temporal trends from 2000 to 2014. The burden of liver cancer through 2030 was projected using age-period-cohort model. Results About 364,800 new cases of liver cancer (268,900 males and 95,900 females) occurred in China, and about 318,800 liver cancer deaths (233,500 males and 85,300 females) in 2014. Western regions of China had the highest incidence and mortality rates. Incidence and mortality rates decreased by about 2.3% and 2.6% per year during the period of 2000−2014, respectively, and would decrease by more than 44% between 2014 and 2030 in China. The young generation, particularly for those aged under 40 years, showed a faster down trend. Conclusions Based on the analysis, incidence and mortality rates of liver cancer are expected to decrease through 2030, but the burden of liver cancer is still serious in China, especially in rural and western areas. Most cases of liver cancer in China can be prevented through vaccination and more prevention efforts should be focused on high risk groups.
An Efficient Protocol for Single-Cell Cloning Human Pluripotent Stem Cells

Genomic manipulation of human pluripotent stem cells (hPSCs) has become essential to introduce genetic modifications and transgenes, and develop reporter lines. One of the major bottlenecks in gene editing is at the stage of single-cell cloning, which is thought to be variable across hPSC lines and is substantially reduced following a transfection. Due to the difficulty of performing fluorescent-assisted cell sorting (FACS) for single-cell isolation of hPSCs, previous approaches rely on manual colony picking, which is both time-consuming and labor-intensive. In this protocol, I provide a method for utilizing FACS to generate single-cell clones of hPSCs with efficiencies approaching 40% within 7–10 days. This can be achieved by sorting cells onto a feeder layer of MEFs in a stem cell defined medium with KSR and a Rock inhibitor, as early as 1–2 days following a transfection, streamlining the gene editing process. The approach described here provides a fundamental method for all researchers utilizing hPSCs for scientific studies.
Brief Metacognitive Therapy for Emotional Distress in Adult Cancer Survivors

Background: Adult cancer survivors often experience substantial psychological morbidity following the completion of acute cancer treatment. Unfortunately, current psychological interventions are of limited efficacy. This study explored if metacognitive therapy (MCT); a brief transdiagnostic psychological intervention was potentially efficacious and could be delivered effectively to adult cancer survivors with psychological morbidity. Methods: An open trial with 3- and 6-month follow-up evaluated the treatment effects of MCT in 27 consecutively referred individuals to a clinical psychology health service specializing in psycho-oncology. Each participant received a maximum of six 1-hour sessions of MCT. Levels of anxiety, depression, fear of cancer recurrence, post-traumatic stress symptoms, health related quality of life, and metacognitive beliefs and processes were assessed using self-report questionnaires. Results: MCT was associated with statistically significant reductions across all outcome measures which were maintained through to 6-month follow-up. In the ITT sample on the primary treatment outcome measure, the Hospital Anxiety and Depression Scale-Total, 59% of participants met recovery criteria at post-treatment and 52% at 6-month follow-up, respectively. No participants significantly deteriorated. In the completer sample (N = 20), 80% recovered at post-treatment and 70% at 6-month follow-up. MCT was acceptable to patients with approximately 75% of patients completing all treatment sessions. Conclusion: MCT, a brief transdiagnostic psychological intervention can be delivered effectively to a heterogenous group of cancer survivors with promising treatment effects. Examining the efficacy of brief MCT against the current gold standard psychological intervention would be a valuable advance toward improving the quality of life of cancer survivors.
Phagosome Escape of Rough Mycobacterium abscessus Strains in Murine Macrophage via Phagosomal Rupture Can Lead to Type I Interferon Production and Their Cell-To-Cell Spread

Mycobacterium abscessus complex (MAB) is a rapidly growing mycobacterium(RGM) whose clinical significance as an emerging human pathogen has been increasing worldwide. It has two types of colony morphology, a smooth (S) type, producing high glycopeptidolipid (GPL) content, and a rough (R) type, which produces low levels of GPLs and is associated with increased virulence. However, the mechanism responsible for their difference in virulence is poorly known. By ultrastructural examination of murine macrophages infected, we found that MAB-R strains could replicate more actively in the macrophage phagosome than the S variants and that they could escape into cytosol via phagosomal rupture. The cytosolic access of MAB-R strains via phagosomal rupture led to enhanced Type I interferon (IFN) production and cell death, which resulted in their cell-to-cell spreading. This behavior can provide an additional niche for the survival of MAB-R strains. In addition, we found that their enhancement of cell death mediated cell spreading are dependent on Type I IFN signaling via comparison of wild-type and IFNAR1 knockout mice. In conclusion, our data indicated that a transition of MAB-S strains into MAB-R variants increased their virulence via enhanced Type I IFN production, which led to enhanced survival in infected macrophage via cell death mediated cell-to-cell spreading. This result provides not only a novel insight into the difference in virulence between MAB-R and -S variants but also hints to their treatment strategy.
Facilitating Positive Spillover Effects: New Insights From a Mixed-Methods Approach Exploring Factors Enabling People to Live More Sustainable Lifestyles

Positive spillover occurs when changes in one behavior influence changes in subsequent behaviors. Evidence for such spillover and an understanding of when and how it may occur are still limited. This paper presents findings of a 1-year longitudinal behavior change project led by a commercial retailer in the United Kingdom and Ireland to examine behavior change and potential spillover of pro-environmental behavior, and how this may be associated with changes in environmental identity and perceptions of ease and affordability as well as perceptions of how participation in the project has helped support behavior change. We draw on both quantitative and qualitative data. Study 1 examines quantitative data from the experimental and a matched control group. Study 2 reports qualitative findings from a follow up interview study with participants of the experimental group. As expected, we found significant changes in reported pro-environmental behavior and identity in the experimental group as well as some indications of behavioral spillover. These changes were not significantly associated with changes in environmental identity. The interviews suggested that group dynamics played an important role in facilitating a sense of efficacy and promoting sustained behavior change and spillover. Moreover, the support by a trusted entity was deemed to be of crucial importance.