Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Skp2 Sensitizes Chronic Myeloid Leukemia Cells to Imatinib

Introduction Skp2 is an E3 ubiquitin ligase that plays an important role in modulating tumor progression. The mechanisms underlying Skp2 in the promotion of proliferation and its function in the primary resistance to tyrosine kinase inhibitors (TKIs) in human CML remain to be determined. This study aimed to investigate the function of Skp2 in CML progression as well as its effects on TKI sensitivity. Methods Expression of Skp2 in leukocytes from patients with CML and normal blood samples was analyzed by qRT-PCR. Cell proliferation was analyzed by EdU incorporation and cell counting assays. Luciferase reporter and chromatin immunoprecipitation assays were used for examination of the effects of CREB on Skp2 expression. The apoptosis in vitro of K562 cells was analyzed by MTT and caspase 3/7 activity assays. Results The present study demonstrates that Skp2 was expressed at a higher level in patients with CML compared with healthy donors, and the elevated expression of Skp2 is critical for CML cell proliferation. Mechanistically, Skp2 was transcriptionally upregulated by CREB responsive to the PI3K/Akt signaling pathway. Furthermore, inhibition of Skp2 expression by shRNAs or blocking the PI3K/Akt/CREB pathway greatly enhances the sensitivity of CML cells to Imatinib treatment. Conclusion We conclude that the PI3K/Akt/CREB axis regulates the sensitivity of K562 cells to Imatinib via mediating Skp2 expression. The present study revealed an unknown role of Skp2 in CML progression and provided new aspects on the Skp2-modulated TKI sensitivity in CML, contributing to the development of potential therapeutic anticancer drugs.
Reducing fertilization: a management tactic against western flower thrips on roses

Fertilization reduction could be a useful pest management tactic for floriculture crops if it reduced pest populations with minimal impact on crop yield and quality. We evaluated the response of the western flower thrips, Frankliniella occidentalis Pergande (Thysanoptera: Thripidae), to different fertilization levels for cut roses, Rosa hybrida L. cv. ‘Tropicana’, and quantified fertilization effects on (i) abundance of F. occidentalis on cut roses, (ii) biological control of F. occidentalis on cut roses and (iii) nutritional quality of the cut flower crop. We tested a commercially available fertilizer (Peters Excel 15‐5‐15 Cal‐Mag; The Scotts Company, Marysville, OH) at 100% and 33% of the recommended nitrogen level (150 ppm N) for rose production using liquid‐feeding and two control measures: no thrips control measure; release of a predatory mite, Amblyseius swirskii (Athias‐Henriot). To maintain equivalent ratios of macro‐ and micronutrients for all our fertilizer treatments, we varied only the concentration of the fertilizer to the levels specified in our experiments. Lowering fertilization rate from 100% to 33% of the recommended level reduced mean F. occidentalis abundance on cut roses by 30%. Combinations of both bottom‐up (fertilization) and top‐down (biological control) tactics provided better F. occidentalis control than either tactic alone. Flower production was not compromised on plants fertilized with 33% of the recommended level. Nitrogen, phosphorous and potassium content of the leaf tissue decreased at 33% of the recommended fertilization level, but all values were within optimal ranges for cut roses. We propose that fertility management may be an effective means of reducing thrips numbers on cut roses.
Noscapine Induces Apoptosis in Human Colon Cancer Cells by Regulating Mitochondrial Damage and Warburg Effect via PTEN/PI3K/mTOR Signaling Pathway

Background Noscapine is an opium alkaloid that has recently been shown to potentiate anti-cancer therapeutic effects by inducing apoptosis in various malignant cells without any detectable toxicity. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. Materials and Methods In this study, we explored the anti-cancer activity of noscapine in 5-fluorouracil (5-FU)-resistant human colon cancer cell lines HT29/5-FU and LoVo/5-FU and investigated the possible underlying mechanism. The apoptosis and mitochondrial morphology of cells were detected by TUNEL assay and transmission electron microscopy (TEM). The mitochondrial membrane potential (MMP) was determined using JC-1. The mitochondrial permeability transition pore (mPTP) opening was detected by the calcein-AM/cobalt assay. The levels of glucose, lactic, and ATP in cells were evaluated by ELISA kits. Relative protein expression levels were detected by Western blot. Results We verified that PTEN was involved in noscapine-induced apoptosis in HT29/5-FU and LoVo/5-FU cells. Noscapine greatly increased mitochondrial damage by altering mitochondrial morphology, inducing mitochondrial membrane potential depolarization, and enabling mitochondrial permeability transition pore opening in HT29/5-FU and LoVo/5-FU cells. In addition, noscapine inhibited the Warburg effect by decreasing the levels of glucose, lactic acid, and ATP and inhibiting the protein expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in HT29/5-FU and LoVo/5-FU cells. However, PTEN interference counteracted the effect of noscapine on mitochondrial damage and the Warburg effect in HT29/5-FU and LoVo/5-FU cells by decreasing the activation of PI3K/mTOR signaling. Conclusion These results indicated that noscapine induced the apoptosis of HT29/5-FU and LoVo/5-FU human colon cancer cells by regulating mitochondria damage and the Warburg effect via PTEN, and the process is closely related to the PI3K/mTOR signaling pathway.
HIV Positive Status Disclosure and Its Associated Factors Among Children on Antiretroviral Therapy in West Shoa Zone, Western Ethiopia, 2019: A Mixed Method Cross-Sectional Study

Background Evidence from previous studies supports the idea that informing children about their HIV status has long-term positive implications in HIV disease management, children’s quality of life, and ART drug adherence. However, in sub-Saharan African Countries, the HIV status disclosure among children ranges from 0% to 69.2%. So it is important to investigate the up to date evidence that will help in designing contextualized approaches for disclosure. Therefore, this study aimed to assess the HIV status disclosure and its associated factors among children on ART in West Shoa Zone, Ethiopia. Materials and Methods Institutional-based observational study was conducted from February to April 2019. Quantitative data were collected from a randomly selected sample of 247 HIV positive children on ART for the last six months, and the qualitative data were collected from caregivers and health care professionals. Results The mean age of the children was 11.11±SD2.8, and 43.6%, (95% CI: 37, 50.9) of the children were fully disclosed. The average age at disclosure was 11±SD2.12. The main reasons for the disclosure were for drug adherence and better self-care while being underage was the commonest reason for non-disclosure. Compared to the age 10–15 years, the child in the age 6–9 was 97% [AOR: 0.027, 95% CI: 0.003, 0.22, P<0.001] less likely to be disclosed. Female children were 2.7 times more likely to be disclosed compared with male children [AOR: 2.73, 95% CI: 1.24, 6, P<0.013]. Conclusion This finding reveals that HIV status disclosure is generally low, and the decision to disclose or not is affected by factors like child-related, caregivers, and health institution-related factors. This may affect the child’s drug adherence, treatment outcome, and disease transmission. Updating health care providers’ knowledge and skills and working on caregivers’ attitude are needed to manage disclosure and challenges following it.
Highly Efficient Targeting of EGFR-Expressing Tumor Cells with UniCAR T Cells via Target Modules Based on Cetuximab®

Introduction Since epithelial growth factor receptor (EGFR) overexpression is linked to a variety of malignancies, it is an attractive target for immune therapy including chimeric antigen receptor (CAR)-engineered T cells. Unfortunately, CAR T cell therapy harbors the risk of severe, even life-threatening side effects. Adaptor CAR T cell platforms such as the previously described UniCAR system might be able to overcome these problems. In contrast to conventional CARs, UniCAR T cells are per se inert. Their redirection towards target cells occurs only in the presence of a tumor-specific target molecule (TM). TMs are bifunctional molecules being able to recognize a tumor-associated antigen and to cross-link the CAR T cell via a peptide epitope recognized by the UniCAR domain. Materials and Methods Here, we compare αEGFR TMs: a nanobody (nb)-based αEGFR TM derived from the camelid αEGFR antibody 7C12 with a murine and humanized single-chain fragment variable (scFv) based on the clinically used antibody Cetuximab®. Results In principle, both the nb- and scFv-based TM formats are able to redirect UniCAR T cells to eliminate EGFR-expressing tumor cells in an antigen-specific and TM-dependent manner. However, the scFv-based αEGFR TM was significantly superior to the nb-based TM especially with respect to lysis of tumor cells. Discussion Improved efficiency of the scFv-based TM allowed the redirection of UniCAR T cells towards tumor cells expressing high as well as low EGFR levels in comparison to nb-based αEGFR TMs.
Effect of CXCR5-Positive Cell Infiltration on the Immune Contexture and Patient Prognosis in Head and Neck Squamous Cell Carcinoma

Purpose CXCR5-positive (CXCR5+) tumor cell infiltration has different prognostic values in different types of cancer. The objective was to evaluate the effect of CXCR5+ cell infiltration in head and neck squamous cell carcinoma (HNSCC). Patients and Methods The study included two patient cohorts: The Cancer Genome Atlas cohort (TCGA, n = 472) and the Renji Hospital cohort (RJHC, n = 201). The TCGA and RJHC cohorts were analyzed for CXCR5-related mRNAs and CXCR5+ cell infiltration, respectively. We then evaluated the correlation between CXCR5 mRNA and CXCR5+ cell infiltration in terms of overall survival and the immune contexture. Results The 5-year overall survival rate was significantly correlated with high CXCR5 mRNA expression and CXCR5+ cell infiltration in the TCGA and RJHC cohorts, respectively (p < 0.01), even after adjusting for confounders. Moreover, high CXCR5 mRNA expression was associated with more CD4+ T cells, CD8+ T cells, plasma cells, and less dendritic cells. A high CXCR5 mRNA expression was also correlated with increased expression of cytotoxic IFNG, TNFSF11 (RANKL), GZMA, GZMB, GZMK, GZMM, and PRF1 and increased expression of the immunosuppressive gene PDCD1 (PD-1), CD274 (PD-L1), CTLA4, LAG3, HAVCR2 (TIM-3), BTLA, and TIGIT. Conclusion HNSCC patients with a high intratumoral CXCR5 expression had a better prognosis than those with low intratumoral CXCR5 expression. Moreover, CXCR5+ cell infiltration could be used as an independent prognostic biomarker or as a potential therapeutic target. The presence of CXCR5+ cells affects the infiltration of immunocytes in head and neck cancer, differently from what was reported in other cancer types. Further randomized controlled trials or studies with more patients are needed to validate our results.
Comparison of Relapse Prevention with 3 Different Paliperidone Formulations in Patients with Schizophrenia Continuing versus Discontinuing Active Antipsychotic Treatment: A Post-Hoc Analysis of 3 Similarly Designed Randomized Studies

Background Sudden discontinuation from antipsychotic treatment is a common occurrence in patients with schizophrenia. Lower rates of relapse could be expected for patients discontinuing treatment from longer-acting formulations vs their shorter-acting equivalents. Objective To compare relapse rates and time-to-relapse between the active (analogous to adherent patients) and placebo (analogous to non-adherent patients in the real-world) arms of three different formulations of paliperidone (oral paliperidone extended release [paliperidone ER], paliperidone palmitate once monthly [PP1M], and paliperidone palmitate three monthly [PP3M] long-acting injectables). Methods Data from three similarly designed, randomized relapse prevention studies in adult patients with schizophrenia were analyzed. Results In total, 922 patients were included (active treatment: 473, placebo: 449). Lowest percentage of patients experienced relapse with PP3M <PP1M <paliperidone and ER, in both the active treatment (PP3M, 9% <PP1M, 18% <paliperidone ER, 22%) and placebo (PP3M, 29% <PP1M, 48% <paliperidone ER, 52%) groups. The post-discontinuation median-time-to-relapse was significantly longer with PP3M (395 days [274 days to “not-reached”])> PP1M (172 days [134–222 days])> paliperidone ER (58 days [42–114 days]) and was “not-estimable” in the active treatment group due to low relapse rates. Hazard ratios (HR) of the three paliperidone formulations relative to their respective placebos were PP3M ([HR: 3.81; 95% CI: 2.08, 6.99; P< 0.0001]> PP1M [HR: 3.60; 95% CI: 2.45, 5.28; P<0.0001]> paliperidone ER [HR: 2.83; 95% CI: 1.73, 4.63; P<0.001]). Conclusion The lower percentage of relapse during active treatment and longer time to relapse after discontinuing active treatment with longer-duration antipsychotic formulations suggests the benefit of longer-acting over shorter-acting formulations, especially in patients susceptible to poor adherence. Clinical trial registration: paliperidone ER (NCT00086320), PP1M (NCT00111189), and PP3M (NCT01529515).
Development and validation of protein biomarkers of health in grizzly bears

Abstract Large carnivores play critical roles in the maintenance and function of natural ecosystems; however, the populations of many of these species are in decline across the globe. Therefore, there is an urgent need to develop novel techniques that can be used as sensitive conservation tools to detect new threats to the health of individual animals well in advance of population-level effects. Our study aimed to determine the expression of proteins related to energetics, reproduction and stress in the skin of grizzly bears (Ursus arctos) using a liquid chromatography and multiple reaction monitoring mass spectrometry assay. We hypothesized that a suite of target proteins could be measured using this technique and that the expression of these proteins would be associated with biological (sex, age, sample location on body) and environmental (geographic area, season, sample year) variables. Small skin biopsies were collected from free-ranging grizzly bears in Alberta, Canada, from 2013 to 2019 (n = 136 samples from 111 individuals). Over 700 proteins were detected in the skin of grizzly bears, 19 of which were chosen as targets because of their established roles in physiological function. Generalized linear mixed model analysis was used for each target protein. Results indicate that sample year influenced the majority of proteins, suggesting that physiological changes may be driven in part by responses to changes in the environment. Season influenced the expression of proteins related to energetics, reproduction and stress, all of which were lower during fall compared to early spring. The expression of proteins related to energetics and stress varied by geographic area, while the majority of proteins that were affected by biological attributes (age class, sex and age class by sex interaction) were related to reproduction and stress. This study provides a novel method by which scientists and managers can further assess and monitor physiological function in wildlife.
Serum BDNF Levels are Not Associated with the Antidepressant Effects of Nonconvulsive Electrotherapy

Objective Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and in the antidepressant response. This study examined whether changes in serum BDNF levels are associated with the antidepressant effects of nonconvulsive electrotherapy (NET). Methods For BDNF analyses, serum samples were collected from 20 patients with treatment-refractory depression (TRD) and from 20 healthy controls. Serum samples were also collected from patients following a course of NET. Results Although significantly lower baseline serum BDNF levels were observed in TRD patients than in healthy controls, no changes in serum BDNF levels were found in TRD patients after a course of NET compared to baseline. No significant association was found between serum BDNF levels and depression severity. Conclusion Serum BDNF levels appear to have no clinical utility in the prediction of the antidepressant effects of NET in patients with TRD. Future studies of higher quality and with larger sample sizes are needed to confirm these findings.
Clinical Comparison of Full-Endoscopic and Microscopic Unilateral Laminotomy for Bilateral Decompression in the Treatment of Elderly Lumbar Spinal stenosis: A Retrospective Study with 12-Month Follow-Up

Purpose Although lumbar spinal stenosis (LSS) is the most common spinal disease in the elderly, there is still a confusion about the appropriate surgical treatment strategy. The aim of this study was to compare the safety and efficacy of full-endoscopic and microscopic unilateral laminotomy for bilateral decompression (ULBD) for LSS in elderly patients. Patients and Methods A retrospective analysis of 61 consecutive elderly patients with LSS who underwent either full-endoscopic (FE group) or microscopic (Micro group) unilateral laminotomy for bilateral decompression was performed. Clinical data were assessed before 2 weeks, 3 months, 6 months and 12 months after surgery using the Visual Analog Scale (VAS), the Oswestry Disability Index (ODI) and the modified MacNab criteria. Results There are no significant differences in VAS (back and leg) and ODI between the two groups. However, the VAS back pain in the FE group was significantly improved compared to the Micro group at 2 weeks. The rate of excellent or good outcomes was 87.88% and 85.71% in the FE and Micro group, respectively (P>0.05). The hospital stay and early ambulation in FE group were shorter than those in Micro group, but the operation time was longer (P<0.05). The complications between the FE group (18.18%) and the Micro group (17.86%) were minor (P>0.05). Conclusion Both full-endoscopic and microscopic decompression have achieved favorable clinical results in treating elderly lumbar spinal stenosis, and the complications are minor. Full-endoscopic decompression has the advantages of small incision and rapid recovery, which can be used as an alternative for the treatment of lumbar spinal stenosis, especially the elderly with comorbidities.
Poultry offal meal as a substitute for fishmeal in diets for mudcatfish Heterobranchus longifilis juveniles

The genus Heterobranchus is of the Clariidae family and is commonly distributed in West Africa (Daget and Iltis, 1965). The juveniles are found in tributary rivers and flood plains during the rainy season. Heterobranchus longifilis is an indigenous species of significance in Nigeria (Eyo, 1999). Grow-out trials confirmed the great potential value of H. longifilis (Oteme et al., 1996). This fish is an omnivorous scavenger (Teugel et al., 1990) and because of the increasing importance of catfish culture in Nigeria, it has become necessary to provide complete ISSN: 2319-7706 Volume 3 Number 2 (2014) pp. 271-280 http://www.ijcmas. com
Comparison of different types and levels of commercial soybean lecithin supplemented in semipurified diets for juvenile Litopenaeus vannamei Boone

Two 6-week growth trials were conducted to determine the dietary phospholipids (PL) requirement of Litopenaeus vannamei juveniles and to compare the eAect of diAerent types of soybean lecithin on shrimp growth and survival. In the first trial, a basal diet and diets containing 1.5, 3 or 5% (dryweight basis) of Type I lecithin (97.6% PL) and 1.5 or 3% of Type II lecithin (71.4% PL) were evaluated. In the second trial, the basal diet and diets containing 1, 2 or 4% of either Type I or Type II lecithin and 1 or 2% of Type III lecithin (48.4% PL) were evaluated. Results showed that there was no interaction between lecithin type and PL level on shrimp growth or survival. Shrimp growth increased with PL levels up to 3‐5% of diet. No significant diAerences were observed for instantaneous growth rate (IGR) of shrimp fed the diAerent types of lecithin at the same inclusion level, and no eAect of PL level and lecithin type on shrimp survival was found. Thus, the recommended level of PL supplementation in diets for L. vannamei juveniles ranges from 3 to 5% of diet.
Molecular and Cellular Neuroscience

article i nfo Administration of certain serotonin-releasing amphetamine derivatives (fenfluramine and/or 3,4- methylenedioxymethamphetamine, MDMA, 'ecstasy') results in dystrophic serotonergic morphology in the mammalian brain. In addition to drug administration, dystrophic serotonergic neurites are also associated with neurodegenerative disorders. We demonstrate here that endogenously elevated serotonin in the Drosophila CNS induces aberrant enlarged varicosities, or spheroids, that are morphologically similar to dystrophic mammalian serotonergic fibers. In Drosophila these spheroids are specific to serotonergic neurons,distinctfromtypicalvaricosities,andformonlyafterprolongedincreasesincytoplasmicserotonin. Our results also suggest that serotonin levels during early development determine later sensitivity of spheroid formation to manipulations of the serotonin transporter (SERT). Elevated serotonin also interacts with canonical protein aggregation and autophagic pathways to form spheroids. The data presented here support a model in which excess cytoplasmic neurotransmitter triggers a cell-specific pathway inducing aberrant morphology in fly serotonergic neurons that may be shared in certain mammalian pathologies.