bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of curcumin and copper acetate against Salmonella Typhimurium infection, intestinal permeability, and cecal microbiota composition in broiler chickens
Authors: Leyva-Diaz Anaisa A. , Hernandez-Patlan Daniel , Solis-Cruz Bruno , Adhikari Bishnu , Kwon Young Min , Latorre Juan D. , Hernandez-Velasco Xochitl , Fuente-Martinez Benjamin , Hargis Billy M. , Lopez-Arellano Raquel , Tellez Guillermo 
Published: November 2020

Abstract
Background: Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance. One of the most studied groups are polyphenolic compounds, given their advantages over other types of additives and their easy potentiation of effects when complexes are formed with metal ions. Therefore, the objective of the present study was to evaluate the impact of dietary supplementation of copper acetate (CA), curcumin (CR), and their combination (CA-CR) against Salmonella Typhimurium colonization, intestinal permeability, and cecal microbiota composition in broiler chickens through a laboratory Salmonella infection model. S. Typhimurium recovery was determined on day 10 post-challenge by isolating Salmonella in homogenates of the right cecal tonsil (12 chickens per group) on Xylose Lysine Tergitol-4 (XLT-4) with novobiocin and nalidixic acid. Intestinal integrity was indirectly determined by the fluorometric measurement of fluorescein isothiocyanate dextran (FITC-d) in serum samples from blood obtained on day 10 post-S. Typhimurium challenge. Finally, microbiota analysis was performed using the content of the left caecal tonsil of 5 chickens per group by sequencing V4 region of 16S rRNA gene.Results: The results showed that in two independent studies, all experimental treatments were able to significantly reduce the S. Typhimurium colonization in cecal tonsils (CT, P< 0.0001) compared to the positive control (PC) group. However, only CA-CR was the most effective treatment in reducing S. Typhimurium counts in both independent studies. Furthermore, the serum fluorescein isothiocyanate dextran (FITC-d) concentration in chickens treated with CR was significantly lower when compared to PC (P= 0.0084), which is related to a decrease in intestinal permeability and therefore intestinal integrity. The effect of dietary treatments in reducing Salmonella was further supported by the analysis of 16S rRNA gene sequences using Linear discriminant analysis effect size (LEfSe) since Salmonella was significantly enriched in PC group (LDA score > 2.0 and P<0.05) compared to the other groups. In addition, Coprobacillus, Eubacterium, and Clostridium were significantly higher in the PC group compared to other treatment groups. On the contrary, Fecalibacterium and Enterococcus in CR, unknown genus of Erysipelotrichaceae at CA-CR, and unknown genus of Lachnospiraceae at CA were significantly more abundant respectively.Conclusions: CR treatment was the most effective treatment to reduce S. Typhimurium intestinal colonization and maintain better intestinal homeostasis which might be achieved through modulation of cecal microbiota.
Enriched environment ameliorates adult hippocampal neurogenesis deficits in Tcf4 haploinsufficient mice
Authors: Braun Katharina , Häberle Benjamin M. , Wittmann Marie-Theres , Lie Dieter Chichung 
Published: November 2020

Abstract
Background: Transcription factor 4 (TCF4) has been linked to human neurodevelopmental disorders such as intellectual disability, Pitt-Hopkins Syndrome (PTHS), autism, and schizophrenia. Recent work demonstrated that TCF4 participates in the control of a wide range of neurodevelopmental processes in mammalian nervous system development including neural precursor proliferation, timing of differentiation, migration, dendritogenesis and synapse formation. TCF4 is highly expressed in the adult hippocampal dentate gyrus – one of the few brain regions where neural stem / progenitor cells generate new functional neurons throughout life.Results: We here investigated whether TCF4 haploinsufficiency, which in humans causes non-syndromic forms of intellectual disability and PTHS, affects adult hippocampal neurogenesis, a process that is essential for hippocampal plasticity in rodents and potentially in humans. Young adult Tcf4 heterozygote knockout mice showed a major reduction in the level of adult hippocampal neurogenesis, which was at least in part caused by lower stem/progenitor cell numbers and impaired maturation and survival of adult-generated neurons. Interestingly, housing in an enriched environment was sufficient to enhance maturation and survival of new neurons and to substantially augment neurogenesis levels in Tcf4 heterozygote knockout mice.Conclusion:The present findings indicate that haploinsufficiency for the intellectual disability- and PTHS-linked transcription factor TCF4 not only affects embryonic neurodevelopment but impedes neurogenesis in the hippocampus of adult mice. These findings suggest that TCF4 haploinsufficiency may have a negative impact on hippocampal function throughout adulthood by impeding hippocampal neurogenesis.
The fibronectin type-III (FNIII) domain of ATF7IP contributes to efficient transcriptional silencing mediated by the SETDB1 complex&nbsp;
Authors: Shinkai Yoichi , Tsusaka Takeshi , Fukuda Kei , Shimura Chikako , Kato Masaki 
Published: November 2020

Abstract
Background: The histone methyltransferase SETDB1 (also known as ESET) represses genes and various types of transposable elements, such as endogenous retroviruses (ERVs) and integrated exogenous retroviruses, through a deposition of trimethylation on lysine 9 of histone H3 (H3K9me3) in mouse embryonic stem cells (mESCs). ATF7IP (also known as MCAF1 or AM), a binding partner of SETDB1, regulates the nuclear localization and enzymatic activities of SETDB1 and plays a crucial role in SETDB1-mediated transcriptional silencing. In this study, we further dissected the ATF7IP function with its truncated mutants in Atf7ip knockout (KO) mESCs.Results: We demonstrated that the SETDB1-interaction region within ATF7IP is essential for ATF7IP-dependent SETDB1 nuclear localization and silencing of both ERVs and integrated retroviral transgenes, whereas its C-terminal fibronectin type-III (FNIII) domain is dispensable for both these functions; rather, it has a role in efficient silencing mediated by the SETDB1 complex. Proteomic analysis identified a number of FNIII domain-interacting proteins, some of which have a consensus binding motif. We showed that one of the FNIII domain-binding proteins, ZMYM2, was involved in the efficient silencing of a transgene by ATF7IP. RNA-seq analysis of Atf7ip KO and WT or the FNIII domain mutant of ATF7IP-rescued Atf7ip KO mESCs showed that the FNIII domain mutant re-silenced most de-repressed SETDB1/ATF7IP-targeted ERVs compared to the WT. However, the silencing activity of the FNIII domain mutant was weaker than that of the ATF7IP WT, and some of the de-repressed germ cell-related genes in Atf7ip KO mESCs were not silenced by the FNIII domain mutant. Such germ cell-related genes are targeted and silenced by the MAX/MGA complex, and MGA was also identified as another potential binding molecule of the ATF7IP FNIII domain in the proteomic analysis. This suggests that the FNIII domain of ATF7IP acts as a binding hub of ATF7IP-interacting molecules possessing a specific interacting motif we named FAM and contributes to one layer of the SETDB1/ATF7IP complex-mediated silencing mechanisms.Conclusions: Our findings contributed to further understanding the function of ATF7IP in the SETDB1 complex, revealed the role of the FNIII domain of ATF7IP in transcriptional silencing, and suggested a potential underlying molecular mechanism for it.
A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19: the DAWn-Antico study
Authors: Vanassche Thomas , Engelen Matthias M , Thillo Quentin Van , Wauters Joost , Gunst Jan , Wouters Carine , Vandenbriele Christophe , Rex Steffen , Liesenborghs Laurens , Wilmer Alexander , Meersseman Philippe , Berghe Greet Van den , Dauwe Dieter , Verbeke Geert , Thomeer Michiel , Fivez Tom , Mesotten Dieter , Ruttens David , Heytens Luc , Dapper Ilse , Tuyls Sebastiaan , De Tavernier Brecht , Verhamme Peter 
Published: November 2020

Abstract
Background The peak of the global COVID-19 pandemic has not yet been reached and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seems to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19.Methods In this adaptive, open-label multicenter randomized clinical trial we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily - or 75 IU anti-Xa twice daily for intensive care (ICU) patients - in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1-receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement. Discussion In this trial we target the thromboinflammatory response at multiple levels. We intensify the dose of low molecular weight heparins to reduce thrombotic complications. Aprotinin is a potent kallikrein pathway inhibitor that reduces fibrinolysis, activation of the contact pathway of coagulation, and local inflammatory response. Additionally, aprotinin has shown in vitro inhibitory effects on SARS-CoV-2 cellular entry. Because the excessive thromboinflammatory response is one of the most adverse prognostic factors in COVID-19, we will add anakinra, a recombinant interleukin-1 receptor antagonist, to the regimen in case of severely increased inflammatory parameters. This way, we hope to modulate the systemic response to SARS-CoV-2 and avoid disease progressions with a potentially fatal outcome. Trial registration This trial is registered in the EU Clinical Trials Register. Registration number: 2020-001739-28. Registered on 2020-04-10.
Incidence and risk factors for trocar-site incisional hernia detected by clinical and ultrasound examination. A prospective observational study​
Authors: Ciscar Ana , Badia Josep Maria , Novell Francesc , Bolivar Santiago , Mans Esther 
Published: November 2020

Abstract
BACKGROUND: Trocar site incisional hernia (TSIH) is the most frequent complication associated with laparoscopic surgery. Few studies currently describe its incidence or risk factors. The aim of this report is to determine the real incidence of TSIH and to identify risk factors. METHODS: A cross-sectional prospective study was performed including consecutive patients who underwent a laparoscopic procedure during a four months period. All the patients were assessed both clinically (TSIHc) and by an ultrasonographic examination (TSIHu). The main variable studied was the incidence of TSIH. A multivariate analysis was performed to identify risk factors. RESULTS: 76 patients were included. 27.6% of patients were clinically diagnosed as having TSIH (TSIHc) but only 23.7% of those cases were radiologically confirmed (TSIHu). In the logistic regression analysis, age > 70 years (OR 3.462 CI 1.14 - 10.515, p = 0.028) and body mass index (BMI) ≥30 Kg / m2 (OR 3.313 CI 1.037-10.588, p = 0.043) were identified as risk factors for TSIH. The size of the trocar also showed statistically significant differences (p <0.001). Mean follow-up time was 34 months.CONCLUSIONS: TSIH is under-diagnosed due to the lack of related symptomatology and the inadequacy of the postoperative follow-up period. We detected discrepancies between the clinical and ultrasonographic examinations. TSIHu should be considered as the gold standard for the diagnosis of TSIH. Risk factors such as age, BMI and size of the trocar were confirmed. Patients should be followed-up for a minimum of 2 years.TRIAL REGISTRATION: The study has been registered in Clinicaltrials.gov, under registration number: NCT04410744.
Delirium in older patients undergoing aortic valve replacement: Incidence, predictors, and cognitive prognosis.
Authors: Humbert Marc , Büla Christophe J , Müller Olivier , Krief Hélène , Monney Pierre 
Published: November 2020

Abstract
Objectives: To determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR).Methods: Patients (N=93) aged 70 years and older, undergoing transcatheter (TAVR, N=66) or surgical (SAVR, N=27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients’ socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR.Results: Delirium occurred in 21 (22.6%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66=20%) than SAVR (8/27=30%) patients, but this difference was not statistically significant (p=.298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0±3.0 vs 28.0±3.0, p=.029), lower performance in IADL (7.0 vs 8.0, p=.038), and higher STS risk scores (4.7±2.7 vs 2.9±2.3, p=.020). In multivariate analyses, patients with intermediate (score>3 to ≤8) and high (score>8) STS risk scores had 4.3 (95%CI 1.2-15.1, p=.025) and 16.5 (95%CI 2.0-138.2, p=.010), respectively, higher odds of incident delirium compared to patients with low (score≤3) STS risk scores. At 3-month follow-up (N=77), patients with delirium still had lower MMSE score (27.0±8.0 vs 28.0±2.0, p=.007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [-3.03-0.80], p=.248).Conclusions: Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions.
Disseminating evidence-based research on mental health and coping to adolescents facing adversity in Lebanon: A pilot of a psychoeducational comic book ‘Somoud’
Authors: Bosqui Tania Josiane , Mayya Anas , Younes Liliane , Baker Myriam Claire , Annan Ismat 
Published: November 2020

Abstract
Background Despite advances in the evidence base and scaling up of mental health and psychosocial interventions for children and adolescents affected by conflict and adversity, a theory-practice gap remains, with limited translation of research findings to affected communities. Methods In order to disseminate findings from a review on mental health and coping for children and adolescents, a psychoeducational comic book ‘Somoud’ was developed and piloted with adolescents and their caregivers in Lebanon, using a qualitative Grounded Theory approach.Results In total, 10 participants (5 adolescents, 5 parents), took part in the study. Using Thematic Content Analysis, 6 themes were identified; 1) psychoeducation versus misinterpretation, 2) balancing depth with accessibility, 3) aesthetic appeal, 4) contextual relevance and realism, 5) daily stressors, and 6) parental and social relationships. Conclusions The findings demonstrate the importance of cultural and contextual piloting of psychoeducational content, and the potential usefulness and accessibility of a comic book format to disseminate information to adolescents. Data from the pilot was used to inform the development of a new version of ‘Somoud’ for sharing with adolescents in Lebanon. Further research is required to establish the effectiveness of the psychoeducational book as a ‘self-help’ tool, and to further improve knowledge exchange between researchers and communities.
Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro.
Authors: Pisano Simone , Wang Xiong , Parra Jezabel Garcia , Gazze Andrea , Edwards Kadie , Feltracco Veronica , Hu Yanzhen , He Le , Gonzalez Deyarina , Francis Lewis , Conlan Robert Steven , Li Chao 
Published: November 2020

Abstract
Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of cancer progression. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration. Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.
The amino acid transporter OsAAP4 contributes to rice tillering and grain yield by regulating neutral amino acid allocation through two splicing variants
Authors: Fang Zhongming , Wu Bowen , Ji Yuanyuan 
Published: November 2020

Abstract
Background: Amino acids, which are transported by amino acid transporters, are the major forms of organic nitrogen utilized by higher plants. Among the 19 Amino Acid Permease transporters (AAPs) in rice, only a small number of these genes have been reported to influence rice growth and development. However, whether other OsAAPs are responsible for rice growth and development is unclear.Results: In this study, we demonstrate that OsAAP4 promoter sequences are divergent between Indica and Japonica, with higher expression in the former, which produces more tillers and higher grain yield than does Japonica. Overexpression of two different splicing variants of OsAAP4 in Japonica ZH11 significantly increased rice tillering and grain yield as result of enhancing the neutral amino acid concentrations of Val, Pro, Thr and Leu. OsAAP4 RNA interference (RNAi) and mutant lines displayed opposite trends compared with overexpresing (OE) lines. In addition, exogenous Val or Pro at 0.5 mM significantly promoted the bud outgrowth of lines overexpressing an OsAAP4a splicing variant compared with ZH11, and exogenous Val or Pro at 2.0 mM significantly enhanced the bud outgrowth of lines overexpressing splicing variant OsAAP4b compared with ZH11. Of note, the results of a protoplast amino acid-uptake assay showed that Val or Pro at different concentrations was specifically transported and accumulated in these overexpressing lines. Transcriptome analysis further demonstrated that OsAAP4 may affect nitrogen transport and metabolism, and auxin, cytokinin signaling in regulating rice tillering.Conclusion: Our results suggested that OsAAP4 contributes to rice tiller and grain yield by regulating neutral amino acid allocation through two different splicing variants and that OsAAP4 might have potential applications in rice breeding.
Loss of MiR-192-5p Initiates a Hyperglycolysis and Stemness Positive Feedback in Hepatocellular Carcinoma.
Authors: Gu Yuanzhuo , Ji Fubo , Liu Niya , Zhao Yongzhi , Wei Xiyang , Hu Shiyuan , Jia Wei , Wang Xin Wei , Budhu Anuradha , Ji Juling , Zhao Bin , Roessler Stephanie , Zheng Xin , Ji Junfang 
Published: November 2020

Abstract
Background: Emerging studies revealed that cancer stem cells (CSCs) possessed peculiar metabolic properties, which however remained largely unknown in hepatocellular carcinoma (HCC). Genetic silencing of liver-abundant miR-192-5p was a key feature for multiple groups of CSC-positive HCCs. We thus aimed to investigate essential metabolic features of hepatic CSCs via using HCCs with miR-192-5p silencing as a model. Methods: Datasets from two independent HCC cohorts were used. Data integration analyses of miR-192-5p with metabolome and mRNA transcriptome in HCC cohort 1 were performed to investigate miR-192-5p related metabolic features, which was further validated in cohort 2. Cellular and molecular assays were performed to examine whether and how miR-192-5p regulated the identified metabolic feature. Co-culture systems consisting of HCC cells and LX2 (human hepatic stellate cell line) or THP1 (human monocyte cell line) were established to explore effects of the identified metabolic property on stemness features of HCC cells via interacting with co-cultured non-tumor cells. Results: High levels of glycolysis-related metabolites and genes presented in HCCs with low miR-192-5p and CSC-positive HCCs in two independent HCC cohorts. miR-192-5p knockout cells displayed CSC features and miR-192-5p loss led to an enhanced glycolytic phenotype via upregulating three bona fide targets, GLUT1 and PFKFB3 (two glycolytic enzymes) and c-Myc (regulating glycolytic genes’ expression). Meanwhile, c-Myc suppressed miR-192-5p transcription, ensuring a low-miR-192-5p/high-c-Myc loop to maintain hyperglycolysis. Moreover, over-produced lactic acid from hyperglycolytic HCC cells stimulated the ERK phosphorylation of co-cultured LX2 and THP1 non-tumor cells partially via NDRG3 and MCT1, which in turn promoted cell malignancy and stemness of HCC cells. Consistently, HCC patients with low level of miR-192-5p in their tumor tissues and high level of NDRG3 or MCT1 in their non-tumor tissues had the shortest overall survival. Conclusions: In CSC-positive HCCs, miR-192-5p loss enhanced glycolysis and over produced lactate might further increase HCC malignant features via interacting with environmental non-tumor cells.