Miracle-dz/UniFAR-FTUs huggingface dataset:
Distribution of Poly(ADP-ribosyl)ation and Cell Death After Cerebral Ischemia in the Neonatal Rat

The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is a key component of molecular mechanisms leading to cell death or survival after an ischemic insult. Oxidative stress damages DNA, and breaks in the DNA strands activate PARP enzyme, leading to poly(ADP-ribosyl)ation of nuclear proteins. In this study, we investigated PARP activation using immunodetection of PAR polymers in the brain of neonatal rat pups subjected to unilateral focal ischemia with reperfusion. PARP activation was detected in the ischemic core between 2 and 18 h, and in the penumbra between 24 and 48 h in the middle cerebral artery (MCA) territory but also in territories of the anterior and posterior cerebral artery, and in white matter tracts. The intranuclear accumulation of PAR in cells preceded a positive terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling, suggesting that PARP activation may actually contribute to delayed cell death. Pretreatment with 3-aminobenzamide (3-AB, 10 mg/kg) strongly reduced PARP activation and cell death. These data suggest that PARP activation represents, in the immature brain, the early sign of ischemic cell death. This raises the possibility of the use of PARP inhibitors not only immediately postischemia but perhaps also later to reduce ischemic lesion in the MCA territory and its connected structures.
Incidence, prevention, and treatment of parenteral nutrition-associated cholestasis and intestinal failure-associated liver disease in infants and children: a systematic review.

BACKGROUND Cholestasis is a significant life-threatening complication in children on parenteral nutrition (PN). Strategies to prevent/treat PN-associated cholestasis (PNAC) and intestinal failure-associated liver disease (IFALD) have reached moderate success with little supporting evidence. Aims of this systematic review were (1) to determine the incidence of PNAC/IFALD in children receiving PN for ≥ 14 days and (2) to review the efficacy of measures to prevent/treat PNAC/IFALD. METHODS Of 4696 abstracts screened, 406 relevant articles were reviewed, and studies on children with PN ≥ 14 days and cholestasis (conjugated bilirubin ≥ 2 mg/dL) were included. Analyzed parameters were (1) PNAC/IFALD incidence by decade and by PN length and (2) PNAC/IFALD prevention and treatment (prospective studies). RESULTS Twenty-three articles (3280 patients) showed an incidence of 28.2% and 49.8% of PNAC and IFALD, respectively, with no evident alteration over the last decades. The incidence of PNAC was directly proportional to the length of PN (from 15.7% for PN ≤ 1 month up to 60.9% for PN ≥ 2 months; P < .0001). Ten studies on PNAC met inclusion criteria. High or intermediate-dose of oral erythromycin and aminoacid-free PN with enteral whey protein gained significant benefits in preterm neonates (P < .05, P = .003, and P < .001, respectively). None of the studies reviewed met inclusion criteria for treatment. CONCLUSIONS The incidence of PNAC/IFALD in children has no obvious decrease over time. PNAC is directly correlated to the length of PN. Erythromycin and aminoacid-free PN with enteral whey protein have shown to prevent PNAC in preterm neonates. There is a lack of high-quality prospective studies, especially on IFALD.
RNA Polymerase II Holoenzyme Modifications Accompany Transcription Reprogramming in Herpes Simplex Virus Type 1-Infected Cells

ABSTRACT During lytic infection, herpes simplex virus type 1 (HSV-1) represses host transcription, recruits RNA polymerase II (RNAP II) to viral replication compartments, and alters the phosphorylation state of the RNAP II large subunit. Host transcription repression and RNAP II modifications require expression of viral immediate-early (IE) genes. Efficient modification of the RNAP II large subunit to the intermediately phosphorylated (IIi) form requires expression of ICP22 and the UL13 kinase. We have further investigated the mechanisms by which HSV-1 effects global changes in RNAP II transcription by analyzing the RNAP II holoenzyme. We find that the RNAP II general transcription factors (GTFs) remain abundant after infection and are recruited into viral replication compartments, suggesting that they continue to be involved in viral gene transcription. However, virus infection modifies the composition of the RNAP II holoenzyme, in particular triggering the loss of the essential GTF, TFIIE. Loss of TFIIE from the RNAP II holoenzyme requires viral IE gene expression, and viral IE proteins may be redundant in mediating this effect. Although viral IE proteins do not associate with the RNAP II holoenzyme, they interact with RNAP II in complexes of lower molecular mass. As the RNAP II holoenzyme containing TFIIE is necessary for activated transcription initiation and RNAP II large subunit phosphorylation in uninfected cells, virus-induced modifications to the holoenzyme may affect both of these processes, leading to aberrant phosphorylation of the RNAP II large subunit and repression of host gene transcription.
Clinicopathologic features and molecular subtypes of breast cancer in young women (age ≤35).

INTRODUCTION Breast cancer in young women is a relatively rare disease; however it tends to be more aggressive and is the leading cause of cancer death in this population. The aim of this study is to investigate the clinical and biological features of breast cancer arising in young Turkish breast cancer patients. MATERIALS AND METHODS Patients with breast cancer aged 35 or less (≤35 years) were selected for the study. In total 211 cases were included. Pathologic features; histologic subtypes, grade, lymphovascular invasion, axillary involvement, and stage were recorded for each. RESULTS The most common subtype was luminal B (36.5%), followed by luminal A (30.8%), triple negative (23.2%) and HER2+(9.5%) subtypes. Twelve percent of the patients had stage 4, 32.7% had stage 3, 46.4% had stage 2, and 6.2% had stage 1 disease at the time of diagnosis. Mean tumour diameter was 3.87 cm (range 0.3-13 cm). The axillary lymph nodes were positive in 74.4% of the patients, while lympho-vascular invasion was seen in 56.4%. Some 9.5% of patients had grade 1, 51.2% had grade 2, and 31.8% had grade 3 tumors. CONCLUSIONS Young women with breast cancer in Turkey are more likely to present with luminal B subtype. Tumors in young women are more likely to present with advanced disease, to be high grade and and to have more lymphovascular invasion. Further research should focus on whether we need new treatment strategies for young patients with breast carcinoma.
Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro

The synthesis and secretion of mucin‐like high‐molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco‐2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H‐glucosamine labelling and chromatography on Sepharose CL‐4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high‐molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N‐glycanase), alkaline‐borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl‐α‐GaINAc, and by CsCl‐density‐gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco‐2 cells, the spontaneous post‐confluent enterocytic differentiation with increased brush‐border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GaINAc transferase and β 1,3‐galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin‐like glycoproteins can be synthesized by cell lines derived from non‐mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.
Selection of Gearbox Ratio and Power Converters Ratings for Wind Turbines Equipped With Doubly-Fed Induction Generators

This paper presents a methodology for the optimal selection of the gearbox ratio and the power converters ratings of a doubly-fed induction generator (DFIG) drive associated to a wind turbine. The design process of such an electromechanical system needs suitable compromises between the performances of the wind turbine on the whole speed range and the respective characteristics of the induction machine, the gearbox and the static converters. The optimal solution in terms of performance and cost must be derived from a global design approach. For a given turbine, a given DFIG and a given annual wind distribution, a suitable compromise must be found between the gearbox ratio and the sizing of the power converters to maximize the annual energy yield. This paper presents a methodology that can be used for the optimal determination of these two important variables of the design process, in terms of annual energy yield and initial cost. The proposed approach is applied to a 2MW wind turbine.
Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice

Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora.
Surfing tourism and local stakeholder collaboration

ABSTRACT Sustainable destination development is significantly facilitated by the involvement of all relevant stakeholder groups including the local community. Stakeholder collaboration is crucial for effective tourism development because it has the potential to achieve common goals among all stakeholders involved, but it presents multifaceted challenges for destination management. This paper examines the current stakeholder collaboration in the Mentawai Islands surfing tourism industry by exploring multiple stakeholder perspectives. Field research was conducted in the period between July and September of 2010, through in-depth interviews with local stakeholder representatives. The research indicates that despite an apparent enthusiasm to participate and collaborate in tourism planning, collaboration between stakeholder groups was in fact limited or largely avoided. Corruption, traditional mistrust of government and lack of an organised collaboration initiative are seen as the major barriers to effective collaboration in the Mentawai Islands surfing tourism industry.
Lower Urinary Tract Symptoms in Patients With Uterine Fibroids: Association With Fibroid Location and Uterine Volume

Objective: To examine the prevalence of lower urinary tract symptoms (LUTS) in women with symptomatic uterine fibroids and investigate their relationship with fibroid location and uterine volume. Methods: This was a cross-sectional study including 78 women seeking surgical treatment for symptomatic uterine fibroids. The validated Bristol Female Lower Urinary Tract Symptom-Scored Form (BFLUTS-SF) questionnaire was administered before surgical intervention. Uterine volume and BFLUTS-SF subscale scores or symptoms were compared using Student t test. Multivariate models explored the association between dominant fibroid location and BFLUTS-SF subscale scores. Results: The most prevalent LUTS were nocturia (91%), urgency (59%), and urinary incontinence (45%-54%). Mean uterine volume and length were 672 ± 714 cm3 and 13 ± 4.24 cm, respectively. Women with moderate and severe urinary urgency had significantly larger uterine volumes (P = 0.017). Mean voiding subscale scores were significantly higher in women with dominant anterior fibroids compared with those with non-anterior fibroids (voiding subscale scores, 2.84 ± 3.03 vs 1.30 ± 2.07, respectively; P < 0.01). This remained significant after adjusting for age, parity, body mass index, and imaging modality. Conclusions: Lower urinary tract symptoms are prevalent in patients with symptomatic uterine fibroids. Further study is needed to determine if surgical therapy improves these LUTSs in this population.
Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression

The TCL1 gene at 14q32.1 is involved in chromosomal translocations and inversions in mature T cell leukemias. These leukemias are classified either as T prolymphocytic leukemias, which occur very late in life, or as T chronic lymphocytic leukemias, which often arise in patients with ataxia telangiectasia (AT) at a young age. In transgenic animals, the deregulated expression of TCL1 leads to mature T cell leukemia, demonstrating the role of TCL1 in the initiation of malignant transformation in T cell neoplasia. Expression of high levels of Tcl1 have also been found in a variety of human tumor-derived B cell lines ranging from pre-B cell to mature B cell. Here we describe the phenotype of transgenic mice, Eμ-TCL1, established with TCL1 under the control of a VH promoter-IgH-Eμ enhancer to target TCL1 expression to immature and mature B cells. Flow cytometric analysis reveals a markedly expanded CD5+ population in the peritoneal cavity of Eμ-TCL1 mice starting at 2 mo of age that becomes evident in the spleen by 3–5 mo and in the bone marrow by 5–8 mo. Analysis of Ig gene rearrangements indicates monoclonality or oligoclonality in these populations, suggesting a preneoplastic expansion of CD5+ B cell clones, with the elder mice eventually developing a chronic lymphocytic leukemia (CLL)-like disorder resembling human B-CLL. Our findings provide an animal model for CLL, the most common human leukemia, and demonstrate that deregulation of the Tcl1 pathway plays a crucial role in CLL pathogenesis.
Switched Inductor Z-Source Inverter

On the basis of the classical Z-source inverter, this paper presents a developed impedance-type power inverter that is termed the switched inductor (SL) Z-source inverter. To enlarge voltage adjustability, the proposed inverter employs a unique SL impedance network to couple the main circuit and the power source. Compared with the classical Z-source inverter, the proposed inverter increases the voltage boost inversion ability significantly. Only a very short shoot-through zero state is required to obtain high voltage conversion ratios, which is beneficial for improving the output power quality of the main circuit. In addition, the voltage buck inversion ability is also provided in the proposed inverter for those applications that need low ac voltages. Similar to the classical Z-source inverter, the proposed concepts of SL Z-source inverter can be applied to various applications of dc-ac, ac-ac, dc-dc, and ac-dc power conversion. A detailed topology analysis and a generalized discussion are given. Both simulation and experimental results verify the analytical results.
Cytotoxicity of luteolin in primary rat hepatocytes: the role of CYP3A‐mediated ortho‐benzoquinone metabolite formation and glutathione depletion

Luteolin (LUT), an active ingredient in traditional Chinese medicines and an integral part of the human diet, has shown promising pharmacological activities with a great potential for clinical use. The purpose of this study was to evaluate the role of cytochrome P450 (CYP450)‐mediated reactive ortho‐benzoquinone metabolites formation and glutathione (GSH) depletion in LUT‐induced cytotoxicity in primary rat hepatocytes. A reactive ortho‐benzoquinone metabolite was identified by liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) in rat liver microsomes (RLMs) and rat hepatocytes. Using a specific chemical inhibitor method, the CYP3A subfamily was found to be responsible for the reactive metabolite formation in RLMs. Induction of CYP3A by dexamethasone enhanced LUT‐induced cytotoxicity, whereas inhibition of CYP3A by ketoconazole (Keto) decreased the cytotoxicity. The cytotoxicity and cell apoptosis induced by LUT were related to the amount of reactive metabolite formation. Furthermore, Keto inhibited the LUT‐induced GSH exhaustion. The cytotoxicity was significantly enhanced by pretreatment with L‐buthionine sulfoximine to deplete the intracellular GSH. A time course experiment showed that GSH depletion by LUT was not via oxidation of GSH and occurred prior to the increase in 2', 7'‐dichlorofluorescein in hepatocytes. Collectively, these data suggest that CYP3A‐mediated reactive metabolite formation plays a critical role in LUT‐induced hepatotoxicity, and the direct GSH depletion is an initiating event in LUT‐mediated cytotoxicity in primary rat hepatocytes. Copyright © 2015 John Wiley & Sons, Ltd.
Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor

Summary. von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high‐molecular‐weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.
Automated measurement of uptake in cerebellum, liver, and aortic arch in full-body FDG PET/CT scans.

PURPOSE The purpose of this work was to develop and validate fully automated methods for uptake measurement of cerebellum, liver, and aortic arch in full-body PET/CT scans. Such measurements are of interest in the context of uptake normalization for quantitative assessment of metabolic activity and/or automated image quality control. METHODS Cerebellum, liver, and aortic arch regions were segmented with different automated approaches. Cerebella were segmented in PET volumes by means of a robust active shape model (ASM) based method. For liver segmentation, a largest possible hyperellipsoid was fitted to the liver in PET scans. The aortic arch was first segmented in CT images of a PET/CT scan by a tubular structure analysis approach, and the segmented result was then mapped to the corresponding PET scan. For each of the segmented structures, the average standardized uptake value (SUV) was calculated. To generate an independent reference standard for method validation, expert image analysts were asked to segment several cross sections of each of the three structures in 134 F-18 fluorodeoxyglucose (FDG) PET/CT scans. For each case, the true average SUV was estimated by utilizing statistical models and served as the independent reference standard. RESULTS For automated aorta and liver SUV measurements, no statistically significant scale or shift differences were observed between automated results and the independent standard. In the case of the cerebellum, the scale and shift were not significantly different, if measured in the same cross sections that were utilized for generating the reference. In contrast, automated results were scaled 5% lower on average although not shifted, if FDG uptake was calculated from the whole segmented cerebellum volume. The estimated reduction in total SUV measurement error ranged between 54.7% and 99.2%, and the reduction was found to be statistically significant for cerebellum and aortic arch. CONCLUSIONS With the proposed methods, the authors have demonstrated that automated SUV uptake measurements in cerebellum, liver, and aortic arch agree with expert-defined independent standards. The proposed methods were found to be accurate and showed less intra- and interobserver variability, compared to manual analysis. The approach provides an alternative to manual uptake quantification, which is time-consuming. Such an approach will be important for application of quantitative PET imaging to large scale clinical trials.
Building livelihood resilience: what role does agroforestry play?

Understanding how to build livelihood resilience to an uncertain future is critical as livelihood systems must adapt to local and regional climatic change. Agroforestry, the integration of trees into an agricultural landscape, is one potential solution. However, while many intuitively link agroforestry with livelihood resilience, there is little factual evidence. This paper utilizes data from semi-arid Isiolo County, Kenya to explore if and how agroforestry is building livelihood resilience for smallholder farmers. This study included 20 qualitative case study households, 339 quantitative household surveys, and key informant interviews. In order to measure livelihood resilience, we drew from the five livelihood capital assets of the sustainable livelihoods approach: financial, human, social, physical, and natural capital. The major benefits of agroforestry were shade and fruit; the main tree species planted included mango, papaya, banana, guava, and neem. The average of all five livelihood capital scores was 10% higher for households practising agroforestry, indicating that those households may have more resilient livelihoods. Livelihood capitals were improved by both on-farm diversification and off-farm livelihood diversification. Agroforestry improved the overall quality of life for respondents. This paper provides four major findings that may be applied to build livelihood resilience through agroforestry.