Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic connectivity of hippocampal subfields in normal elderly and mild cognitive impairment patients

Hippocampal connectivity has been widely described but connectivity specificities of hippocampal subfields and their changes in early AD are poorly known. The aim of this study was to highlight hippocampal subfield networks in healthy elderly (HE) and their changes in amnestic patients with mild cognitive impairment (aMCI). Thirty‐six HE and 27 aMCI patients underwent resting‐state functional MRI scans. Specific intrinsic connectivity of bilateral CA1, SUB (subiculum), and CA2/3/4/DG was identified in HE (using seeds derived from manually delineation on high‐resolution scans) and compared between HE and aMCI. Compared to the other subfields, CA1 was more strongly connected to the amygdala and occipital regions, CA2/3/4/DG to the left anterior cingulate cortex, temporal, and occipital regions, and SUB to the angular, precuneus, putamen, posterior cingulate, and frontal regions. aMCI patients showed reduced connectivity within the SUB network (with frontal and posterior cingulate regions). Our study highlighted for the first time three specific and distinct hippocampal subfield functional networks in HE, and their alterations in aMCI. These findings are important to understand AD specificities in both cognitive deficits and lesion topography, given the role of functional connectivity in these processes. Hum Brain Mapp 38:4922–4932, 2017. © 2017 Wiley Periodicals, Inc.
The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes

OBJECTIVE There is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality. RESEARCH DESIGN AND METHODS We conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996–1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure. RESULTS There were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27–3.20), all-cause mortality (HR 1.73, 95% CI 1.38–2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15–2.34), and cancer mortality (HR 2.49, 95% CI 1.46–4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk. CONCLUSIONS Severe hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.
Clinicopathologic Evaluation of the Mueller Muscle in Thyroid-Associated Orbitopathy

Purpose: To study the histopathologic features of the Mueller muscle in chronic eyelid retraction caused by thyroid-associated orbitopathy. To investigate if the degree of eyelid retraction correlates with any histopathologic finding. Methods: A prospective case series of 23 consecutive patients with thyroid-associated orbitopathy was studied. Specimens were obtained during a standard muellerectomy. Formalin-preserved specimens were studied with the use of hematoxylin-eosin, periodic acid–Schiff, Masson trichrome, and Giemsa stains. Immunostaining against leukocyte common antigen, L26, CD3, and KP-1 was performed. Three control specimens were also evaluated in a similar fashion. Fresh tissue was placed in cold glutaraldehyde overnight, postfixed, dehydrated, and infiltrated with epoxy resin. Silver (70 nm) sections were cut and stained with uranyl acetate and lead citrate for electron microscopic examination. Results: On light microscopy, fibrosis and mast cell infiltration was present in all 23 specimens. Fat infiltration was noted in 16 of 23 specimens and did not correlate with increasing age of the patient. Interstitial edema and lymphocytic infiltration were not observed. On immunohistochemistry, leukocyte common antigen was positive, confirming the presence of inflammation. L26, CD3, and KP1 were negative. Electron microscopy demonstrated fibrosis, mast cells, and abundant contracting Mueller cells. The degree of clinical retraction in millimeters did not correlate with fibrosis, inflammation, or fat infiltration. The control specimens demonstrated rare fat and mast cell infiltration and no fibrosis. Conclusions: Contrary to previous reports, the Mueller muscle is involved in the inflammation and fibrosis that characterizes thyroid-associated orbitopathy. The Mueller muscle is grossly enlarged. On histopathologic inspection, fibrosis, fatty infiltration, and increased mast cell presence accompany focal atrophy of the Mueller muscle. In concordance with prior descriptions, many Mueller cells are in an actively contracting state on electron microscopy.
ANALISA KESENJANGAN TATA KELOLA TEKNOLOGI INFORMASI UNTUK PROSES PENGELOLAAN DATA MENGGUNAKAN COBIT (STUDI KASUS BADANG PEMERIKSA KEUANGAN REPUBLIK INDONESIA)

Tata kelola teknologi informasi pada proses pengelolaan data adalah manajemen pengelolaan data yang merupakan aset penting bagi perusahaan ataupun organisasi. Tata kelola teknologi informasi pada proses pengelolaan data yang kurang baik akan menimbulkan beberapa permasalahan. Badan Pemeriksa Keuangan Republik Indonesia (BPK RI) merupakan instansi pemerintah yang melaksanakan pemeriksaan atas pengelolaan dan tanggung jawab keuangan Negara memerlukan suatu tata kelola teknologi informasi pada proses pengelolaan data dalam kegiatan operasionalnya. Agar tata kelola teknologi dapat meminimalisasi risiko tersebut, maka diperlukan suatu perbaikan tata kelola secara kontinu. Untuk itu diperlukan adanya analisa untuk mengetahui kesenjangan antara kondisi tata kelola saat ini dengan kondisi tata kelola yang diharapkan. Analisa kesenjangan dilakukan dengan cara pengumpulan data dan informasi melalui tinjauan kepustakaan, wawancara dan penyebaran kuesioner mengenai tata kelola teknologi informasi kepada pegawai BPK RI. Data yang diperoleh akan dianalisa untuk mendapatkan identifikasi kondisi tata kelola proses pengelolaan data saat ini dan kondisi yang diharapkan. Setelah itu dilakukan analisa kesenjangan kondisi tata kelola tersebut untuk dijadikan dasar strategi perbaikan tata kelola teknologi informasi. Hasil penelitian memperoleh hasil bahwa tata kelola teknologi informasi pada proses pengelolaan data di BPK RI saat ini secara umum telah cukup baik. Hal ini ditunjukan dengan atribut tingkat kematangan tata kelola teknologi informasi yang sebagian besar berada pada tingkat kematangan level 2 (repeatable but intuitive) dan level 3 (defined process). Berdasarkan analisa kesenjangan (gap) yang dilakukan, terdapat kesenjangan antara kondisi tata kelola teknologi informasi saat ini dengan kondisi yang diharapkan oleh BPK RI. Untuk menghilangkan kesenjangan tersebut dan mencapai kondisi tata kelola teknologi informasi yang diharapkan, maka dilakukan perbaikan tata kelola teknologi informasi secara bertahap. Perbaikan difokuskan pada atribut yang mempunyai tingkat kematangan terendah. Setelah tercapai keseimbangan tingkat kematangan atribut, perbaikan dilakukan untuk mencapai tingkat kematangan berikutnya.
Sec61 blockade by mycolactone inhibits antigen cross-presentation independently of endosome-to-cytosol export

Significance Aside from its undisputed role in the import of newly synthesized proteins into the endoplasmic reticulum (ER), the Sec61 translocon was proposed to ensure the reverse transport of misfolded proteins to the cytosol. Based on this model, Sec61 was also proposed to be the channel exporting internalized antigens from endosomes to the cytosol, for degradation and cross-presentation. Establishing Sec61’s contribution to these connected trafficking pathways has nevertheless proven difficult, due to a technical incapacity to blunt its activity acutely. Here, we took advantage of a recently identified Sec61 blocker to determine whether or not Sec61 can mediate retrograde protein transport. Both ER-to-cytosol and endosome-to-cytosol protein export were intact in mycolactone-treated cells, which argues against Sec61 operating as a retrotranslocon. Although antigen cross-presentation in dendritic cells (DCs) is critical to the initiation of most cytotoxic immune responses, the intracellular mechanisms and traffic pathways involved are still unclear. One of the most critical steps in this process, the export of internalized antigen to the cytosol, has been suggested to be mediated by Sec61. Sec61 is the channel that translocates signal peptide-bearing nascent polypeptides into the endoplasmic reticulum (ER), and it was also proposed to mediate protein retrotranslocation during ER-associated degradation (a process called ERAD). Here, we used a newly identified Sec61 blocker, mycolactone, to analyze Sec61’s contribution to antigen cross-presentation, ERAD, and transport of internalized antigens into the cytosol. As shown previously in other cell types, mycolactone prevented protein import into the ER of DCs. Mycolactone-mediated Sec61 blockade also potently suppressed both antigen cross-presentation and direct presentation of synthetic peptides to CD8+ T cells. In contrast, it did not affect protein export from the ER lumen or from endosomes into the cytosol, suggesting that the inhibition of cross-presentation was not related to either of these trafficking pathways. Proteomic profiling of mycolactone-exposed DCs showed that expression of mediators of antigen presentation, including MHC class I and β2 microglobulin, were highly susceptible to mycolactone treatment, indicating that Sec61 blockade affects antigen cross-presentation indirectly. Together, our data suggest that the defective translocation and subsequent degradation of Sec61 substrates is the cause of altered antigen cross-presentation in Sec61-blocked DCs.
Analysis of clustered competing risks data using subdistribution hazard models with multivariate frailties

Competing risks data often exist within a center in multi-center randomized clinical trials where the treatment effects or baseline risks may vary among centers. In this paper, we propose a subdistribution hazard regression model with multivariate frailty to investigate heterogeneity in treatment effects among centers from multi-center clinical trials. For inference, we develop a hierarchical likelihood (or h-likelihood) method, which obviates the need for an intractable integration over the frailty terms. We show that the profile likelihood function derived from the h-likelihood is identical to the partial likelihood, and hence it can be extended to the weighted partial likelihood for the subdistribution hazard frailty models. The proposed method is illustrated with a dataset from a multi-center clinical trial on breast cancer as well as with a simulation study. We also demonstrate how to present heterogeneity in treatment effects among centers by using a confidence interval for the frailty for each individual center and how to perform a statistical test for such heterogeneity using a restricted h-likelihood.
Research in Acute Lung Injury and Pulmonary Fibrosis Modiﬁed mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model

Modiﬁed mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model. Am J Physiol Lung Cell Mol Physiol 313: different preclinical models have demonstrated a favorable role for bone marrow-derived mesenchymal stem cells (B-MSC) in preventing ﬁbrosis, this protective effect is not observed with late administration of these cells, when ﬁbrotic changes are consolidated. We sought to investigate whether the late administration of B-MSCs overexpressing microRNAs (miRNAs) let-7d (antiﬁbrotic) or miR-154 (proﬁbrotic) could alter lung ﬁbrosis in a murine bleomycin model. Using lentiviral vectors, we transduced miRNAs (let-7d or miR-154) or a control sequence into human B-MSCs. Overexpression of let-7d or miR-154 was associated with changes in the mesenchymal properties of B-MSCs and in their cytokine expression. Modiﬁed B-MSCs were intravenously administered to mice at day 7 after bleomycin instilla-tion, and the mice were euthanized at day 14 . Bleomycin-injured animals that were treated with let-7d cells were found to recover quicker from the initial weight loss compared with the other treatment groups. Interestingly, animals treated with miR-154 cells had the lowest survival rate. Although a slight reduction in collagen mRNA levels was observed in lung tissue from let-7d mice, no signiﬁcant differences were observed in Ashcroft score and OH-proline. How-ever, the distinctive expression in cytokines and CD45-positive cells in the lung suggests that the differential effects observed in both miRNA mice groups were related to an effect on the immunomodulation function. Our results establish the use of miRNA-modiﬁed mesenchymal stem cells as a potential future research in lung ﬁbrosis. in B-MSCs is successful. Human bone-mesenchymal stem cells (B-MSCs) were stably transfected with let-7d, miR-154, or an empty vector control using lentiviral particles. To conﬁrm successful transduction, we evaluated the presence of green ﬂuorescent protein (GFP) using a ﬂuorescent microscope, due to the expression of GFP in the expression lentivirus construct. Using FACS, we quantiﬁed the efﬁciency of the transduction ( A ). We also evaluated let-7d and miR-154 expression levels using qPCR ( n (cid:4) 3) ( B and C ). * P (cid:5) 0.05. Group com- parisons were made using an unpaired, two-tailed Student’s t -test or one-way ANOVA with Bonferroni correction for multiple compari- sons. Weight loss was analyzed with two-way ANOVA and Bonfer-roni-corrected multiple-comparison tests among different groups. Sur- vival analysis of mice was performed using Kaplan-Meier curves and the log-rank (Mantel-Cox) test. Signiﬁcant enrichment of overexpres- sion of miRNAs in speciﬁc chromosomal locations was determined using Fisher’s exact test. A P value of less than 0.05 was considered to be signiﬁcant.
Different children’s perspectives on their learning environment

Abstract This article reports and discusses findings from an ethnographic case study, aiming to gain a deeper understanding of how different children perceive their learning environment in the first grade of primary school, with regard to social as well as academic aspects. The theoretical framework is based on an interactional perspective, where children’s learning and development are considered to take place in a dynamic and ecological system. The reported results are based on interviews with 16 children, and observed teaching situations during the first year of primary school. Research among children demands special ethical considerations, such as how to avoid questions and interest from the researcher affecting the position of children being vulnerable in some way. The findings show that, within a group of children, facing a similar learning environment, there are significant differences between the experiences expressed. The findings presented support the importance of listening to children when planning educational settings. Listening to and taking into account the children’s different voices is an essential part of research and education that strives for inclusion, learning and well-being of all children.
Membrane proteome profiling of Mentha arvensis leaves in response to Alternaria alternata infection identifies crucial candidates for defense response

ABSTRACT The leaf spot disease of Mentha arvensis, caused by Alternaria alternata, is a devastating foliar disease worldwide and leads to considerable economic losses. In this investigation, 2-dimensional gel electrophoresis (2-DE) was used to identify the membrane proteins potentially involved in M. arvensis - A. alternata interaction. Membrane proteins, isolated from leaves of control and infected plants, were analyzed by 2-DE and identified using mass spectrometry (MALDI TOF–TOF MS/MS). Our analysis identified 21 differentially expressed membrane proteins including several interesting receptors and channel proteins. Of these identified proteins, 34% were found to be involved in plant defense responses. Leucine-rich repeat family protein/ protein kinase family protein which plays critical role in stress response and nucleotide-binding site–leucine-rich repeat (NBS-LRR) which is involved in detecting the advent of pathogen on plant surface were identified to be up-regulated in our study. Interestingly, AKT1-like potassium channel protein which is known to play a crucial role in maintaining ion homeostasis within the cell was also upregulated in the infected sample. In addition, ADP ribolysation factor (ARF)-GTPase activating domain containing protein, a membrane trafficking protein, was also up-regulated in the current study. Protein-protein interaction network analysis followed by functional enrichment revealed that transmembrane ion transport-related proteins represented a major class in this network followed by nucleic acid binding proteins and proteins with kinase activities respectively. Together, our investigation identified several key defense-related proteins which are crucial sensors for detecting pathogen invasion and can serve as a potential resource to understand disease resistance mechanism in mint.
Metabolic factors and oxidative stress in osteoarthritis: a case–control study

Abstract Previous studies suggest that metabolic disturbances might be involved in the development of osteoarthritis (OA). Associations have been found between the individual components of metabolic syndrome (MetS) and OA. MetS has been associated with increased oxidative stress (OxS). The study aimed to clarify the role of MetS components in OA and to evaluate the levels of OxS in OA patients and in age-matched controls. Fifty-five patients with end-stage OA (age 63 ± 7 years) prior to hip or knee joint replacement surgery and 55 age-, gender- and body mass index matched controls (61 ± 8 years) were enrolled in the study. Serum levels of glucose, insulin, c-peptide, cholesterols and OxS markers were recorded. Homeostasis model assessment for insulin resistance was used as the proxy measure of insulin resistance. Radiographic severity was assessed using the Kellgren–Lawrence score. The OA patients had higher total peroxide concentration and oxidative stress index [488 (250–612) μmol/L vs. 326 (168–442) μmol/L, p = . 011 and 34 (17–51) vs. 20 (11–28), p = . 002, respectively] and decreased total antioxidant capacity (1.49 ± 0.27 vs. 1.66 ± 0.27 mmol trolox equivalent/L, p= .008) compared with the controls. In addition, OA group had significantly higher level of C-peptide compared with the controls [1.8 (0.94–2.47) vs. 1.3 (0.46–1.42) ng/mL, p < . 001, respectively]. Furthermore, OA radiographic severity was independently associated with LDL-cholesterol (p = .007) and oxidized LDL (p = .022). This study demonstrates that end-stage OA patients have increased levels of OxS and decreased antioxidant capacity. OA is associated with impaired lipid metabolism and dysglycemia. Our results underline the importance OxS and metabolic disturbances in the pathogenesis of OA.
Acute exposure to DEHP metabolite, MEHP cause genotoxicity, mutagenesis and carcinogenicity in mammalian Chinese hamster ovary cells

Di-(2-ethylhexyl) phthalate (DEHP), the common plasticizer used in the production of polyvinyl chloride, can be converted to the more potent metabolite mono-ethylhexyl phthalate (MEHP). Epidemiological studies have shown an association with elevated induction of rat hepatic cancer and reproductive toxicity in response to MEHP exposure. However, the mechanism of genotoxicity and carcinogenicity induced by MEHP treatment remains unclear. As a means to elucidate the mechanisms of action, lethality and mutagenicity in the adenine phosphoribosyltransferase (aprt+/-) gene induced in several CHO cell types by MEHP were assessed. Dose-response relationships were determined in the parental AA8 cell line, its nucleotide repair-deficient UV5 and base repair-deficient EM9 subclones, and also in AS52 cells harboring the bacterial guanine-hypoxanthine phosphoribosyltransferase (gpt) gene and its derived AS52-XPD-knockdown and AS52-PARP-1-knockdown cells. Treatment of AS52 with MEHP led to intracellular production of reactive oxygen species (ROS) and DNA strand breaks in a dose-dependent manner. Separately, mutations in the gpt gene of AS52 cells were characterized and found to be dominated by G:C to A:T and A:T to G:C transitions. Independent AS52-mutant cell (ASMC) clones were collected for the sequential in vivo xenograft tumorigenic studies, 4 of total 20 clones had aggressive tumor growth. Moreover, microarray analysis indicated miR-let-7a and miR-125b downregulated in ASMC, which might raise oncogenic MYC and RAS level and activate ErbB pathway. Comparative evaluation of the results indicates that the principal mechanism of this mutagenic action is probably to be through generation of ROS, causing base excision damage resulting in carcinogenicity.
Drinking, Drug Use, and Related Consequences Among University Students Completing Study Abroad Experiences: A Systematic Review

ABSTRACT Background: University students who complete study abroad experiences are potentially exposed to behaviors, in particular alcohol and drug use, that place their health at risk. There is a need to identify risk and protective factors and highlight knowledge gaps. Methods: A systematic review adopting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Relevant bibliographic databases and online repositories were systematically searched for both qualitative and quantitative peer-reviewed studies. Results: Eighteen articles were eligible for inclusion. Degree mobility students (DMSs—students pursuing a full bachelor or master degree in a foreign country) and Credit Mobility Students (CMSs—students participating in short term or semester study abroad programmes) show different patterns of at-risk behaviors compared to pre-departure, and to domestic or non-study abroad students. DMSs mostly consumed less alcohol and illicit substances compared to domestic students, but little information on pre-travel behavior and predictors of at-risk behaviors while abroad was available on DMSs. Most studies indicated that CMSs increased their alcohol use while abroad and reduced it when they returned home. However, there is no evidence of an increase in the negative consequences associated with alcohol misuse while abroad. Different pre-departure and abroad factors (e.g., perceptions of peer drinking norms, psychological and sociocultural adjustment abroad) were related to at-risk behaviors in the host country. Conclusions: University students who study abroad are understudied and potentially at risk from alcohol and drug use. Knowledge gaps are discussed in relation to possible future qualitative, mixed methods and longitudinal research.