bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTERNAL TOURISM DEVELOPMENT STRATEGY INCREASING REGIONAL ORIGINAL INCOME (PAD) IN JAYAPURA CITY PAPUA PROVINCE
Authors: Mebri Fredrick Hendrick , Suradinata Ermaya , Kusworo Kusworo 
Published: October 2022

ABSTRAK. Pendapatan Asli Daerah (PAD) merupakan gambaran potensi keuangan daerah, dimana terdapat berbagai sektor yang dapat dikembangkan untuk meningkatkan Pendapatan asli daerah salah satunya adalah sektor pariwisata, sehingga keberadaan pariwisata diharapkan mampu menjadi salah satu penyumbang bagi pendapatan asli daerah, namun sektor pariwisata di Kota Jayapura belum dikelola dan dimanfaatkan secara optimal, dalam kenyataannya banyaknya aset wisata di Kota Jayapura yang masih dikuasai oleh pemilik hak ulayat dengan melakukan pungutan liar, kurangnya hubungan kerjasama dengan dinas-dinas terkait dalam membangun dan mengembangkan objek wisata, dan kurangnya partisipasi masyarakat dalam mengembangkan objek wisata. Berdasarkan hal tersebut maka penulis tertarik untuk melakukan penelitian dengan judul; "Strategi Pengembangan Pariwisata Dalam Meningkatkan Pendapatan Asli Daerah (PAD) di Kota Jayapura Provinsi Papua. Penelitian ini menggunakan metode kualitatif dengan pendekatan deskriptif untuk menggambarkan tentang keadaan di lapangan yang kemudian diteliti untuk menemukan pemecahan masalah yang bersifat umum. Data yang dihimpun untuk penelitian ini adalah data yang terkait dengan analisis ASOCA terhadap strategi pengembangan pariwisata dalam meningkatkan pendapatan asli daerah (PAD) serta implikasinya dalam menentukan strategi yang akan dilakukan oleh Dinas Pariwisata Kota Jayapura Provinsi Papua. Penelitian ini dibuat untuk mengetahui dan memaparkan sejauh mana strategi Dinas Pariwisata dalam pengembangan pariwisata untuk meningkatkan pendapatan asli daerah di Kota Jayapura seiring dengan fenomena yang menggambarkan hambatan yang dihadapi dan upaya dalam mengatasi hambatan.
Kata kunci: Strategi, Pendapatan Asli Daerah (Pad), Pariwisata.
Identification of energy metabolism-related biomarkers for risk prediction of heart failure patients using random forest algorithm
Authors: Chen Hao , Jiang Rui , Huang Wentao , Chen Kequan , Zeng Ruijie , Wu Huihuan , Yang Qi , Guo Kehang , Li Jingwei , Wei Rui , Liao Songyan , Tse Hung-Fat , Sha Weihong , Zhuo Zewei 
Published: October 2022

ObjectiveEnergy metabolism plays a crucial role in the improvement of heart dysfunction as well as the development of heart failure (HF). The current study is designed to identify energy metabolism-related diagnostic biomarkers for predicting the risk of HF due to myocardial infarction.MethodsTranscriptome sequencing data of HF patients and non-heart failure (NF) people (GSE66360 and GSE59867) were obtained from gene expression omnibus (GEO) database. Energy metabolism-related differentially expressed genes (DEGs) were screened between HF and NF samples. The subtyping consistency analysis was performed to enable the samples to be grouped. The immune infiltration level among subtypes was assessed by single sample gene set enrichment analysis (ssGSEA). Random forest algorithm (RF) and support vector machine (SVM) were applied to identify diagnostic biomarkers, and the receiver operating characteristic curves (ROC) was plotted to validate the accuracy. Predictive nomogram was constructed and validated based on the result of the RF. Drug screening and gene-miRNA network were analyzed to predict the energy metabolism-related drugs and potential molecular mechanism.ResultsA total of 22 energy metabolism-related DEGs were identified between HF and NF patients. The clustering analysis showed that HF patients could be classified into two subtypes based on the energy metabolism-related genes, and functional analyses demonstrated that the identified DEGs among two clusters were mainly involved in immune response regulating signaling pathway and lipid and atherosclerosis. ssGSEA analysis revealed that there were significant differences in the infiltration levels of immune cells between two subtypes of HF patients. Random-forest and support vector machine algorithm eventually identified ten diagnostic markers (MEF2D, RXRA, PPARA, FOXO1, PPARD, PPP3CB, MAPK14, CREB1, MEF2A, PRMT1) for risk prediction of HF patients, and the proposed nomogram resulted in good predictive performance (GSE66360, AUC = 0.91; GSE59867, AUC = 0.84) and the clinical usefulness in HF patients. More importantly, 10 drugs and 15 miRNA were predicted as drug target and hub miRNA that associated with energy metabolism-related genes, providing further information on clinical HF treatment.ConclusionThis study identified ten energy metabolism-related diagnostic markers using random forest algorithm, which may help optimize risk stratification and clinical treatment in HF patients.
Risk of severe COVID-19 infection in persons with diabetes during the first and second waves in Denmark: A nationwide cohort study
Authors: Stidsen Jacob V. , Green Anders , Rosengaard Louise , Højlund Kurt 
Published: October 2022

ObjectiveCoronavirus disease-2019 (COVID-19) increases risk of hospitalization and death in diabetes and diabetes-related conditions. We examined the temporal trends in COVID-19-related hospitalization and mortality in the total Danish population by diabetes and diabetes-related conditions in the two first waves of COVID-19 in Denmark.Materials and methodsWe identified all persons with diabetes in the whole Danish population using national registries. COVID-19-related risks of hospitalization and death were assessed using Cox regression analysis in wave 1 (1 March-31 August 2020) and wave 2 (1 September 2020-28 February 2021) of the pandemic for persons with (n=321,933) and without diabetes (n=5,479,755). Analyses were stratified according to status of hypertension, obesity, cardiovascular and microvascular disease.ResultsThe cumulative incidence of COVID-19 hospitalization increased from wave 1 to wave 2 in both persons without (from 4 to 10 in 10,000) and with diabetes (from 16 to 54 per 10,000). The relative risk of hospitalization, however, increased more in patients with diabetes compared to persons without (age-, sex- and co-morbidity-adjusted HR [aHR] 1.40 (95% CI 1.27, 1.55) versus 1.76 (1.65, 1.87), p&lt;0.001 for interaction with wave). The mortality rate, according to the whole population, increased similarly in persons without and with diabetes from wave 1 to wave 2 (from 0.63 to 1.5 versus from 4.3 to 10 in 10,000; aHR 1.65; 1.34, 2.03 and 1.64; 1.43, 1.88). However, when mortality was restricted to the hospitalized population, the crude mortality fell from 26.8% to 19.6% in persons with diabetes, while only a minor decrease was seen in persons without diabetes (from 16.7% to 15.5%).ConclusionThe risk of COVID-19-related hospitalization increased more in persons with than without diabetes from wave 1 to wave 2 of the COVID-19 pandemic in the Danish population. However, mortality according to the whole population did not change, due to reduced mortality among hospitalized persons with diabetes.
Body mass index, basal insulin and glycemic control in children with type 1 diabetes treated with the advanced hybrid closed loop system remain stable - 1-year prospective, observational, two-center study
Authors: Seget Sebastian , Jarosz-Chobot Przemysława , Ochab Agnieszka , Polanska Joanna , Rusak Ewa , Witoszek Paulina , Chobot Agata 
Published: October 2022

BackgroundInformation on the influence of insulin treatment using advanced hybrid closed loop systems (AHCL) on body weight of young patients with type 1 diabetes (T1D) is scarce. The aim of this study was to observe whether there were any changes in body mass index (BMI) of children and adolescents with T1D treated using the Medtronic Minimed 780G AHCL after 1 year of follow up and to analyze potential associations between these changes and the insulin doses.Materials and methodsFor 50 children and adolescents (age 5.4-16.8 years, 24 (48%) boys, T1D for 3.9 ± 2.56 years) using an AHCL system anthropometric and AHCL data were collected prospectively. BMI Z-scores and two-week AHCL records obtained after AHCL enrollment were compared with data after 6 months and also 1 year after starting AHCL.ResultsThe BMI Z-score of the patients at 1 year follow-up did not change from time of AHCL initiation (0.51 ± 2.79 vs 0.57 ± 2.85, p&gt;0.05). There was a slight increase in total daily insulin per kg of body weight (0.67 ± 0.21 U/kg vs 0.80 ± 0.21 U/kg, p &lt;0.001), but the percent of basal insulin was unchanged (34.88 ± 6.91% vs 35.08 ± 6.30%, p&gt;0.05). We observed also no change (AHCL start vs after 1 year) in glycemic control parameters: average sensor glucose (131.36± 11.04 mg/dL vs 132.45 ± 13.42 mg/dL, p&gt;0.05), coefficient of variation (34.99± 5.17% vs 34.06 ± 5.38%, p&gt;0.05), glucose management indicator (6.45 ± 0.26% vs 6.48 ± 0.32%, p&gt;0.05), and time spent in the range of 70–180 mg/dL (79.28 ± 8.12% vs 80.40 ± 8.25%, p&gt;0.05).ConclusionDuring the 1 year of follow-up the BMI of children and adolescents with T1D treated with an AHCL system remained stable. Although there was a slight increase in the total daily insulin dose, the percent of basal insulin was unchanged. The patients maintained recommended glycemic control.
Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes
Authors: Al-Saoudi Elaf , Christensen Marie M. B. , Nawroth Peter , Fleming Thomas , Hommel Eva E. , Jørgensen Marit E. , Fleischer Jesper , Hansen Christian S. 
Published: October 2022

Aims/hypothesisAdvanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).MethodsThis cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) “glycolytic dysfunction”, ii) “lipid peroxidation”, iii) “oxidative stress”, and iv) “glucotoxicity”.ResultsA higher z-score of “glycolytic dysfunction” was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), “lipid peroxidation” was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and “glucotoxicity” was associated with lower SDNN (−4.20% (95% CI −8.1416; −0.0896), p = 0.047). No significance remained after adjustment for multiple testing.Conclusions/interpretationsIn young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.
Ovariectomy-induced hormone deprivation aggravates Aβ1-42 deposition in the basolateral amygdala and cholinergic fiber loss in the cortex but not cognitive behavioral symptoms in a triple transgenic mouse model of Alzheimer’s disease
Authors: Farkas Szidónia , Szabó Adrienn , Török Bibiána , Sólyomvári Csenge , Fazekas Csilla Lea , Bánrévi Krisztina , Correia Pedro , Chaves Tiago , Zelena Dóra 
Published: October 2022

Alzheimer’s disease is the most common type of dementia, being highly prevalent in elderly women. The advanced progression may be due to decreased hormone synthesis during post-menopause as estradiol and progesterone both have neuroprotective potentials. We aimed to confirm that female hormone depletion aggravates the progression of dementia in a triple transgenic mouse model of Alzheimer’s disease (3xTg-AD). As pathological hallmarks are known to appear in 6-month-old animals, we expected to see disease-like changes in the 4-month-old 3xTg-AD mice only after hormone depletion. Three-month-old female 3xTg-AD mice were compared with their age-matched controls. As a menopause model, ovaries were removed (OVX or Sham surgery). After 1-month recovery, the body composition of the animals was measured by an MRI scan. The cognitive and anxiety parameters were evaluated by different behavioral tests, modeling different aspects (Y-maze, Morris water maze, open-field, social discrimination, elevated plus maze, light–dark box, fox odor, operant conditioning, and conditioned fear test). At the end of the experiment, uterus was collected, amyloid-β accumulation, and the cholinergic system in the brain was examined by immunohistochemistry. The uterus weight decreased, and the body weight increased significantly in the OVX animals. The MRI data showed that the body weight change can be due to fat accumulation. Moreover, OVX increased anxiety in control, but decreased in 3xTg-AD animals, the later genotype being more anxious by default based on the anxiety z-score. In general, 3xTg-AD mice moved less. In relation to cognition, neither the 3xTg-AD genotype nor OVX surgery impaired learning and memory in general. Despite no progression of dementia-like behavior after OVX, at the histological level, OVX aggravated the amyloid-β plaque deposition in the basolateral amygdala and induced early cholinergic neuronal fiber loss in the somatosensory cortex of the transgenic animals. We confirmed that OVX induced menopausal symptoms. Removal of the sexual steroids aggravated the appearance of AD-related alterations in the brain without significantly affecting the behavior. Thus, the OVX in young, 3-month-old 3xTg-AD mice might be a suitable model for testing the effect of new treatment options on structural changes; however, to reveal any beneficial effect on behavior, a later time point might be needed.
Seasonal distribution of deep groundwater fluoride, geochemical factors and ecological risk for irrigation in the Shendong mining area, China
Authors: Hao Chunming , Wang Yantang , He Kaikai , Gui Herong 
Published: October 2022

High-fluoride (F-) deep groundwater in the vicinity of mining areas poses severe ecological risks. In this study, we aimed to characterize and reveal the seasonal distribution and influencing factors of elevated F- concentrations in the deep groundwater in the Shendong mining area, Shaanxi and Inner Mongolia province, China. In addition, the ecological risks associated with F- concentrations in irrigation water were assessed. During the wet and dry seasons, the F- concentrations in mine water samples ranged between 0.12 and 13.92 mg/L (mean: 4.24 mg/L) and between 0.20 and 17.58 mg/L (mean: 4.59 mg/L), respectively. The F- content of mine water was clearly higher during the dry season than that during the wet season. F- concentrations in deep groundwater exhibited consistent spatial distributions during both the dry and wet seasons, with an evident increase from southeast to northwest. The dissolution and precipitation of F--bearing and calcium minerals, cation exchange, competitive adsorption, evaporation, and anthropogenic activities during both the wet and dry seasons were identified as important factors influencing F- concentrations in deep groundwater. In addition, the ecological assessment revealed that 100% and 88.89% of low-F- deep groundwater samples were suitable for practices during the dry and wet seasons, respectively. In contrast 84.00% and 84.62% of high-F- deep groundwater samples were unsuitable for irrigation practices during the dry and wet seasons, respectively. This research provided useful prevention policies of deep groundwater extraction to mitigate environment problems associated with excessive F- irrigation.
Epigenome-wide association study of biomarkers of liver function identifies albumin-associated DNA methylation sites among male veterans with HIV
Authors: Titanji Boghuma K. , Lee Mitch , Wang Zeyuan , Chen Junyu , Hui Qin , Lo Re III Vincent , So-Armah Kaku , Justice Amy C. , Xu Ke , Freiberg Matthew , Gwinn Marta , Marconi Vincent C. , Sun Yan V. 
Published: October 2022

Background: Liver disease (LD) is an important cause of morbidity and mortality for people with HIV (PWH). The molecular factors linked with LD in PWH are varied and incompletely characterized. We performed an epigenome-wide association study (EWAS) to identify associations between DNA methylation (DNAm) and biomarkers of liver function—aspartate transaminase, alanine transaminase, albumin, total bilirubin, platelet count, FIB-4 score, and APRI score—in male United States veterans with HIV.Methods: Blood samples and clinical data were obtained from 960 HIV-infected male PWH from the Veterans Aging Cohort Study. DNAm was assessed using the Illumina 450K or the EPIC 850K array in two mutually exclusive subsets. We performed a meta-analysis for each DNAm site measured by either platform. We also examined the associations between four measures of DNAm age acceleration (AA) and liver biomarkers.Results: Nine DNAm sites were positively associated with serum albumin in the meta-analysis of the EPIC and 450K EWAS after correcting for multiple testing. Four DNAm sites (cg16936953, cg18942579, cg01409343, and cg12054453), annotated within the TMEM49 and four of the remaining five sites (cg18181703, cg03546163, cg20995564, and cg23966214) annotated to SOCS3, FKBP5, ZEB2, and SAMD14 genes, respectively. The DNAm site, cg12992827, was not annotated to any known coding sequence. No significant associations were detected for the other six liver biomarkers. Higher PhenoAA was significantly associated with lower level of serum albumin (β = -0.007, p-value = 8.6 × 10–4, CI: -0.011116, -0.002884).Conclusion: We identified epigenetic associations of both individual DNAm sites and DNAm AA with liver function through serum albumin in men with HIV. Further replication analyses in independent cohorts are warranted to confirm the epigenetic mechanisms underlying liver function and LD in PWH.
Prognostic significance of modified lung immune prognostic index in osteosarcoma patients
Authors: He Xuanhong , Tang Fan , Zou Chang , Li Longqing , Wang Yang , Kenmegne Guy Romeo , Zhou Yong , Lu Minxun , Min Li , Luo Yi , Tu Chongqi 
Published: October 2022

Purpose: Osteosarcoma is the most common primary malignancy of bone with a dismal prognosis for patients with pulmonary metastases. Evaluation of osteosarcoma prognosis would facilitate the prognosis consultation as well as the development of personalized treatment decisions. However, there is limited effective prognostic predictor at present. Lung Immune Prognostic Index (LIPI) is a novel prognostic factor in pulmonary cancers, whereas, the prognostic significance of LIPI in osteosarcoma has not yet been well clarified. In this study, we firstly explore the prognostic role of LIPI and further modify this predictive model in osteosarcoma.Patients and methods: A retrospectively study was conducted at Musculoskeletal Tumor Center of West China Hospital between January 2016 and January 2021. Hematological factors and clinical features of osteosarcoma patients were collected and analyzed. The area under curve (AUC) and optimal cuff-off of each single hematological factor was calculated.Results: In this study, lactate dehydrogenase (LDH), derived neurtrophil to lymphocyte ratio (dNLR), and Hydroxybutyrate dehydrogenase (HBDH) have higher AUC values. LIPI was composed of LDH and dNLR and was further modified by combing the HBDH, forming the osteosarcoma immune prognostic index (OIPI). OIPI divided 223 osteosarcoma patients divided into four groups, none, light, moderate, and severe (p &lt; 0.0001). OIPI has a higher AUC value than LIPI and other hematological indexes in t-ROC curve. According to the univariate and multivariate analysis, pathological fracture, metastasis, NLR, platelet–lymphocyte ratio (PLR), and OIPI were associated with the prognosis; and metastasis and OIPI were independent prognostic factors of osteosarcoma patients. An OIPI-based nomogram was also established and could predict the 3-year and 5-year overall survival. In addition, OIPI was also revealed correlated with metastasis and pathological fracture in osteosarcoma.Conclusion: This study first explore the prognostic significance of LIPI in osteosarcoma patients. In addition, we developed a modified LIPI, the OIPI, for osteosarcoma patients. Both the LIPI and OIPI could predict the overall survival of osteosarcoma patients well, while OIPI may be more suitable for osteosarcoma patients. In particular, OIPI may have the ability to identify some high-risk patients from clinically low-risk patients.
Exploring metabolism in scleroderma reveals opportunities for pharmacological intervention for therapy in fibrosis
Authors: Cantanhede Isabella Gomes , Liu Huan , Liu Huan , Balbuena Rodriguez Vestaen , Shiwen Xu , Ong Voo H. , Denton Christopher P. , Ponticos Markella , Xiong Guo , Lima-Filho José Luiz , Abraham David , Abu-Hanna Jeries , Taanman Jan-Willem 
Published: October 2022

BackgroundRecent evidence has indicated that alterations in energy metabolism play a critical role in the pathogenesis of fibrotic diseases. Studies have suggested that ‘metabolic reprogramming’ involving the glycolysis and oxidative phosphorylation (OXPHOS) in cells lead to an enhanced generation of energy and biosynthesis. The aim of this study was to assess the molecular basis of changes in fibrotic metabolism in systemic sclerosis (Scleroderma; SSc) and highlight the most appropriate targets for anti-fibrotic therapies.Materials and methodsDermal fibroblasts were isolated from five SSc patients and five healthy donors. Cells were cultured in medium with/without TGF-β1 and with/without ALK5, pan-PIM or ATM kinase inhibitors. Extracellular flux analyses were performed to evaluate glycolytic and mitochondrial respiratory function. The mitochondrial network in TMRM-stained cells was visualized by confocal laser-scanning microscopy, followed by semi-automatic analysis on the ImageJ platform. Protein expression of ECM and fibroblast components, glycolytic enzymes, subunits of the five OXPHOS complexes, and dynamin-related GTPases and receptors involved in mitochondrial fission/fusion were assessed by western blotting.ResultsEnhanced mitochondrial respiration coupled to ATP production was observed in SSc fibroblasts at the expense of spare respiratory capacity. Although no difference was found in glycolysis when comparing SSc with healthy control fibroblasts, levels of phophofructokinase-1 isoform PFKM were significantly lower in SSc fibroblasts (P&lt;0.05). Our results suggest that the number of respirasomes is decreased in the SSc mitochondria; however, the organelles formed a hyperfused network, which is thought to increase mitochondrial ATP production through complementation. The increased mitochondrial fusion correlated with a change in expression levels of regulators of mitochondrial morphology, including decreased levels of DRP1, increased levels of MIEF2 and changes in OPA1 isoform ratios. TGF-β1 treatment strongly stimulated glycolysis and mitochondrial respiration and induced the expression of fibrotic markers. The pan-PIM kinase inhibitor had no effect, whereas both ALK5 and ATM kinase inhibition abrogated TGF-β1-mediated fibroblast activation, and upregulation of glycolysis and respiration.ConclusionsOur data provide evidence for a novel mechanism(s) by which SSc fibroblasts exhibit altered metabolic programs and highlight changes in respiration and dysregulated mitochondrial morphology and function, which can be selectively targeted by small molecule kinase inhibitors.