Miracle-dz/UniFAR-FTUs huggingface dataset:
The Heritability of HbA1c and Fasting Blood Glucose in Different Measurement Settings

Abstract In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 < r < 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 < r < 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information.
Aqueous Flare as an Indicator of Response to Dexamethasone Treatment in Retinal Vein Occlusions: A Pilot Study

Abstract Purpose: To investigate aqueous flare change patterns in retinal vein occlusions (RVO) following intravitreal application of dexamethasone implant. To evaluate the correlations between central macular thickness (CMT), best corrected visual acuity (BCVA) and aqueous flare values. Methods: This prospective, interventional pilot study included 40 eyes of 40 patients with macular edema associated with RVO. All patients received intravitreal injection of dexamethasone implant at baseline visit. Full ophthalmologic examination, CMT and aqueous flare measurements were performed prior to injection and repeated at months 1, 3, and 5. Aqueous flare, BCVA and CMT changes between visits were assessed. Further statistical analysis was performed to investigate correlations between these three parameters. Results: The patients consist of 23 (57.5%) men and 17 (42.5%) women with a mean age of 65.7 ± 6.2 years. Of the 40 eyes, 24 (60%) had branch retinal vein occlusion and 16 (40%) had central retinal vein occlusion. BCVA (log MAR) was significantly correlated with aqueous flare at each visit (r = 0.436, p = 0.005; r = 0.349, p = 0.027; r = 0.357, p = 0.024; r = 0.551, p = 0.000, respectively). Flare values were also correlated with CMT measurements in 3rd and 5th months (r = 0.324, p = 0.042; r = 0.556, p = 0.000, respectively). Comparing the percentage change in CMT and flare values over time, the change in CMT from baseline to 3rd and 5th months (r = 0.441, p = 0.004, r = 0.448, p = 0.004), from 1st month to 3rd and 5th months (r = 0.441, p = 0.004; r = 0.461, p = 0.003) and from 3rd month to 5th month were directly correlated with aqueous flare changes (r = 0.584, p = 0.000). Twenty-two eyes (55%) required second dexamethasone implant application at 5th month. Conclusion: Considering the inflammatory base of RVO, dexamethasone implants effectively decreased the flare values in the anterior chamber. The CMT change was directly correlated with aqueous flare values.
Combinatorial Antileukemic Disruption of Oxidative Homeostasis and Mitochondrial Stability by the Redox Reactive Thalidomide 2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49) and Flavopiridol

2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole-1,3(2H)-dione (CPS49) is a member of a recently identified class of redox-reactive thalidomide analogs that show selective killing of leukemic cells by increasing intracellular reactive oxygen species (ROS) and targeting multiple transcriptional pathways. Flavopiridol is a semisynthetic flavonoid that inhibits cyclin-dependent kinases and also shows selective lethality against leukemic cells. The purpose of this study is to explore the efficacy and mechanism of action of the combinatorial use of the redox-reactive thalidomide CPS49 and the cyclin-dependent kinase inhibitor flavopiridol as a selective antileukemic therapeutic strategy. In combination, CPS49 and flavopiridol were found to induce selective cytotoxicity associated with mitochondrial dysfunction and elevations of ROS in leukemic cells ranging from additive to synergistic activity at low micromolar concentrations. Highest synergy was observed at the level of ROS generation with a strong correlation between cell-specific cytotoxicity and reciprocal coupling of drug-induced ROS elevation with glutathione depletion. Examination of the transcriptional targeting of CPS49 and flavopiridol combinations reveals that the drugs act in concert to initiate a cell specific transcriptional program that manipulates nuclear factor-κB (NF-κB), E2F-1, and p73 activity to promote enhanced mitochondrial instability by simultaneously elevating the expression of the proapoptotic factors BAX, BAD, p73, and PUMA while depressing expression of the antiapoptotic genes MCL1, XIAP, BCL-xL, SURVIVIN, and MDM2. The coadministration of CPS49 and flavopiridol acts through coordinate targeting of transcriptional pathways that enforce selective mitochondrial dysfunction and ROS elevation and is therefore a promising new therapeutic combination that warrants further preclinical exploration.
Factors affecting the prognosis of cancer patients in general intensive care units in a Chinese population

Background: More and more cancer patients are admitted to intensive care units (ICUs) with acute lifethreatening conditions. In West, the mortality of cancer patients admitted to ICUs has been substantially reduced thanks to advances in diagnosis and treatment. However, there is a paucity of data regarding the current situation of cancer patients admitted to ICUs in China. Methods: We performed a detailed retrospective review of 255 cancer patients admitted to the ICUs of three university-affiliated hospitals in Hunan province over a five-year period. Outcome measure was ICU mortality rate, and was correlated with physiologic and therapeutic factors. We also evaluated the performance of two severity-of-illness scoring systems in this population. Results: During the studying period, the medical ICU plus Respiratory ICU (RICU) beds occupied 1.02% of all inpatients beds and received 1.8% of all inpatient admissions. The rates for ICU, one-month and six-month mortalities were 49.0%, 75.7% and 85.1%, respectively. Patients with lung cancer had better prognosis than other malignancies. No change or increased Sequential Organ Failure Assessment (SOFA) score, higher Acute Physiology and Chronic Health Evaluation (APACHE II) score at admission, and the need for invasive mechanical ventilation (IMV) and vasopressors were independently associated with ICU mortality. Conclusions: Cancer patients had less access to the intensive care resources in Hunan province of China than western countries. Both systemic illness and requirement for specific measures for organ failure predicted ICU mortality in this population. Based on our results, we proposed a set of clinical parameters to guide patient management when considering ICU transfers.
Biofilm Morphotypes and Population Structure among Staphylococcus epidermidis from Commensal and Clinical Samples

Bacterial species comprise related genotypes that can display divergent phenotypes with important clinical implications. Staphylococcus epidermidis is a common cause of nosocomial infections and, critical to its pathogenesis, is its ability to adhere and form biofilms on surfaces, thereby moderating the effect of the host’s immune response and antibiotics. Commensal S. epidermidis populations are thought to differ from those associated with disease in factors involved in adhesion and biofilm accumulation. We quantified the differences in biofilm formation in 98 S. epidermidis isolates from various sources, and investigated population structure based on ribosomal multilocus typing (rMLST) and the presence/absence of genes involved in adhesion and biofilm formation. All isolates were able to adhere and form biofilms in in vitro growth assays and confocal microscopy allowed classification into 5 biofilm morphotypes based on their thickness, biovolume and roughness. Phylogenetic reconstruction grouped isolates into three separate clades, with the isolates in the main disease associated clade displaying diversity in morphotype. Of the biofilm morphology characteristics, only biofilm thickness had a significant association with clade distribution. The distribution of some known adhesion-associated genes (aap and sesE) among isolates showed a significant association with the species clonal frame. These data challenge the assumption that biofilm-associated genes, such as those on the ica operon, are genetic markers for less invasive S. epidermidis isolates, and suggest that phenotypic characteristics, such as adhesion and biofilm formation, are not fixed by clonal descent but are influenced by the presence of various genes that are mobile among lineages.
Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis

Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 PCNSTLs. Fifteen cases were classified as peripheral T-cell lymphoma, not otherwise specified, 2 of which were of &ggr;&dgr; T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma, ALK-positive and 2 anaplastic large cell lymphoma, ALK-negative. Median age was 58.5 years (range, 21 to 81 y), with an M:F ratio of 11:7. Imaging results showed that 15 patients had supratentorial lesions. Regardless of subtype, necrosis and perivascular cuffing of tumor cells were frequently observed (11/18 cases). CD3 was positive in all cases but 1; 10/17 were CD8-positive, and 5/17 were CD4-positive. Most cases studied had a cytotoxic phenotype with expression of TIA1 (13/15) and granzyme-B (9/13). Polymerase chain reaction analysis of T-cell receptor &ggr; rearrangement confirmed a T-cell clone in 14 cases with adequate DNA quality. Next-generation sequencing showed somatic mutations in 36% of cases studied; 2 had >1 mutation, and none showed overlapping mutations. These included mutations in DNMT3A, KRAS, JAK3, STAT3, STAT5B, GNB1, and TET2 genes, genes implicated previously in other T-cell neoplasms. The outcome was heterogenous; 2 patients are alive without disease, 4 are alive with disease, and 6 died of disease. In conclusion, PCNSTLs are histologically and genomically heterogenous with frequent phenotypic aberrancy and a cytotoxic phenotype in most cases.
SRM targeted proteomics in search for biomarkers of HCV‐induced progression of fibrosis to cirrhosis in HALT‐C patients

The current gold standard for diagnosis of hepatic fibrosis and cirrhosis is the traditional invasive liver biopsy. It is desirable to assess hepatic fibrosis with noninvasive means. Targeted proteomic techniques allow an unbiased assessment of proteins and might be useful to identify proteins related to hepatic fibrosis. We utilized selected reaction monitoring (SRM) targeted proteomics combined with an organ‐specific blood protein strategy to identify and quantify 38 liver‐specific proteins. A combination of protein C and retinol‐binding protein 4 in serum gave promising preliminary results as candidate biomarkers to distinguish patients at different stages of hepatic fibrosis due to chronic infection with hepatitis C virus (HCV). Also, alpha‐1‐B glycoprotein, complement factor H and insulin‐like growth factor binding protein acid labile subunit performed well in distinguishing patients from healthy controls.
Climate seasonality limits carbon assimilation and storage in tropical forests

The seasonal climate drivers of the carbon cycle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combination of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measurements and 35 litter productivity measurements), their associate canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonality in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positively to precipitation when rainfall is < 2000 mm.yr−1 (water-limited forests) and to radiation otherwise (light-limited forests); on the other hand, independent of climate limitations, wood productivity and litterfall are driven by seasonal variation in precipitation and evapotranspiration respectively. Consequently, light-limited forests present an asynchronism between canopy photosynthetic capacity and wood productivity. Precipitation first-order control indicates an overall decrease in tropical forest productivity in a drier climate. (Resume d'auteur)
Structural Basis for Ubiquitin Recognition by Ubiquitin-Binding Zinc Finger of FAAP20

Several ubiquitin-binding zinc fingers (UBZs) have been reported to preferentially bind K63-linked ubiquitin chains. In particular, the UBZ domain of FAAP20 (FAAP20-UBZ), a member of the Fanconi anemia core complex, seems to recognize K63-linked ubiquitin chains, in order to recruit the complex to DNA interstrand crosslinks and mediate DNA repair. By contrast, it is reported that the attachment of a single ubiquitin to Rev1, a translesion DNA polymerase, increases binding of Rev1 to FAAP20. To clarify the specificity of FAAP20-UBZ, we determined the crystal structure of FAAP20-UBZ in complex with K63-linked diubiquitin at 1.9 Å resolution. In this structure, FAAP20-UBZ interacts only with one of the two ubiquitin moieties. Consistently, binding assays using surface plasmon resonance spectrometry showed that FAAP20-UBZ binds ubiquitin and M1-, K48- and K63-linked diubiquitin chains with similar affinities. Residues in the vicinity of Ala168 within the α-helix and the C-terminal Trp180 interact with the canonical Ile44-centered hydrophobic patch of ubiquitin. Asp164 within the α-helix and the C-terminal loop mediate a hydrogen bond network, which reinforces ubiquitin-binding of FAAP20-UBZ. Mutations of the ubiquitin-interacting residues disrupted binding to ubiquitin in vitro and abolished the accumulation of FAAP20 to DNA damage sites in vivo. Finally, structural comparison among FAAP20-UBZ, WRNIP1-UBZ and RAD18-UBZ revealed distinct modes of ubiquitin binding. UBZ family proteins could be divided into at least three classes, according to their ubiquitin-binding modes.
PENGARUH MOTIVASI TERHADAP KEPUASAN KERJA

Research is intended to test influence Motivation against Job Satisfaction work lecturer at Economics Faculty, "T" University in Jakarta. The sample used purposive sampling technique, where samples selected totaled 100 respondents who works as a lecturer at the Economics Faculty, "T" University during at least 24 months. Instrument analysis of data used is multiple regression analysis by the aid SPSS program. Based on the results of the study found that there is a positive relationship but tends to be weak between satisfaction job satisfaction variables namely only capable of amounting to 22.1% described by the motivational variable while another 77,9% is explained by the variation of variables outside motivation.Keywords : Motivation, Job satisfaction, University
RGD PET: From Lesion Detection to Therapy Response Monitoring

501 Objectives Tumor hypoxia has a major negative predictive value for local tumor progression, likeliness of metastasis, and overall tumor prognosis in several types of human cancers. [18F]FAZA is a PET biomarker for non-invasive identification and quantification of regional tumor hypoxia, presenting a more favourable tumor-to-background ratio with respect to the widely used hypoxia tracer [18F]FMISO. However, no studies are actually available on [18F]FAZA human biodistribution and its dosimetry. Aim of the present study was to firstly evaluate in non-small cell lung cancer (NSCLC) patients the PET-based human dosimetry and biodistribution of [18F]FAZA. Methods Five NSCLC patients referred to surgical treatment underwent whole body PET and CT scans after injection of 371±37 MBq of [18F]FAZA. Following 10-min dynamic imaging of the heart to calculate the activity in blood, four total body studies were acquired at 10, 64, 120 and 240 min post injection (PI). Urine samples were collected after each imaging session and at 360 min PI. Regions of interest were drawn around visually identifiable sources organs to generate time activity curves. Residence time were determined from these curves, and dose to individual organs and body as a whole were calculated using OLINDA/EXM 1.1. Results Blood clearance was characterized by a rapid distribution phase, followed by a first order elimination phase. The main radiation source regions in [18F]FAZA distribution were bladder, kidney, liver, spleen, and muscle. The highest uptake was found in the muscle and liver with a peak of 42.7±5.3% and 5.3±0.6% of injected activity, respectively. The total urinary excretion was 4.5±1.2 MBq of injected activity. The highest absorbed dose was to the bladder wall (0.019 mGy/MBq with 2 hours voiding interval) and liver (0.001 mGy/MBq). The effective dose (ED) was 0.0098±0.0014 mSv/MBq. Conclusions The estimate [18F]FAZA ED for 370 MBq injection is 3.7 mSv that is lower than that reported for [18F]FMISO (4.4 mSv). This finding is in line with literature of preclinical studies that show a lower half-life in the normal tissue of [18F]FAZA with respect to [18F]FMISO. The favorable radiation risk profile associated to whole body PET with [18F]FAZA is definitely feasible for clinical hypoxia evaluation, also allowing patients to safely receive consecutive PET/CT studies.
Clinico Histopathological Overview of GIT Lesions in a Rural Hospital

Introduction: Gastrointestinal tract (GIT) is the important site for wide variety of lesions especially malignant tumors. GIT cancers constitute 15-25% of all cancer burdens. The primary aim of GI pathology is to provide essential diagnostic and prognostic information allowing physicians and surgeons the best clinical management of the individual patient. Aim: We undertake this study to find out the various histopathological spectrum of the GIT lesions and to correlate them with clinical presentations, age, sex and to find the density of various GIT lesions in rural area. Materials and Methods: The prospective study of 800 patients having gastrointestinal lesion were included in this study over a period of 30 months from Jan 2012 to July 2014. The materials were collected in the form of biopsy and resected specimens of gastrointestinal tract with relevant clinical history. The superficial biopsy, biopsy with artifacts and inadequate material/history were excluded from the study. The histopathological diagnoses were categorized as inflammatory and tumors -benign and malignant lesion. Results: Amongst 800 cases studied of GI lesions, majority were inflammatory lesions as acute appendicitis and chronic appendicitis comprising 88.5% with a peak incidence in the 20-30 decades. In tumors, malignant lesions of gastrointestinal tract constituted 88.3% while benign tumor constituted 11.6% only. Colorectal cancers were seen having highest frequency (61.5%) followed by oesophagus (18.8%), stomach (7.5%), small intestine (1.8%). Male patient were outnumbered by female patients in both inflammatory and tumors category. Conclusion: Histopathological evaluation is the gold standard for the early detection of GI tract lesions especially malignant one hence it helps in their early management. Our study of gastrointestinal tract lesions throws a light on early diagnosis by histopathology beneficial for the patients in rural area.
In vivo imaging of spinal cord atrophy in neuroinflammatory diseases

Spinal cord atrophy is prominent in chronic progressive neurologic diseases such as human T‐cell lymphotropic virus type 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Here we compared the spinal cord cross‐sectional area (SCCSA) in HAM/TSP and MS patients to that of healthy volunteers (HVs).
Racial disparities in stage-specific gastric cancer: analysis of results from the Surveillance Epidemiology and End Results (SEER) program database

The incidence of gastric cancer is declining in western countries but continues to represent a serious health problem worldwide, especially in Asia and among Asian Americans. This study aimed to investigate ethnic disparities in stage-specific gastric cancer, including differences in incidence, treatment and survival. The cohort study was analyzed using the data set of patients with gastric cancer registered in the Surveillance, Epidemiology, and End Results (SEER) program from 2004 to 2013. Among 54,165 patients with gastric cancer, 38,308 were whites (70.7%), 7546 were blacks (13.9%), 494 were American Indian/Alaskan Natives (0.9%) and 7817 were Asians/Pacific Islanders (14.4%). Variables were patient demographics, disease characteristics, surgery/radiation treatment, overall survival (OS) and cause specific survival (CSS). Asians/Pacific Islanders demonstrated the highest incidence rates for gastric cancer compared with other groups and had the greatest decline in incidence during the study period (13.03 to 9.28 per 100,000/year), as well as the highest percentage of patients with American Joint Committee on Cancer (AJCC) early stage gastric cancer. There were significant differences between groups in treatment across stages I–IV (all p<0.001); Asians/Pacific Islanders had the highest rate of surgery plus radiation (45.1%). Significant differences were found in OS and CSS between groups (p<0.001); OS was highest among Asians/Pacific Islanders. Multivariate analysis revealed that age, race, grade, stage, location, and second primary cancer were valid prognostic factors for survival. Marked ethnic disparities exist in age-adjusted incidence of primary gastric cancer, with significant differences between races in age, gender, histological type, grade, AJCC stage, location, second cancer, treatment and survival.