Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations in functional networks during cue-reactivity in Internet gaming disorder

Background Cue-induced brain reactivity has been suggested to be a fundamental and important mechanism explaining the development, maintenance, and relapse of addiction, including Internet gaming disorder (IGD). Altered activity in addiction-related brain regions has been found during cue-reactivity in IGD using functional magnetic resonance imaging (fMRI), but less is known regarding the alterations of coordinated whole brain activity patterns in IGD. Methods To investigate the activity of temporally coherent, large-scale functional brain networks (FNs) during cue-reactivity in IGD, independent component analysis was applied to fMRI data from 29 male subjects with IGD and 23 matched healthy controls (HC) performing a cue-reactivity task involving Internet gaming stimuli (i.e., game cues) and general Internet surfing-related stimuli (i.e., control cues). Results Four FNs were identified that were related to the response to game cues relative to control cues and that showed altered engagement/disengagement in IGD compared with HC. These FNs included temporo-occipital and temporo-insula networks associated with sensory processing, a frontoparietal network involved in memory and executive functioning, and a dorsal-limbic network implicated in reward and motivation processing. Within IGD, game versus control engagement of the temporo-occipital and frontoparietal networks were positively correlated with IGD severity. Similarly, disengagement of temporo-insula network was negatively correlated with higher game-craving. Discussion These findings are consistent with altered cue-reactivity brain regions reported in substance-related addictions, providing evidence that IGD may represent a type of addiction. The identification of the networks might shed light on the mechanisms of the cue-induced craving and addictive Internet gaming behaviors.
PARP Inhibition Increases the Response to Chemotherapy in Uveal Melanoma

Uveal melanoma (UM) remains without effective therapy at the metastatic stage, which is associated with BAP-1 (BRCA1 associated protein) mutations. However, no data on DNA repair capacities in UM are available. Here, we use UM patient-derived xenografts (PDXs) to study the therapeutic activity of the PARP inhibitor olaparib, alone or in combination. First, we show that the expression and the activity of PARP proteins is similar between the PDXs and the corresponding patient’s tumors. In vivo experiments in the PDX models showed that olaparib was not efficient alone, but significantly increased the efficacy of dacarbazine. Finally, using reverse phase protein arrays and immunohistochemistry, we identified proteins involved in DNA repair and apoptosis as potential biomarkers predicting response to the combination of olaparib and dacarbazine. We also observed a high increase of phosphorylated YAP and TAZ proteins after dacarbazine + olaparib treatment. Our results suggest that PARP inhibition in combination with the alkylating agent dacarbazine could be of clinical interest for UM treatment. We also observe an interesting effect of dacarbazine on the Hippo pathway, confirming the importance of this pathway in UM.
Leaf anatomical adaptations have central roles in photosynthetic acclimation to humidity.

Rates of photosynthesis can be lower in plants grown under conditions of high leaf to air vapor pressure difference (VPD) than under low VPD. Leaf phenotype plasticity is a primary factor determining photosynthetic responses to environmental stimuli. However, it remains unclear how changes in leaf anatomical traits drive photosynthetic acclimation to high VPD. Thus, here we examined the role of leaf anatomy in the differing photosynthetic responses of two tomato cultivars (Jinpeng and Zhongza) to long-term growth under high and low VPD. Photosynthesis was not affected by VPD in Jinpeng. This was attributed to homeostasis in stomatal conductance (gs), and to a lesser extent, mesophyll conductance (gm). Disruption of synchronised changes to cell size in the epidermis and mesophyll meant that growth under high VPD reduced stomatal density in Jinpeng, but that minor vein density remained unchanged. Thus, water supplied by the veins could support the increased transpirational demand preventing stomatal closure. Variation in VPD did not affect mesophyll cell structures in Jinpeng, and therefore gm. By contrast, photosynthesis in Zhongza was reduced under high VPD, which was primarily attributed to decreased gs and gm. The former was mainly induced by decreased stomatal aperture. Thus, transpirational demand exceeded water supply in Zhongza. This was likely due to coordinated decreases in stomatal and minor vein density that were driven by synchronised increases in epidermal and mesophyll cell size under high VPD conditions. Liquid-phase limitation was primarily responsible for the declined gm in Zhongza under high VPD. High VPD induced an increase in liquid-phase resistance by reducing mesophyll surface area exposed to intercellular air spaces and increasing cytosolic resistance. The results suggest that plasticity in epidermal and mesophyll cell size provides an efficient way for regulating photosynthesis during acclimation to long-term high VPD.
The Cell Death-promoting Gene DP5, Which Interacts with the BCL2 Family, Is Induced during Neuronal Apoptosis Following Exposure to Amyloid β Protein*

DP5, which contains a BH3 domain, was cloned as a neuronal apoptosis-inducing gene. To confirm that DP5 interacts with members of the Bcl-2 family, 293T cells were transiently co-transfected with DP5 and Bcl-xl cDNA constructs, and immunoprecipitation was carried out. The 30-kDa Bcl-xl was co-immunoprecipitated with Myc-tagged DP5, suggesting that DP5 physically interacts with Bcl-xl in mammalian cells. Previously, we reported that DP5 is induced during neuronal apoptosis in cultured sympathetic neurons. Here, we analyzed DP5 gene expression and the specific interaction of DP5 with Bcl-xl during neuronal death induced by amyloid-β protein (A β). DP5 mRNA was induced 6 h after treatment with A β in cultured rat cortical neurons. The protein encoded by DP5 mRNA showed a specific interaction with Bcl-xl. Induction of DP5 gene expression was blocked by nifedipine, an inhibitor of l-type voltage-dependent calcium channels, and dantrolene, an inhibitor of calcium release from the endoplasmic reticulum. These results suggested that the induction of DP5 mRNA occurs downstream of the increase in cytosolic calcium concentration caused by A β. Moreover, DP5 specifically interacts with Bcl-xl during neuronal apoptosis following exposure to A β, and its binding could impair the survival-promoting activities of Bcl-xl. Thus, the induction of DP5 mRNA and the interaction of DP5 and Bcl-xl could play significant roles in neuronal degeneration following exposure to A β.
ECHOCARDIOGRAPHIC MYOCARDIAL CHANGES IN ACROMEGALY: A CROSS-SECTIONAL ANALYSIS IN A TERTIARY CENTER IN BULGARIA.

Context Cardiomyopathy is the most frequent cardiovascular complication in acromegaly. Objective We aimed to compare some echocardiographic markers in acromegaly patients with controls and find a correlation with disease duration, disease activity, levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Design We conducted a cross-sectional case-control study for the period of 2008-2012. Subjects and methods Acromegaly patients altogether 146 (56 men and 90 women), were divided into four groups according to disease activity and the presence of arterial hypertension (AH). The control group included 83 subjects, matching the patient groups by age, gender and presence of AH. GH was measured by an immunofluorometric method, while IGF-1 by IRMA method. All patients and controls were subjected to one- and two-dimensional transthoracic echocardiography, color and pulse Doppler. Results We found a thickening of the left ventricular walls and an increase in the left ventricular mass. However, these changes were not statistically significant in all groups and no correlation with disease duration could be demonstrated. As markers of diastolic dysfunction, increased deceleration time and isovolumetric relaxation were registered, which were dependent mainly on age in a binary logistic regression analysis, but not GH or IGF-1. Using absolute values, ejection and shortening fractions were increased in some groups. Using cut-off values, a higher percentage of systolic dysfunction was demonstrated in patients compared to their corresponding controls. Engagement of the right heart ventricle was also found - increased deceleration time and decreased e/a tric ratio. Conclusions In conclusion, functional impairments of both ventricles were present, with a predominance of left ventricular diastolic dysfunction.
Axial allometry in a neutrally buoyant environment: effects of the terrestrial‐aquatic transition on vertebral scaling

Ecological diversification into new environments presents new mechanical challenges for locomotion. An extreme example of this is the transition from a terrestrial to an aquatic lifestyle. Here, we examine the implications of life in a neutrally buoyant environment on adaptations of the axial skeleton to evolutionary increases in body size. On land, mammals must use their thoracolumbar vertebral column for body support against gravity and thus exhibit increasing stabilization of the trunk as body size increases. Conversely, in water, the role of the axial skeleton in body support is reduced, and, in aquatic mammals, the vertebral column functions primarily in locomotion. Therefore, we hypothesize that the allometric stabilization associated with increasing body size in terrestrial mammals will be minimized in secondarily aquatic mammals. We test this by comparing the scaling exponent (slope) of vertebral measures from 57 terrestrial species (23 felids, 34 bovids) to 23 semi‐aquatic species (pinnipeds), using phylogenetically corrected regressions. Terrestrial taxa meet predictions of allometric stabilization, with posterior vertebral column (lumbar region) shortening, increased vertebral height compared to width, and shorter, more disc‐shaped centra. In contrast, pinniped vertebral proportions (e.g. length, width, height) scale with isometry, and in some cases, centra even become more spool‐shaped with increasing size, suggesting increased flexibility. Our results demonstrate that evolution of a secondarily aquatic lifestyle has modified the mechanical constraints associated with evolutionary increases in body size, relative to terrestrial taxa.
Pioglitazone ameliorates hepatic damage in irradiated rats via regulating anti-inflammatory and antifibrogenic signalling pathways

Abstract Hepatic irradiation during radiotherapy is associated with liver damage. The current study was designed to investigate the possible modulatory effects of pioglitazone against γ irradiation-induced hepatic damage in rats. Animals were exposed to a single dose of 6 Gy and received pioglitazone (10 mg/kg/day) orally for 4 weeks starting on the same day of irradiation. Results showed that irradiation increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as serum triglyceride (TG) and total cholesterol (TC) levels. Furthermore, it elevated inflammatory mediators; tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6); nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in hepatic tissues. Moreover, it increased levels of serum fibrotic markers; hyaluronic acid (HA), laminin (LN), and type III procollagen (PCIII). Additionally, hepatic fibrotic markers; transforming growth factor-β1 (TGF-β1) and hydroxyproline (HP) levels were elevated. Histological analysis of H&E and MT staining of liver sections exhibited cellular infiltration and fibrous deposition in irradiated rats. It was observed that pioglitazone modulated the described deviations. In conclusion, pioglitazone could serve as a promising therapeutic tool for attenuating radiation-induced liver injury in patients with radiotherapy which might be attributed to its anti-inflammatory and antifibrotic activities.
Determinants and efficiency of Pakistan’s chemical products’ exports: An application of stochastic frontier gravity model

The estimation of efficiency of industry-specific exports is very important to find exports’ gap and to frame exports promotion policy for targeted industry. This study attempts to investigate the main determinants of chemical products’ exports of Pakistan with 62 trading partners by applying Stochastic Frontier Analysis (SFA) on an augmented gravity model for a period 1995–2015. The results corroborate that chemical products’ exports follow gravity patterns. This study finds a negative and significant impact of import tariff on exports of chemical products while the positive impact of devaluation has been observed. Further, the estimations also take into account the impact of Preferential Trade Agreements (PTA), colonial links, common language, political disputes and contiguity by incorporating dummy variable for each variable and the expected positive effects are found except an insignificant effect of Contiguity. Further, the negative impact of political disputes is observed. The exports’ efficiency analyses reveal that Pakistan’s chemical exports are well below the optimal level and there exists a huge untapped exports’ potential with its neighboring, Middle Eastern and European countries.
Postoperative Hearing Preservation in Patients Undergoing Retrosigmoid Craniotomy for Resection of Vestibular Schwannomas: A Systematic Review of 2034 Patients.

BACKGROUND Vestibular schwannomas (VS) are benign tumors derived from Schwann cells ensheathing the vestibulocochlear nerve. The retrosigmoid (RS) surgical approach is useful to resect tumors of multiple sizes while affording the possibility of preserving postoperative hearing. OBJECTIVE To conduct a systematic review of published literature investigating hearing preservation rates in patients who underwent the RS approach for VS treatment. METHODS The PubMed, Scopus, and Embase databases were surveyed for studies that reported preoperative and postoperative hearing grades on VS patients who underwent RS treatment. Hearing preservation rates were calculated, and additional patient demographic data were extracted. Tumor size data were stratified to compare hearing preservation rates after surgery for intracanalicular, small (0-20 mm), and large (>20 mm) tumors. RESULTS Of 383 deduplicated articles, 26 studies (6.8%) met eligibility criteria for a total of 2034 patients with serviceable preoperative hearing, for whom postoperative hearing status was evaluated. Aggregate hearing preservation was 31% and 35% under a fixed and random effects model, respectively. A mixed effects model was used to determine hearing preservation rates depending on tumor size, which were determined to be 57%, 37%, and 12% for intracanalicular, small, and large tumors, respectively. Significant cross-study heterogeneity was found (I2 = 93%, τ2 = .964, P < .01; Q = 287.80, P = < .001), with rates of hearing preservation ranging from 0% to 100%. CONCLUSION Tumor size may have an effect on hearing preservation rates, but multiple factors should be considered. Discussion of a patient's expectations for hearing preservation is critical when deciding on VS treatment plans.
A constant absolute bandwidth tunable filter using varactor-loaded open-loop resonators

This paper presents a new type of lager tuning rate tunable filters using varactor-loaded open-loop resonators. The filter is based on capacitively loaded folded λ/2 resonators that are coupled to each other with mixed electrical and magnetic coupling. By adjusting the value of the varactors between the open gaps in a mixed coupled filter, the coupling coefficients and external quality can be tuned to meet the requirement of constant absolute bandwidth. The fabricated filter shows a tuning rate of 460 MHz/pF. To our knowledge, this planar tunable filter represents state-of-the art tuning rate characteristics among the varactor-tuned filter.
Parsing out the role of dopamine D4 receptor gene (DRD4) on alcohol‐related phenotypes: A meta‐analysis and systematic review

Genetics account for moderate variation of individual differences in developing alcohol use disorder (AUD), but it is unclear which genetic variations contribute to AUD risk. One candidate gene investigated due to its association with AUD is the dopamine D4 receptor gene (DRD4), which contains a 48–base pair variable number tandem repeat (VNTR) in exon 3 of its coding region. To date, no quantitative synthesis of the published literature on the effects of DRD4 VNTR variation on alcohol‐related phenotypes has been conducted. MEDLINE, Embase, Web of Science, and PsycInfo were searched for studies that reported on alcohol craving, alcohol consumption, severity of AUD, and case‐control (AUD versus no diagnosis of AUD) studies in DRD4L (seven repeats or more) carriers compared with DRD4S (six repeats or less) homozygotes. Random‐effects meta‐analysis was used for all analyses. A pooled sample size of 655 to 13,360 of 28 studies were included. Compared with DRD4S homozygotes, DRD4L carriers had increased number of drinking days (SMD: 0.205; 95% CI: 0.008 to 0.402), binge drinking days (SMD: 0.217; 95% CI: 0.0532 to 0.380), and severity of AUD (SMD: 0.143; 95% CI: 0.028 to 0.259). There was no difference between DRD4 VNTR genotypes on drinks per drinking day, largest number of drinks per day/occasion, and case‐control analysis. It was not possible to conduct a meta‐analysis of the craving data, but a systematic review of this literature found mixed results on DRD4 VNTR genotype effect. The present meta‐analysis suggests DRD4 VNTR variation may be a risk factor for problematic alcohol use. Our findings are limited, however, by the absence of ancestry data from studies included in our analysis, precluding our ability to adjust for population stratification. Due to the likelihood of type I error in candidate gene approaches, our work highlights the critical need for studies with larger and more inclusive samples that account for sex and genetic ancestry to fully understand this relationship.
Management of vaso‐occlusive episodes in the day hospital decreases admissions in children with sickle cell disease

Acute vaso‐occlusive episodes (VOE) are the most common reason for presentation to the Emergency Department (ED) and inpatient admission in people living with sickle cell disease (SCD). The goal of this study was to compare the hospital admission rate for VOE from our centre’s day hospital (Pediatric Ambulatory Chemotherapy and Transfusion Unit; PACT) versus the ED, and to determine which factors influence admission rate. The study included a total of 370 visits involving 140 children with SCD with a mean age of 10·9 ± 5·5 years. The timing from triage to the first analgesic was significantly different between the PACT and the ED (median, 32 vs. 70 min, P < 0·0001). The initial choice of opioid dosage adhered to our centre’s guidelines 84% of the time in the PACT v. 45% in the ED for morphine (P = 0·0003) and 100% in the PACT vs. 43% (P = 0·002) for hydromorphone. The admission rate from the ED (57%) was significantly higher than that of the PACT (29%) even when accounting for differences in baseline variables (P = 0·0001). In conclusion, the odds of being admitted were 3·8 times higher if the patient was treated in the ED. Timely administration and appropriate dosing of intravenous opioids may change this outcome in the future.
Inferring the direction of a causal link and estimating its effect via a Bayesian Mendelian randomization approach

The use of genetic variants as instrumental variables – an approach known as Mendelian randomization – is a popular epidemiological method for estimating the causal effect of an exposure (phenotype, biomarker, risk factor) on a disease or health-related outcome from observational data. Instrumental variables must satisfy strong, often untestable assumptions, which means that finding good genetic instruments among a large list of potential candidates is challenging. This difficulty is compounded by the fact that many genetic variants influence more than one phenotype through different causal pathways, a phenomenon called horizontal pleiotropy. This leads to errors not only in estimating the magnitude of the causal effect but also in inferring the direction of the putative causal link. In this paper, we propose a Bayesian approach called BayesMR that is a generalization of the Mendelian randomization technique in which we allow for pleiotropic effects and, crucially, for the possibility of reverse causation. The output of the method is a posterior distribution over the target causal effect, which provides an immediate and easily interpretable measure of the uncertainty in the estimation. More importantly, we use Bayesian model averaging to determine how much more likely the inferred direction is relative to the reverse direction.
New Insight into microRNA Functions in Cancer: Oncogene–microRNA–Tumor Suppressor Gene Network

Tumorigenesis is a multi-step and complex process with multi-factors involved. Deregulated oncogenes and tumor suppressor genes (TSGs) induced by genetic and epigenetic factors are considered as the driving force in the development and progression of cancer. Besides, microRNAs (miRNAs) act vital roles in tumorigenesis through regulating some oncogenes and TSGs. Interestingly, miRNAs are also regulated by oncogenes and TSGs. Considering the entangled regulation, here we propose a new insight into these regulation relationships in cancer: oncogene–miRNA–TSG network, which further emphasizes roles of miRNA, as well as highlights the network regulation among oncogene, miRNA, and TSG during tumorigenesis. The oncogene–miRNA–TSG network demonstrates that oncogenes and TSGs not only show functional synergy, but also there are regulatory relationships among oncogenes and TSGs during tumorigenesis, which could be mediated by miRNAs. In view of the oncogene–miRNA–TSG network involved in many oncogenes, miRNAs, and TSGs, as well as occurring in various tumor types, the anomaly of this network may be a common event in cancers and participates in tumorigenesis. This hypothesis broadens horizons of molecular mechanisms underlying tumorigenesis, and may provide a new promising venue for the prediction, diagnosis, and even therapy of cancer.
Colorectal cancer and dysplasia in inflammatory bowel disease : a review of disease epidemiology , pathophysiology , and management Running Title : Colorectal Cancer in Inflammatory Bowel Disease

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) characterized by recurrent episodes of mucosal inflammation. This chronic mucosal inflammation has several potential consequences, one of which is the occurrence of colitis associated colorectal cancer (CRC). Over the past decade our understanding of the epidemiology, pathophysiology, and overall approach to diagnosing and managing colitis associated CRC, has grown considerably. In the current review article, we outline these advancements and highlight areas in need of further research. Cancer Research. on November 3, 2017. © 2016 American Association for cancerpreventionresearch.aacrjournals. org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on September 27, 2016; DOI: 10.1158/1940-6207.CAPR-16-0124