Miracle-dz/UniFAR-FTUs huggingface dataset:
Exposure to graphene nanoparticles induces changes in measures of vascular/renal function in a load and form-dependent manner in mice

ABSTRACT Graphenes isolated from crystalline graphite are used in several industries. Employees working in the production of graphenes may be at risk of developing respiratory problems attributed to inhalation or contact with particulate matter (PM). However, graphene nanoparticles might also enter the circulation and accumulate in other organs. The aim of this study was to examine how different forms of graphene affect peripheral vascular functions, generation of reactive oxygen species (ROS) and changes in gene expression that may be indicative of cardiovascular and/or renal dysfunction. In the first investigation, different doses of graphene nanoplatelets were administered to mice via oropharyngeal aspiration. These effects were compared to those of dispersion medium (DM) and carbon black (CB). Gene expression alterations were observed in the heart for CB and graphene; however, only CB produced changes in peripheral vascular function. In the second study, oxidized forms of graphene were administered. Both oxidized forms increased the sensitivity of peripheral blood vessels to adrenoreceptor-mediated vasoconstriction and induced changes in ROS levels in the heart. Based upon the results of these investigations, exposure to graphene nanoparticles produced physiological and alterations in ROS and gene expression that may lead to cardiovascular dysfunction. Evidence indicates that the effects of these particles may be dependent upon dose and graphene form to which an individual may be exposed to.
Electrically Conductive, Transparent Polymeric Nanocomposites Modified by 2D Ti3C2Tx (MXene)

The electrically conductive, transparent, and flexible self-standing thin nanocomposite films based on copolyamide matrix (coPA:Vestamelt X1010) modified with 2D Ti3C2Tx (MXene) nanosheets were prepared by casting and their electrical, mechanical and optical properties and then, were investigated. The percolation threshold of the MXene filler within the coPA matrix was found to be 0.05 vol. %, and the highest determined electrical conductivity was 1.4 × 10−2 S·cm−1 for the composite filled with 5 wt. % (1.8 vol. %) of MXene. The electrical conductivity of the as-prepared MXene was 9.1 S·cm−1, and the electrical conductivity of the MAX phase (the precursor for MXene preparation) was 172 S·cm−1. The transparency of the prepared composite films exceeded 75%, even for samples containing 5 wt. % of MXene, as confirmed by UV spectroscopy. The dynamic mechanical analysis confirmed the improved mechanical properties, such as the storage modulus, which improved with the increasing MXene content. Moreover, all the composite films were very flexible and did not break under repeated twisting. The combination of the relatively high electrical conductivity of the composites filled with low filler content, an appropriate transparency, and good mechanical properties make these materials promising for applications in flexible electronics.
Altered neuronal activity in the auditory brainstem following sound stimulation in thalidomide‐induced autism model rats

Auditory hypersensitivity in autism is frequently observed in clinics. Dysfunction in the auditory brainstem has been suspected. We have established autism model rats using prenatal thalidomide exposure. Here we investigated whether abnormal response occurs in the brainstem following sound stimulus in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic days 9 and 10 in pregnant rats. Then, the animals were exposed to 16‐kHz pure tone auditory stimulus and c‐Fos immunostaining was performed to examine the neuronal activity on postnatal day 49 to 51. Following sound stimulus, increased number of c‐Fos‐positive neurons was observed in the medial nucleus of the trapezoid body of autism model rats compared with the control rats. These results suggest that prenatal thalidomide might cause altered processing of auditory stimulus, leading to the characteristics of auditory hypersensitivity in autism.
Evaluation of Electron Induced Crosslinking of Masticated Natural Rubber at Different Temperatures

In this work, natural rubber (NR) was masticated using an internal mixer to fit the requirements of reactive blending with polylactide and characterized by size exclusion chromatography (SEC), Fourier-transform infrared (FT-IR) spectroscopy and dynamic rheology measurements. Subsequently, the effect of elevated temperatures (25 °C, 80 °C, and 170 °C) on the electron beam (EB) induced crosslinking and degradation of masticated natural rubber (mNR) in a nitrogen atmosphere without adding crosslinking agents has been investigated. The sol gel investigation showed that the gel dose of mNR slightly increased with increasing irradiation temperature, which is also confirmed by the swelling test. The chain scission to crosslinking ratio (Gs/Gx) was found to be less than 1 for irradiated mNR at 25 °C and 80 °C, suggesting a dominating crosslinking behavior of mNR. However, a significant increase of Gs/Gx ratio (~1.12) was observed for mNR irradiated at 170 °C due to the enhanced thermal degradation behavior at high temperature. A remarkably improved elasticity (higher complex viscosity, higher storage modulus, and longer relaxation time) for EB modified mNR was demonstrated by dynamic rheological analysis. Particularly, the samples modified at higher temperatures represented more pronounced elasticity behavior which resulted from the higher number of branches and/or the longer branched chains.
Novel Semi-Replicative Retroviral Vector Mediated Double Suicide Gene Transfer Enhances Antitumor Effects in Patient-Derived Glioblastoma Models

As glioblastomas are mostly localized infiltrative lesions, gene therapy based on the retroviral replicating vector (RRV) system is considered an attractive strategy. Combinations of multiple suicide genes can circumvent the limitations associated with each gene, achieving direct and synergistic cytotoxic effects, along with bystander cell killing. In this study, we constructed a semi-and pseudotyped-RRV (sp-RRV) system harboring two suicide genes—herpes simplex virus type 1 thymidine kinase (TK) and yeast cytosine deaminase (CD)—to verify the dissemination and antitumor efficacy of our sp-RRV system (spRRVe-sEF1α-TK/sRRVgp-sEF1α-CD) in seven patient-derived glioblastoma stem-like cells (GSCs). Flow cytometry and high-content analysis revealed a wide range of transduction efficiency and good correlation between the delivery of therapeutic genes and susceptibility to the prodrugs ganciclovir and 5-fluorocytosine in patient-derived GSCs in vitro. Intra-tumoral delivery of spRRVe-sEF1α-TK/sRRVgp-sEF1α-CD, combined with prodrug treatment, synergistically inhibited cell proliferation and angiogenesis while increasing apoptosis and the depletion of tumor-associated macrophages in orthotopic glioblastoma xenografts. Genomic profiling of patient-derived GSCs revealed that the key genes preventing sp-RRV infection and transmission were associated with cell adhesion, migration, development, differentiation, and proliferation. This is the first report demonstrating that a novel sp-RRV-mediated TK/CD double suicide gene transfer system has high oncolytic power against extremely heterogeneous and treatment-refractory glioblastomas.
Hypothalamic-Pituitary Disorders in Childhood Cancer Survivors: Prevalence, Risk Factors and Long-Term Health Outcomes.

CONTEXT Data on hypothalamic-pituitary (HP) disorders in systematically evaluated childhood cancer survivors are limited. OBJECTIVE To describe prevalence, risk factors and associated adverse health outcomes of deficiencies in GH (GHD), TSH (TSHD), LH/FSH (LH/FSHD) and ACTH (ACTHD) along with central precocious puberty (CPP). DESIGN Retrospective with cross-sectional health outcomes analysis. SETTING Established cohort; tertiary care center. PATIENTS 3141 participants (median age, 31.7 years) followed for median 24.1 years. MAIN OUTCOME MEASURE Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals for associations between HP disorders, tumor- and treatment-related risk factors and health outcomes. RESULTS The estimated prevalence was 40.2% for GHD, 11.1% for TSHD, 10.6% for LH/FSHD, 3.2% for ACTHD, and 0.9% for CPP among participants treated with HP radiotherapy (n=1089) and 6.2% for GHD, and <1% for other HP disorders in the absence of this treatment. Clinical factors independently associated with HP disorders included HP radiotherapy (at any dose for GHD, TSHD, LH/FSHD, >30 Gy for ACTHD), alkylating agents (GHD, LH/FSHD), intrathecal chemotherapy (GHD), hydrocephalus with shunt placement (GHD, LH/FSHD), seizures (TSHD, ACTHD) and stroke (GHD, TSHD, LH/FSHD, ACTHD). Adverse health outcomes independently associated with HP disorders included short stature (GHD, TSHD), severe bone mineral density deficit (GHD, LH/FSHD), obesity (LH/FSHD), frailty (GHD), impaired physical health-related quality of life (TSHD), sexual dysfunction (LH/FSHD), impaired memory and processing speed (GHD, TSHD). CONCLUSIONS HP radiotherapy, CNS injury and, to a lesser extent, chemotherapy are associated with HP disorders, which are associated with adverse health outcomes.
A Terahertz (THz) Single-Polarization-Single-Mode (SPSM) Photonic Crystal Fiber (PCF)

This paper presents a novel approach to attain a single-polarization-single-mode (SPSM) photonic crystal fiber (PCF) in the terahertz (THz) regime. An initial circular hole PCF design is modified by introducing asymmetry in the first ring of six air holes in the cladding, i.e., epsilon-near-zero (ENZ) material is introduced into only four of those air holes and the other two remain air-filled but have different diameters. The resulting fundamental X-polarized (XP) and Y-polarized (YP) modes have distinctly different electric field distributions. The asymmetry is arranged so that the YP mode has a much larger amount of the field distributed in the ENZ material than the XP mode. Since the ENZ material is very lossy, the YP mode suffers a much higher loss than the XP mode. Consequently, after a short propagation distance, the loss difference (LD) between the XP and YP modes will be large enough that only the XP mode still realistically exists in the PCF. To further enhance the outcome, gain material is introduced into the core area to increase the LDs between the wanted XP mode and any unwanted higher order (HO) modes, as well as to compensate for the XP mode loss without affecting the LD between the XP and YP modes. The optimized PCF exhibits LDs between the desired XP mode and all other modes greater than 8.0 dB/cm across a wide frequency range of 0.312 THz. Consequently, the reported PCF only needs a length of 2.5 cm to attain an SPSM result, with the unwanted modes being more than 20 dB smaller than the wanted mode over the entire operational band.
Colonic Intramucosal Cancer in the Interposed Colon Treated with Endoscopic Mucosal Resection: A Case Report and Review of Literature

Colon interposition is a surgical procedure used for maintenance of luminal conduit after esophagectomy. Although epithelial neoplasia, such as adenoma and adenocarcinoma, may develop in the interposed colon, there are only few case reports on the condition. Due to the rarity of this condition, there is no definite consensus on recommending screening endoscopy for the early detection of neoplasia in the interposed colons. Here, we report a case of intramucosal adenocarcinoma in an interposed colon. Initial endoscopic resection for this tumor failed to accomplish complete resection. A subsequent endoscopic resection was performed 1 month later and complete resection was achieved. Based on our experience and recommendation on screening endoscopy for gastric cancer in Korea, we suggest that regular screening esophagogastroduodenoscopies should be performed following esophagectomy to detect early neoplasia in the stomach and interposed colon and avoid adverse results induced by delayed detection.
Revision cochlear implantation: The Irish experience

Objectives: To report a long-term experience on revision cochlear implantation (RCI) in a single institution, categorize their indications and to identify predictive parameters of implant failure. Methods: A retrospective study was conducted on a prospective database of a national cochlear implant unit. Patients requiring RCI between January 1995 and June 2016 were identified and stratified into adult and paediatric group. Medical records, investigation reports and device analysis reports were reviewed and analysed. Results/Discussion: A total of 37 children and 21 adults were identified requiring RCI on 60 devices. 63.3% of the RCI was indicated due to the device failure, while 36.7% was due to various medical reasons. Higher device failure rate was reported in the paediatric group, due to the high number of direct head trauma, which was not observed in the adult group. The leading medical indication for RCI was due to wound infection (10%). The overall RCI rate was 5.0%, among which 3.1% was due to device failures. A brief discussion on various medical indications, surgical challenges, and the mechanism of thought process to consider RCI, including treatment planning was outlined. Conclusion: RCI in the paediatric population poses a unique challenge. Integrity testing is helpful in identifying a potential device malfunction; however, regular clinical follow-up with multidisciplinary assessments is invaluable in the decision process for RCI.
Short Periods of Hypoxia Upregulate Sphingosine Kinase 1 and Increase Vasodilation of Arteries to Sphingosine 1-Phosphate (S1P) via S1P3

Sphingosine kinase [(SK), isoforms SK1 and SK2] catalyzes the formation of the bioactive lipid, sphingosine 1-phosphate (S1P). This can be exported from cells and bind to S1P receptors to modulate vascular function. We investigated the effect of short-term hypoxia on SK1 expression and the response of arteries to S1P. SK1 expression in rat aortic and coronary artery endothelial cells was studied using immunofluorescence and confocal microscopy. Responses of rat aortic rings were studied using wire myography and reversible hypoxia induced by bubbling myography chambers with 95% N2:5% CO2. Inhibitors were added 30 minutes before induction of hypoxia. S1P induced endothelium-dependent vasodilation via activation of S1P3 receptors and generation of nitric oxide. Hypoxia significantly increased relaxation to S1P and this was attenuated by (2R)-1-[[(4-[[3-methyl-5-[(phenylsulfonyl)methyl] phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol [(PF-543), SK1 inhibitor] but not (R)-FTY720 methyl ether [(ROMe), SK2 inhibitor]. Hypoxia also increased vessel contractility to the thromboxane mimetic, 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α, which was further increased by PF-543 and ROMe. Hypoxia upregulated SK1 expression in aortic and coronary artery endothelial cells and this was blocked by PF-543 and 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole [(SKi), SK1/2 inhibitor]. The effects of PF-543 and SKi were associated with increased proteasomal/lysosomal degradation of SK1. A short period of hypoxia increases the expression of SK1, which may generate S1P to oppose vessel contraction. Under hypoxic conditions, upregulation of SK1 is likely to lead to increased export of S1P from the cell and vasodilation via activation of endothelial S1P3 receptors. These data have significance for perfusion of tissue during episodes of ischemia.
The prevention of child drowning: the causal factors and social determinants impacting fatalities in portable pools.

ISSUE ADDRESSED There is a scarcity of research into portable pool drowning and its prevention. This total population study examines fatal drowning among children under five in portable pools in Australia. METHODS All child drowning deaths in portable pools for the period 1-July-2002 to 30-June-2018 were identified. A portable pool was defined as any structure used for swimming and wading which, when emptied, can be moved. RESULTS Twenty-three children (aged 0-17 years) drowned in portable pools. The drowning rate for children less than 5 years of age was (0.09 per 100,000 population). The peak age of death was 12-23 months (RR=2.99; CI: 1.09-8.23), with the majority (n=20 deaths) aged 16-31 months. Ninety percent followed a fall into water. None were supervised. Children commonly resided in areas classified as socially and economically disadvantaged (85%; n=17). Drowning rates in very remote areas were 15 times greater (RR=15.41; CI: 0.03-7579.65) than city children. Eleven (55%) drowning deaths occurred in pools with a depth >300mm, of which 10 (91%) were known to be unfenced. CONCLUSIONS Social determinants impact child drowning in portables pools, which can occur quickly and in just 150mm of water. Active supervision and a regulation-compliant barrier are effective prevention stratagems, factors which were absent from the deaths in this study. SO WHAT? : Portable pool drowning disproportionately impacts those aged 16-31 months who reside in very remote areas and areas classified as having high socio-economic disadvantage. Education for these groups on fencing and supervision of children must be provided.
GLP‐1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta‐analysis including the REWIND and PIONEER 6 trials

A meta‐analysis of cardiovascular outcome trials (CVOTs) comparing glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta‐analysis of available trial data was undertaken, using a random‐effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56 004 patients (68.9% with established cardiovascular disease) were included. GLP‐1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80–0.96; P = 0.011) with a non‐significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P = 0.220). GLP‐1RA also reduced the risk of cardiovascular death by 12%, of non‐fatal stroke by 16%, of hospitalization for heart failure by 9%, of all‐cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68–0.86]; P = 0.003). GLP‐1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all‐cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease.
Cognitive and mood side effects of lower urinary tract medication

ABSTRACT Introduction: Muscarinic receptor antagonists, 5α-reductase inhibitors and α1-adrenoceptor antagonists are frequently used drug classes for the treatment of lower urinary tract symptoms including those of overactive bladder syndrome and benign prostatic enlargement/benign prostatic obstruction. Areas covered: The authors review the evidence for adverse effects of these drug classes on cognitive function, mood and other functions of the central nervous system and discuss such effects against the evidence for mechanistic plausibility. Expert opinion: Muscarinic antagonists carry a risk for impaired cognition and other brain functions that differs quantitatively between compounds, being highest with oral formulations of oxybutynin. 5□-Reductase inhibitors can cause depressive symptoms even at low doses and starting several months after discontinuation of treatment. The evidence for α1-adrenoceptor antagonists and specifically tamsulosin to cause dementia is controversial and lacks mechanistic plausibility. We recommend that physicians treating patients with lower urinary tract symptoms carefully monitor mental status prior to prescribing and periodically thereafter.
Familial aggregation of inflammatory bowel disease in India: prevalence, risks and impact on disease behavior

Background/Aims Information about familial aggregation of inflammatory bowel disease (IBD) in Asia is limited. We aimed to analyze the prevalence and risk of familial IBD in an Indian cohort and compare familial and sporadic cases. Methods Familial IBD cases were identified from a large prospectively maintained IBD registry. The prevalence of IBD in first- and seconddegree relatives of index cases was evaluated. The disease behavior was compared to that of sporadic cases. Results Total 3,553 patients (ulcerative colitis [UC], 2,053; Crohn’s disease [CD], 1,500) were included. Familial IBD was noted in 4.13% of CD and 4.34% of UC patients. Family history was commoner in pediatric group (< 18 years) (P= 0.0002; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6–4.8). Majority had paternal transmission (UC, 67.42%; CD, 70.97%). Concordance of disease type was higher in UC (79.7%) compared to CD (37.1%). Familial IBD was associated with higher cumulative relapse rate (CD, P< 0.001; UC, P< 0.001), higher cumulative rate of surgery (CD, P< 0.001; UC, P< 0.001) and higher rate of biologic use (CD, P= 0.010; UC, P= 0.015). Pan-colitis was higher in familial UC (P= 0.003; OR, 1.935; 95% CI, 1.248–3.000). Fistulizing disease was commoner in familial CD (P= 0.041; OR, 2.044; 95% CI, 1.030–4.056). Conclusions The prevalence of familial IBD in India appears comparable to rest of Asia but lower than the West. It is associated with a younger age of onset, higher incidence of pan-colitis in UC and fistulizing complications in CD. Familial IBD has higher cumulative relapse, surgery and biologic use rates. Hence, family history of IBD could have important prognostic implications.
The Association between FLAIR Vascular Hyperintensity and Stroke Outcome Varies with Time from Onset

BACKGROUND AND PURPOSE: FLAIR vascular hyperintensity has been recognized as a marker of collaterals in ischemic stroke, but the impact on outcome is still controversial. We hypothesized that the association between FLAIR vascular hyperintensity and outcome varies with time. MATERIALS AND METHODS: We included 459 consecutive patients with middle cerebral artery stroke and divided them into 3 groups by symptom-to-MR imaging time (group 1, ≤7 days; group 2, 8–14 days; group 3, ≥15 days). The FLAIR vascular hyperintensity score, ranging from 0 to 3 points, was based on territory distributions of different MCA segments. The associations between FLAIR vascular hyperintensity and outcome with time were analyzed qualitatively and quantitatively. RESULTS: No patients underwent MR imaging within 6 hours of onset. The proportion of FLAIR vascular hyperintensity (+) and severe stenosis or occlusion of MCA was not significantly dependent on time. In groups 1 and 2, FLAIR vascular hyperintensity (+) was significantly associated with larger lesions, the prevalence of flow injury, and unfavorable outcome (mRS ≥ 2). There were no such associations in group 3. Multiple logistic regressions demonstrated that FLAIR vascular hyperintensity (+) was an independent risk factor for unfavorable outcome in group 2. Infarction volume tended to increase with the increase of the distal FLAIR vascular hyperintensity score in groups 1 and 2, while declining in group 3. CONCLUSIONS: FLAIR vascular hyperintensity is associated with unfavorable outcome within 6 hours to 14 days of onset, while the wider distribution of distal FLAIR vascular hyperintensity may be favorable beyond 14 days of onset in MCA infarction. Symptom-to-MR imaging time should be considered when assessing the prognostic value of FLAIR vascular hyperintensity.