This study surveyed the characteristics of white matter (WM) micro-integrity in patients who were diagnosed with major depressive disorder (MDD) without co-morbidities.
A total of 44 patients with ...MDD and 27 normal controls were enrolled in our study. Diffusion tensor imaging images of patients and controls were pre-processed and analysed to estimate differences in WM micro-integrity between patients and controls by performing comparisons of the values obtained from fractional anisotropy (FA). FA outputs of patients and controls were compared by a non-parametric permutation-based method with global brain volume, age and gender as covariates. In addition, the between-group differences of radial diffusivity (RD) and axial diffusivity (AD) were assessed to explain the alterations in FA values. Correlations between clinical variables (such as depression severity, anxiety severity, illness duration) and FA values were also estimated in each group and across both groups.
The patients with MDD had significantly lower FA values than the controls, for the left superior longitudinal fasciculus (SLF) and the right anterior thalamic radiation (ATR). The reductions in FA values occurred in combination with elevated RD values in the bilateral SLF and decreased AD values in the bilateral ATR. FA values were negatively correlated with depression severity in the SLF and with illness duration in the right SLF and ATR.
MDD patients had significant alterations in the WM micro-integrity of the left SLF and the right ATR.
Background & Aims: Recent studies have emphasized causative links between microRNA (miRNA) deregulations and cancer development. In hepatocellular carcinoma (HCC), information on differentially ...expressed miRNA remained largely undefined. Methods: Array-based miRNA profiling was performed on HCC cells that were derived from chronic carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV), and nonviral-associated patients. Specific microRNA (miR)-223 and miR-222 deregulations were verified in an independent series of tumors. The functional effect of miR-223 was examined further. An integrative analysis of messenger RNA (mRNA) array with in silico predictions defined potential downstream targets of miR-223. A luciferase reporter assay was conducted to confirm target association. Results: Distinct up-regulations of miR-222, miR-221, and miR-31, and down-regulations of miR-223, miR-126, and miR-122a were identified. Further investigations suggested the highly deregulated miR-223 and miR-222 could unequivocally distinguish HCC from adjacent nontumoral liver, irrespective of viral associations ( P ≤ .0002). Re-expression of miR-223 in HBV, HCV, and non-HBV non-HCV–related HCC cell lines revealed a consistent inhibitory effect on cell viability ( P < .01). Integrative analysis further implicated Stathmin 1 ( STMN1 ) as a downstream target of miR-223. A strong inverse relationship between STMN1 mRNA and miR-223 expressions was shown ( P = .006). A substantial reduction in STMN1 protein was further demonstrated upon restoration of miR-223 expression in HCC cell lines. We further showed that miR-223 readily could suppress the luciferase activity in reporter construct containing the STMN1 3' untranslated region ( P = .02). Conclusions: Our study revealed specific miRNA differential expressions in HCC and underscores the potential importance of miR-223 down-regulations in the development of HCC.
The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. ...This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients’ 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Reducing building energy use, a linchpin of climate change mitigation, is a daunting challenge across the world. Gaining increasing attention, retro-commissioning (RCx) is a systematic process that ...can improve building energy performance. Using a techno-legal lens to review statutes and guides on RCx, this study reveals that in China, a national standard on building commissioning has taken effect yet RCx statutes are hitherto not found. The United States has RCx statutes enacted over 14 states; scrutinizing the statutes of five cities unveils similarities and differences in their scope of control and compliance requirements. In the absence of a specific RCx statute, the guide of Hong Kong, China provides detailed guidance for energy saving practices. While these findings can serve as reference for other places planning to formulate laws or guidance on RCx, the need to further study the effectiveness of mandating RCx for reducing building energy use is highlighted. A conceptual analysis of cost variation with statutory control, which could help policymakers consider from an economic perspective whether or to what extent statutory RCx requirements should be imposed, is also illustrated. This not only contributes insights to the pursuit of an optimal balance between statutory control and voluntary action for energy reduction but also adds to the debate on building energy policies.
Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in ...a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva.
This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated.
Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776–0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%–96.2%) and 100% (97.3%–100%), respectively, for saliva, and were 96.1% (88.9%–99.2%) and 98.5% (94.7%–99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA.
Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.
Epidermal growth factor receptor (EGFR) regulates multiple signaling cascades essential for cell proliferation, growth and differentiation. Using a genetic approach, we found that Drosophila FERM and ...PDZ domain-containing protein tyrosine phosphatase, dPtpmeg, negatively regulates border cell migration and inhibits the EGFR/Ras/mitogen-activated protein kinase signaling pathway during wing morphogenesis. We further identified EGFR pathway substrate 15 (Eps15) as a target of dPtpmeg and its human homolog PTPN3. Eps15 is a scaffolding adaptor protein known to be involved in EGFR endocytosis and trafficking. Interestingly, PTPN3-mediated tyrosine dephosphorylation of Eps15 promotes EGFR for lipid raft-mediated endocytosis and lysosomal degradation. PTPN3 and the Eps15 tyrosine phosphorylation-deficient mutant suppress non-small-cell lung cancer cell growth and migration in vitro and reduce lung tumor xenograft growth in vivo. Moreover, depletion of PTPN3 impairs the degradation of EGFR and enhances proliferation and tumorigenicity of lung cancer cells. Taken together, these results indicate that PTPN3 may act as a tumor suppressor in lung cancer through its modulation of EGFR signaling.
Belle II is a new-generation B-factory experiment, dedicated to exploring new physics beyond the standard model of elementary particles in the flavor sector. Belle II started data-taking in April ...2018, using a synchronous data acquisition (DAQ) system based on pipelined trigger flow control. The Belle II DAQ system is designed to handle a 30-kHz trigger rate with approximately 1% of dead time, under the assumption of a raw event size of 1 MB. The DAQ system is reliable, and the overall data-taking efficiency reached 84.2% during the run period of January 2020-June 2020. The current readout system cannot be operated in the terms of ten years from the viewpoint of DAQ maintainability; meanwhile, the readout system is obstructing high-speed data transmission. A solution involving a peripheral component interconnect (PCI)-express-based readout module with high data throughput of up to 100 Gb/s was adopted to upgrade the Belle II DAQ system. We particularly focused on the design of firmware and software based on this new generation of readout board, called PCIe40, with an Altera Arria 10 field-programmable gate array chip. The 48-Gb transceiver (GBT) serial links, PCI-express hard IP-based direct memory access (DMA) architecture, interface of timing and trigger distribution system, and slow control system were designed to integrate with the current Belle II DAQ system. This article describes the performances accomplished during the data readout and slow control tests conducted using a test bench and a demonstration performed using on-site front-end electronics, specifically involving Belle II TOP and KLM subdetectors.
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders ...the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.
Objectives
The primary objective was to investigate the clinical presentation, hormonal dysfunction, imaging characteristics and natural history of RCCs that were managed conservatively. Secondary ...objective was to identify factors associated with cyst progression.
Methods
A retrospective review of patients with the clinical diagnosis of RCC—identified from word search from radiology reports that were followed up from January 1999 to March 2019 was performed. The demographics, clinical data, radiological features and outcomes were reviewed and analyzed.
Results
105 patients were identified with a median follow up of 6 years. 68 patients (64.8%) were managed conservatively from diagnosis till last follow up while 37 patients (35.2%) underwent surgery, with 26 operated at time of diagnosis and 11 operated upon monitoring. For patients managed conservatively from diagnosis till last follow up, incidental finding was the most common presentation. 19.1% had either one or more axes of hormonal dysfunction, with hypogonadism and hypocortisolemia being the commonest ones. Imaging features were variable. 66.2% of patients had T2W hyperintensity on MRI. Pathognomonic feature of intracystic nodule was present in only 14.7% of patients. Among the 79 patients with repeated MRI imaging (68 from conservative group and 11 from surgical group), 32.9% of patients developed cyst progression while 67.1% had either static disease or regression in size of RCC. Median time to progression of cyst was 14 months. Longer median follow up duration and presence of pituitary stalk displacement at presentation were associated with cyst progression. Only one patient developed new endocrine dysfunction.
Conclusion
2/3 of the RCCs had static disease or even regression in the size of the cyst. They rarely gave rise to additional endocrine dysfunction by adopting observant approach. Cyst progression was demonstrated in 1/3 of patients. Conservative treatment remained a reasonable treatment for patients without significant symptoms.
Background
In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys‐regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates ...microglia in the spinal dorsal horn (SDH). However, information on diabetes‐induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain.
Methods
Sixty‐six rats were divided into diabetic and control groups: control rats (n = 18; 1 mL of normal saline via the right femoral vein) and diabetic rats n = 48; 60 mg/kg streptozotocin (STZ) via the right femoral vein. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration.
Results
All diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up‐regulation of Nav1.3 and down‐regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ‐induced diabetes was mediated, in part, by phosphorylation of p‐38 mitogen‐activated protein kinase.
Conclusions
Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.
PDF
