Search

Soft tissue tumors encompass a wide variety of mesenchymal neoplasms exhibiting diverse clinical, pathologic, and molecular features. Among these, osteoid and/or chondroid matrix deposition in some soft tissue tumors represents a noticeable characteristic. Unlike matrices present in bone tumors where they likely reveal the respective cells of origin (i.e., osteoblastic or chondroblastic precursors), those existing in soft tissue tumors more often denote a metaplastic phenomenon and reflect the diversity of differentiation these tumors can display. While many soft tissue tumor types can occasionally harbor metaplastic bone or cartilage as an incidental component or heterologous differentiation, in some other tumor types, the production of these matrices is a frequent and distinctive, if not diagnostic, feature. This review focuses on the latter tumor types where emerging immunohistochemical and molecular evidence has significantly improved our understanding of their respective pathogenesis and histopathological spectra. These tumor types include ossifying fibromyxoid tumor, phosphaturic mesenchymal tumor, synovial chondromatosis, soft tissue chondroma, calcifying aponeurotic fibroma, giant cell tumor of soft tissue, myositis ossificans and related diseases, mesenchymal chondrosarcoma, and extraskeletal osteosarcoma.

Although several epidemiologic and animal studies have revealed correlations between obesity and neurodegenerative disorders, such as Parkinson disease (PD), the underlying pathological mechanisms of obesity-induced PD remain unclear. Our study aimed to assess the effect of diet-induced obesity on the brain dopaminergic pathway. For five months, starting from weaning, we gave C57BL/6 mice a high-fat diet (HFD) to generate an obese mouse model and investigate whether the diet reprogrammed the midbrain dopaminergic system. Tyrosine hydroxylase staining showed that the HFD resulted in fewer dopaminergic neurons in the substantia nigra (SN), but not the striatum. It also induced neuroinflammation, with increased astrogliosis in the SN and striatum. Dendritic spine density in the SN of HFD-exposed mice decreased, which suggested that prolonged HFD altered dopaminergic neuroplasticity. All three peroxisome proliferator-activated receptor (PPAR) subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area of HFD mice when compared to those in controls. This study showed that a prolonged HFD induced neuroinflammation, suppressed PPAR levels, caused degeneration of midbrain dopaminergic neurons, and resulted in symptoms reminiscent of human PD. To our knowledge, this is the first study documenting the effects of an HFD on PPARs in dopaminergic neurons.

The interaction of light with biological tissues has been considered for various therapeutic applications. Light-induced neurite growth has the potential to be a clinically useful technique for neuron repair. However, most previous studies used either a large illumination area to accelerate overall neurite growth or employed a light spot to guide a growing neurite. It is not clear if optical stimulation can induce the regrowth of a retracted neurite. In the present work, we used blue light (wavelength: 473 nm) to cause neurite retraction, and we proved that using a red-light (wavelength: 650 nm) spot to illuminate the soma near the junction of the retracted neurite could induce neurite regrowth. As a comparison, we found that green light (wavelength 550 nm) had a 62% probability of inducing neurite regrowth, while red light had a 75% probability of inducing neurite regrowth at the same power level. Furthermore, the neurite regrowth length induced by red light was increased by the pre-treatment with inhibitors of myosin functions. We also observed actin propagation from the soma to the tip of the re-growing neurite following red-light stimulation of the soma. The red light-induced extension and regrowth were abrogated in the calcium-free medium. These results suggest that illumination with a red-light spot on the soma may trigger the regrowth of a neurite after the retraction caused by blue-light illumination.

Despite III-V semiconductors demonstrating extraordinary solar-to-hydrogen (STH) conversion efficiencies, high cost and poor stability greatly impede their practical implementation in photoelectrochemical (PEC) water splitting applications. Here, we present a simple and efficient strategy for III-V-based photoelectrodes that functionally and spatially decouples the light harvesting component of the device from the electrolysis part that eliminates parasitic light absorption, reduces the cost, and enhances the stability without any compromise in efficiency. The monolithically integrated PEC cell was fabricated by an epitaxial lift-off and transfer of inversely grown InGaP/GaAs to a robust Ni-substrate and the resultant photoanode exhibits an STH efficiency of ~9% with stability ~150 h. Moreover, with the ability to access both sides of the device, we constructed a fully-integrated, unassisted-wireless "artificial leaf" system with an STH efficiency of ~6%. The excellent efficiency and stability achieved herein are attributed to the light harvesting/catalysis decoupling scheme, which concurrently improves the optical, electrical, and electrocatalytic characteristics.

NUTM1 gene rearrangement is the genetic hallmark of NUT carcinoma, an aggressive tumor that most commonly affects the thoracic and head and neck regions and often exhibits squamous differentiation. The most common fusion partner gene is BRD4, followed by BRD3 and NSD3. Recently, NUTM1 gene rearrangement has been identified in rare tumors from soft tissues, intracranial locations, and other visceral organs. These tumors often show high grade malignant epithelioid to round cell histomorphology and lack evidence of squamous and/or epithelial differentiation. Therefore, their relationship with classic NUT carcinoma is still uncertain. Here, we present a primary mandible bone tumor of a 21-year-old female exhibiting monotonous epithelioid and rhabdoid cytomorphology, vesicular chromatin, and prominent nucleoli. The initial immunohistochemical workup was non-specific, showing only CD34 positivity while being negative for cytokeratin (AE1/AE3), EMA, p63, etc. INI-1 expression was retained. RNA sequencing was performed and identified a rare ZNF532-NUTM1 gene fusion, which had only been reported in a single case of pulmonary NUT carcinoma. The fusion was confirmed by FISH for NUTM1 gene rearrangement and supported by diffuse and strong NUT immunoreactivity. MYC mRNA up-regulation and immunoreactivity, a common finding in NUT carcinoma, was also observed in this tumor, suggesting a possible common pathogenetic mechanism and potential treatment target. The patient presented with a non-metastatic disease status and received hemimandibulectomy, selective neck dissection (level Ib), and post-operative radiation therapy. She remained disease free 3.6 years after the initial diagnosis., (© 2019 Wiley Periodicals, Inc.)

Stand-off Raman spectroscopy combines the advantages of both Raman spectroscopy and remote detection to retrieve molecular vibrational fingerprints of chemicals at inaccessible sites. However, it is currently restricted to the detection of pure solids and liquids and not widely applicable for dispersed molecules in air. Herein, we realize real-time stand-off SERS spectroscopy for remote and multiplex detection of atmospheric airborne species by integrating a long-range optic system with a 3D analyte-sorbing metal-organic framework (MOF)-integrated SERS platform. Formed via the self-assembly of Ag@MOF core-shell nanoparticles, our 3D plasmonic architecture exhibits micrometer thick SERS hotspot to allow active sorption and rapid detection of aerosols, gas, and volatile organic compounds down to parts-per-billion levels, notably at a distance up to 10 m apart. The platform is highly sensitive to changes in atmospheric content, as demonstrated in the temporal monitoring of gaseous CO 2 in several cycles. Importantly, we demonstrate the remote and multiplex quantification of polycyclic aromatic hydrocarbon mixtures in real time under outdoor daylight. By overcoming core challenges in current remote Raman spectroscopy, our strategy creates an opportunity in the long-distance and sensitive monitoring of air/gaseous environment at the molecular level, which is especially important in environmental conservation, disaster prevention, and homeland defense.

A major breakthrough in the classification of soft tissue tumors has been the recent identification of NTRK-fusion related neoplasms which are amenable to highly effective targeted therapies. Despite these therapeutic opportunities, diagnostic challenges have emerged in recognizing tumors characterized by protein kinase fusions, as they are associated with a wide morphologic spectrum, variable risk of malignancy and a rather nonspecific immunoprofile. As such, NTRK-related fusions may occur in infantile fibrosarcoma, lipofibromatosis-like neural tumors (LPF-NTs), tumors resembling malignant peripheral nerve sheath tumors, etc. Triggered by an index case resembling LPF-NT but harboring RET gene rearrangement, we investigated our files for cases showing RET gene abnormalities to establish their clinicopathologic features. Tumors were tested with a combination of targeted RNA sequencing and fluorescence in situ hybridization methods. Six cases with RET gene rearrangements were identified, all except 1 occurred in children, including 4 infants. Their morphologic spectrum was quite diverse, but closely reproduced the phenotype of NTRK-fusion-positive tumors, including LPF-NTs (n=3), infantile fibrosarcoma-like tumor (n=2) and malignant peripheral nerve sheath tumor-like (n=1). Three cases showed coexpression of S100 and CD34, whereas the remaining 3 had a nonspecific immunoprofile. The tumors ranged morphologically and clinically from benign to highly malignant. None of the LPF-NT cases recurred, whereas 2 patients with malignant histology had a highly aggressive course with distant metastases to lung and other viscera. By targeted RNA sequencing these tumors harbored RET fusions with an identical break in exon 12, which retains the tyrosine kinase domain in the fusion oncoprotein and involving various gene partners (CLIP2, CCDC6, SPECC1L, MYH10, and NCOA4). Our results suggest that RET fusion-positive neoplasms share a similar phenotypic spectrum with the NTRK-positive tumors, displaying either fibroblastic or neural-like differentiation, and spanning a wide spectrum of clinical behavior. These findings open new avenues for targeted therapy with RET inhibitors currently available in clinical trials.

Zwitterionic hydrogels have promising potential as a result of their anti-fouling and biocompatible properties, but they have recently also gained further attention due to their controllable stimuli responses. We successfully synthesized two zwitterionic polymers, poly(2-methacryloyloxyethyl phosphorylcholine) (poly-MPC) and poly(2-(methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide) (poly-DMAPS), which have complementary ionic sequences in their respective zwitterionic side groups and likely form an interpenetrating double network to improve their mechanical strength. The synthesized poly-MPC was blended in a poly-DMAPS matrix (MD gel) and showed high viscosity, while poly-DMAPS was blended in a poly-MPC hydrogel (DM gel) and revealed UCST behavior as the temperature increased. In addition, cross-section images of the MD hydrogel exhibited its compact and uniform structure, while the DM gel was found to exhibit a porous micro-structure with clear boundaries. The results explained the low viscosity of the DM gel, which was also confirmed via 3D Raman mapping. To sum up, the preliminary data demonstrated that binary zwitterionic hydrogels have thermosensitive mechanical properties, promoting further bio-applications in the future, such as in wound healing., Competing Interests: All authors have seen and approved the revised manuscript and have no conflicts of interest concerning this publication., (This journal is © The Royal Society of Chemistry.)

Aim: This study aimed to investigate the association between males with pinworm infections and the risk of developing psychiatric disorders., Method: A total of 2044 enrolled patients, with 511 pinworm subjects and 1533 unexposed subjects (1:3) matched for sex, age and index year, from Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting for confounding factors, the Cox regression model was used to compare the risk of developing psychiatric disorders during the 15 years of follow-up., Results: Of all the enrollees, 24 in the pinworm cohort and 18 in the unexposed cohort (343.10 vs 84.96 per 100,000 person-year) developed psychiatric disorders. The Cox regression model revealed that, after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 4.581 (95% CI: 2.214-9.480, p < .001, p < .001). Pinworm infections were associated with the increased risk in anxiety disorders, depressive disorders, and sleep disorders, respectively., Conclusion: Patients who suffered from pinworm infections have a higher risk of developing psychiatric disorders, and this finding should be considered as a timely reminder for the clinicians to provide much more attention for these patients because of their mental health issues., (Copyright © 2019. Published by Elsevier Inc.)

This study aims to investigate the association between pulmonary embolism (PE) and the risk of psychiatric disorders. A total of 21,916 patients aged ≥20 years with PE between January 1, 2000, and December 31, 2015, were selected from the National Health Insurance Research Database of Taiwan, along with 65,748 (1:3) controls matched for sex and age. Cox regression model revealed the crude HR was 1.539 (95% CI 1.481 to 1.599; p<0.001), and after adjusting all the covariates, the adjusted HR was 1.704 (95% CI 1.435 to 1.991, p<0.001), for the risk of psychiatric disorders in the PE cohort. PE was associated with the overall psychiatric disorders, dementia, anxiety, depression, and sleep disorders, after the exclusion of the psychiatric diagnoses in the first year. PE was associated with the overall psychiatric disorders, dementia, anxiety, and depression, after the exclusion of the psychiatric diagnoses in the first 5 years. The patients with PE were associated with psychiatric disorders. This finding could serve as a reminder to the physicians to be more watchful and aware in the long-term follow-up of patients with PE for their care and potential mental health problems., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Information on functional strengths and weaknesses of mucopolysaccharidosis (MPS) patients is important for early intervention programs and enzyme replacement therapy (ERT)., Methods: We used the Functional Independence Measure for Children (WeeFIM) questionnaire to assess the functional skills of 63 Taiwanese MPS patients (median age, 13 years 3 months; range, 3-20 years) from January 2012 to December 2018., Results: Mean total WeeFIM score was 75.4 of a potential score of 126. Mean total WeeFIM scores of each type (MPS I, MPS II, MPS IIIB, MPS IVA, and MPS VI) were 103.8, 76.2, 41.6, 92.2, and 113.6, respectively. Mean scores for self-care, mobility, and cognition domains were 30 (maximum 56), 23 (maximum 35), and 22 (maximum 35), respectively. MPS type IIIB patients had the lowest scores in self-care, mobility, cognition, and total domains compared to other types of MPS. All patients with ERT in MPS I, II, and IVA had higher scores in self-care and mobility domains than patients without ERT. Most patients required assistance for self-care skills, especially in grooming and bathing., Conclusion: MPS patients require support and supervision in self-care tasks. For cognition tasks, MPS IIIB patients also require help. This questionnaire is useful to identify the strengths and limitations of MPS patients., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background: Lower gestational age may increase autism spectrum disorder (ASD) vulnerability; however, the incidence of ASD diagnosis through a direct assessment on every very preterm birth child on the population base remains unclear. Moreover, the behavioral characteristics of preterm birth ASD are unknown., Methods: Every very preterm birth child (gestational age < 32 weeks; birth weight < 1500 g) who was discharged from neonatal intensive care units in Southern Taiwan and prospectively followed to 5 years of age was evaluated using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R). The term birth (gestational age > 37 weeks) ASD children characterized by ADOS and ADI-R were group matched to the preterm birth ASD by age at examination for comparison. ADOS severity scores were calculated by the Mann-Whitney U test and ADI-R by multivariate analysis of variance and canonical discriminant analysis., Results: Two hundred forty-six (87%) of the 283 very preterm survivors were followed prospectively to 5 years of age. Nineteen (7.7%) of the 246 children fulfilled the diagnostic criteria of ASD. After excluding 1 patient with cerebral palsy and profound mental disability, 18 preterm ASD children were compared with 44 term birth ASD children. The two ASD groups were comparable for age at examination, gender, and intelligence quotient. The two groups showed comparable ADOS severity scores in social affect deficits, restricted repetitive behaviors, and total score, but had differences in qualitative abnormalities in reciprocal social interaction (Wilks lambda F value = 6.2, P  < 0.001) of ADI-R. Compared to term birth ASD children, preterm birth ASD children exhibited worse nonverbal behaviors that regulate social interaction (OR 2.59, 95% CI 1.41-4.73, P  = 0.002) but more favorable peer relationships (OR 0.58, 95% CI 0.38-0.90, P  = 0.01) and socioemotional reciprocity (OR 0.55, 95% CI 0.33-0.92, P  = 0.02). In contrast to the heterogeneous severity of social reciprocity in the term ASD group, the behavioral characteristics of the preterm ASD group showed a homogeneous reciprocal social interaction pattern., Conclusions: The 5-year incidence rate of ASD was high in very preterm birth children. Preterm birth ASD exhibited a specific behavioral phenotype of reciprocal social interaction., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Objective: This study aimed to investigate the association between adults with ADHD and the risk of developing dementia., Method: Utilizing National Health Insurance Research Database of Taiwan, ADHD patients were identified and compared with age- and gender-matched controls (1:3)., Results: Of the study participants, 37 (5.48%) developed dementia compared with 81 (4.0%) in the control group. Cox proportional hazards regression analysis revealed that the study participants were more likely to develop dementia. The crude hazard ratio (HR) is 3.418 (95% confidence interval [CI] = [2.289, 5.106], p < .001), and adjusted HR is 4.008 (95% CI = [2.526, 6.361], p < .001) in risk of developing dementia after adjusted for age, gender, comorbidities, geographical area of residence, urbanization level of residence, and monthly income., Conclusion: Adults with ADHD have a 3.4-fold risk of developing dementia, and other large or national data sets should be explored to support the current findings.

Uterine mesenchymal tumors are genetically heterogenous; those with uniform cytomorphology, best exemplified by endometrial stromal tumors, often contain various fusion genes. Novel fusions involving ESR1 and GREB1, key factors in sex hormone pathways, have been implicated in rare uterine mesenchymal tumors. Particularly, the fusions between 5'-ESR1/GREB1 and 3'-NCOA2/NCOA3 were recently identified in 4 uterine tumors resembling ovarian sex-cord tumor (UTROSCT). By RNA sequencing, pathology review, and FISH screening, we identified 4 uterine sarcomas harboring rearranged GREB1, including GREB1-NCOA2 and the novel GREB1-NR4A3, GREB1-SS18, and GREB1-NCOA1, validated by RT-PCR and/or FISH. They occurred in the myometrium of postmenopausal women and were pathologically similar despite minor differences. Tumor cells were generally uniform and epithelioid, with vesicular nuclei and distinct to prominent nucleoli. Growth patterns included solid sheets, trabeculae/cords, nests, and fascicles. Only 1 tumor showed small foci of definitive sex-cord components featuring well-formed tubules, retiform structures, Leydig-like cells, and lipid-laden cells and exhibiting convincing immunoreactivity to sex-cord markers (calretinin, α-inhibin, and Melan-A). In contrast, all the 4 classic UTROSCT we collected occurred in premenopausal patients, consisted predominantly of unequivocal sex-cord elements, prominently expressed multiple sex-cord markers, and harbored ESR1-NCOA3 fusion. Combined with previously reported cases, GREB1-rearranged tumors involved significantly older women (P=0.001), tended to be larger and more mitotically active, showed more variable and often inconspicuous sex-cord differentiation, and appeared to behave more aggressively than ESR1-rearranged UTROSCT. Therefore, these 2 groups of tumors might deserve separate consideration, despite some overlapping features and the possibility of belonging to the same disease spectrum.

Study Objectives: To examine the risk of hospitalization for motor vehicle accident injury (MVAI) in patients with narcolepsy and the effects of stimulant use on MVAI occurrence in patients with narcolepsy., Methods: This is a population-based, retrospective cohort study using Taiwan's National Health Insurance Research Database between 2000 and 2013. We included patients with narcolepsy based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, 347. The case and matched control participants were selected in a ratio of 1:3, and the traffic accident (ICD-9-CM codes: E810-E819) plus injury codes (ICD-9-CM codes: 800.xx-999.xx) due to MVAI following hospitalization were used for the study outcome. The type of injury, causes, intentionality, and the effects of stimulant use on patients with narcolepsy were also assessed., Results: A total of 1,316 participants were enrolled, including 329 participants with narcolepsy and 987 participants without narcolepsy. During a 14-year follow-up period, a total of 104 participants had MVAI, of whom 47 (1,559.54 per 100,000 person-years) belonged to the narcolepsy cohort and 57 (556.21 per 100,000 person-years) to the non-narcolepsy cohort. After adjusting for covariates, the risk of hospitalization for MVAI among participants with narcolepsy was still significantly higher than those without narcolepsy (adjusted hazard ratio = 6.725; 95% confidence interval = 4.421-10.231; P < .001). The use of modafinil or methylphenidate, as monotherapy or combined treatment, was associated with a lower risk of MVAI in the narcolepsy cohort., Conclusions: Patients with narcolepsy may have a higher risk of hospitalization for MVAI and stimulant use could mitigate such risk., (© 2019 American Academy of Sleep Medicine.)

BCOR immunoreactivity is a sensitive and highly specific marker for clear cell sarcoma of the kidney (CCSK). However, a subset of adult renal sarcomas which overexpress BCOR are negative for BCOR genetic alterations, including BCOR gene fusions or BCOR-internal tandem duplication, and thus remain unclassified. We report 5 such undifferentiated renal/perirenal sarcomas which raised the differential diagnosis of CCSK due to their morphologic appearance and strong BCOR immunoreactivity, but which on RNA sequencing proved to be malignant solitary fibrous tumors (SFTs). The neoplasms occurred in patients at an age range of 30 to 62 years. Three patients were females and 2 male. Four were primary renal neoplasms while one was perirenal. All 5 neoplasms were cellular, nonpleomorphic, undifferentiated sarcomas with branching capillary vasculature composed of primitive round to ovoid neoplastic cells with scant cytoplasm and nuclei having fine, evenly dispersed chromatin. None of the cases demonstrated the typical hyperchromatic fusiform nuclei, prominent collagen deposition, or hemangiopericytomatous vasculature of SFT. All 5 cases were strongly immunoreactive for BCOR. Three cases were CD34 negative, where the other 2 were only focally CD34 positive. STAT6 was subsequently found to be positive by immunohistochemistry in all 5 cases. In summary, we report a previously unrecognized mimic of CCSK: malignant SFTs with an undifferentiated/small round cell phenotype along with branching capillary vasculature, strong immunoreactivity for BCOR, and minimal or no immunoreactivity for CD34. As CCSK is treated with a specific chemotherapy regimen, this distinction has therapeutic implications.

No studies have examined the effects of fronto-temporal transcranial direct current stimulation (tDCS) on cognitive insight and neurocognitive function in schizophrenia patients and the dynamic interplay between tDCS-induced changes in these two outcomes. In this double-blind, randomized, sham-controlled study, we investigated the effects of fronto-temporal tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5 days] on illness severity, psychosocial functioning, cognitive insight and neurocognitive function in schizophrenia patients (N = 60). The authors observed significant trends that tDCS ameliorated the severity of total and general psychopathology as measured by the Positive and Negative Syndrome Scale. No significant effects were observed for other psychopathological symptoms and psychosocial functioning. Cognitive insight as measured by the Beck Cognitive Insight Scale (BCIS) was rapidly enhanced by 10-session tDCS (F = 10.80, Cohen's d = 0.44, p = 0.002) but the beneficial effect became borderline significant 1 month after stimulation. A trend-level improvement with tDCS of planning ability (F = 6.40, Cohen's d = 0.339, p = 0.014) as measured by the accuracy in Tower of London task was also observed. In the active tDCS group, the change in cognitive insight from baseline to immediately after tDCS assessment was positively correlated with that in planning ability (r = 0.46, p = 0.015), which was independent of the corresponding change in illness severity. The promising results regarding the fast-acting beneficial effects of tDCS on cognitive insight and planning ability in schizophrenia require confirmation in future replication studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Spindle cell/sclerosing rhabdomyosarcomas (SC/SRMS) feature spindled and/or rounded rhabdomyosarcomatous cells within variably hyalinised stroma. Only 30-67% of SC/SRMSs harbour neomorphic MYOD1 p.L122R mutations, indicating heterogeneity in this RMS type. We compared MYOD1-mutant and non-mutant cases to characterise the histological and genetic spectrum of mutated SC/SRMS., Methods and Results: Seventeen RMSs with spindled, sclerosing or hybrid histology were sequenced to identify MYOD1 and PIK3CA mutations and reappraised to assess histological features and myogenic immunophenotypes. Twelve SC/SRMSs harboured MYOD1 mutations, including homozygous p.L122R (n = 8), heterozygous p.L122R (n = 3) and heterozygous p.E118K (n = 1). MYOD1-mutant tumours affected nine females and three males aged 8-64 years (median = 22.5), had a median size of 4.2 cm (range = 2-22) and involved the head and neck (n = 7), extremities (n = 4) and mediastinum (n = 1). Fascicular/spindle histology was predominant in four cases, including one with heterologous lipoblasts in focally myxoid stroma. Four sclerosing cases mainly comprised rounded cells, including one with multinucleated tumour cells. Four cases were histologically hybrid. The only PIK3CA (p.H1047R) mutation was detected in a predominantly spindled MYOD1-p.L122R-mutated case, but not in its laser-microdissected lipoblast-containing area. All MYOD1-mutant cases exhibited diffuse MYOD1 expression but patchy myogenin reactivity. At final follow-up (median = 13.5 months), recurrences (n = 4), metastases (n = 2) or both (n = 1) occurred in seven MYOD1-mutant cases; one had died of disease. Five non-mutated cases were reclassified as spindle embryonal (n = 3), dense embryonal (n = 1) and unclassifiable (n = 1) RMSs., Conclusion: MYOD1-mutant RMSs are uncommonly mutated with PIK3CA and behave aggressively with an expanded morphological and genetic spectrum, including lipoblastic differentiation, multinucleated cells and the alternative p.E118K mutation., (© 2019 John Wiley & Sons Ltd.)

The integration of III-V and Si multi-junction solar cells as photovoltaic devices has been studied in order to achieve high photovoltaic conversion efficiency. However, large differences in the coefficients of thermal expansion and the lattice parameters of GaAs, Si, and InGaAs have made it difficult to obtain high-efficiency solar cells grown as epilayers on Si and InP substrates. In this paper, two types of devices, including GaInP/GaAs stacked on Si (GaInP/GaAs//Si) and GaInP/GaAs stacked on InGaAs (GaInP/GaAs//InGaAs), are fabricated via mechanical stacking and wire bonding technologies. Mechanically stacked GaInP/GaAs//Si and GaInP/GaAs//InGaAs triple-junction solar cells are prepared via glue bonding. Current-voltage measurements of the two samples are made at room temperature. The short-circuit current densities of the GaInP/GaAs//Si and GaInP/GaAs//InGaAs solar cells are 13.37 and 13.66 mA/cm 2 , while the open-circuit voltages of these two samples are measured to be 2.71 and 2.52 V, respectively. After bonding the GaInP/GaAs dual-junction with the Si and InGaAs solar cells, the conversion efficiency is relatively improved by 32.6% and 30.9%, respectively, compared to the efficiency of the GaInP/GaAs dual-junction solar cell alone. This study demonstrates the high potential of combining mechanical stacked with wire bonding and ITO films to achieve high conversion efficiency in solar cells with three or more junctions.

Beliefs about and attitudes toward mental illness may be influenced by cultural- or country-specific contexts. Through a national survey, the current study investigated beliefs and attitudes toward people with schizophrenia and depression among the general public in Taiwan. A random-digit-dialing telephone-based cross-sectional survey was administered to Taiwanese adults aged 20-64 years (n = 1600). The data were analyzed through binary logistic regressions to test for differences between these disorders in causal beliefs, stereotypes, emotional reactions, desire for social distance, and help-seeking behavior. The results revealed that respondents were more concerned with biogenetic causal explanations for people with schizophrenia than for those with depression. Significantly more respondents perceived people with schizophrenia as more likely to be unpredictable and violent toward others. A similar trend was observed for the desire for social distance. For both disorders, respondents were significantly more likely to express compassion than to express anger toward the person described in the vignette. Respondents also expressed more desire for social distance from someone like the vignette who have received psychiatric treatment. These findings provide useful directions for the implementation of optimal psychoeducation among such communities. ., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aimed to investigate the association between males with psychosexual disorders (PSDs) and the risk of developing psychiatric disorders. A total of 34,972 enrolled patients, with 8,743 subjects who had suffered from PSD and 26,229 controls (1:3) matched for age and index year, from Taiwan's Longitudinal Health Insurance Database (LHID) from 2000 to 2015, selected from the National Health Insurance Research Database (NHIRD). After adjusting all the confounding factors, the multivariate Cox regression model was used to compare the risk of developing psychiatric disorders, between the PSD and non-PSD groups, during the 15 years of follow-up. Of the all enrollees, 1,113 in the PSD cohort and 2,611 in the non-PSD cohort (1,180.96 vs. 954.68 per 100,000 person-year) developed psychiatric disorders. Multivariate Cox regression model survival analysis revealed that, after adjusting for gender, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted hazard ratio (HR) was 2.448 (95% CI [2.227, 2.633], p < .001). PSD has been associated with the increased risk in anxiety disorders, depressive disorders, bipolar disorders, sleep disorders, and psychotic disorders, respectively. Sexual dysfunctions, paraphilia, and gender identity disorders were associated with the overall psychiatric disorders with adjusted HRs as 1.990 ( p < .001), 11.622 ( p < .001), and 5.472 ( p < .001), respectively. Male patients who suffered from PSD have a higher risk of developing psychiatric disorders, and this finding should be considered as a timely reminder for the clinicians to provide much more attention for these patients because of their mental health issues.

Background: Signet ring cell adenocarcinoma is a histological classification based on the WHO classification. The presence of this specific histological type is associated with a worse pathological appearance. The prognosis of signet ring cell adenocarcinoma in gastric cancer patients after curative surgery is still under debate., Methods: From January 1988 to December 2012, a total of 2971 patients, including 819 early and 2152 advanced gastric cancer patients underwent curative resection for gastric cancer. Among them, there were 185 cases of signet ring cell adenocarcinoma in early gastric cancer patients, while there were 570 cases in advanced gastric cancer patients., Results: The overall incidence of signet ring cell adenocarcinoma was 25.4%. Our results showed that the 5-year overall survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 90.7 and 83.2%, respectively (P = 0.001). The 5-year disease-free survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 87.4 and 81.6%, respectively (P = 0.003). The 5-year overall survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 32.1 and 37.9%, respectively (P = 0.041). The 5-year disease-free survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 28.6 and 35.2%, respectively (P = 0.037). Signet ring cell adenocarcinoma was an independent predictor for overall survival in advanced gastric cancer (P = 0.017)., Conclusion: The clinical features and prognosis of signet ring cell adenocarcinoma are different between early and advanced gastric cancer. Signet ring cell adenocarcinoma is a poor prognostic factor in advanced gastric cancer after curative resection.

Study Objectives: This study has investigated the risk of major adverse cardiovascular events (MACEs), including acute myocardial infarction, coronary artery disease, peripheral artery disease, and acute stroke, among children and adolescents (age younger than 20 years) with obstructive sleep apnea (OSA)., Methods: In this study, the population-based National Health Insurance Research Database of Taiwan was used to identify patients in whom OSA had been first diagnosed between 2000 and 2015. Children and adolescents with OSA (n = 6,535) were included with 1:3 ratio by age, sex, and index year of control participants without OSA (n = 19,605). The Cox proportional regression model was used to evaluate the risk of MACEs in this cohort study., Results: After a 15-year follow-up, the incidence rate of MACEs was higher in the OSA cohort when compared with the non-OSA control cohort (15.97 and 8.20 per 100,000 person-years, respectively). After adjusting for covariates, the risk of MACEs among children and adolescents with OSA was still significantly higher (hazard ratio = 2.050; 95% confidence interval = 1.312-3.107; P = .010). No MACEs were found in the children and adolescents with OSA who received continuous airway positive pressure treatment or pharyngeal surgery., Conclusions: This study found a significantly higher risk of MACEs in children and adolescents with OSA. These findings strongly suggest that clinicians should provide careful follow-up and medical treatment for children and adolescents with OSA., (© 2019 American Academy of Sleep Medicine.)

An SHG-active noncentrosymmetric (3,4)-connected Zn(ii)-organic framework, {[Zn2(4-abpt)(3,4-pydc)2]·2DMAc·3MeOH·H2O}n (1-Zn), was synthesized using a mixed-ligand system. The 1-Zn framework undergoes metal metathesis, with the complete exchange of the tetrahedrally coordinated ZnII ions with CuII ions while retaining the integrity of the network.

Surface-enhanced Raman scattering (SERS) is a molecule-specific spectroscopic technique with diverse applications in (bio)chemistry, clinical diagnosis and toxin sensing. While hotspot engineering has expedited SERS development, it is still challenging to detect molecules with no specific affinity to plasmonic surfaces. With the aim of improving detection performances, we venture beyond hotspot engineering in this tutorial review and focus on emerging material design strategies to capture and confine analytes near SERS-active surfaces as well as various promising hybrid SERS platforms. We outline five major approaches to enhance SERS performance: (1) enlarging Raman scattering cross-sections of non-resonant molecules via chemical coupling reactions; (2) targeted chemical capturing of analytes through surface-grafted agents to localize them on plasmonic surfaces; (3) physically confining liquid analytes on non-wetting SERS-active surfaces and (4) confining gaseous analytes using porous materials over SERS hotspots; (5) synergizing conventional metal-based SERS platforms with functional materials such as graphene, semiconducting materials, and piezoelectric polymers. These approaches can be integrated with engineered hotspots as a multifaceted strategy to further boost SERS sensitivities that are unachievable using hotspot engineering alone. Finally, we highlight current challenges in this research area and suggest new research directions towards efficient SERS designs critical for real-world applications.

Population-based cohort study investigating the risk of depression and other psychiatric disorders for patients with overactive bladder (OAB) syndrome is unavailable. This study investigated the subsequent risk of psychiatric disorders among patients with OAB in an Asian population. Using data from the National Health Insurance Research Database of Taiwan, we established a cohort with 811 patients in an exposed group with OAB between January 1, 2000 and December 31, 2000, and a non-exposed group, without OAB, of 2433 patients without OAB matched by age and year of diagnosis. The occurrence of psychiatric disorders and Cox regression model measured adjusted HRs (aHR) were monitored until the end of 2013. The overall incidence of psychiatric disorders was 41.7% higher in the exposed group with OAB than in the non-exposed group without OAB (14.2% vs 10.1%, p<0.001), with an aHR of 1.34 (95% CI 1.12 to 1.80, p<0.001) for the OAB cohort. OAB was associated with the increased risk of dementia, anxiety, depressive, sleep, and psychotic disorders, with aHRs as 1.53 (p=0.040), 1.61 (p<0.001), 2.10 (p<0.001), 1.43 (p<0.001), and 2.49 (p=0.002), respectively. The risk of psychiatric disorders, including depression and anxiety, is significantly higher in patients with OAB than in those without OAB. Evaluation of psychiatric status in patients with OAB is strongly recommended., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Pediatric soft tissue tumors are relatively rare and show significant overlap in morphology and immunoprofile, often posing diagnostic and management challenges. Thus, their classification remains often subjective or lumped under "unclassified categories," as a number of lesions lack objective and reproducible criteria in diagnosis. Although in a subset of cases immunohistochemistry has been proved useful to identify a specific line of differentiation, most tumors lack a readily defined histogenesis, being characterized by a rather non-specific immunoprofile. Furthermore, tumors with an ambiguous diagnosis are difficult to grade and their risk of malignancy or clinical management remains uncertain. Advances in molecular genetics, including the more wide application of next generation sequencing in routine clinical practice, have improved diagnosis and refined classification based on objective molecular markers. Importantly, some soft tissue tumors in children are characterized by recurrent gene fusions involving either growth factors (eg, PDGFB) or protein kinases (eg, ALK, ROS, NTRK, BRAF), which have paved the way for new targeted treatments that block the respective upregulated downstream pathways. However, the majority of gene fusions or mutations detected in soft tissue tumors result in an abnormal function of transcription factors or chromatin remodeling. The present review focuses on the latest genetic discoveries in the spectrum of both benign and malignant pediatric soft tissue neoplasia. These genetic abnormalities promise to provide relevant insight for their proper classification, prognosis, and treatment. The entities discussed herein are grouped either based on their shared genetic mechanism or based on their presumed line of differentiation., (© 2018 Wiley Periodicals, Inc.)

Gas-liquid reactions form the basis of our everyday lives, yet they still suffer poor reaction efficiency and are difficult to monitor in situ, especially at ambient conditions. Now, an inert gas-liquid reaction between aniline and CO 2 is driven at 1 atm and 298 K by selectively concentrating these immiscible reactants at the interface between metal-organic framework and solid nanoparticles (solid@MOF). Real-time reaction SERS monitoring and simulations affirm the formation of phenylcarbamic acid, which was previously undetectable because they are unstable for post-reaction treatments. The solid@MOF ensemble gives rise to a more than 28-fold improvement to reaction efficiency as compared to ZIF-only and solid-only platforms, emphasizing that the interfacial nanocavities in solid@MOF are the key to enhance the gas-liquid reaction. Our strategy can be integrated with other functional materials, thus opening up new opportunities for ambient-operated gas-liquid applications., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This study examined the relationships among insight, self-stigma, self-esteem, hope, quality of life, and suicidal behavior in individuals diagnosed as having schizophrenia. Hypotheses concerning mediating and moderating effects were examined. A total of 170 community-dwelling patients with schizophrenia participated in the study. The results revealed a negative association between insight and suicide ideation, which was partially mediated by self-stigma. Moreover, this indirect link was stronger among patients with suicide attempts than among those without attempts. We discuss the implications of these results for preventing or reducing the considerable risks of suicide in this population., (© 2017 The American Association of Suicidology.)

Pentabromopseudilin (PBrP) is a marine antibiotic isolated from the marine bacteria Pseudomonas bromoutilis and Alteromonas luteoviolaceus. PBrP exhibits antimicrobial, anti-tumour, and phytotoxic activities. In mammalian cells, PBrP is known to act as a reversible and allosteric inhibitor of myosin Va (MyoVa). In this study, we report that PBrP is a potent inhibitor of transforming growth factor-β (TGF-β) activity. PBrP inhibits TGF-β-stimulated Smad2/3 phosphorylation, plasminogen activator inhibitor-1 (PAI-1) protein production and blocks TGF-β-induced epithelial-mesenchymal transition in epithelial cells. PBrP inhibits TGF-β signalling by reducing the cell-surface expression of type II TGF-β receptor (TβRII) and promotes receptor degradation. Gene silencing approaches suggest that MyoVa plays a crucial role in PBrP-induced TβRII turnover and the subsequent reduction of TGF-β signalling. Because, TGF-β signalling is crucial in the regulation of diverse pathophysiological processes such as tissue fibrosis and cancer development, PBrP should be further explored for its therapeutic role in treating fibrotic diseases and cancer.

Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true "at risk" penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset., Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain., Results: The mean volume of oligemia was 24.7 ± 14.1 mm 3 , that of TP was 81.3 ± 62.6 mm 3 , and that of IC was 123.0 ± 85.2 mm 3 at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences ( p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points., Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

Acute ischemic stroke is followed by a complex interplay between the brain and the immune system in which ischemia-reperfusion leads to a detrimental inflammatory response that causes brain injury. In the brain, IL-15 is expressed by astrocytes, neurons and microglia. Previous study showed that ischemia-reperfusion induces expression of IL-15 by astrocytes. Transgenic over-expression of IL-15 in astrocytes aggravates ischemia-reperfusion brain damage by increasing the levels and promoting the effector functions of CD8 + T and NK cells. Treatment of neonatal rats with IL-15 neutralizing antibody before hypoxia-ischemia induction reduces the infarct volume. However, as stroke-induced inflammatory responses differ between neonate and adult brain, the effects of IL-15 blockade on the injury and immune response arising from stroke in adult animals has remained unclear. In this study, we examined the effect of post-ischemia/reperfusion IL-15 blockade on the pathophysiology of cerebral ischemia-reperfusion in adult mice. Using a cerebral ischemia-reperfusion model, we compared infarct size and the infiltrating immune cells in the brain of wild type (WT) mice and Il15 -/- mice lacking NK and memory CD8 + T cells. We also evaluated the effects of IL-15 neutralizing antibody treatment on brain infarct volume, motor function, and the status of brain-infiltrating immune cells in WT mice. Il15 -/- mice show a smaller infarct volume and lower numbers of activated brain-infiltrating NK, CD8 + T, and CD4 + T cells compared to WT mice after cerebral ischemia-reperfusion. Post-ischemia/reperfusion IL-15 blockade reduces infarct size and improves motor and locomotor activity. Furthermore, IL-15 blockade reduces the effector function of NK, CD8 + T, and CD4 + T cells in the ischemia-reperfusion brain of WT mice. Ablation of IL-15 responses after cerebral ischemia-reperfusion ameliorates brain injury in adult mice. Therefore, targeting IL-15 is a potential effective therapy for ischemic stroke., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study aimed to investigate the association between charcoal-burning suicide attempts and the risk of developing dementia. A nationwide, matched cohort, population-based study enrolled a total of 4103 patients with newly diagnosed charcoal-burning suicide attempts, between 2000 and 2010, which were selected from the National Health Insurance Research Database of Taiwan, along with 12,309 controls matched for sex and age. After adjusting for confounding factors, Fine and Gray's competing risk analysis was used to compare the risk of developing dementia during the 10-year follow-up period. Of the enrolled patients (n=16,412), dementia developed in 303 (1.85%), including 2.56% in the study group (105 in 4103) and 1.61% (198 in 12,309) in the control group. The Fine and Gray's survival analysis revealed that the patients with charcoal-burning suicide attempts were likely to develop dementia, with a crude HR of 5.170 (95% CI 4.022 to 6.644, p<0.001). After adjusting for age, sex, comorbidity, geographic area and urbanization level of residence, and monthly insured premium, the adjusted HR was 4.220 (95% CI 3.188 to 5.586, p<0.001). Suicide attempts were associated with an increased risk of degenerative dementia in this study. Patients with charcoal-burning suicide attempts had a fourfold risk of dementia than the control group., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: The nonlinear pseudoelastic behavior of a native/decellularized vascular tissue is closely related to the detailed composition and microstructure of the extracellular matrix and is important in maintaining the patency of a small-caliber vascular graft. A commonly used enzyme-detergent based decellularization protocol is effective in cell component removal but it also changes the microstructure and composition of the decellularized tissues. Previous studies provide limited information to correlate the mechanical property change with the alterations in composition and microstructure in a decellularization process. In this study, the correlations were studied by implementing a previously established fiber-progressive-engagement model to describe the nonlinear pseudoelastic behavior of a vascular tissue and to evaluate the effects of trypsin concentration and exposure duration on porcine coronary artery decellularization RESULTS: Results showed that tissue length and width increased and thickness and wet weight decreased with the exposure of trypsin. The effects of trypsin exposure times on the four mechanical parameters, i.e. initial strain, turning strain, initial modulus and stiffness modulus, in the longitudinal and circumferential directions were similar, but stronger in the circumferential direction. Major components of the extracellular matrix were vulnerable to the trypsin-based decellularization process. The decreases in initial and turning strain and the increase in initial modulus in circumferential direction were correlated with the significant decrease of collagen and glycosaminoglycans in the media layer., Conclusions: Although trypsin-based decellularization achieved cell component removal and preservation of ultimate tensile stress, the microstructure and composition changed with alterations in the pseudoelastic behavior of the porcine coronary artery. Taken together, the current observations suggested less waviness, early engagement, or re-alignment of insoluble collagen fibers in the media layer, which resulted in turning from anisotropic into isotropic uniaxial mechanical property of porcine vascular tissue. Selecting the proper trypsin concentration (< 0.03-0.5%) and duration (< 12 h) of trypsin exposure in combination with other methods will achieve optimal porcine coronary artery decellularization., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Electroconvulsive therapy (ECT) is an effective treatment for schizophrenia, bipolar disorder, and major depressive disorder, and a temporary memory loss may occur after ECT. However, the association between ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, and the risk of dementia is yet to be examined. Objective: This study aimed to clarify as to whether ECT is associated with the risk of dementia after ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, using Taiwan's National Health Insurance Research Database (NHIRD). Methods: A total of 3,796 enrolled participants (schizophrenia, 46.68%; bipolar disorder, 11.77%; and major depressive disorder, 41.55%) with 994 patients who had received ECT and 2,982 controls matched for sex and age, between January 1, and December 31, 2000, were selected from the NHIRD. After adjusting for confounding factors, Fine and Gray's survival analysis was used to compare the risk of developing dementia during the 10 years of follow-up. Results: Of the study patients, 45 (4.53%) of them developed dementia when compared to 149 (5.0%) in the control group. Fine and Gray's survival analysis revealed that the study patients were not associated with an increased risk of dementia [hazard ratio (HR) = 0.612, 95% confidence interval (CI) = 0.438-1.854, P = 0.325]. After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 0.633 (95% CI = 0.448 - 1.895, P = 0.304). Conclusion: This study supports that ECT was not associated with the increased risk of dementia in patients with schizophrenia, bipolar disorder, and major depressive disorder, using the NHIRD.

Microribonucleic acids (miRNAs) play a pivotal role in numerous aspects of the nervous system and are increasingly recognized as key regulators in neurodegenerative diseases. This study hypothesized that miR-34c, a miRNA expressed in mammalian hippocampi whose expression level can alter the hippocampal dendritic spine density, could induce memory impairment akin to that of patients with Alzheimer's disease (AD) in mice. In this study, we showed that miR-34c overexpression in hippocampal neurons negatively regulated dendritic length and spine density. Hippocampal neurons transfected with miR-34c had shorter dendrites on average and fewer filopodia and spines than those not transfected with miR-34c (control mice). Because dendrites and synapses are key sites for signal transduction and fundamental structures for memory formation and storage, disrupted dendrites can contribute to AD. Therefore, we supposed that miR-34c, through its effects on dendritic spine density, influences synaptic plasticity and plays a key role in AD pathogenesis.

Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transition (EMT). Sorafenib is believed to antagonize tumour progression by inhibiting TGF-β-induced EMT. It improves survival of patients but HCC later develops resistance and relapses. The underlying mechanism of resistance is unknown. Understanding of the molecular mechanism of sorafenib inhibition of TGF-β-induced signalling or responses in HCC may lead to development of adjunctive effective therapy for HCC. In this study, we demonstrate that sorafenib suppresses TGF-β responsiveness in hepatoma cells, hepatocytes, and animal liver, mainly by downregulating cell-surface type II TGF-β receptors (TβRII) localized in caveolae/lipid rafts and non-lipid raft microdomains via caveolae/lipid rafts-mediated internalization and degradation. Furthermore, sorafenib-induced downregulation and degradation of cell-surface TβRII is prevented by simultaneous treatment with a caveolae disruptor or lysosomal inhibitors. On the other hand, sorafenib only downregulates cell-surface TβRII localized in caveolae/lipid rafts but not localized in non-lipid raft microdomains in hepatic stellate cells. These results suggest that sorafenib inhibits TGF-β signalling mainly by inducing caveolae/lipid raft-mediated internalization and degradation of cell-surface TβR-II in target cells. They may also imply that treatment with agents which promote formation of caveolae/lipid rafts, TGF-β receptor kinase inhibitors (e.g., LY2157299) or TGF-β peptide antagonists (by liver-targeting delivery) may be considered as effective adjunct therapy with sorafenib for HCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: In our study, we aimed to investigate the association between a traumatic brain injury (TBI) and subsequent erectile dysfunction (ED). This is a population-based study using the claims dataset from The National Health Insurance Research Database., Methods: We included 72,642 patients with TBI aged over 20 years, retrospectively, selected from the longitudinal health insurance database during 2000-2010, according to the ICD-9-CM. The control group consisted of 217,872 patients without TBI that were randomly chosen from the database at a ratio of 1:3, with age- and index year matched. Cox proportional hazards analysis was used to estimate the association between the TBI and subsequent ED., Results: After a 10-year follow-up, the incidence rate of ED was higher in the TBI patients when compared with the non-TBI control group (24.66 and 19.07 per 100,000, respectively). Patients with TBI had a higher risk of developing ED than the non-TBI cohort after the adjustment of the confounding factors, such as age, comorbidity, residence of urbanization and locations, seasons, level of care, and insured premiums (adjusted hazard ratio (HR) = 2.569, 95% CI [1.890, 3.492], p < .001)., Conclusion: This is the first study using a comprehensive nationwide database to analyze the association of ED and TBI in the Asian population. After adjusted the confounding factors, patients with TBI have a significantly higher risk of developing ED, especially organic ED, than the general population. This finding might remind clinicians that it's crucial in early identification and treatment of ED in post-TBI patients.

BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72%, which was relatively similar to ES (79%, P=0.738) and significantly better than CIC-DUX4 sarcomas (43%, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60% necrosis in posttherapy resections. Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.

Background/objective: Allergic diseases, such as bronchial asthma, allergic rhinitis, atopic dermatitis, and psychiatric disorders, are major health issues. There have been reports that allergic diseases were associated with depression or anxiety disorders. This study aimed to investigate the association between these allergic diseases and the risk of developing overall psychiatric disorders in patients from Taiwan., Methods: This cohort study used the database of the Taiwan National Health Insurance Program. A total of 186,588 enrolled patients, with 46,647 study subjects who had suffered from allergic diseases, and 139,941 controls matched for sex and age, from the Longitudinal Health Insurance Dataset of 2000-2015, were selected from a sub-dataset of the National Health Insurance Research Database. Fine and Gray's competing risk model analysis was used to explore the hazard ratio (HR), and 95% confidence interval, for the risk of allergic diseases being associated with the risk of developing psychiatric disorders during the 15 years of follow-up., Results: Of the study subjects, 5,038 (10.8%) developed psychiatric disorders when compared to 9,376 (6.7%) in the control group, with significant difference ( p  < 0.001). Fine and Gray's competing risk model analysis revealed that the adjusted HR was 1.659 (95% CI = 1.602-1.717, p  < 0.001). In this study, we found that the groups of atopic dermatitis alone and the allergic rhinitis + atopic dermatitis were associated with a lower risk of psychiatric disorders, but all the other four groups, such as bronchial asthma alone, allergic rhinitis alone, bronchial asthma + allergic rhinitis, bronchial asthma + atopic dermatitis, and the combination of all these three allergic diseases, were associated with a higher risk of psychiatric disorders., Conclusion: Allergic diseases are therefore associated with a 1.66-fold increased hazard of psychiatric disorders in Taiwan.

Pentachloropseudilin (PClP) is a chlorinated phenylpyrrole compound that was first isolated from Actinoplanes (ATCC33002), and its structure has been confirmed by chemical synthesis. PClP shows broad antimicrobial activity against Gram-negative and Gram-positive bacteria, protozoa, fungi, and yeast. In mammalian cells, PClP is known to act as a reversible and allosteric inhibitor of myosin 1c (Myo1c). Herein, we report that PCIP is a potent inhibitor of transforming growth factor-β (TGF-β)-stimulated signaling. PCIP inhibits TGF-β-stimulated Smad2/3 phosphorylation and plasminogen activator inhibitor-1 (PAI-1) promoter activation with an IC 50 of 0.1 μm in target cells (A549, HepG2, and Mv1Lu cells). In addition, PCIP attenuates TGF-β-stimulated expression of vimentin, N-cadherin, and fibronectin and, thus, blocks TGF-β-induced epithelial to mesenchymal transition (EMT) in these cells. Furthermore, cell-surface labeling and immunoblot analysis indicates that PCIP suppresses TGF-β-stimulated cellular responses by attenuating cell-surface expression of the type II TGF-β receptor through accelerating caveolae-mediated internalization followed by primarily lysosome-dependent degradation of the receptor, as demonstrated by sucrose density gradient analysis and immune fluorescence staining., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aims: Poor insight is prevalent in patients with schizophrenia and has been associated with acute illness severity, medication non-adherence and poor treatment outcomes. Paradoxically, high insight has been associated with various undesirable outcomes, including low self-esteem, depression and low subjective quality of life (QoL) in patients with schizophrenia. Despite the growing body of studies conducted in Western countries supporting the pernicious effects of improved insight in psychosis, which bases on the level of self-stigma, the effects are unclear in non-Western societies. The current study examined the role of self-stigma in the relationship between insight and psychosocial outcomes in a Chinese population., Methods: A total of 170 outpatients with schizophrenia spectrum disorders were recruited from two general university hospitals. Sociodemographic data and clinical variables were recorded and self-report scales were employed to measure self-stigma, depression, insight, self-esteem and subjective QoL. Structural equation modelling (SEM) was used to analyse the cross-sectional data., Results: High levels of self-stigma were reported by 39% of the participants (n = 67). The influences of insight, self-stigma, self-esteem and depression on subjective QoL were confirmed by the SEM results. Our model with the closest fit to the data (χ 2 = 33.28; df = 20; p = 0.03; χ 2/df = 1.66; CFI = 0.98; TLI = 0.97; RMSEA = 0.06) demonstrated that self-stigma might fully mediate the association of insight with low self-esteem, depression and poor subjective QoL. High insight into illness contributed to self-stigma, which caused low self-esteem and depression and, consequently, low QoL. Notably, insight did not directly affect self-esteem, depression or QoL. Furthermore, the association of insight with poor psychosocial outcomes was not moderated by self-stigma., Conclusions: Our findings support the mediating model of insight relevant to the poor psychosocial outcomes of individuals diagnosed with schizophrenia in non-Western societies, in which self-stigma plays a pivotal role. These findings elucidate the direct and indirect effects of insight on psychosocial outcomes and imply that identifying and correcting self-stigma in people with schizophrenia could be beneficial. Additional studies are required to identify whether several other neurocognitive or psychosocial variables mediate or moderate the association of insight with self-esteem, depression and QoL in patients with schizophrenia. Studies with detailed longitudinal assessments are necessary to confirm our findings.

Benign/low-grade fibroblastic tumors encompass a broad spectrum of tumors with different morphologies and molecular genetic abnormalities. However, despite significant progress in recent genomic characterization, there are still tumors in this histologic spectrum that are difficult to classify, lacking known molecular characteristics. Triggered by a challenging congenital spindle cell neoplasm arising in the heel of a 1-year-old boy, we applied RNA sequencing for genetic discovery and identified a novel EWSR1-SMAD3 gene fusion. On the basis of the index case superficial acral location and fibroblastic appearance with a nonspecific immunophenotype, we searched our files for similar cases and screened them by fluorescence in situ hybridization for these abnormalities. Thus an identical EWSR1-SMAD3 fusion was identified in 2 additional spindle cell tumors with similar clinicopathologic features. Both cases occurred in the feet of adult women (58 and 61 y old) and were characterized by distinctive nodular growth with zonation pattern of peripheral hypercellular areas arranged in short fascicles, transitioning to hypocellular central areas of hyalinization and infarction. Focal stippled calcification in the collagenous area was present in 1 case. All 3 tumors had similar immunoprofiles, being negative for SMA, CD34, CD31, and S100, but showing consistent ERG positivity of uncertain significance. Follow-up information was available in 2 patients who developed local recurrences after incomplete initial excisions, at 5 and 14 months, respectively. None developed metastatic disease. In summary, we report a group of locally recurrent superficial acral tumors, characterized by bland spindle cell fascicular growth, occasional zonation pattern, ERG positivity, and recurrent EWSR1-SMAD3 gene fusions.

This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using Taiwan's National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2000. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing dementia in the HSV cohort. This analysis revealed an adjusted hazard ratio of 2.564 (95% CI: 2.351-2.795, P < 0.001) for the development of dementia in the HSV-infected cohort relative to the non-HSV cohort. Thus, patients with HSV infections may have a 2.56-fold increased risk of developing dementia. A risk reduction of dementia development in patients affected by HSV infections was found upon treatment with anti-herpetic medications (adjusted HR = 0.092 [95% CI 0.079-0.108], P < 0.001). The usage of anti-herpetic medications in the treatment of HSV infections was associated with a decreased risk of dementia. These findings could be a signal to clinicians caring for patients with HSV infections. Further research is, therefore, necessary to explore the underlying mechanism(s) of these associations.

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E NPs) as theranostic probe that can potentially provide a new avenue for monitoring drug delivering through noninvasive magnetic resonance imaging. MRI ΔR2* relaxivity measurements offer an opportunity to quantitatively evaluate the uptake of FeDC-E NPs at cellular and tumoral levels. Additionally, NF-κB reporter gene system provides NF-κB activation status monitoring to validate the therapeutic efficiency of FeDC-E NPs. FeDC-E NPs not only inhibit the tumor growth and NF-κB-modulated antiapoptotic mechanism but also trigger extrinsic and intrinsic apoptotic pathways. Taken together, dual functional FeDC-E NPs offer diagnostic and therapeutic benefits against lung cancers, indicating that our presented probe could be applied in clinical., (Copyright © 2018. Published by Elsevier Inc.)

This study aimed to investigate the associations among dementia, psychotropic medications and the risk of overall injuries. In this nationwide matched cohort study, a total of 144 008 enrolled patients ≥age of 50, with 36 002 study subjects who suffered from dementia and 108 006 controls matched for sex and age, from the Inpatient Dataset, for the period 2000-2010 in Taiwan were selected from the National Health Insurance Research Database, according to International Classification of Diseases, 9th Revision, Clinical Modification. When adjusting for the confounding factors, a Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 10 years of follow-up. Of the study subjects, 6701 (18.61%) suffered injury when compared with 20 919 (19.37%) in the control group. The Cox regression analysis revealed that the study subjects were more likely to develop an injury (HR: 2.294, 95% CI=2.229 to 2.361, P<0.001) after adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities. Psychotropic medications in the subjects with dementia were associated with the risk of injury (adjusted HR=0.217, 95% CI: 0.206 to 0.228, P<0.001). Cognitive enhancers, including acetylcholinesterase inhibitors and memantine, were associated with the risk of injury in the study subjects after being adjusted for all comorbidities and medications (adjusted HR=0.712(95% CI=0.512 to 0.925, P<0.01)). In conclusion, patients who suffered dementia had a higher risk of developing injury, and the cognitive enhancers were associated with the decreased risk of injury., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Dementia is an increasing world-wide health problem, and the association between dementia and adjudication of crimes has rarely been studied. The data in this study are described and analyzed by gender, psychiatric diagnosis, type of crime, and the acceptance rate by the courts of opinions tendered by forensic psychiatric examiners. The source data are derived from the databank of the Judicial Yuan (Judicial Department) of the Republic of China Law and Regulations Retrieval System. There was a male predominance of 85.1 percent. Larceny (42.6%) was the most frequent crime. There was also a high judicial acceptance rate of 91.5 percent of the professional opinions received from forensic psychiatric evaluators who examined defendants at the request of the courts. Psychiatrists play an important role in providing their professional opinions for the Taiwanese courts with regard to adjudication of evaluees with dementia. Most courts accepted psychiatrists' professional opinions about offenders with dementia, and the rate of acceptance was reflected in the judicial rulings of criminal responsibility., (© 2018 American Academy of Psychiatry and the Law.)

Background: Fibromyalgia is a syndrome of chronic pain and other symptoms and is associated with patient discomfort and other diseases. This nationwide matched-cohort population-based study aimed to investigate the association between fibromyalgia and the risk of developing dementia, and to clarify the association between fibromyalgia and dementia., Materials and Methods: A total of 41,612 patients of age ≥50 years with newly diagnosed fibromyalgia between January 1, and December 31, 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 124,836 controls matched for sex and age. After adjusting for any confounding factors, Fine and Gray competing risk analysis was used to compare the risk of developing dementia during the 10 years of follow-up., Results: Of the study subjects, 1,704 from 41,612 fibromyalgia patients (21.23 per 1,000 person-years) developed dementia when compared to 4,419 from 124,836 controls (18.94 per 1,000 person-years). Fine and Gray competing risk analysis revealed that the study subjects were more likely to develop dementia (hazard ratio: 2.29, 95% CI: 2.16-2.42; P < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region of residence and comorbidities the hazard ratio was 2.77 (95% CI: 2.61-2.95, P < 0.001). Fibromyalgia was associated with increased risk of all types of dementia in this study., Conclusions: The study subjects with fibromyalgia had a 2.77-fold risk of dementia in comparison to the control group. Therefore, further studies are needed to elucidate the underlying mechanisms of the association between fibromyalgia and the risk of dementia., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)