bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal miR‐1246 derived from human umbilical cord blood mesenchymal stem cells attenuates hepatic ischemia reperfusion injury by modulating T helper 17/regulatory T balance
Authors: Xie Kun , Liu Lei , Chen Jiangming , Liu Fubao 
Published: August 2019

AbstractThe purpose of this study was to explore the mechanism by which human umbilical cord blood mesenchymal stem cells (hUCB‐MSCs)‐derived exosomes exerted protective effect in hepatic ischemia/reperfusion injury (IRI). hUCB‐MSCs‐derived exosomes were administrated into hepatic IRI mice or cocultured with naïve CD4+ T cells exposed to hepatic hypoxia/reoxygenation microenvironment. Hepatic function was assessed by determining serum transaminases. Histological changes were observed using hematoxylin and eosin staining. The proportion of T helper 17 (Th17) and regulatory T (Treg) cells were analyzed by flow cytometry. The concentration of inflammatory cytokines was determined by enzyme‐linked immunosorbent assay. The interaction between miR‐1246 and interleukin 6 (IL‐6) signal transducer (also known as gp130) was verified by luciferase activity assay. The miR‐1246 expression, Th17/Treg‐related genes, and gp130‐signal transducer and activator of transcription 3 (STAT3) pathway were detected by quantitative real‐time polymerase chain reaction and western blotting. hUCB‐MSCs‐derived exosomes ameliorated IRI‐induced hepatic dysfunction and decreased Th17/Treg ratio in CD4+ T cells in vitro, whereas treatment of hUCB‐MSCs with miR‐1246 inhibitor showed opposite effects, which was mediated via the IL‐6‐gp130‐STAT3 pathway. hUCB‐MSCs‐derived exosomes could alleviate hepatic IRI through modulating the balance between Tregs and Th17 cells via miR‐1246‐mediated IL‐6‐gp130‐STAT3 axis.
The inner clock—Blue light sets the human rhythm
Authors: Wahl Siegfried , Engelhardt Moritz , Schaupp Patrick , Lappe Christian , Ivanov Iliya V. 
Published: August 2019

AbstractVisible light synchronizes the human biological clock in the suprachiasmatic nuclei of the hypothalamus to the solar 24‐hour cycle. Short wavelengths, perceived as blue color, are the strongest synchronizing agent for the circadian system that keeps most biological and psychological rhythms internally synchronized. Circadian rhythm is important for optimum function of organisms and circadian sleep–wake disruptions or chronic misalignment often may lead to psychiatric and neurodegenerative illness. The beneficial effect on circadian synchronization, sleep quality, mood, and cognitive performance depends not only on the light spectral composition but also on the timing of exposure and its intensity. Exposure to blue light during the day is important to suppress melatonin secretion, the hormone that is produced by the pineal gland and plays crucial role in circadian rhythm entrainment. While the exposure to blue is important for keeping organism's wellbeing, alertness, and cognitive performance during the day, chronic exposure to low‐intensity blue light directly before bedtime, may have serious implications on sleep quality, circadian phase and cycle durations. This rises inevitably the need for solutions to improve wellbeing, alertness, and cognitive performance in today's modern society where exposure to blue light emitting devices is ever increasing.
Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva‐Derived Endothelial Cells
Authors: Sánchez‐Duffhues Gonzalo , Williams Eleanor , Benderitter Pascal , Orlova Valeria , van Wijhe Michiel , Garcia de Vinuesa Amaya , Kerr Georgina , Caradec Josselin , Lodder Kirsten , de Boer Hetty C. , Goumans Marie‐José , Eekhoff Elisabeth M W , Morales‐Piga Antonio , Bachiller‐Corral Javier , Koolwijk Pieter , Bullock Alex N. , Hoflack Jan , ten Dijke Peter 
Published: August 2019

ABSTRACTFibrodysplasia ossificans progressiva (FOP) is an extremely rare congenital form of heterotopic ossification (HO), caused by heterozygous mutations in the activin A type I receptor (ACVR1), that encodes the bone morphogenetic protein (BMP) type I receptor ALK2. These mutations enable ALK2 to induce downstream signaling in response to activins, thereby turning them into bone‐inducing agents. To date, there is no cure for FOP. The further development of FOP patient‐derived models may contribute to the discovery of novel biomarkers and therapeutic approaches. Nevertheless, this has traditionally been a challenge, as biopsy sampling often triggers HO. We have characterized peripheral blood‐derived endothelial colony‐forming cells (ECFCs) from three independent FOP donors as a new model for FOP. FOP ECFCs are prone to undergo endothelial‐to‐mesenchymal transition and exhibit increased ALK2 downstream signaling and subsequent osteogenic differentiation upon stimulation with activin A. Moreover, we have identified a new class of small molecule macrocycles with potential activity against ALK2 kinase. Finally, using FOP ECFCs, we have selected OD36 and OD52 as potent inhibitors with excellent kinase selectivity profiles that potently antagonize mutant ALK2 signaling and osteogenic differentiation. We expect that these results will contribute to the development of novel ALK2 clinical candidates for the treatment of FOP. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Evaluation of lactulose, lactose, and fructose breath testing in clinical practice: A focus on methane
Authors: Harvie Ruth M , Tuck Caroline J , Schultz Michael 
Published: August 2019

Background and AimBreath testing (BT) is used to identify carbohydrate malabsorption and small intestine bacterial overgrowth. Measuring methane alongside hydrogen is advocated to reduce false‐negative studies, but the variability of methane production is unknown. The aim of this study is to examine the effect of high methane production on hydrogen excretion after ingesting lactulose, fructose, or lactose.MethodsA retrospective audit was performed of patients with gastrointestinal symptoms who underwent BT. Following a low fermentable carbohydrate diet for 24‐h, a fasting BT before consuming 35 ml lactulose, 35 g fructose, or lactose in 200 ml water, followed by BT every 10–15 min for up to 3‐h, was performed. A positive test was defined as a ≥20 ppm rise of hydrogen or methane from baseline. A high methane producer had an initial reading of ≥5 ppm. Breath hydrogen and methane production were measured as area under the curve. Chi‐squared tests were used to compare proportions of those meeting the cut‐off criteria.ResultsOf patients, 26% (28/106) were high methane producers at their initial lactulose test. The test–retest repeatability of methane production was high, with the same methane production status before ingesting lactose in all (70/70) and before ingesting fructose in most (71/73). Methane production was highly variable during testing, with 38% (10/26) having ≥1 reading lower than baseline. Hydrogen produced by high or low methane producers did not differ (1528 [960–3645] ppm min vs 2375 [1810–3195] ppm min [P = 0.11]). Symptoms and breath test results were not positively related.ConclusionThe validity of including an increase of ≥20 ppm methane to identify carbohydrate malabsorption or small intestine bacterial overgrowth should be questioned due to the variability of readings during testing.
Morphological patterns of cell death in ovarian follicles of primary and secondary growth and postovulatory follicle complex of the annual killifish Millerichthys robustus (Cyprinodontiformes: Cynolebiidae)
Authors: Domínguez‐Castanedo Omar , Uribe Mari Carmen , Muñoz‐Campos Tessy M. 
Published: August 2019

AbstractThe dynamics of cellular development and homeostasis of the ovary depend on the balance between proliferation and cell death throughout the reproductive cycle. Millerichthys robustus is an annual fish whose ovarian follicles develop asynchronously, allowing daily reproduction from sexual maturity until death. The objective of this research is to describe, histologically, the processes of follicular atresia and regression of postovulatory follicular complexes (POC) throughout a reproductive cycle of M. robustus. Patterns of cell death were documented by apoptosis in atretic follicles and POC, and necrosis in the POC after ovulation with an associated inflammatory response. Atretic follicles were seen from the onset of sexual maturity, during week three post‐hatching (PH), both in primary growth (from the Cortical alveoli step, with folliculogenesis completed) and secondary growth Stages, with a higher prevalence in the latter. POCs were observed in different stages of regression from week four PH until the death of the fish. The apoptotic characteristics found were: (i) fragmentation of the nuclear membrane and zona pellucida, and liquefaction of the cortical alveoli and yolk; (ii) follicular cells becoming phagocytic, increasing their size, and migrating within the oocyte; and (iii) formation of an intrafollicular lumen, a product of phagocytosis of the oocyte constituents and dispersed pigments that remain after the digestion of yolk and cortical alveoli. The morphological changes of the follicular cells of the POC, from a squamous morphology after ovulation to columnar during its regression with PAS+ contents, was documented, suggesting a secretory activity.
Five‐Year Impacts of Family Stressors and Combat Threat on the Mental Health of Afghanistan and Iraq War Veterans
Authors: Sanders Wesley , Smith Brian N. , Fox Annie B. , Vogt Dawne 
Published: August 2019

AbstractIt has been well established that warfare‐related stress puts service members at risk for a range of mental health problems after they return from deployment. Less is known about service members’ experience of family stressors during deployment. The aims of this study were to (a) evaluate whether family stressors would contribute unique variance to posttraumatic stress disorder (PTSD) and depressive symptoms above and beyond combat threat during deployment and (b) examine whether family stressors would amplify the negative effects of combat threat on postmilitary mental health 5 years postdischarge. Study participants reported their experience of objective and subjective family stressors and combat threat during deployment. Objective family stressors demonstrated unique associations with PTSD and depression symptoms and remained significant after accounting for ongoing family stressors reported at follow‐up. A significant interaction was found between objective family stressors and combat threat on PTSD symptoms, r = −.10. Although the association between combat threat and PTSD was significant for participants who reported high, B = 0.04; and low, B = 0.09, exposure to family stressors, the steeper slope for those exposed to fewer family stressors indicates a stronger effect of combat threat. Follow‐up analyses revealed that veterans who experienced high amounts of family stress and high levels of combat threat reported significantly worse PTSD symptoms than those who reported low family stress, t(256) = 3.98, p < .001. Findings underscore the importance of attending to the role that family stressors experienced during deployment play in service members’ postmilitary mental health.
Radiomics With Attribute Bagging for Breast Tumor Classification Using Multimodal Ultrasound Images
Authors: Li Yongshuai , Liu Yuan , Zhang Mengke , Zhang Guanglei , Wang Zhili , Luo Jianwen 
Published: August 2019

ObjectivesWe aimed to develop radiomics with attribute bagging, which leverages multimodal ultrasound (US) images to improve the classification accuracy of breast tumors.MethodsA retrospective study was conducted. B‐mode US, shear wave elastographic, and contrast‐enhanced US images of 178 patients with 181 tumors (67 malignant and 114 benign) were included. Radiomics with attribute bagging consisted of extraction of 1226 radiomic features and analysis of them with attribute bagging. Histologic examination results acted as the reference standard. Radiomics with several feature selection algorithms were used for comparison. Cross‐validation and a holdout test were performed to evaluate their performances.ResultsThe accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of radiomics with attribute bagging with the multimodal US images were 84.12%, 92.86%, 78.80%, and 0.919, respectively, exceeding all the comparison methods.ConclusionsRadiomics with attribute bagging combined with multimodal US images has the potential to be used for accurate diagnosis of breast tumors in the clinic.
Variability in pathologic interpretation of mandibular invasion
Authors: Namin Arya W. , Zitsch Robert P. , Layfield Lester J. 
Published: August 2019

Objectives/HypothesisOur objective was to identify the accuracy, sensitivity, and specificity of pathological interpretation of mandibular invasion by oral cavity squamous cell carcinoma (SCC) and compare the sensitivity of detecting mandibular invasion in the erosive versus the infiltrative patterns of invasion. We also aimed to describe the significance of the terminology the carcinoma “abuts the mandible” in pathologic interpretation of mandibular invasion.Study DesignRetrospective case series.MethodsMandibulectomy specimens from patients who underwent surgical treatment for oral cavity SCC between January 1, 2005 and December 31, 2015 were retrospectively reviewed by a board‐certified anatomic pathologist. The accuracy of pathologic interpretation of mandibular invasion was calculated using the retrospective interpretation of bone invasion as the true interpretation, which was compared to the interpretation on the original pathology report. Incidence of encountering the terminology the carcinoma “abuts the mandible” in the pathology report was calculated.ResultsA series of 108 consecutive mandibulectomy specimens were reviewed. Sixty‐nine percent (74/108) of cases were interpreted as having mandibular invasion. The accuracy of interpreting mandibular invasion was 84%. The sensitivities for interpretation of mandibular invasion for the erosive and infiltrative patterns of invasion were 77% (30/39) and 91% (32/35), respectively (P = .08). Nine percent (10/108) of pathology reports utilized the terminology the carcinoma “abuts the mandible,” and 80% (8/10) of these cases exhibited mandibular invasion.ConclusionsThe accuracy of identifying mandibular invasion is 84%, indicating a certain degree of sampling error and variability in interpretation. A precise pathologic definition of mandibular invasion should be applied during the interpretation of these specimens to minimize variability.Level of Evidence4 Laryngoscope, 130:1721–1724, 2020
A structured histopathology‐based analysis of surgical outcomes in chronic rhinosinusitis with and without nasal polyps
Authors: Marino Michael J. , Garcia J. Omar , Zarka Matthew , Lal Devyani 
Published: August 2019

ObjectivesStructured histopathology reporting has been recently described for detailing immunopathological characteristics of chronic rhinosinusitis (CRS), and can be utilized for subtyping CRS and personalizing management. This study scrutinized elements of structured histopathology to identify characteristics that prognosticate outcomes following endoscopic sinus surgery (ESS) for CRS patients with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP).MethodsOutcomes following ESS were measured using the patient‐reported 22‐item sinonasal outcome test (SNOT‐22). Changes in total SNOT‐22 scores at 6 and 12 months postoperatively were analyzed. Thirteen parameters reported in structured histopathology of sinus surgical tissue were studied for association with outcomes postsurgery. The overall cohort of all CRS patients was studied, along with subgroup analyses of CRSwNP and CRSsNP patients.ResultsIn the entire CRS cohort (n = 171), eosinophil count >10 per high power field (HPF) was associated with greater improvement in SNOT‐22 scores at 6 months post‐ESS (P = .039). At 12 months follow‐up, no histopathological characteristic was associated with change in total SNOT‐22 score. In the CRSwNP (n = 66) subgroup, the presence of fibrosis (P = .006) and eosinophil count ≤10 per HPF (P = .025) were associated with less favorable changes in SNOT‐22 scores at 12 months follow‐up. Fibrosis remained statistically significant in multivariable analysis (P = .007).ConclusionsAt 6 months post‐ESS, tissue eosinophilia is associated with significantly higher improvement in SNOT‐22 scores, but this difference is diluted by 12 months. Fibrosis was associated with less favorable outcomes in SNOT‐22 scores for CRSwNP patients at 12 months and may be a prognosticator for poorer long‐term outcomes.Level of Evidence4
Thermoresponsive Water Transportation in Dually Electrostatically Crosslinked Nanocomposite Hydrogels
Authors: Huang Heqin , Yang Yang , Wang Xiaojie , Rehfeldt Florian , Zhang Kai 
Published: August 2019

AbstractControlling water transportation within hydrogels makes hydrogels attractive for diverse applications, but it is still a very challenging task. Herein, a novel type of dually electrostatically crosslinked nanocomposite hydrogel showing thermoresponsive water absorption, distribution, and dehydration processes are developed. The nanocomposite hydrogels are stabilized via electrostatic interactions between negatively charged poly(acrylic acid) and positively charged layered double hydroxide (LDH) nanosheets as well as poly(3‐acrylamidopropyltrimethylammonium chloride). Both LDH nanosheets as crosslinkers and the surrounding temperatures played pivotal roles in tuning the water transportation within these nanocomposite hydrogels. By changing the surrounding temperature from 60 to 4 °C, these hydrogels showed widely adjustable swelling times between 2 and 45 days, while the dehydration process lasted between 7 and 27 days. A swift temperature decrease, for example, from 60 to 25 °C, generated supersaturation within these nanocomposite hydrogels, which further retarded the water transportation and distribution in hydrogel networks. Benefiting from modified water transportation and rapidly alternating water uptake capability during temperature change, pre‐loaded compounds can be used to track and visualize these processes within nanocomposite hydrogels. At the same time, the discharge of water and loaded compounds from the interior of hydrogels demonstrates a thermoresponsive sustained release process.
Investigation of bacterial diversity and pathogen abundances in gibel carp (Carassius auratus gibelio) ponds during a cyprinid herpesvirus 2 outbreak
Authors: Gao Tianming , Cui Bingjian , Kong Xiao , Bai Zhihui , Zhuang Xuliang , Qian Zhi 
Published: August 2019

AbstractCyprinid herpesvirus 2 (CyHV‐2) infection is detrimental to gibel carp health and may result in severe economic loss in freshwater aquaculture. However, information regarding the interaction of this pathogen with the aquatic environment is scarce. In this study, quantitative polymerase chain reaction (qPCR) and high‐throughput sequencing were used to determine the abundances of pathogens and bacterial community compositions in two aquaculture ponds in Jiangsu Province, China. The results indicate that the concentrations of six selected pathogens were higher in the water than in the sediment and that these concentrations peaked during disease outbreak. In total, 8,326 and 18,244 operational taxonomic units were identified from water and sediment samples, respectively. The dominant phyla were Proteobacteria, Actinobacteria, Cyanobacteria, Bacteroidetes, and Chlorobi in water samples and Proteobacteria, Firmicutes, Actinobacteria, Chloroflexi, and Bacteroidetes in sediment samples. Bacterial communities were similar at the phylum level in different ponds, although significant differences were observed at the genus level. In addition, bacterial diversity was associated with environmental factors (temperature, chemical oxygen demand, NO2−‐N, NO3−‐N, and NH4+‐N) in the pond where the outbreak occurred. Additionally, CyHV‐2 abundance was positively correlated with dissolved oxygen levels and Aeromonas spp. abundance in pond water (p < .01). This study provides comprehensive insight into the mechanisms of interaction between potential pathogens and the freshwater environment of aquaculture ponds during CyHV‐2 disease outbreaks. Furthermore, the results from this study can contribute to improvement of the aquatic environment and establishment of disease prevention and control measures.
Neuropathologic basis of frontotemporal dementia in progressive supranuclear palsy
Authors: Sakae Nobutaka , Josephs Keith A. , Litvan Irene , Murray Melissa E. , Duara Ranjan , Uitti Ryan J. , Wszolek Zbigniew K. , Graff‐Radford Neil R. , Dickson Dennis W. 
Published: August 2019

AbstractBackgroundProgressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by neuronal loss in the extrapyramidal system with pathologic accumulation of tau in neurons and glia. The most common clinical presentation of PSP, referred to as Richardson syndrome, is that of atypical parkinsonism with vertical gaze palsy, axial rigidity, and frequent falls. Although cognitive deficits in PSP are often ascribed to subcortical dysfunction, a subset of patients has dementia with behavioral features similar to the behavioral variant of frontotemporal dementia. In this study we aimed to identify the clinical and pathological characteristics of PSP presenting with frontotemporal dementia.MethodsIn this study, we compared clinical and pathologic characteristics of 31 patients with PSP with Richardson syndrome with 15 patients with PSP with frontotemporal dementia. For pathological analysis, we used semiquantitative methods to assess neuronal and glial lesions with tau immunohistochemistry, as well image analysis of tau burden using digital microscopic methods.ResultsWe found greater frontal and temporal neocortical neuronal tau pathology in PSP with frontotemporal dementia compared with PSP with Richardson syndrome. White matter tau pathology was also greater in PSP with frontotemporal dementia than PSP with Richardson syndrome. Genetic and demographic factors were not associated with atypical distribution of tau pathology in PSP with frontotemporal dementia.ConclusionsThe results confirm the subset of cognitive‐predominant PSP mimicking frontotemporal dementia in PSP. PSP with frontotemporal dementia has distinct clinical features that differ from PSP with Richardson syndrome, as well as differences in distribution and density of tau pathology. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.