bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of Potential Protein Markers Predicting Chemoradioresistance in Early Cervical Cancer by Immunohistochemistry
Authors: Jeong Soo Young , Chung Joon-Yong , Byeon Sun-Ju , Kim Chul Jung , Lee Yoo-Young , Kim Tae-Joong , Lee Jeong-Won , Kim Byoung-Gie , Chae Ye Lin , Oh So Young , Choi Chel Hun
Published: July 2021

Background

In a previous study, a proteomic panel consisting of BCL-2, HER2, CD133, CAIX, and ERCC1 significantly predicted survival in patients with locally advanced cervical cancer. However, the prognostic significance of these proteins has not been assessed in early cervical cancer. The present study investigated the clinical significance and chemoradioresistance prediction power of these proteins in patients with early-stage cervical cancer.

Materials and Methods

BCL-2, HER2, CD133, CAIX, and ERCC1 expression was determined by the immunohistochemical staining of 336 cervical cancer tissue microarrays. The associations of these proteins with clinicopathologic characteristics and disease progression were assessed.

Results

There was a trend of low CAIX expression (p=0.082) and high ERCC1 expression (p=0.059) in patients with a favorable response to adjuvant radiation. High HER2 expression was significantly associated with shorter disease-free survival (DFS) in the total group (5-year DFS of 80.1% vs. 92.2%, p=0.004). A prognostic significance remained in multivariate analysis (Hazard ratio, HR=2.10, p=0.029). In the adjuvant radiation group, low CAIX and high ERCC1 expression indicated significantly unfavorable DFS (75.0% vs. 89.0%, p=0.026 and 76.8% vs. 88.6%, p=0.022, respectively). Low CAIX expression remained an independent prognostic marker in multivariate analysis (HR=0.45, p=0.037). The combined molecular-clinical model using random survival forest method predicted DFS with improved power compared with that of the clinical variable model (C-index 0.77 vs. 0.71, p=0.006).

Conclusion

HER2, CAIX, and ERCC1 expression can be predictive protein markers for clinical outcomes in early cervical cancer patients treated primarily with radical surgery with or without adjuvant radiation.
Mucosal Melanoma: Pathological Evolution, Pathway Dependency and Targeted Therapy
Authors: Ma Yanni , Xia Ronghui , Ma Xuhui , Judson-Torres Robert L. , Zeng Hanlin
Published: July 2021

Mucosal melanoma (MM) is a rare melanoma subtype that originates from melanocytes within sun-protected mucous membranes. Compared with cutaneous melanoma (CM), MM has worse prognosis and lacks effective treatment options. Moreover, the endogenous or exogenous risk factors that influence mucosal melanocyte transformation, as well as the identity of MM precursor lesions, are ambiguous. Consequently, there remains a lack of molecular markers that can be used for early diagnosis, and therefore better management, of MM. In this review, we first summarize the main functions of mucosal melanocytes. Then, using oral mucosal melanoma (OMM) as a model, we discuss the distinct pathologic stages from benign mucosal melanocytes to metastatic MM, mapping the possible evolutionary trajectories that correspond to MM initiation and progression. We highlight key areas of ambiguity during the genetic evolution of MM from its benign lesions, and the resolution of which could aid in the discovery of new biomarkers for MM detection and diagnosis. We outline the key pathways that are altered in MM, including the MAPK pathway, the PI3K/AKT pathway, cell cycle regulation, telomere maintenance, and the RNA maturation process, and discuss targeted therapy strategies for MM currently in use or under investigation.
Differential Expression Profile of lncRNA in Glioma Cells and the Effect of lncRNA NKX3-1 on Glioma Cells Through Fem1b/SPDEF Pathway
Authors: Cai Yang , Wang Ming , Cui Yan , Tan Zhigang , Jiang Yugang
Published: July 2021

Objective

To investigate the differential expression of lncRNA in glioma cells, as well as the effect of lncRNA NKX3-1 on glioma cells.

Methods

Glioma-related data were first downloaded from the TCGA database and analyzed using bioinformatics, after which the lncRNA NKX3-1 was chosen for further experiments. The expression of the lncRNA NKX3-1 in glioma tumor samples was detected using qRT-PCR. The subcellular localization of lncRNA NKX3-1 was determined using fluorescence in situ hybridization (FISH). CCK-8, flow cytometry, cell scratch, and transwell assays were used to detect cell proliferation, apoptosis, and invasion. The downstream pathway of lncRNA NKX3-1 was investigated using luciferase assays and detected using western blot, transwell, and cell scratch assays.

Results

The differential expression profile of lncRNA in glioma was obtained. NKX3-1 lncRNA was found to be significantly increased in glioma tumor tissues. LncRNA NKX3-1 was found in the nucleus. Proliferation, invasion, and migration of glioma cells were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group, while apoptosis ability was significantly decreased (P <0.05). Tumor volume and weight were significantly increased in the lncRNA NKX3-1 overexpression group in nude mice (P <0.05). LncRNA NKX3-1 significantly increased the luciferase activity of Fem1b 3’-UTR-WT reporter genes (P <0.05) as well as the levels of SPDEF protein (P <0.05). The protein level of FEM1B was significantly reduced. Cell invasion and migration were significantly increased (P <0.05) in the lncRNA NKX3-1 overexpression group plus SPDEF group.

Conclusion

We investigated the differential expression profile of lncRNAs in glioma and discovered that the lncRNA NKX3-1 plays an important role in cancer promotion via the Fem1b/SPDEF pathway.
Measuring Maximum Head Circumference Within the Picture Archiving and Communication System: A Fully Automatic Approach
Authors: Yepes-Calderon Fernando , Wihardja Frisca , Sloan Andrea , Kim Janet , Nelson Marvin D. , McComb J. Gordon
Published: July 2021

This study describes an automatic technique to accurately determine the maximum head circumference (MHC) measurement from MRI studies within the Picture Archiving and Communications System, and can automatically add this measurement to the final radiology report. Participants were selected through a retrospective chart review of patients referred to the neurosurgery clinic. Forty-nine pediatric patients with ages ranging from 5 months to 11 years were included in the study. We created 14 printed ring structures to mirror the head circumference values at various ages along the x-axis of the Nellhaus chart. The 3D-printed structures were used to create MRI phantoms. Analytical obtainment of circumference values from the 3D objects and phantom images allowed for a fair estimation and correction of errors on the image-based-measuring instrument. Then, standard manual MHC measurements were performed and compared to values obtained from the patients' MRI T1 images using the tuned instrument proposed in this document. AT-test revealed no statistical difference between the manual assessments and the ones obtained by the automationp= 0.357, α = 0.05. This automatic application augments the more error-prone manual MHC measurement, and can add a numerical value to the final radiology report as a standard application.
Perspective of Immunopathogenesis and Immunotherapies for Kawasaki Disease
Authors: Chang Lung , Yang Horng-Woei , Lin Tang-Yu , Yang Kuender D.
Published: July 2021

Kawasaki Disease (KD) is an acute inflammatory illness that mostly occurs in children below 5 years of age, with intractable fever, mucocutaneous lesions, lymphadenopathy, and lesions of the coronary artery (CAL). KD is sharing clinical symptoms with systemic inflammatory syndrome in children (MIS-C) which is related to COVID-19. Certain genes are identified to be associated with KD, but the findings usually differ between countries and races. Human Leukocyte Antigen (HLA) allele types and toll-like receptor (TLR) expression are also correlated to KD. The acute hyperinflammation in KD is mediated by an imbalance between augmented T helper 17 (Th17)/Th1 responses with high levels of interleukin (IL)-6, IL-10, IL-17A, IFN-γ, and IP-10, in contrast to reduced Th2/Treg responses with lower IL-4, IL-5, FoxP3, and TGF-β expression. KD has varying phenotypic variations regarding age, gender, intravenous immunoglobulin (IVIG) resistance, macrophage activation and shock syndrome. The signs of macrophage activation syndrome (MAS) can be interpreted as hyperferritinemia and thrombocytopenia contradictory to thrombocytosis in typical KD; the signs of KD with shock syndrome (KDSS) can be interpreted as overproduction of nitric oxide (NO) and coagulopathy. For over five decades, IVIG and aspirin are the standard treatment for KD. However, some KD patients are refractory to IVIG required additional medications against inflammation. Further studies are proposed to delineate the immunopathogenesis of IVIG-resistance and KDSS, to identify high risk patients with genetic susceptibility, and to develop an ideal treatment regimen, such as by providing idiotypic immunoglobulins to curb cytokine storms, NO overproduction, and the epigenetic induction of Treg function.
Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence
Authors: Bloomfield Marketa , Klocperk Adam , Zachova Radana , Milota Tomas , Kanderova Veronika , Sediva Anna
Published: July 2021

Activated phosphoinositide 3-kinase delta syndrome (APDS), caused by mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits, is a primary immunodeficiency affecting both humoral and cellular immunity, which shares some phenotypic similarities with hyper-IgM syndromes and common variable immunodeficiency (CVID). Since its first description in 2013, over 200 patients have been reported worldwide. Unsurprisingly, many of the newly diagnosed patients were recruited later in life from previously long-standing unclassified immunodeficiencies and the early course of the disease is, therefore, often less well-described. In this study, we report clinical and laboratory features of eight patients followed for APDS, with particular focus on early warning signs, longitudinal development of their symptoms, individual variations, and response to therapy. The main clinical features shared by our patients included recurrent bacterial and viral respiratory tract infections, gastrointestinal disease, non-malignant lymphoproliferation, autoimmune thyroiditis, and susceptibility to EBV. All patients tolerated vaccination with both attenuated live and subunit vaccines with no adverse effects, although some failed to mount adequate antibody response. Laboratory findings were characterized by dysgammaglobulinaemia, elevated serum IgM, block in B-cell maturation with high transitional B cells, and low naïve T cells with CD8 T-cell activation. All patients benefited from immunoglobulin replacement therapy, whereas immunosuppression with mTOR pathway inhibitors was only partially successful. Therapy with specific PI3K inhibitor leniolisib was beneficial in all patients in the clinical trial. These vignettes, summary data, and particular tell-tale signs should serve to facilitate early recognition, referral, and initiation of outcome-improving therapy.
Berberine Reduces Aβ42 Deposition and Tau Hyperphosphorylation via Ameliorating Endoplasmic Reticulum Stress
Authors: Wu Yue , Chen Qingjie , Wen Bing , Wu Ninghua , He Benhong , Chen Juan
Published: July 2021

Alzheimer’s disease (AD) is tightly related to endoplasmic reticulum stress (ER stress), which aggravates two dominant pathological manifestations of AD: senile plaques and neurofibrillary tangles. Berberine is widely applied in the clinical treatment of many diseases and is reported to have anti-AD effects. In the present study, berberine was shown to ameliorate ER stress and cognitive impairment in APP/PS1 mice. We found ER stress plays a role as a central hub for signal transduction, which was evidenced by the hyperactivation of glycogen synthase kinase 3β (GSK3β) to phosphorylate tau and the activation of PRKR-like endoplasmic reticulum kinase (PERK) subsequently to phosphorylate eukaryotic translation initiation factor-2 α (eIF2α). Also, eIF2α has regulated the expression of beta-site APP cleaving enzyme-1 (BACE1), which cleaves APP into pro-oligomerized amyloid beta 42 (Aβ42), the main component of senile plaques, proven by using siRNA targeting at eIF2α. Mechanically, berberine can reduce GSK3β activity, contributing to the downregulation of tau phosphorylation. Berberine also suppressed Aβ42 production via inhibiting the PERK/eIF2α/BACE1 signaling pathway. Taken together, these findings indicated that berberine had the potential to ameliorate two major pathological manifestations of AD mainly by suppressing ER stress. Our work provided knowledge on the pharmacological intervention of AD and the possible targets for future drug development.
Targeting Glycogen Synthase Kinase 3 Beta Regulates CD47 Expression After Myocardial Infarction in Rats via the NF-κB Signaling Pathway
Authors: Xu Li-Na , Wang Shu-Hui , Su Xue-Ling , Komal Sumra , Fan Hong-Kun , Xia Li , Zhang Li-Rong , Han Sheng-Na
Published: July 2021

The aim of this study was to investigate the effects of the GSK-3β/NF-κB pathway on integrin-associated protein (CD47) expression after myocardial infarction (MI) in rats. An MI Sprague Dawley rat model was established by ligating the left anterior descending coronary artery. The rats were divided into three groups: Sham, MI, and SB + MI (SB216763) groups. Immunohistochemistry was used to observe the changes in cardiac morphology. A significant reduction in the sizes of fibrotic scars was observed in the SB + MI group compared to that in the MI group. SB216763 decreased the mRNA and protein expression of CD47 and NF-κB during MI. Primary rat cardiomyocytes (RCMs) and the H9c2 cell line were used to establish in vitro hypoxia models. Quantitative real-time PCR and western blotting analyses were conducted to detect mRNA and protein expression levels of CD47 and NF-κB and apoptosis-related proteins, respectively. Apoptosis of hypoxic cells was assessed using flow cytometry. SB216763 reduced the protein expression of CD47 and NF-κB in RCMs and H9c2 cells under hypoxic conditions for 12 h, and alleviated hypoxia-induced apoptosis. SN50 (an NF-κB inhibitor) also decreased CD47 protein expression in RCMs and H9c2 cells under hypoxic conditions for 12 h and protected cells from apoptosis. GSK-3β upregulates CD47 expression in cardiac tissues after MI by activating NF-κB, which in turn leads to myocardial cell damage and apoptosis.
Relationship Between Mean Vancomycin Trough Concentration and Mortality in Critically Ill Patients: A Multicenter Retrospective Study
Authors: Hou Yanli , Ren Jiajia , Li Jiamei , Jin Xuting , Gao Ya , Li Ruohan , Zhang Jingjing , Wang Xiaochuang , Li Xinyu , Wang Gang
Published: July 2021

Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs).

Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: <10, 10–15, 15–20, and >20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality.

Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014–1.063]) and hospital (1.025 [1.005–1.046]) mortalities. As a categorical variable, mean VTC of 10–15 mg/L was not associated with reduced ICU (1.705 [0.975–2.981]) and hospital (1.235 [0.829–1.841]) mortalities. Mean VTC of 15–20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924–2.029]). Moreover, mean VTCs of 15–20 and >20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111–3.332]; 2.428 [1.385–4.258]), and mean VTC of >20 mg/L with higher hospital mortality (1.585 [1.053–2.387]) than mean VTC of <10 mg/L. Similar results were observed in patients with different Acute Physiology and Chronic Health Evaluation IV score, creatinine clearance, age, and body mass index subgroups.

Conclusion: Mean VTC was not associated with reduced ICU/hospital related mortality. Our results suggested that VTC monitoring might not guarantee vancomycin efficacy for ICU patients.
Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling
Authors: Wang Xin , Ren Rui , Xu Zehui , Huang Haidi , Jiang Wanglin , Ma Jinbo
Published: July 2021

Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. This study assessed the impact of KX-01 on cobalt chloride (CoCl2)-treated L929 cells and bleomycin (BLM)-induced pulmonary fibrosis in rats to evaluate the efficacy of this compound in vitro and in vivo, respectively. In CoCl2-treated L929 cells, KX-01 significantly reduced the expression of smooth muscle actin (α-SMA), collagen I, collagen III, hypoxia inducing factor (HIF-1α), signal transducers and transcriptional activators (p-STAT3), and p-Src. In BLM-induced pulmonary fibrosis rats, KX-01 reduced pathological scores, collagen deposition, α-SMA, collagen I, collagen III, p-Src, HIF-1α, and p-STAT3. Overall, these findings revealed that KX-01 can alleviate experimental pulmonary fibrosis via suppressing the p-SRC/p-STAT3 signaling pathways.
Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma
Authors: Al-Odat Omar S. , von Suskil Max , Chitren Robert J. , Elbezanti Weam O. , Srivastava Sandeep K. , Budak-Alpddogan Tulin , Jonnalagadda Subash C. , Aggarwal Bharat B. , Pandey Manoj
Published: July 2021

Multiple myeloma (MM) is a plasma cells neoplasm. The overexpression of Bcl-2 family proteins, particularly myeloid cell leukemia 1 (Mcl-1), plays a critical role in the pathogenesis of MM. The overexpression of Mcl-1 is associated with drug resistance and overall poor prognosis of MM. Thus, inhibition of the Mcl-1 protein considered as a therapeutic strategy to kill the myeloma cells. Over the last decade, the development of selective Mcl-1 inhibitors has seen remarkable advancement. This review presents the critical role of Mcl-1 in the progression of MM, the most prominent BH3 mimetic and semi-BH3 mimetic that selectively inhibit Mcl-1, and could be used as single agent or combined with existing therapies.
Comparison of the Safety and Efficacy of Interferon Alpha-2a and Cyclosporine-A When Combined With Glucocorticoid in the Treatment of Refractory Behçet’s Uveitis: A Randomized Controlled Prospective Study
Authors: Qian Yujing , Qu Yi , Gao Fei , Pei Minghang , Liang Anyi , Xiao Junyan , Zhao Chan , Zhang Meifen
Published: July 2021

Purpose: To evaluate and compare the efficacy and safety of interferon alpha-2a (IFN-α2a) and cyclosporine-A (CsA) in patients with refractory Behçet’s uveitis (BU).

Methods: In this 12-month randomized, controlled, prospective trial, 26 participants (44 eyes) completed the study. Patients were randomly allocated to the IFN-α2a or CsA groups. All patients in both groups received a standardized prednisone burst and tapering schedule as per protocol. The primary outcome measures were response rate, complete remission rate, and tolerance rate. The secondary outcome measures included time to achieve complete remission, the logarithm of the minimum angle of resolution (logMAR) of best-corrected visual acuity (BCVA), and Behçet’s disease ocular attack score 24 (BOS24). T-tests and non-parametric tests were used to compare quantitative variables, and chi-square tests were performed to compare qualitative variables.

Results: The response and complete remission rates were 85.7% (12/14 patients) and 50.0% (7/14 patients) in the IFN-α2a group, compared with 66.7% (8/12 patients) and 25.0% (3/12 patients) in the CsA group, respectively (p > 0.05). Complete remission was achieved at 3.3 and 7.0 months after initiation of IFN-α2a and CsA (p = 0.023). LogMAR BCVA significantly improved 1 month after IFN-α2a initiation (23 eyes) (p = 0.002), and this beneficial effect remained statistically significant during the entire follow-up period (p < 0.05); however, this improvement was not observed in the CsA group (21 eyes). At the endpoint, LogMAR BCVA in the IFN-α2a group was significantly better (0.22 vs. 0.31, p = 0.031) with a higher improvement rate (60.9 vs. 47.6%, p > 0.05). Moreover, compared to the CsA group, more eyes in the IFN-α2a group had a lower BOS24 score (87.0 vs. 57.1%, p = 0.042). None of the patients had any side effects that influenced the medication adherence.

Conclusion: Compared to CsA plus corticosteroid, IFN-α2a plus corticosteroid appears to induce a better treatment response, a significantly greater improvement in visual acuity, and more stable remission of intraocular inflammation in a 12-month study period.
Coarse Graining Nonisothermal Microswimmer Suspensions
Authors: Auschra Sven , Chakraborty Dipanjan , Falasco Gianmaria , Pfaller Richard , Kroy Klaus
Published: July 2021

We investigate coarse-grained models of suspended self-thermophoretic microswimmers. Upon heating, the Janus spheres, with hemispheres made of different materials, induce a heterogeneous local solvent temperature that causes the self-phoretic particle propulsion. Starting from molecular dynamics simulations that schematically resolve the molecular composition of the solvent and the microswimmer, we verify the coarse-grained description of the fluid in terms of a local molecular temperature field, and its role for the particle’s thermophoretic self-propulsion and hot Brownian motion. The latter is governed by effective nonequilibrium temperatures, which are measured from simulations by confining the particle position and orientation. They are theoretically shown to remain relevant for any further spatial coarse-graining towards a hydrodynamic description of the entire suspension as a homogeneous complex fluid.
Programming Self-Assembled Materials With DNA-Coated Colloids
Authors: Zhang Tianran , Lyu Dengping , Xu Wei , Mu Yijiang , Wang Yufeng
Published: July 2021

Introducing the concept of programmability paves the way for designing complex and intelligent materials, where the materials’ structural information is pre-encoded in the components that build the system. With highly tunable interactions, DNA-coated particles are promising building elements to program materials at the colloidal scale, but several grand challenges have prevented them from assembling into the desired structures and phases. In recent years, the field has seen significant progress in tackling these challenges, which has led to the realization of numerous colloidal structures and dynamics previously inaccessible, including the desirable colloidal diamond structure, that are useful for photonic and various other applications. We review this exciting progress, focusing in detail on how DNA-coated colloids can be designed to have a sophisticatedly tailored surface, shape, patches, as well as controlled kinetics, which are key factors that allow one to program in principle a limitless number of structures. We also share our view on how the field may be directed in future.
Effective Repulsion Between Oppositely Charged Particles in Symmetrical Multivalent Salt Solutions: Effect of Salt Valence
Authors: Li Yao , Dong Hai-Long , Zhang Jin-Si , Lin Cheng , Tan Zhi-Jie
Published: July 2021

Salt ions play critical roles in the assembly of polyelectrolytes such as nucleic acids and colloids since ions can regulate the effective interactions between them. In this work, we investigated the effective interactions between oppositely charged particles in symmetrical (z:z) salt solutions by Monte Carlo simulations with salt valence z ranging from 1 to 4. We found that the effective interactions between oppositely charged particles are attractive for 1:1 and low multivalent salts, while they become apparently repulsive for high multivalent salts. Moreover, such effective repulsion becomes stronger as z increases from 2 to 3, while it becomes weaker when z increases from 3 to 4. Our analyses reveal that the overall effective interactions are attributed to the interplay between ion translational entropy and electrostatic energy, and the non-monotonic salt-valence dependence of the effective repulsions is caused by the rapid decrease of attractive electrostatic energy between two oppositely charged particles with their over-condensed counterions of opposite charges when z exceeds 3. Our further MC simulations show that the involvement of local-ranged counterion–co-ion repulsions can enhance the effective repulsions through weakening the attractive electrostatic energy, especially for higher salt valence.
Olfactory Proteins and Their Expression Profiles in the Eucalyptus Pest Endoclita signifier Larvae
Authors: Zhang Xiaoyu , Yang Zhende , Yang Xiuhao , Ma Hongxuan , Liu Xiumei , Hu Ping
Published: July 2021

Endoclita signifier Walker (Lepidoptera: Hepialidae), a polyphagous insect, has become a new wood-boring pest in Eucalyptus plantations in southern China since 2007, which represents a typical example of native insect adaptation to an exotic host. After the third instar, larvae move from soil to standing trees and damage the plants with a wormhole. Although females disperse to lay eggs, larvae can accurately find eucalyptus in a mingled forest of eight species, which leads us to hypothesize that the larval olfactory system contributes to its host selection. Herein, we investigated the transcriptomes of the head and tegument of E. signifer larvae and explored the expression profiles of olfactory proteins. We identified 15 odorant-binding proteins (OBPs), including seven general OBPs (GOPBs), six chemosensory proteins (CSPs), two odorant receptors (ORs), one gustatory receptor (GR), 14 ionotropic receptors (IRs), and one sensory neuron membrane protein (SNMP). Expression profiles indicated that all olfactory proteins, except for EsigCSP1, were expressed in the head, and most were also detected in non-olfactory tissues, especially thorax tegument. Furthermore, EsigOBP2, EsigOBP8, EsigGOBP1, EsigGOBP2, EsigGOBP5, EsigCSP3, EsigCSP5, and EsigOR1 were expressed most strongly in the head; moreover, EsigCSP3 expressed abundantly in the head. EsigGR1 exhibited the highest expression among all tissues. Besides phylogenetic analysis shows that EsigGOBP7 probably is the pheromone-binding protein (PBP) of E. signifier. This study provides the molecular basis for future study of chemosensation in E. signifier larvae. EsigCSP3 and EsigGR1, which have unique expression patterns, might be factors that govern the host choice of larvae and worth further exploration.
Downregulation of Interleukin-13 Receptor α2 Inhibits Angiogenic Formation Mediated by Chitinase 3-Like 1 in Late Atherosclerotic Lesions of apoE−/− Mice
Authors: Xue Qi , Chen Lei , Yu Jianwu , Sun Kewang , Ye Lifang , Zheng Jianlei
Published: July 2021

Aim: Chitinase 3-like 1 (CHI3L1) has the potential to prompt proliferation and angiogenic formation. Interleukin-13 receptor α2 (IL-13Rα2) was regarded as a receptor of CHI3L1; however, it is unknown whether CHI3L1 adjusts the neovascularization in late atherosclerotic lesions of apoE−/− mice via IL-13Rα2.

Methods: Silicone collars were placed around one of the common carotid arteries of apoE−/− mice fed with a high-fat diet. The mice were further injected with Ad.CHI3L1 alone or Ad.CHI3L1 + Ad.IL-13Rα2 shRNA through the caudal vein. The plaque areas in the whole aorta and aortic root were evaluated by Oil Red O staining and H&E staining. The contents of CD31, CD42b, and collagen in carotid plaques were investigated by immunohistochemistry and Masson trichrome staining. The role of CHI3L1 in migration and tube formation of human umbilical vein endothelial cells (HUVECs) was determined by transwell and Matrigel tests. The effect of CHI3L1 on the expression of AKT and extracellular signal-regulated kinase (ERK) was evaluated with the Western blot.

Results: The plaque loads in the aorta were significantly more extensive in apoE−/− mice injected with Ad.CHI3L1 than those with Ad.CHI3L1 + Ad.IL-13Rα2 shRNA. CHI3L1 significantly increased the contents of CD31 and CD42b and decreased the element of collagen in late-stage atherosclerotic lesions of the carotid arteries. The effects of CHI3L1 on migration, tube formation, and upregulation of phospho-AKT and phospho-ERK of HUVECs were prohibited by inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) as well as IL-13Rα2 shRNA.

Conclusion: To some extent, CHI3L1 promotes migration and tube formation of HUVECs and neovascularization in atherosclerotic plaques possibly mediated by IL-13Rα2 through AKT and ERK signal pathways.
Calculation of Transpulmonary Pressure From Regional Ventilation Displayed by Electrical Impedance Tomography in Acute Respiratory Distress Syndrome
Authors: Scaramuzzo Gaetano , Spadaro Savino , Spinelli Elena , Waldmann Andreas D. , Bohm Stephan H. , Ottaviani Irene , Montanaro Federica , Gamberini Lorenzo , Marangoni Elisabetta , Mauri Tommaso , Volta Carlo Alberto
Published: July 2021

Transpulmonary driving pressure (DPL) corresponds to the cyclical stress imposed on the lung parenchyma during tidal breathing and, therefore, can be used to assess the risk of ventilator-induced lung injury (VILI). Its measurement at the bedside requires the use of esophageal pressure (Peso), which is sometimes technically challenging. Recently, it has been demonstrated how in an animal model of ARDS, the transpulmonary pressure (PL) measured with Peso calculated with the absolute values method (PL = Paw—Peso) is equivalent to the transpulmonary pressure directly measured using pleural sensors in the central-dependent part of the lung. We hypothesized that, since the PL derived from Peso reflects the regional behavior of the lung, it could exist a relationship between regional parameters measured by electrical impedance tomography (EIT) and driving PL (DPL). Moreover, we explored if, by integrating airways pressure data and EIT data, it could be possible to estimate non-invasively DPL and consequently lung elastance (EL) and elastance-derived inspiratory PL (PI). We analyzed 59 measurements from 20 patients with ARDS. There was a significant intra-patient correlation between EIT derived regional compliance in regions of interest (ROI1) (r = 0.5, p = 0.001), ROI2 (r = −0.68, p < 0.001), and ROI3 (r = −0.4, p = 0.002), and DPL. A multiple linear regression successfully predicted DPL based on respiratory system elastance (Ers), ideal body weight (IBW), roi1%, roi2%, and roi3% (R2 = 0.84, p < 0.001). The corresponding Bland-Altmann analysis showed a bias of −1.4e-007 cmH2O and limits of agreement (LoA) of −2.4–2.4 cmH2O. EL and PI calculated using EIT showed good agreement (R2 = 0.89, p < 0.001 and R2 = 0.75, p < 0.001) with the esophageal derived correspondent variables. In conclusion, DPL has a good correlation with EIT-derived parameters in the central lung. DPL, PI, and EL can be estimated with good accuracy non-invasively combining information coming from EIT and airway pressure.
The Circulatory Effects of Increased Hydrostatic Pressure Due to Immersion and Submersion
Authors: Weenink Robert P. , Wingelaar Thijs T.
Published: July 2021

Increased hydrostatic pressure as experienced during immersion and submersion has effects on the circulation. The main effect is counteracting of gravity by buoyancy, which results in reduced extravasation of fluid. Immersion in a cold liquid leads to peripheral vasoconstriction, which centralizes the circulation. Additionally, a pressure difference usually exists between the lungs and the rest of the body, promoting pulmonary edema. However, hydrostatic pressure does not exert an external compressing force that counteracts extravasation, since the increased pressure is transmitted equally throughout all tissues immersed at the same level. Moreover, the vertical gradient of hydrostatic pressure down an immersed body part does not act as a resistance to blood flow. The occurrence of cardiovascular collapse when an immersed person is rescued from the water is not explained by removal of hydrostatic squeeze, but by sudden reinstitution of the effect of gravity in a cold and vasoplegic subject.
Pioglitazone Ameliorates Renal Ischemia-Reperfusion Injury via Inhibition of NF-κB Activation and Inflammation in Rats
Authors: Zou Gaode , Zhou Zhiyu , Xi Xiaoqing , Huang Ruizhen , Hu Honglin
Published: July 2021

Renal ischemia-reperfusion injury (IRI) is considered as a major cause of acute kidney injury. In this study, we investigated the role of the NF-κB signaling pathway and inflammation in the amelioration of renal IRI using pioglitazone. Sprague–Dawley (SD) rats were subjected to bilateral renal artery clamping for 45 min followed by perfusion restoration for establishing a simulated renal IRI model. At 24 h post-operatively, we assessed the serum levels of creatinine and urea nitrogen, expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ) and NF-κB-related (p-IKK-β and IκB-α) proteins, and mRNA expression levels of the inflammatory cytokines, including TNF-α and MCP-1, in the renal tissue of various study groups. The histopathological evaluation of renal tissue was also conducted. In rat renal tissue, pioglitazone treatment decreased the serum levels of post-renal IRI creatinine and urea nitrogen, as well as necrosis. Furthermore, it elevated the expression of PPAR-γ protein and decreased the expression of NF-κB-related proteins. Pioglitazone also decreased the mRNA expression of TNF-α and MCP-1 in the renal tissue. Thus, pioglitazone ameliorates renal IRI by inhibiting the NF-κB signaling pathway and inflammatory response in rats.
Phylogenetic Typology
Authors: Jäger Gerhard , Wahle Johannes
Published: July 2021

In this article we propose a novel method to estimate the frequency distribution of linguistic variables while controlling for statistical non-independence due to shared ancestry. Unlike previous approaches, our technique uses all available data, from language families large and small as well as from isolates, while controlling for different degrees of relatedness on a continuous scale estimated from the data. Our approach involves three steps: First, distributions of phylogenies are inferred from lexical data. Second, these phylogenies are used as part of a statistical model to estimate transition rates between parameter states. Finally, the long-term equilibrium of the resulting Markov process is computed. As a case study, we investigate a series of potential word-order correlations across the languages of the world.
The Influencing Mechanism of Interaction Quality of UGC on Consumers’ Purchase Intention – An Empirical Analysis
Authors: Geng Ruoshi , Chen Jun
Published: July 2021

User-generated content (UGC) refers to online information created and shared by consumers that can influence other users’ purchase decisions. Due to the rapid development of new technologies in business, marketers’ dependency on UGC is rising. This study aims to explain how the interaction quality of UGC affects its credibility as a source and the usefulness of its information, as well as how it influences consumers’ online purchase intention. In addition, we examine the moderating effect of product involvement. We collected data from 272 users of social media in China to conduct empirical research. The SPSS and Amos were used to analyze the data and test the hypotheses. The results reveal that UGC interaction quality is positively related to purchase intention, and this relationship is mediated by perceived usefulness and trust. Further, consumers’ product involvement negatively moderates the effect of perceived usefulness and trust on purchase intention. Findings from this study are expected to extend the literature on UGC and give benefits to marketers and online business operators.
Psychological Distress, Somatic Complaints, and Their Relation to Negative Psychosocial Factors in a Sample of Swedish High School Students
Authors: Kerekes Nóra , Zouini Btissame , Tingberg Sofia , Erlandsson Soly
Published: July 2021

Background: Adolescence is a period in life characterized by major neurobiological, physiological, and psychological changes. Those changes may give rise to worsened mental health and an increased prevalence of somatic complaints combined with a negative psychosocial environment. Rapid changes in society, which may also affect young people in several ways, call for a renewed screening of today's adolescents' mental and somatic well-being.

Aim: The present study's primary aim was to measure the level of self-rated psychological distress and the prevalence of somatic complaints in a sample of Swedish high school students. As a secondary aim, it identifies gender-specific patterns and examines mental and somatic health in relation to negative psychosocial factors (such as parental alcohol use problems or the experience of physical or psychological abuse).

Method: Two hundred and eighty-seven Swedish high school students completed a survey including the Brief Symptom Inventory (BSI) and a questionnaire about the presence of defined somatic complaints. In order to examine the relationship between negative psychosocial factors and mental and somatic health, three groups were formed: those reporting (i) parental substance use problems, (ii) previous experience of abuse, (iii) none of these problems.

Results: The majority of the Swedish high-school students (>80%) reported no or only a few problems with psychological distress and no or only one somatic complaint. Female students disclosed a significantly higher psychological distress level captured by each BSI domain. The number of somatic complaints was similarly distributed between the genders. The students rarely reported parental substance use problems, but almost 40% of the male and 50% of the female students indicated the experience of physical and/or psychological abuse. Such negative psychosocial circumstances were related to an increased level of anxiety in the male and an increased general level of psychological distress in female students.

Conclusions: The study confirmed female students' higher psychological distress level. Gender differences in the type of somatic complaints, but not in the number were detected. The experience of physical and/or psychological abuse was found to significantly worsen psychological distress in students of both genders.
Impact of the COVID-19 Pandemic on the Lifestyles and Quality of Life of Women With Fertility Problems: A Cross-Sectional Study
Authors: Biviá-Roig Gemma , Boldó-Roda Ana , Blasco-Sanz Ruth , Serrano-Raya Lola , DelaFuente-Díez Elena , Múzquiz-Barberá Pedro , Lisón Juan Francisco
Published: July 2021

Background: The COVID-19 pandemic has implied worldwide the imposition of confinement measures and mobility restrictions, to a greater or lesser extent. It has also meant the closure of some public medical services such as reproductive care. This situation may have impacted the health-related behaviour and quality of life of women with fertility problems.

Objective: The objective of this study was to analyse the effects of confinement and the suspension of reproductive medical care on the lifestyle (diet, physical exercise, and smoking habits), anxiety and depression, and quality of life of infertile women by comparing their pre- and post-confinement situations.

Methods: We carried out a cross-sectional, internet-based study. Information was collected on these women's adherence to the Mediterranean diet (MEDAS questionnaire), physical exercise (IPAQ-SF), anxiety and depression (HADS), and quality of life related to fertility (FertiQol) before, during, and after confinement. The survey was conducted between 1 September and 28 October 2020.

Results: A total of 85 women participated. There had been a significant increase in anxiety and depression levels (P < 0.001) and an increase in tobacco consumption among female smokers during confinement vs. pre-confinement (62.5% had increased their consumption). The participants had also increased the mean number of hours they spent sitting (P < 0.001). There had also been an increase in vigorous and moderate exercise levels by 40 and 30%, respectively (P = 0.004). However, no differences were observed in these patients' eating habits as a result of confinement (P = 0.416). When the reproduction service was resumed, the participants showed higher anxiety level scores (P = 0.001) with respect to the pre-confinement situation as well as lower mean FertiQol scale score (P = 0.008).

Conclusions: Confinement had increased anxiety and depression levels among these infertile women as well as tobacco use among the participants who were smokers. The prolonged closure of reproductive care units decreased the quality of life of the participants of this study. These results suggest the need to implement online programs to improve healthy habits and quality of life of this population group.
Information and Empowerment of Families of Children With Cerebral Palsy in Brazil: The Knowledge Translation Role of Nossa Casa Institute
Authors: Airoldi Marina J. , Vieira Beatriz S. , Teplicky Rachel , Chalfun Deborah , Bonfim Rafael G. A. S. , Mancini Marisa C. , Rosenbaum Peter , Brandão Marina B.
Published: July 2021

Knowledge translation (KT) is gaining attention in the pediatric rehabilitation field. Nossa Casa Institute is the first organization in Brazil aiming to foster cerebral palsy (CP) awareness and empower families by discussing reliable information. This study aims to build a network where individuals with CP and their families, researchers, health care professionals, and services can communicate and share experiences. In this article, we describe the experience of planning and conducting an educational and interactive online workshop to foster principles of family-centered service (FCS). We used the action cycle from the Knowledge to Action (KTA) framework to describe and ground the proposed activities. In Module 1, “Challenges and barriers to incorporate family-centered principles,” we discussed the historical perspective, main principles, and challenges related to FCS implementation. Module 2, “What is my contribution to the family-centered service?” was aimed to foster strategies to improve the implementation of principles of FCS in the care of children with disabilities. In Module 3, “What can we do together?” the groups presented their ideas and suggestions. This interactive and educational workshop was an opportunity for Nossa Casa Institute to disseminate accessible and reliable information regarding FCS and to empower families to participate actively in the rehabilitation process and advocate for the best provision of care for their children. Future actions of Nossa Casa Institute include the coordination of a national conference to connect families, individuals with CP, healthcare and rehabilitation professionals, and researchers. There is also a need, and opportunity, for formal evaluation of these KT activities.
Compositional RL Agents That Follow Language Commands in Temporal Logic
Authors: Kuo Yen-Ling , Katz Boris , Barbu Andrei
Published: July 2021

We demonstrate how a reinforcement learning agent can use compositional recurrent neural networks to learn to carry out commands specified in linear temporal logic (LTL). Our approach takes as input an LTL formula, structures a deep network according to the parse of the formula, and determines satisfying actions. This compositional structure of the network enables zero-shot generalization to significantly more complex unseen formulas. We demonstrate this ability in multiple problem domains with both discrete and continuous state-action spaces. In a symbolic domain, the agent finds a sequence of letters that satisfy a specification. In a Minecraft-like environment, the agent finds a sequence of actions that conform to a formula. In the Fetch environment, the robot finds a sequence of arm configurations that move blocks on a table to fulfill the commands. While most prior work can learn to execute one formula reliably, we develop a novel form of multi-task learning for RL agents that allows them to learn from a diverse set of tasks and generalize to a new set of diverse tasks without any additional training. The compositional structures presented here are not specific to LTL, thus opening the path to RL agents that perform zero-shot generalization in other compositional domains.
Reinforcement Learning and Control of a Lower Extremity Exoskeleton for Squat Assistance
Authors: Luo Shuzhen , Androwis Ghaith , Adamovich Sergei , Su Hao , Nunez Erick , Zhou Xianlian
Published: July 2021

A significant challenge for the control of a robotic lower extremity rehabilitation exoskeleton is to ensure stability and robustness during programmed tasks or motions, which is crucial for the safety of the mobility-impaired user. Due to various levels of the user’s disability, the human-exoskeleton interaction forces and external perturbations are unpredictable and could vary substantially and cause conventional motion controllers to behave unreliably or the robot to fall down. In this work, we propose a new, reinforcement learning-based, motion controller for a lower extremity rehabilitation exoskeleton, aiming to perform collaborative squatting exercises with efficiency, stability, and strong robustness. Unlike most existing rehabilitation exoskeletons, our exoskeleton has ankle actuation on both sagittal and front planes and is equipped with multiple foot force sensors to estimate center of pressure (CoP), an important indicator of system balance. This proposed motion controller takes advantage of the CoP information by incorporating it in the state input of the control policy network and adding it to the reward during the learning to maintain a well balanced system state during motions. In addition, we use dynamics randomization and adversary force perturbations including large human interaction forces during the training to further improve control robustness. To evaluate the effectiveness of the learning controller, we conduct numerical experiments with different settings to demonstrate its remarkable ability on controlling the exoskeleton to repetitively perform well balanced and robust squatting motions under strong perturbations and realistic human interaction forces.