bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditory Cortical Changes Precede Brainstem Changes During Rapid Implicit Learning: Evidence From Human EEG
Authors: Skoe Erika , Krizman Jennifer , Spitzer Emily R. , Kraus Nina
Published: August 2021

The auditory system is sensitive to stimulus regularities such as frequently occurring sounds and sound combinations. Evidence of regularity detection can be seen in how neurons across the auditory network, from brainstem to cortex, respond to the statistical properties of the soundscape, and in the rapid learning of recurring patterns in their environment by children and adults. Although rapid auditory learning is presumed to involve functional changes to the auditory network, the chronology and directionality of changes are not well understood. To study the mechanisms by which this learning occurs, auditory brainstem and cortical activity was simultaneously recorded via electroencephalogram (EEG) while young adults listened to novel sound streams containing recurring patterns. Neurophysiological responses were compared between easier and harder learning conditions. Collectively, the behavioral and neurophysiological findings suggest that cortical and subcortical structures each provide distinct contributions to auditory pattern learning, but that cortical sensitivity to stimulus patterns likely precedes subcortical sensitivity.
Revealing Sex Differences During Upper and Lower Extremity Neuromuscular Fatigue in Older Adults Through a Neuroergonomics Approach
Authors: Mehta Ranjana K. , Rhee Joohyun
Published: August 2021

Background: Sex differences in neuromuscular fatigue is well-documented, however the underlying mechanisms remain understudied, particularly for the aging population.

Objective: This study investigated sex differences in fatigability of the upper and lower extremity of older adults using a neuroergonomics approach.

Methods: Thirty community-dwelling older adults (65 years or older; 15 M, 15 F) performed intermittent submaximal fatiguing handgrip and knee extension exercises until voluntary exhaustion on separate days. Muscle activity from prime muscles of the hand/arm and knee extensors were monitored using electromyography, neural activity from the frontal, motor, and sensory areas were monitored using functional near infrared spectroscopy, and force output were obtained.

Results: While older males were stronger than females across both muscle groups, they exhibited longer endurance times and greater strength loss during knee extension exercises. These lower extremity findings were associated with greater force complexity over time and concomitant increase in left motor and right sensory motor regions. While fatigability during handgrip exercises was comparable across sexes, older females exhibited concurrent increases in the activation of the ipsilateral motor regions over time.

Discussion: We identified differences in the underlying central neural strategies adopted by males and females in maintaining downstream motor outputs during handgrip fatigue that were not evident with traditional ergonomics measures. Additionally, enhanced neural activation in males during knee exercises that accompanied longer time to exhaustion point to potential rehabilitation/exercise strategies to improve neuromotor outcomes in more fatigable older adults.
Graphene-Induced Hyperthermia (GIHT) Combined With Radiotherapy Fosters Immunogenic Cell Death
Authors: Podolska Malgorzata J. , Shan Xiaomei , Janko Christina , Boukherroub Rabah , Gaipl Udo S. , Szunerits Sabine , Frey Benjamin , Muñoz Luis E.
Published: August 2021

Radiotherapy and chemotherapy are the standard interventions for cancer patients, although cancer cells often develop radio- and/or chemoresistance. Hyperthermia reduces tumor resistance and induces immune responses resulting in a better prognosis. We have previously described a method to induce tumor cell death by local hyperthermia employing pegylated reduced graphene oxide nanosheets and near infrared light (graphene-induced hyperthermia, GIHT). The spatiotemporal exposure/release of heat shock proteins (HSP), high group mobility box 1 protein (HMGB1), and adenosine triphosphate (ATP) are reported key inducers of immunogenic cell death (ICD). We hypothesize that GIHT decisively contributes to induce ICD in irradiated melanoma B16F10 cells, especially in combination with radiotherapy. Therefore, we investigated the immunogenicity of GIHT alone or in combination with radiotherapy in melanoma B16F10 cells. Tumor cell death in vitro revealed features of apoptosis that is progressing fast into secondary necrosis. Both HSP70 and HMGB1/DNA complexes were detected 18 hours post GIHT treatment, whereas the simultaneous release of ATP and HMGB1/DNA was observed only 24 hours post combined treatment. We further confirmed the adjuvant potential of these released DAMPs by immunization/challenge experiments. The inoculation of supernatants of cells exposed to sole GIHT resulted in tumor growth at the site of inoculation. The immunization with cells exposed to sole radiotherapy rather fostered the growth of secondary tumors in vivo. Contrarily, a discreet reduction of secondary tumor volumes was observed in mice immunized with a single dose of cells and supernatants treated with the combination of GIHT and irradiation. We propose the simultaneous release of several DAMPs as a potential mechanism fostering anti-tumor immunity against previously irradiated cancer cells.
Epigenetic Inactivation of Acetyl-CoA Acetyltransferase 1 Promotes the Proliferation and Metastasis in Nasopharyngeal Carcinoma by Blocking Ketogenesis
Authors: Lu Yunliang , Zhou Xiaohui , Zhao Weilin , Liao Zhipeng , Li Bo , Han Peipei , Yang Yanping , Zhong Xuemin , Mo Yingxi , Li Ping , Huang Guangwu , Xiao Xue , Zhang Zhe , Zhou Xiaoying
Published: August 2021

The dysregulation of epigenetic modification and energy metabolism cooperatively contribute to the tumorigenesis of nasopharyngeal carcinoma (NPC). However, the detailed mechanisms underlying their joint contribution to NPC development and progression remain unclear. Here, we investigate the role of Acy1 Coenzyme A Acyltransferases1 (ACAT1), a key enzyme in the metabolic pathway of ketone bodies, in the proliferation and metastasis of NPC and to elucidate the underlying molecular mechanisms. Ketogenesis, plays a critical role in tumorigenesis. Previously, we reported two enzymes involved in ketone body metabolism mediate epigenetic silencing and act as tumor suppressor genes in NPC. Here, we identify another key enzyme, Acetyl-CoA acetyltransferase 1 (ACAT1), and show that its transcriptional inactivation in NPC is due to promoter hypermethylation. Ectopic overexpression of ACAT1 significantly suppressed the proliferation and colony formation of NPC cells in vitro. The migratory and invasive capacity of NPC cells was inhibited by ACAT1. The tumorigenesis of NPC cells overexpressing ACAT1 was decreased in vivo. Elevated ACAT1 in NPC cells was accompanied by an elevated expression of CDH1 and a reduced expression of vimentin and SPARC, strongly indicating that ACAT1 is involved in regulating epithelial-mesenchymal transition (EMT). We also found that ACAT1 contributes to increased intracellular levels of β-hydroxybutyrate (β-HB). Exogenously supplied β-HB significantly inhibits the growth of NPC cells in a dose-dependent manner. In summary, ACAT1 may function as a tumor suppressor via modulation of ketogenesis and could thus serve as a potential therapeutic target in NPC. In summary, our data suggest that regulation of ketogenesis may serve as adjuvant therapy in NPC.
Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting
Authors: Pappalardo Annalisa , Giunta Emilio Francesco , Tirino Giuseppe , Pompella Luca , Federico Piera , Daniele Bruno , De Vita Ferdinando , Petrillo Angelica
Published: August 2021

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes.
Radiomic Score as a Potential Imaging Biomarker for Predicting Survival in Patients With Cervical Cancer
Authors: Li Handong , Zhu Miaochen , Jian Lian , Bi Feng , Zhang Xiaoye , Fang Chao , Wang Ying , Wang Jing , Wu Nayiyuan , Yu Xiaoping
Published: August 2021

Objectives

Accurate prediction of prognosis will help adjust or optimize the treatment of cervical cancer and benefit the patients. We aimed to investigate the incremental value of radiomics when added to the FIGO stage in predicting overall survival (OS) in patients with cervical cancer.

Methods

This retrospective study included 106 patients with cervical cancer (FIGO stage IB1–IVa) between October 2017 and May 2019. Patients were randomly divided into a training cohort (n = 74) and validation cohort (n = 32). All patients underwent contrast-enhanced computed tomography (CT) prior to treatment. The ITK-SNAP software was used to delineate the region of interest on pre-treatment standard-of-care CT scans. We extracted 792 two-dimensional radiomic features by the Analysis Kit (AK) software. Pearson correlation coefficient analysis and Relief were used to detect the most discriminatory features. The radiomic signature (i.e., Radscore) was constructed via Adaboost with Leave-one-out cross-validation. Prognostic models were built by Cox regression model using Akaike information criterion (AIC) as the stopping rule. A nomogram was established to individually predict the OS of patients. Patients were then stratified into high- and low-risk groups according to the Youden index. Kaplan–Meier curves were used to compare the survival difference between the high- and low-risk groups.

Results

Six textural features were identified, including one gray-level co-occurrence matrix feature and five gray-level run-length matrix features. Only the FIGO stage and Radscore were independent risk factors associated with OS (p < 0.05). The C-index of the FIGO stage in the training and validation cohorts was 0.703 (95% CI: 0.572–0.834) and 0.700 (95% CI: 0.526–0.874), respectively. Correspondingly, the C-index of Radscore was 0.794 (95% CI: 0.707–0.880) and 0.754 (95% CI: 0.623–0.885). The incorporation of the FIGO stage and Radscore achieved better performance, with a C-index of 0.830 (95% CI: 0.738–0.922) and 0.772 (95% CI: 0.615–0.929), respectively. The nomogram based on the FIGO stage and Radscore could individually predict the OS probability with good discrimination and calibration. The high-risk patients had shorter OS compared with the low-risk patients (p < 0.05).

Conclusion

Radiomics has the potential for noninvasive risk stratification and may improve the prediction of OS in patients with cervical cancer when added to the FIGO stage.
Glycosylation in Cervical Cancer: New Insights and Clinical Implications
Authors: Xu Zhiwei , Zhang Yaqin , Ocansey Dickson K. W. , Wang Bo , Mao Fei
Published: August 2021

Cervical cancer has become the most frequent female malignancy and presents as a general health challenge in many countries undergoing economic development. Various human papillomaviruses (HPV) types have appeared as one of the most critically identifiable causes of widespread cervical cancers. Conventional cervical cytological inspection has limitations of variable sensitivity according to cervical cytology. Glycobiology has been fundamental in related exploration in various gynecologic and reproductive fields and has contributed to our understanding of cervical cancer. It is associated with altered expression of N-linked glycan as well as abnormal expression of terminal glycan structures. The analytical approaches available to determine serum and tissue glycosylation, as well as potential underlying molecular mechanisms involved in the cellular glycosylation alterations, are monitored. Moreover, cellular glycosylation influences various aspects of cervical cancer biology, ranging from cell surface expressions, cell-cell adhesion, cancer signaling, cancer diagnosis, and management. In general, discoveries in glycan profiling make it technically reproducible and affordable to perform serum glycoproteomic analyses and build on previous work exploring an expanded variety of glycosylation markers in the majority of cervical cancer patients.
Nasal High-Frequency Oscillatory Ventilation vs. Nasal Continuous Positive Airway Pressure as Therapy for Postextubation Respiratory Failure in Infants After Congenital Heart Surgery
Authors: Wu Hong-Lin , Lei Yu-Qing , Xie Wen-Peng , Chen Qiang , Zheng Yi-Rong
Published: August 2021

Objective: This study aimed to evaluate the effects of nasal high-frequency oscillatory ventilation (NHFOV) vs. nasal continuous positive airway pressure (NCPAP) on postextubation respiratory failure (PRF) in infants after congenital heart surgery (CHS).

Method: Eighty infants underwent postoperative invasive mechanical ventilation for more than 12 h and planned extubation. The infants were randomized to undergo either NHFOV or NCPAP after extubation. Primary outcomes were the incidence of PRF and reintubation, the average PaCO2 level, the average oxygenation index (OI), and pulmonary recruitment in the early extubation phase. Secondary outcomes included the NCPAP/NHFOV time, length of hospital stay, treatment intolerance, signs of discomfort, pneumothorax, adverse hemodynamic effects, nasal trauma, and mortality.

Results: Except for PaCO2 within 12 after extubation (39.3 ± 5.8 vs. 43.6 ± 7.3 mmHg, p = 0.05), there was no statistically significant difference for any of the primary outcome measure (PRF, reintubation within 12 h after extubation, oxygenation index within 12 h after extubation, or lung volumes on X-ray after extubation) or secondary outcome measures (duration of non-invasive ventilation, duration of hospital stay, ventilation intolerance, signs of discomfort, pneumothorax, nasal trauma, adverse hemodynamic effects, or death prior to discharge), p > 0.1 for each comparison.

Conclusion: NHFOV therapy after extubation in infants after CHS was more efficient in improving CO2 cleaning than NCPAP therapy, but there was no difference in other outcomes (PRF, reintubation, oxygenation index, and pulmonary recruitment).
Prediction of Past SARS-CoV-2 Infections: A Prospective Cohort Study Among Swiss Schoolchildren
Authors: Blankenberger Jacob , Haile Sarah R. , Puhan Milo A. , Berger Christoph , Radtke Thomas , Kriemler Susi , Ulyte Agne
Published: August 2021

Objective: To assess the predictive value of symptoms, sociodemographic characteristics, and SARS-CoV-2 exposure in household, school, and community setting for SARS-CoV-2 seropositivity in Swiss schoolchildren at two time points in 2020.

Design: Serological testing of children in primary and secondary schools (aged 6–13 and 12–16 years, respectively) took place in June–July (T1) and October–November (T2) 2020, as part of the longitudinal, school-based study Ciao Corona in the canton of Zurich, Switzerland. Information on sociodemographic characteristics and clinical history was collected with questionnaires to parents; information on school-level SARS-CoV-2 infections was collected with questionnaires to school principals. Community-level cumulative incidence was obtained from official statistics. We used logistic regression to identify individual predictors of seropositivity and assessed the predictive performance of symptom- and exposure-based prediction models.

Results: A total of 2,496 children (74 seropositive) at T1 and 2,152 children (109 seropositive) at T2 were included. Except for anosmia (odds ratio 15.4, 95% confidence interval [3.4–70.7]) and headache (2.0 [1.03–3.9]) at T2, none of the individual symptoms were significantly predictive of seropositivity at either time point. Of all the exposure variables, a reported SARS-CoV-2 case in the household was the strongest predictor for seropositivity at T1 (12.4 [5.8–26.7]) and T2 (10.8 [4.5–25.8]). At both time points, area under the receiver operating characteristic curve was greater for exposure-based (T1, 0.69; T2, 0.64) than symptom-based prediction models (T1, 0.59; T2, 0.57).

Conclusions: In children, retrospective identification of past SARS-CoV-2 infections based on symptoms is imprecise. SARS-CoV-2 seropositivity is better predicted by factors of SARS-CoV-2 exposure, especially reported SARS-CoV-2 cases in the household. Predicting SARS-CoV-2 seropositivity in children in general is challenging, as few reliable predictors could be identified. For an accurate retrospective identification of SARS-CoV-2 infections in children, serological tests are likely indispensable.

Trial registration number: NCT04448717.
A Systematic Study of the Mechanism of Acacetin Against Sepsis Based on Network Pharmacology and Experimental Validation
Authors: Ouyang Yuanshuo , Rong Yi , Wang Yanming , Guo Yanli , Shan Liya , Yu Xiushi , Li Li , Si Junqiang , Li Xinzhi , Ma Ketao
Published: August 2021

Sepsis is a dysregulated systemic response to infection, and no effective treatment options are available. Acacetin is a natural flavonoid found in various plants, including Sparganii rhizoma, Sargentodoxa cuneata and Patrinia scabiosifolia. Studies have revealed that acacetin potentially exerts anti-inflammatory and antioxidative effects on sepsis. In this study, we investigated the potential protective effect of acacetin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation and molecular docking. First, we found that acacetin significantly suppressed pathological damage and pro-inflammatory cytokine expression in mice with LPS-induced fulminant hepatic failure and acute lung injury, and in vitro experiments further confirmed that acacetin attenuated LPS-induced M1 polarization. Then, network pharmacology screening revealed EGFR, PTGS2, SRC and ESR1 as the top four overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 20 enriched biological processes and signalling pathways associated with the therapeutic effects of acacetin on sepsis. Further network pharmacological analysis indicated that gap junctions may be highly involved in the protective effects of acacetin on sepsis. Finally, molecular docking verified that acacetin bound to the active sites of the four targets predicted by network pharmacology, and in vitro experiments further confirmed that acacetin significantly inhibited the upregulation of p-src induced by LPS and attenuated LPS-induced M1 polarization through gap junctions. Taken together, our results indicate that acacetin may protect against sepsis via a mechanism involving multiple targets and pathways and that gap junctions may be highly involved in this process.
Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway
Authors: Zhang Xi , Chang Aie , Zou Yanqiang , Xu Heng , Cui Jikai , Chen Zhang , Li Yuan , Du Yifan , Wu Jie , Yu Jizhang , Du Xinling
Published: August 2021

Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. However, the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection.

Methods: The model of MHC-mismatched (BALB/c to B6 mice) heterotopic heart transplantation was established and administered intraperitoneal injection with aspirin. The severity of allograft rejection, transcriptional levels of cytokines, and characteristics of immune cells were assessed. Bone marrow-derived dendritic cells (BMDCs) were generated with or without aspirin. The function of DCs was determined via mixed lymphocyte reaction (MLR). The signaling pathway of DCs was detected by Western blotting.

Results: Aspirin significantly prolonged the survival of cardiac allograft in mouse, inhibited the production of pro-inflammatory cytokines and the differentiation of effector T cells (Th1 and Th17), as well as promoted the regulatory T cells (Treg). The maturation of DCs in the spleen was obviously suppressed with aspirin treatment. In vitro, aspirin decreased the activation of NF-κB signaling of DCs, as well as impeded MHCII and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs. Moreover, both the pro-inflammatory cytokines and function of DCs were suppressed by aspirin.

Conclusion: Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection.
Short-and Long-Term Expression of Vegf: A Temporal Regulation of a Key Factor in Diabetic Retinopathy
Authors: Bucolo Claudio , Barbieri Annalisa , Viganò Ilaria , Marchesi Nicoletta , Bandello Francesco , Drago Filippo , Govoni Stefano , Zerbini Gianpaolo , Pascale Alessia
Published: August 2021

To investigate the role of vascular endothelial growth factor (VEGF) at different phases of diabetic retinopathy (DR), we assessed the retinal protein expression of VEGF-A164 (corresponding to the VEGF165 isoform present in humans, which is the predominant member implicated in vascular hyperpermeability and proliferation), HIF-1α and PKCβ/HuR pathway in Ins2Akita (diabetic) mice at different ages. We used C57BL6J mice (WT) at different ages as control. Retina status, in terms of tissue morphology and neovascularization, was monitored in vivo at different time points by optical coherence tomography (OCT) and fluorescein angiography (FA), respectively. The results showed that VEGF-A164 protein expression increased along time to become significantly elevated (p < 0.05) at 9 and 46 weeks of age compared to WT mice. The HIF-1α protein level was significantly (p < 0.05) increased at 9 weeks of age, while PKCβII and HuR protein levels were increased at 46 weeks of age compared to WT mice. The thickness of retinal nerve fiber layer as measured by OCT was decreased in Ins2Akita mice at 9 and 46 weeks of age, while no difference in the retinal vasculature were observed by FA. The present findings show that the retina of the diabetic Ins2Akita mice, as expected for mice, does not develop proliferative retinopathy even after 46 weeks. However, diabetic Ins2Akita mice recapitulate the same evolution of patients with DR in terms of both retinal neurodegeneration and pro-angiogenic shift, this latter indicated by the progressive protein expression of the pro-angiogenic isoform VEGF-A164, which can be sustained by the PKCβII/HuR pathway acting at post-transcriptional level. In agreement with this last concept, this rise in VEGF-A164 protein is not paralleled by an increment of the corresponding transcript. Nevertheless, the observed increase in HIF-1α at 9 weeks indicates that this transcription factor may favor, in the early phase of the disease, the transcription of other isoforms, possibly neuroprotective, in the attempt to counteract the neurodegenerative effects of VEGF-A164. The time-dependent VEGF-A164 expression in the retina of diabetic Ins2Akita mice suggests that pharmacological intervention in DR might be chosen, among other reasons, on the basis of the specific stages of the pathology in order to pursue the best clinical outcome.
Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis
Authors: Li Shan-Shan , Sun Qian , Hua Meng-Ru , Suo Ping , Chen Jia-Rong , Yu Xiao-Yong , Zhao Ying-Yong
Published: August 2021

The Wnt/β-catenin signaling pathway plays important roles in embryonic development and tissue homeostasis. Wnt signaling is induced, and β-catenin is activated, associated with the development and progression of renal fibrosis. Wnt/β-catenin controls the expression of various downstream mediators such as snail1, twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1, transient receptor potential canonical 6, and renin-angiotensin system components in epithelial cells, fibroblast, and macrophages. In addition, Wnt/β-catenin is usually intertwined with other signaling pathways to promote renal interstitial fibrosis. Actually, given the crucial of Wnt/β-catenin signaling in renal fibrogenesis, blocking this signaling may benefit renal interstitial fibrosis. There are several antagonists of Wnt signaling that negatively control Wnt activation, and these include soluble Fzd-related proteins, the family of Dickkopf 1 proteins, Klotho and Wnt inhibitory factor-1. Furthermore, numerous emerging small-molecule β-catenin inhibitors cannot be ignored to prevent and treat renal fibrosis. Moreover, we reviewed the knowledge focusing on anti-fibrotic effects of natural products commonly used in kidney disease by inhibiting the Wnt/β-catenin signaling pathway. Therefore, in this review, we summarize recent advances in the regulation, downstream targets, role, and mechanisms of Wnt/β-catenin signaling in renal fibrosis pathogenesis. We also discuss the therapeutic potential of targeting this pathway to treat renal fibrosis; this may shed new insights into effective treatment strategies to prevent and treat renal fibrosis.
Dantrolene Prevents the Lymphostasis Caused by Doxorubicin in the Rat Mesenteric Circulation
Authors: Van Serena , Pal Soumiya , Garner Brittney R. , Steed Kate , Sridharan Vijayalakshmi , Mu Shengyu , Rusch Nancy J. , Stolarz Amanda J.
Published: August 2021

Background and Purpose: Doxorubicin (DOX) is a risk factor for arm lymphedema in breast cancer patients. We reported that DOX opens ryanodine receptors (RYRs) to enact “calcium leak,” which disrupts the rhythmic contractions of lymph vessels (LVs) to attenuate lymph flow. Here, we evaluated whether dantrolene, a clinically available RYR1 subtype antagonist, prevents the detrimental effects of DOX on lymphatic function.

Experimental Approach: Isolated rat mesenteric LVs were cannulated, pressurized (4–5 mm Hg) and equilibrated in physiological salt solution and Fura-2AM. Video microscopy recorded changes in diameter and Fura-2AM fluorescence tracked cytosolic free calcium ([Ca2+i]). High-speed in vivo microscopy assessed mesenteric lymph flow in anesthetized rats. Flow cytometry evaluated RYR1 expression in freshly isolated mesenteric lymphatic muscle cells (LMCs).

Key Results: DOX (10 μmol/L) increased resting [Ca2+i] by 17.5 ± 3.7% in isolated LVs (n = 11). The rise in [Ca2+i] was prevented by dantrolene (3 μmol/L; n = 10). A single rapid infusion of DOX (10 mg/kg i.v.) reduced positive volumetric lymph flow to 29.7 ± 10.8% (n = 7) of baseline in mesenteric LVs in vivo. In contrast, flow in LVs superfused with dantrolene (10 μmol/L) only decreased to 76.3 ± 14.0% (n = 7) of baseline in response to DOX infusion. Subsequently, expression of the RYR1 subtype protein as the presumed dantrolene binding site was confirm in isolated mesenteric LMCs by flow cytometry.

Conclusion and Implications: We conclude that dantrolene attenuates the acute impairment of lymph flow by DOX and suggest that its prophylactic use in patients subjected to DOX chemotherapy may lower lymphedema risk.
Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study
Authors: Armentaro Giuseppe , D’Arrigo Graziella , Magurno Marcello , Toscani Alfredo F. , Condoleo Valentino , Miceli Sofia , Cassano Velia , Maio Raffaele , Arturi Franco , Tripepi Giovanni , Sesti Giorgio , Sciacqua Angela
Published: August 2021

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) <35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e’ ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.
Research on Image Defect Detection of Silicon Panel Based on Prewitt and Canny Operator
Authors: Zhang Yifeng , Wang Zhiwen , Wang Yuhang , Zhang Canlong , Zhao Biao
Published: August 2021

The silicon panel is the core component of photovoltaic power generation, whose surface quality is related to its service life and power generation efficiency. However, microcracks, fragments, incomplete welding, broken grids, and other defects often occur in industrial production. The edge detection algorithm is usually used to detect defects in silicon panels, but the common edge detection algorithm has an impact on defect detection because of the grid shadow of the panel. The current mainstream defect detection algorithm based on convolutional neural network requires a large number of positive and negative samples of image data sets for pretraining the model, which consumes a lot of time and GPU computing power, and the steps are cumbersome. To solve the problem, a defect detection method based on Prewitt and Canny operators is proposed in this article. In this method, Prewitt and Canny operators are combined to eliminate the effect of grids on the detection. The microcrack defects and their specific positions can be detected efficiently and intuitively, therefore improving the detection accuracy. The experimental results indicate that the purity and integrity of the defect profile of the image processed by the algorithm are greatly improved. The foreground edge is clear, and the defect recognition accuracy is higher, which effectively prevent the impact of grid shadow on weld testing.
Impaired Cuticle Functionality and Robust Resistance to Botrytis cinerea in Arabidopsis thaliana Plants With Altered Homogalacturonan Integrity Are Dependent on the Class III Peroxidase AtPRX71
Authors: Lorrai Riccardo , Francocci Fedra , Gully Kay , Martens Helle J. , De Lorenzo Giulia , Nawrath Christiane , Ferrari Simone
Published: August 2021

Pectin is a major cell wall component that plays important roles in plant development and response to environmental stresses. Arabidopsis thaliana plants expressing a fungal polygalacturonase (PG plants) that degrades homogalacturonan (HG), a major pectin component, as well as loss-of-function mutants for QUASIMODO2 (QUA2), encoding a putative pectin methyltransferase important for HG biosynthesis, show accumulation of reactive oxygen species (ROS), reduced growth and almost complete resistance to the fungal pathogen Botrytis cinerea. Both PG and qua2 plants show increased expression of the class III peroxidase AtPRX71 that contributes to their elevated ROS levels and reduced growth. In this work, we show that leaves of PG and qua2 plants display greatly increased cuticle permeability. Both increased cuticle permeability and resistance to B. cinerea in qua2 are suppressed by loss of AtPRX71. Increased cuticle permeability in qua2, rather than on defects in cuticle ultrastructure or cutin composition, appears to be dependent on reduced epidermal cell adhesion, which is exacerbated by AtPRX71, and is suppressed by the esmeralda1 mutation, which also reverts the adhesion defect and the resistant phenotype. Increased cuticle permeability, accumulation of ROS, and resistance to B. cinerea are also observed in mutants lacking a functional FERONIA, a receptor-like kinase thought to monitor pectin integrity. In contrast, mutants with defects in other structural components of primary cell wall do not have a defective cuticle and are normally susceptible to the fungus. Our results suggest that disrupted cuticle integrity, mediated by peroxidase-dependent ROS accumulation, plays a major role in the robust resistance to B. cinerea of plants with altered HG integrity.
Characterization of Dynamic Regulatory Gene and Protein Networks in Wheat Roots Upon Perceiving Water Deficit Through Comparative Transcriptomics Survey
Authors: Rahimi Yousef , Ingvarsson Pär K. , Bihamta Mohammad Reza , Alipour Hadi , Taleei Alireza , Khoshnoodi Jabar Abadi Shaghayegh
Published: August 2021

A well-developed root system benefits host plants by optimizing water absorption and nutrient uptake and thereby increases plant productivity. In this study we have characterized the root transcriptome using RNA-seq and subsequential functional analysis in a set of drought tolerant and susceptible genotypes. The goal of the study was to elucidate and characterize water deficit-responsive genes in wheat landraces that had been through long-term field and biochemical screening for drought tolerance. The results confirm genotype differences in water-deficit tolerance in line with earlier results from field trials. The transcriptomics survey highlighted a total of 14,187 differentially expressed genes (DEGs) that responded to water deficit. The characterization of these genes shows that all chromosomes contribute to water-deficit tolerance, but to different degrees, and the B genome showed higher involvement than the A and D genomes. The DEGs were mainly mapped to flavonoid, phenylpropanoid, and diterpenoid biosynthesis pathways, as well as glutathione metabolism and hormone signaling. Furthermore, extracellular region, apoplast, cell periphery, and external encapsulating structure were the main water deficit-responsive cellular components in roots. A total of 1,377 DEGs were also predicted to function as transcription factors (TFs) from different families regulating downstream cascades. TFs from the AP2/ERF-ERF, MYB-related, B3, WRKY, Tify, and NAC families were the main genotype-specific regulatory factors. To further characterize the dynamic biosynthetic pathways, protein-protein interaction (PPI) networks were constructed using significant KEGG proteins and putative TFs. In PPIs, enzymes from the CYP450, TaABA8OH2, PAL, and GST families play important roles in water-deficit tolerance in connection with MYB13-1, MADS-box, and NAC transcription factors.
Psychological Distress in Intracranial Neoplasia: A Comparison of Patients With Benign and Malignant Brain Tumours
Authors: Fehrenbach Michael Karl , Brock Hannah , Mehnert-Theuerkauf Anja , Meixensberger Jürgen
Published: August 2021

Objective: We aimed to assess psychological distress in patients with intracranial neoplasia, a group of patients who suffer from severe functional, neurocognitive and neuropsychological side effects, resulting in high emotional distress.

Methods: We conducted a cross-sectional study, including inpatients with brain tumours. Eligible patients completed validated self-report questionnaires measuring depression, anxiety, distress, symptoms of posttraumatic stress disorder (PTSD), fear of progression and health-related quality of life. The questionnaire set was completed after brain surgery and receiving diagnosis and before discharge from hospital.

Results: A total of n = 31 patients participated in this survey. Fourteen of them suffered from malignant (n = 3 metastatic neoplasia) and 17 from benign brain tumours. Mean values of the total sample regarding depression (M = 9.28, SD = 6.08) and anxiety (M = 6.00, SD = 4.98) remained below the cut-off ≥ 10. Mean psychosocial distress (M = 16.30, SD = 11.23, cut-off ≥ 14) and posttraumatic stress (M = 35.10, SD = 13.29, cut-off ≥ 32) exceeded the clinically relevant cut-off value in all the patients with intracranial tumours. Significantly, more patients with malignant (79%) than benign (29%) brain tumours reported PTSD symptoms (p = 0.006).

Conclusion: Distress and clinically relevant PTSD symptoms in patients with intracranial neoplasia should be routinely screened and treated in psycho-oncological interventions immediately after diagnosis. Especially, neuro-oncological patients with malignant brain tumours or metastases need targeted support to reduce their emotional burden.
The Influence of COVID-19 Pandemic on Physical Health–Psychological Health, Physical Activity, and Overall Well-Being: The Mediating Role of Emotional Regulation
Authors: Dai Jianhui , Sang Xuehui , Menhas Rashid , Xu Xia , Khurshid Sumaira , Mahmood Sajid , Weng Yu , Huang Jiaai , Cai Yuwei , Shahzad Babar , Iqbal Waseem , Gul Maryam , Saqib Zulkaif Ahmed , Alam Muhammad Nurul
Published: August 2021

Background: Highly infectious respiratory disease COVID-19 emerged in Wuhan, China, and spread worldwide. Different measures have been adopted worldwide to contain the COVID-19, and these measures have various impacts on health-related quality of life (HRQoL). This study aimed to assess the impact of the COVID-19 pandemic (CP) and lockdown policy on physical health (PH)–psychological health (PsH), physical activity (PA), and overall well-being (OW) in the context of HRQoL, exploring the mediating role of emotional regulation (ER).

Method: The current study was conducted in two provincial cities of China. An online survey was conducted in both the cities to collect the data. After quantifying the data, a total of 2,200 respondents data were analyzed through appropriate statistical techniques.

Results: The study results indicate that CP was found significantly and negatively related to PH (β = −0.157, t = 9.444, p < 0.001). A significant relationship was found between CP and PsH (β = 0.779, t = 45.013, p < 0.001). The third prediction revealed a significant negative relationship between the CP and OW (β = −0.080, t = 5.261, p < 0.001). The CP and PA had a significant negative relationship (β = −0.047, t = 3.351, p < 0.001).

Conclusion: The PH, PsH, and OW of the Chinese people were affected due to the CP and lockdown measures. It is suggested that ER intervention reduces the negative psychological impacts for improving quality of life. ER can function one's sentiments in their social environment effectively for quality of life.
Comparing the Effect of Product-Based Metrics on the Translation Process
Authors: Vanroy Bram , Schaeffer Moritz , Macken Lieve
Published: August 2021

Characteristics of the translation product are often used in translation process research as predictors for cognitive load, and by extension translation difficulty. In the last decade, user-activity information such as eye-tracking data has been increasingly employed as an experimental tool for that purpose. In this paper, we take a similar approach. We look for significant effects that different predictors may have on three different eye-tracking measures: First Fixation Duration (duration of first fixation on a token), Eye-Key Span (duration between first fixation on a token and the first keystroke contributing to its translation), and Total Reading Time on source tokens (sum of fixations on a token). As predictors we make use of a set of established metrics involving (lexico)semantics and word order, while also investigating the effect of more recent ones concerning syntax, semantics or both. Our results show a, particularly late, positive effect of many of the proposed predictors, suggesting that both fine-grained metrics of syntactic phenomena (such as word reordering) as well as coarse-grained ones (encapsulating both syntactic and semantic information) contribute to translation difficulties. The effect on especially late measures may indicate that the linguistic phenomena that our metrics capture (e.g., word reordering) are resolved in later stages during cognitive processing such as problem-solving and revision.
Non-medical Use of Prescription Stimulants Among College Students: Non-oral Routes of Administration, Risk Factors, Motivations, and Pathways
Authors: Butler Stephen F. , Faraone Stephen V. , Rostain Anthony L. , Newcorn Jeffrey H. , Antshel Kevin M. , Robbins Rebekkah S. , Green Jody L.
Published: August 2021

Introduction: Non-medical use (NMU) of prescription stimulant medications is a continuing public health concern. Stimulant medications prescribed for attention-deficit/hyperactivity disorder (ADHD) are widely available on college campuses, and, as a consequence, college students may have multiple opportunities to engage in prescription stimulant NMU. This online self-report survey examined prescription stimulant NMU among college students, including: (1) patterns of non-oral route of administration (ROA); (2) motivations for non-oral ROAs; and (3) retrospectively recalled pathways of initiation.

Method: The survey sample was created from a pool of 3,379 respondents, who were matched to a sampling frame constructed from the 18–26-year-old, college student sample of the 2016 American Community Survey (ACS). About 14% (n = 486) from the overall pool were identified as college students with self-reported prescription stimulant NMU, all of whom completed the survey. The survey covered user characteristics, prescription and illicit substance use, age of first NMU, motivations for NMU, sources of procurement, and ROAs used.

Results: Among 486 students reporting prescription stimulant NMU, 43% had a lifetime diagnosis of ADHD. More than 90% reported polysubstance use, with 55% using illicit substances other than marijuana. Slightly more than 2 in 5 (43.3%) reported using illicit substances prior to prescription stimulant NMU, 24.6% used both at the same age, and 32.0% engaged in NMU of prescription stimulants prior to using illicit substances. Prescription stimulant NMU preceded prescription opioid NMU 45% of the time. More than a quarter of those engaged in prescription stimulant NMU (27.9%) initiated prescription stimulants alone or at the same age as other drugs. Most prescription stimulant NMU was oral, however 23.0% reported any non-oral use: snorting (20.4%), smoking (6.0%)and/or injection (3.5%). Non-oral use was associated with being male, obtaining medication from a dealer, use to get high, and/or a substance use disorder diagnosis.

Conclusions: Prescription stimulant NMU often occurs in the larger context of other substance use among college students. Injection, an under-researched route for prescription stimulants, was associated with male gender, history of substance use and higher likelihood of illicit substance use. Nearly a quarter of college student survey respondents reported use with non-oral routes, which is associated with other high-risk behaviors. Efforts to reduce non-oral prescription stimulant NMU in college students are warranted.
Internalizing Symptom Profiles Among Youth in Foster Care: A Comparison Study
Authors: Moussavi Yasmin , Breivik Kyrre , Wergeland Gro Janne , Haugland Bente Storm Mowatt , Larsen Marit , Lehmann Stine
Published: August 2021

Background:A high prevalence of anxiety and depression is found among youth in foster care. There is limited knowledge on the anxiety and depression symptom profiles of youth in foster care. We examined latent profiles of anxiety and depression symptoms across three unique youth samples and whether youth in foster care were more or less likely to belong to specific symptom profiles than their peers recruited from clinical or general youth populations. We also investigated if these profiles were predicted by sex and age.

Methods:Self-reported anxiety and depression symptoms were assessed by Spence Children's Anxiety Scale and Short Mood and Feelings Questionnaire. Data were pooled from three youth samples (N= 2,005; mean age = 13.9 years, range = 11–18 years) comprising youth in foster care (n= 245), a clinical youth sample (n= 107), and a general population youth sample (n= 1,653). Symptom profiles were identified using latent profile analyses. Multinominal logistic regression was used to predict the latent profile membership.

Results:Three profiles that differed both in symptom level and shape were identified and labeled as low, medium, and high symptom profile. Compared to the general population youth sample, youth in foster care had a higher likelihood of belonging to the high symptom profile, but not the medium symptom profile. Youth from the clinical sample had an increased risk of belonging to the medium and high symptom profiles compared to the youth in foster care and general population youth samples. Across samples, girls yielded a higher likelihood of having a medium or high symptom profile. Increasing age was associated with a higher likelihood of being in the high symptom profile.

Conclusion:Compared to their counterparts in the general population, youth in foster care are at risk of belonging to a class of youth with high symptom levels across subtypes of internalizing symptoms, indicating the importance of systematic and broad assessment of internalizing symptoms among these youth. Knowledge on the symptom profiles of anxiety subtypes and depression increases our understanding of the treatment needs of youth in foster care.
Pictures Library of Smoking Cravings: Development and Verification of Smokers and Non-smokers
Authors: Gu Zhongke , Zheng Hui , Yin Zhifei , Cai Huiting , Li Yongqiang , Zhao Chunchun , Zhai Yujia , Xu Kai , Xue Lian , Xu Xingjun , Shen Ying , Yuan Ti-Fei
Published: August 2021

Background: The cue-induced craving by addiction related materials is commonly employed in addiction research; however, no existing standardized picture database based on the expectation model of craving has been developed. We prepared and validated a Pictures Library of Smoking Cravings (PLSC) in this study.

Methods: We captured pictures 366 smoking and 406 control pictures (matched in content). We selected 109 smoking pictures and 115 control pictures and asked participants to provide ratings of craving, familiarity, valence, and arousal induced in them. Participants were divided into three groups: non-smokers (n = 211), light smokers (n = 504), and heavy smokers (n = 101).

Results: The results showed that smoking pictures evoked a greater craving, familiarity, and arousal than control pictures in smokers (ps < 0.01). In addition, craving caused by smoking pictures was positively associated with the Fagerström test for nicotine dependence score in dependent smokers.

Conclusions: Overall, the contemporary results showed that PLSC is effective and can be used in smoking-related studies.