bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthy Lifestyle Factors, Cancer Family History, and Gastric Cancer Risk: A Population-Based Case-Control Study in China
Authors: Man Jinyu , Ni Yingchun , Yang Xiaorong , Zhang Tongchao , Yuan Ziyu , Chen Hui , Chen Xingdong , Lu Ming , Ye Weimin
Published: December 2021

Background: We aimed to explore the relationship between lifestyle factors, cancer family history, and gastric cancer risk.

Methods: We examined the association between lifestyle factors, cancer family history, and gastric cancer risk based on a population-based case-control study in Taixing, China, with 870 cases and 1928 controls. A lifestyle score was constructed considering body shape, smoking, alcohol drinking, tooth brushing habit, and food storage method. Unconditional logistic regression models were used to calculate odd ratios (ORs) and 95% confidence intervals (CIs).

Results: Compared with participants with a lifestyle score of 0, subjects with a lifestyle score of 1 (OR 0.59, 95%CI 0.43–0.83), 2 (OR 0.42, 95%CI 0.30–0.59), 3 (OR 0.29, 95%CI 0.20–0.41), 4 (OR 0.20, 95%CI 0.13–0.32), or 5 (OR 0.10, 95%CI 0.04–0.22) had a lower risk of gastric cancer (P for trend < 0.001). Overall, 34% of gastric cancer cases (95%CI 27–41%) can be attributed to non-compliance with ≥3 healthy lifestyle. Family history of early-onset cancer is closely related to the occurrence of gastric cancer, with an OR ranging from 1.77 to 3.27. Regardless of family history, a good lifestyle is associated with a reduced risk of gastric cancer, with an OR value between 0.38 and 0.70.

Conclusions: The early-onset cancer family history is closely related to the occurrence of gastric cancer and a good lifestyle is associated with a reduced risk of gastric cancer regardless of family history. Our results provide a basis for identifying and providing behavior guidance of high-risk groups of gastric cancer.
Shifting to a Sustainable Dietary Pattern in Iranian Population: Current Evidence and Future Directions
Authors: Sobhani Seyyed Reza , Omidvar Nasrin , Abdollahi Zahra , Al Jawaldeh Ayoub
Published: December 2021

The need for a shift in diet toward a more sustainable one has reached an urgency in certain regions, including Iran, due to more rapid climate change and a higher level of vulnerability. This study was undertaken to identify and summarize available data on changes required in the current Iranian diet to make it more sustainable and the extent to which current policies in the country have addressed such a shift. In this study, PubMed, Scopus, and Web of science, as well as Iranian scientific search engines, including Scientific Information Database and Magiran, were systematically searched from January 1990 to July 2021. A total of 11 studies and policy analyses were included in this study. Based on the findings, moving Iranian diet toward sustainability will require increase in consumption of dairy, fruits, vegetables, cereals, poultry, and legumes and decrease in consumption of bread, rice, pasta, red meat, eggs, fats, sugars, and sweets. There has been a great deal of effort and investment on policies and strategies to decrease the amount of sugar, salt, and fat (specifically trans-fatty acids) in the Iranian diet, which makes it more sustainable healthwise. Several policies and programs have been implemented to tackle non-communicable diseases (NCDs) by reducing access to unhealthy foods, which is in line with health dimension of a sustainable diet. However, there is almost no direct address to ecological aspect of sustainable diet in the food and nutrition policy documents in the ccountry. Development of an enabling environment to a sustainable diet will require policy and actions to improve public awareness, support study to provide evidence and identify possible alternatives, and plan and implement interventions/programs to promote and facilitate healthy and sustainable diets.
Adipose-Derived Stem Cells Facilitate Ovarian Tumor Growth and Metastasis by Promoting Epithelial to Mesenchymal Transition Through Activating the TGF-β Pathway
Authors: Liu Xiaowu , Zhao Guannan , Huo Xueyun , Wang Yaohong , Tigyi Gabor , Zhu Bing-Mei , Yue Junming , Zhang Wenjing
Published: December 2021

Adipose-derived stem cells (ADSC) are multipotent mesenchymal stem cells derived from adipose tissues and are capable of differentiating into multiple cell types in the tumor microenvironment (TME). The roles of ADSC in ovarian cancer (OC) metastasis are still not well defined. To understand whether ADSC contributes to ovarian tumor metastasis, we examined epithelial to mesenchymal transition (EMT) markers in OC cells following the treatment of the ADSC-conditioned medium (ADSC-CM). ADSC-CM promotes EMT in OC cells. Functionally, ADSC-CM promotes OC cell proliferation, survival, migration, and invasion. We further demonstrated that ADSC-CM induced EMT via TGF-β growth factor secretion from ADSC and the ensuing activation of the TGF-β pathway. ADSC-CM-induced EMT in OC cells was reversible by the TGF-β inhibitor SB431542 treatment. Using an orthotopic OC mouse model, we also provide the experimental evidence that ADSC contributes to ovarian tumor growth and metastasis by promoting EMT through activating the TGF-β pathway. Taken together, our data indicate that targeting ADSC using the TGF-β inhibitor has the therapeutic potential in blocking the EMT and OC metastasis.
The Relationship Between Body Mass Index and Different Regional Patterns of Lymph Node Involvement in Papillary Thyroid Cancers
Authors: Li Changlin , Dionigi Gianlorenzo , Liang Nan , Guan Haixia , Sun Hui
Published: December 2021

Introduction

Lymph node (LN) metastasis is the first site of metastasis of papillary thyroid cancer (PTC). LN status influences clinical management and the prognosis of patients. We explored the relationship between patient obesity and regional patterns of LN involvement in PTC.

Materials and Methods

This study retrospectively analyzed the data from 12,772 PTC patients. The rate of LN metastasis, number of LN metastasis, maximum diameter of positive LN, number of dissected LN, and LN ratios (LNR) were compared between normal-weight and obese patients. Statistical methods have been adjusted for the confounders in hypothesis testing.

Results

Overweight and obesity were independent risk factor for metastatic LNs (OR1 = 1.125, 95% CI 1.042-1.214, P1 = 0.003; OR2 = 1.554, 95% CI 1.339-1.802, P2<0.001). Obesity was an independent risk factor for the number of metastatic CLNs (OR=1.159, 95% CI 0.975-1.377, P=0.045), however not for number of metastatic lateral LNs (P=0.907). Furthermore, obesity was not an independent risk factor for number of CLNs when dissected more than five (P=0.653), still an independent risk factors for number of metastatic lateral LNs when more than six (OR=1.185, 95% CI 1.010-1.391, P=0.037). As for LNR, obesity was an independent risk factor for the central LNR when more than 0.12 (OR adjusted 1 = 1.099, 95% CI 1.011-1.194, P1 = 0.027; OR adjusted 2 = 1.177, 95% CI 1.003-1.381, P2 = 0.045), for the lateral LNR more than 0.05 (P2 = 0.283).

Conclusions

Obesity was associated with poor prognoses with PTC respecting LNs. Surgeons should be extreme caution when performing central neck dissection in obese patients.
Clinical Complete Remission of An Advanced Gastric Adenocarcinoma After Camrelizumab Plus Chemotherapy Followed by Camrelizumab Plus Capecitabine: A Case Report
Authors: Lin Jieheng , Yang Jianying , Wang Wenping , Lin Xiaotong , Cao Yang
Published: December 2021

We report a rare case of PDL1-negative advanced gastric adenocarcinoma that improved significantly after camrelizumab plus chemotherapy followed by camrelizumab plus capecitabine as first-line therapy. A 65-year-old woman was diagnosed with a gastric adenocarcinoma in 2017 via contrast-enhanced computed tomography (CT) and endoscopic biopsy. She stabilised after preoperative neoadjuvant chemotherapy, surgery, and postoperative adjuvant chemotherapy. In September 2019, positron emission tomography (PET)/CT re-examination suggested a peritoneal metastasis and multiple lymph node metastases. She then received six cycles of camrelizumab plus chemotherapy. PET/CT indicated that the metastatic foci had disappeared and that she had achieved a clinical complete response(CCR). She was followed-up with camrelizumab plus capecitabine (maintenance therapy). At the time of writing, her progression-free survival is more than 14 months and her quality of life is good. Thus, camrelizumab plus chemotherapy is a useful first-line treatment for HER2- and PD-L1-negative advanced gastric adenocarcinoma.
Case Report: Combination of Olaparib With Chemotherapy in a Patient With ATM-Deficient Colorectal Cancer
Authors: Papageorgiou Georgios I. , Fergadis Evangelos , Skouteris Nikos , Christakos Evridiki , Tsakatikas Sergios A. , Lianos Evangelos , Kosmas Christos
Published: December 2021

Poly-ADP ribose polymerase (PARP) inhibitors are constantly increasing in their indications for use as anti-cancer treatment in various neoplasms, the majority of which are linked with BRCA deficiency. Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting “BRCAness” or homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. With the current report we present the case of a heavily pretreated 55-year-old male patient diagnosed with stage IV ATM-deficient CRC, who was effectively treated with an off-label olaparib-irinotecan combination after exhaustion of all available treatment choices; furthermore, we discuss the existing data providing evidence for the use of PARP inhibitors in ATM-deficient CRC and encourage the implementation of next-generation sequencing (NGS) in patients with no other available treatment options.
Evaluation of Serum miR-17-92 Cluster as Noninvasive Biomarkers for Bladder Cancer Diagnosis
Authors: Wang Jingyao , Peng Xiqi , Li Rongkang , Liu Kaihao , Zhang Chunduo , Chen Xuan , Huang Guocheng , Zhao Liwen , Chen Zebo , Lai Yongqing
Published: December 2021

Previous studies have shown that the miR-17-92 cluster is involved in the occurrence and development of bladder cancer. However, the role of serum miR-17-92 cluster in the diagnosis of bladder cancer has not been studied. In the present study, we evaluated the expression of miR-17-92 cluster members in bladder cancer tissues by analyzing 428 cases from TCGA database. Next, we collected the sera of 74 bladder cancer patients and 90 controls, and used qRT-PCR to detect the relative expression of the cluster. The results showed that the expression of the cluster members in the sera of patients were significantly higher than that of the controls, and they were positively correlated with the clinical stage and pathological grade of the patients. We evaluated their ability to diagnose bladder cancer using ROC, of which miR-92a-3p (AUC = 0.902), miR-17-5p (AUC = 0.845) and miR-20a-5p (AUC = 0.806) were the most prominent. Finally, we established a diagnostic model by logistic regression (AUC = 0.969). We further validated the results of the study using another dataset from the GEO database. Moreover, we evaluated the prognostic value of the cluster. The results revealed that miR-20a-5p was correlated with recurrence of bladder cancer. In summary, the present study validated the overexpression of serum miR-17-92 cluster in bladder cancer. The model composed of the three cluster members were confirmed to be a promising noninvasive biomarker for bladder cancer diagnosis.
Pre-Birth and Early-Life Factors Associated With the Timing of Adiposity Peak and Rebound: A Large Population-Based Longitudinal Study
Authors: Lin Dan , Chen Didi , Huang Jun , Li Yun , Wen Xiaosa , Wang Ling , Shi Huijing
Published: December 2021

Background: The late occurrence of adiposity peak (AP) and the early occurrence of adiposity rebound (AR) are considered the earliest indicators for obesity and its related health conditions later in life. However, there is still limited information for their upstream factors. Therefore, in this study, we aimed to identify the parental and child factors associated with the timing of AP and AR in the early stage of life.

Methods: This is a population-based longitudinal study conducted in Shanghai, China. The BMI data of children born between September 2010 and October 2013 were followed from birth to 80 months. Subject-specific body mass index trajectories were fitted by non-linear mixed-effect models with natural cubic spline functions, and the individual's age at AP and AR was estimated. The generalized linear regression models were applied to identify the upstream factors of late occurrence of AP and early occurrence AR.

Results: For 7,292 children with estimated AP, boys were less likely to have a late AP [adjusted risk ratio (RR) = 0.83, 95% confidence interval (CI): 0.77–0.90, p < 0.001], but preterm born children had a higher risk of a late AP (adjusted RR = 1.25, 95% CI: 1.07–1.47, p < 0.01). For 10,985 children with estimated AR, children with breastfeeding longer than 4 months were less likely to have an early AR (adjusted RR = 0.80, 95% CI: 0.73–0.87, p < 0.001), but children who were born to advanced-age mothers and who were born small for gestational age had a higher risk of having an early AR (adjusted RR = 1.21, 95% CI: 1.07–1.36, p < 0.01; adjusted RR = 1.20, 95% CI: 1.04–1.39, p = 0.01).

Conclusions: Modifiable pre-birth or early-life factors associated with the timing of AP or AR were found. Our findings may help develop prevention and intervention strategies at the earliest stage of life to control later obesity and the health conditions and diseases linked to it.
Respiratory Adherence Care Enhancer Questionnaire: Identifying Self-Management Barriers of Inhalation Corticosteroids in Asthma
Authors: Visser Claire D. , Linthorst Jip M. , Kuipers Esther , Sont Jacob K. , Lacroix Joyca P. W. , Guchelaar Henk-Jan , Teichert Martina
Published: December 2021

Introduction: Suboptimal self-management of inhaled corticosteroids (ICS) in asthma patients is frequently observed in clinical practice and associated with poor asthma control. Driving factors for suboptimal self-management are complex and consist of a range of behavioral barriers (cognitive, affective and practical) with a considerable inter-individual variability. Identification of individual barriers facilitates the use of corresponding behavior change techniques and tailored care to improve asthma treatment outcomes.

Objective: This study describes the development and validation of the ‘Respiratory Adherence Care Enhancer’ (RACE) questionnaire to identify individual barriers to self-management of ICS therapy in asthma patients.

Methods: The development included: 1) an inventory of self-management barriers based on a literature review, 2) expert assessment on relevance and completeness of this set, linking these barriers to behavioral domains of the Theoretical Domains Framework (TDF) and 3) the formulation of corresponding questions assessing each of the barriers. A cross-sectional study was performed for validation. Primary care asthma patients were invited to fill out the RACE-questionnaire prior to a semi-structured telephonic interview as golden standard. Barriers detected from the questionnaire were compared to those mentioned in the interview.

Results: The developed questionnaire is made up of 6 TDF-domains, covering 10 self-management barriers with 23 questions. For the validation 64 patients completed the questionnaire, of whom 61 patients were interviewed. Cronbach’s alpha for the consistency of questions within the barriers ranged from 0.58 to 0.90. Optimal cut-off values for the presence of barriers were determined at a specificity between 67 and 92% with a sensitivity between 41 and 83%. Significant Areas Under the Receiver Operating Curves values were observed for 9 barriers with values between 0.69 and 0.86 (p-value <0.05), except for ‘Knowledge of ICS medication’ with an insignificant value of 0.53.

Conclusion: The RACE-questionnaire yields adequate psychometric characteristics to identify individual barriers to self-management of ICS therapy in asthma patients, facilitating tailored care.
Insights Into Amentoflavone: A Natural Multifunctional Biflavonoid
Authors: Xiong Xifeng , Tang Nan , Lai Xudong , Zhang Jinli , Wen Weilun , Li Xiaojian , Li Aiguo , Wu Yanhua , Liu Zhihe
Published: December 2021

Amentoflavone is an active phenolic compound isolated fromSelaginella tamariscinaover 40 years. Amentoflavone has been extensively recorded as a molecule which displays multifunctional biological activities. Especially, amentoflavone involves in anti-cancer activity by mediating various signaling pathways such as extracellular signal-regulated kinase (ERK), nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and emerges anti-SARS-CoV-2 effect via binding towards the main protease (Mpro/3CLpro), spike protein receptor binding domain (RBD) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Therefore, amentoflavone is considered to be a promising therapeutic agent for clinical research. Considering the multifunction of amentoflavone, the current review comprehensively discuss the chemistry, the progress in its diverse biological activities, including anti-inflammatory, anti-oxidation, anti-microorganism, metabolism regulation, neuroprotection, radioprotection, musculoskeletal protection and antidepressant, specially the fascinating role against various types of cancers. In addition, the bioavailability and drug delivery of amentoflavone, the molecular mechanisms underlying the activities of amentoflavone, the molecular docking simulation of amentoflavone throughin silicoapproach and anti-SARS-CoV-2 effect of amentoflavone are discussed.
Autoimmune Progressive Fibrosing Interstitial Lung Disease: Predictors of Fast Decline
Authors: Nagy Alexandra , Nagy Tamas , Kolonics-Farkas Abigel Margit , Eszes Noemi , Vincze Krisztina , Barczi Eniko , Tarnoki Adam Domonkos , Tarnoki David Laszlo , Nagy György , Kiss Emese , Maurovich-Horvat Pal , Bohacs Aniko , Müller Veronika
Published: December 2021

A subset of interstitial lung diseases (ILDs) with autoimmune traits—including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)—develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 (n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group (p < 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients (n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group.
Impact of the Pilot Volume-Based Drug Purchasing Policy in China: Interrupted Time-Series Analysis with Controls
Authors: Chen Yilin , Ji Xu , Xiao Hong , Unger Joseph M , Cai Yi , Mao Zongfu , Yeung Kai
Published: December 2021

Centralizing procurement for prescription drugs has the potential to reduce drug spending by creating economies of scale and by improving purchasing power. In March 2019, the Chinese government launched a volume-based purchasing (VBP) pilot program using a competitive bidding process to purchase accredited generic drugs for which branded drug substitutes were available. We performed an interrupted time-series design to estimate the change in monthly drug purchase quantity and spending comparing 14 months before and 7 months after the VBP pilot. We obtained monthly prescription drug purchase data for all purchases from public medical institutions in the three large pilot cities (Beijing, Shanghai and Xi’an) and two non-pilot cities (Changsha and Zhengzhou) between January 2018 to September 2019. We used negative binomial regression and log-linked Gamma Generalized Linear Model for purchase quantity and spending respectively. We evaluated heterogeneity of impact by pilot city, drug type (selected or non-selected drugs), and therapeutic class (cardiovascular disease, mental disorder and cancer) separately. The implementation of the pilot reform was associated with a 132% (95%-CI: 104–165%, p < 0.001) increase in the purchase quantity of selected drugs in pilot cities compared to an 17% decrease (95%-CI: 9–25%, p < 0.001) in control cities. In contrast, the purchase quantity of branded and other drugs in pilot cities decreased by 38% (95%-CI: 27–46%, p < 0.001) and 77% (95%-CI: 71–81%, p < 0.001), respectively; while in control cities, these remained at similar levels. Overall, in pilot cities, there was a 35% (95%-CI: 28–41%, p < 0.001) decrease in the purchase spending for all drugs in the first post-policy month, from 8.1 billion CNY estimated in the absence of VBP down to 5.3 billion CNY; in control cities, the change was negligible. The largest reduction in spending occurred for drugs for the treatment of cardiovascular diseases. The evidence suggests a positive impact of the VBP pilot in reducing overall drug spending and increasing the use of accredited generics in three pilot cities. This overall trend is not observed in two non-pilot cities. Assessments of long-term impact of the VBP policy on additional key outcomes including drug prescriptions, drug utilization, patients’ health outcomes and payments on drugs are needed.
Elevated N-Glycosylation Contributes to the Cisplatin Resistance of Non-Small Cell Lung Cancer Cells Revealed by Membrane Proteomic and Glycoproteomic Analysis
Authors: Zeng Wenjuan , Zheng Shanshan , Mao Yonghong , Wang Shisheng , Zhong Yi , Cao Wei , Su Tao , Gong Meng , Cheng Jingqiu , Zhang Yong , Yang Hao
Published: December 2021

Chemoresistance is the major restriction on the clinical use of cisplatin. Aberrant changes in protein glycosylation are closely associated with drug resistance. Comprehensive study on the role of protein glycosylation in the development of cisplatin resistance would contribute to precise elucidation of the complicated mechanism of resistance. However, comprehensive characterization of glycosylated proteins remains a big challenge. In this work, we integrated proteomic and N-glycoproteomic workflow to comprehensively characterize the cisplatin resistance-related membrane proteins. Using this method, we found that proteins implicated in cell adhesion, migration, response to drug, and signal transduction were significantly altered in both protein abundance and glycosylation level during the development of cisplatin resistance in the non-small cell lung cancer cell line. Accordingly, the ability of cell migration and invasion was markedly increased in cisplatin-resistant cells, hence intensifying their malignancy. In contrast, the intracellular cisplatin accumulation was significantly reduced in the resistant cells concomitant with the down-regulation of drug uptake channel protein, LRRC8A, and over-expression of drug efflux pump proteins, MRP1 and MRP4. Moreover, the global glycosylation was elevated in the cisplatin-resistant cells. Consequently, inhibition of N-glycosylation reduced cell resistance to cisplatin, whereas promoting the high-mannose or sialylated type of glycosylation enhanced the resistance, suggesting that critical glycosylation type contributes to cisplatin resistance. These results demonstrate the high efficiency of the integrated proteomic and N-glycoproteomic workflow in discovering drug resistance-related targets, and provide new insights into the mechanism of cisplatin resistance.
The Hexosamine Biosynthetic Pathway Links Innate Inflammation With Epithelial-Mesenchymal Plasticity in Airway Remodeling
Authors: Brasier Allan R. , Qiao Dianhua , Zhao Yingxin
Published: December 2021

Disruption of the lower airway epithelial barrier plays a major role in the initiation and progression of chronic lung disease. Here, repetitive environmental insults produced by viral and allergens triggers metabolic adaptations, epithelial-mesenchymal plasticity (EMP) and airway remodeling. Epithelial plasticity disrupts epithelial barrier function, stimulates release of fibroblastic growth factors, and remodels the extracellular matrix (ECM). This review will focus on recent work demonstrating how the hexosamine biosynthetic pathway (HBP) links innate inflammation to airway remodeling. The HBP is a core metabolic pathway of the unfolded protein response (UPR) responsible for protein N-glycosylation, relief of proteotoxic stress and secretion of ECM modifiers. We will overview findings that the IκB kinase (IKK)-NFκB pathway directly activates expression of the SNAI-ZEB1 mesenchymal transcription factor module through regulation of the Bromodomain Containing Protein 4 (BRD4) chromatin modifier. BRD4 mediates transcriptional elongation of SNAI1-ZEB as well as enhancing chromatin accessibility and transcription of fibroblast growth factors, ECM and matrix metalloproteinases (MMPs). In addition, recent exciting findings that IKK cross-talks with the UPR by controlling phosphorylation and nuclear translocation of the autoregulatory XBP1s transcription factor are presented. HBP is required for N glycosylation and secretion of ECM components that play an important signaling role in airway remodeling. This interplay between innate inflammation, metabolic reprogramming and lower airway plasticity expands a population of subepithelial myofibroblasts by secreting fibroblastic growth factors, producing changes in ECM tensile strength, and fibroblast stimulation by MMP binding. Through these actions on myofibroblasts, EMP in lower airway cells produces expansion of the lamina reticularis and promotes airway remodeling. In this manner, metabolic reprogramming by the HBP mediates environmental insult-induced inflammation with remodeling in chronic airway diseases.
A Novel Clock Skew Estimator and Its Performance for the IEEE 1588v2 (PTP) Case in Fractional Gaussian Noise/Generalized Fractional Gaussian Noise Environment
Authors: Avraham Yehonatan , Pinchas Monika
Published: December 2021

Papers in the literature dealing with the Ethernet network characterize packet delay variation (PDV) as a long-range dependence (LRD) process. Fractional Gaussian noise (fGn) or generalized fraction Gaussian noise (gfGn) belong to the LRD process. This paper proposes a novel clock skew estimator for the IEEE1588v2 applicable for the white-Gaussian, fGn, or gfGn environment. The clock skew estimator does not depend on the unknown asymmetry between the fixed delays in the forward and reverse paths nor on the clock offset between the Master and Slave. In addition, we supply a closed-form-approximated expression for the mean square error (MSE) related to our new proposed clock skew estimator. This expression is a function of the Hurst exponent H, as a function of the parameter a for the gfGn case, as a function of the total sent Sync messages, as a function of the Sync period, and as a function of the PDV variances of the forward and reverse paths. Simulation results confirm that our closed-form-approximated expression for the MSE indeed supplies the performance of our new proposed clock skew estimator efficiently for various values of the Hurst exponent, for the parameter a in gfGn case, for different Sync periods, for various values for the number of Sync periods and for various values for the PDV variances of the forward and reverse paths. Simulation results also show the advantage in the performance of our new proposed clock skew estimator compared to the literature known ML-like estimator (MLLE) that maximizes the likelihood function obtained based on a reduced subset of observations (the first and last timing stamps). This paper also presents designing graphs for the system designer that show the number of the Sync periods needed to get the required clock skew performance (MSE = 10–12). Thus, the system designer can approximately know in advance the total delay or the time the system has to wait until getting the required system’s performance from the MSE point of view.
The Molecular Basis for the Calcium-Dependent Slow Afterhyperpolarization in CA1 Hippocampal Pyramidal Neurons
Authors: Sahu Giriraj , Turner Ray W.
Published: December 2021

Neuronal signal transmission depends on the frequency, pattern, and timing of spike output, each of which are shaped by spike afterhyperpolarizations (AHPs). There are classically three post-spike AHPs of increasing duration categorized as fast, medium and slow AHPs that hyperpolarize a cell over a range of 10 ms to 30 s. Intensive early work on CA1 hippocampal pyramidal cells revealed that all three AHPs incorporate activation of calcium-gated potassium channels. The ionic basis for a fAHP was rapidly attributed to the actions of big conductance (BK) and the mAHP to small conductance (SK) or Kv7 potassium channels. In stark contrast, the ionic basis for a prominent slow AHP of up to 30 s duration remained an enigma for over 30 years. Recent advances in pharmacological, molecular, and imaging tools have uncovered the expression of a calcium-gated intermediate conductance potassium channel (IK, KCa3.1) in central neurons that proves to contribute to the slow AHP in CA1 hippocampal pyramidal cells. Together the data show that the sAHP arises in part from a core tripartite complex between Cav1.3 (L-type) calcium channels, ryanodine receptors, and IK channels at endoplasmic reticulum-plasma membrane junctions. Work on the sAHP in CA1 pyramidal neurons has again quickened pace, with identified contributions by both IK channels and the Na-K pump providing answers to several mysteries in the pharmacological properties of the sAHP.
Novel Design of Imputation-Enabled SNP Arrays for Breeding and Research Applications Supporting Multi-Species Hybridization
Authors: Keeble-Gagnère Gabriel , Pasam Raj , Forrest Kerrie L. , Wong Debbie , Robinson Hannah , Godoy Jayfred , Rattey Allan , Moody David , Mullan Daniel , Walmsley Tresslyn , Daetwyler Hans D. , Tibbits Josquin , Hayden Matthew J.
Published: December 2021

Array-based single nucleotide polymorphism (SNP) genotyping platforms have low genotype error and missing data rates compared to genotyping-by-sequencing technologies. However, design decisions used to create array-based SNP genotyping assays for both research and breeding applications are critical to their success. We describe a novel approach applicable to any animal or plant species for the design of cost-effective imputation-enabled SNP genotyping arrays with broad utility and demonstrate its application through the development of the Illumina Infinium Wheat Barley 40K SNP array Version 1.0. We show that the approach delivers high quality and high resolution data for wheat and barley, including when samples are jointly hybridised. The new array aims to maximally capture haplotypic diversity in globally diverse wheat and barley germplasm while minimizing ascertainment bias. Comprising mostly biallelic markers that were designed to be species-specific and single-copy, the array permits highly accurate imputation in diverse germplasm to improve the statistical power of genome-wide association studies (GWAS) and genomic selection. The SNP content captures tetraploid wheat (A- and B-genome) and Aegilops tauschii Coss. (D-genome) diversity and delineates synthetic and tetraploid wheat from other wheat, as well as tetraploid species and subgroups. The content includes SNP tagging key trait loci in wheat and barley, as well as direct connections to other genotyping platforms and legacy datasets. The utility of the array is enhanced through the web-based tool, Pretzel (https://plantinformatics.io/) which enables the content of the array to be visualized and interrogated interactively in the context of numerous genetic and genomic resources to be connected more seamlessly to research and breeding. The array is available for use by the international wheat and barley community.
Monitoring of Salinity, Temperature, and Drought Stress in Grafted Watermelon Seedlings Using Chlorophyll Fluorescence
Authors: Shin Yu Kyeong , Bhandari Shiva Ram , Lee Jun Gu
Published: December 2021

Chlorophyll fluorescence (CF) is used to measure the physiological status of plants affected by biotic and abiotic stresses. Therefore, we aimed to identify the changes in CF parameters in grafted watermelon seedlings exposed to salt, drought, and high and low temperatures. Grafted watermelon seedlings at the true three-leaf stage were subjected to salinity levels (0, 50, 100, 150, and 200 mM) and temperature [low (8°C), moderate (24°C), and high (40°C)] stresses for 12 days under controlled environmental conditions independently. Eight CF parameters were measured at 2-day intervals using the FluorCam machine quenching protocol of the FluorCam machine. The seedlings were also exposed to drought stress for 3 days independent of salinity and temperature stress; CF parameters were measured at 1-day intervals. In addition, growth parameters, proline, and chlorophyll content were evaluated in all three experiments. The CF parameters were differentially influenced depending on the type and extent of the stress conditions. The results showed a notable effect of salinity levels on CF parameters, predominantly in maximum quantum yield (Fv/Fm), non-photochemical quenching (NPQ), the ratio of the fluorescence decrease (Rfd), and quantum yield of non-regulated energy dissipation in PSII [Y(NO)]. High temperature had significant effects on Rfd and NPQ, whereas low temperature showed significant results in most CF parameters: Fv/Fm, Y(NO), NPQ, Rfd, the efficiency of excitation capture of open photosystem II (PSII) center (Fv′/Fm′), and effective quantum yield of photochemical energy conversion in PSII [Y(PSII)]. Only NPQ and Rfd were significantly influenced by severe drought stress. Approximately, all the growth parameters were significantly influenced by the stress level. Proline content increased with an increase in stress levels in all three experiments, whereas the chlorophyll (a and b) content either decreased or increased depending upon the stressor. The results provided here may be useful for understanding the effect of abiotic stresses on CF parameters and the selection of index CF parameters to detect abiotic stresses in grafted watermelon seedlings.
Time-Course of Changes in Photosynthesis and Secondary Metabolites in Canola (Brassica napus) Under Different UV-B Irradiation Levels in a Plant Factory With Artificial Light
Authors: Lee Jin-Hui , Shibata Seina , Goto Eiji
Published: December 2021

This study aimed to evaluate short-duration (24 h) UV-B irradiation as a preharvest abiotic stressor in canola plants. Moreover, we quantified the expression levels of genes related to bioactive compounds synthesis in response to UV-B radiation. Canola seedlings were cultivated in a plant factory under artificial light (200 μmol m–2 s–1 photosynthetic photon flux density; white LED lamps; 16 h on/8 h off), 25°C/20°C daytime/nighttime air temperature, and 70% relative humidity. Eighteen days after sowing, the seedlings were subjected to supplemental UV-B treatment. The control plants received no UV-B irradiation. The plants were exposed to 3, 5, or 7 W m–2 UV-B irradiation. There were no significant differences in shoot fresh weight between the UV-B-irradiated and control plants. With increasing UV-B irradiation intensity and exposure time, the H2O2 content gradually increased, the expression levels of genes related to photosynthesis downregulated, and phenylpropanoid and flavonoid production, and also total phenolic, flavonoid, antioxidant, and anthocyanin concentrations were significantly enhanced. The genes related to secondary metabolite biosynthesis were immediately upregulated after UV-B irradiation. The relative gene expression patterns identified using qRT-PCR corroborated the variations in gene expression that were revealed using microarray analysis. The time point at which the genes were induced varied with the gene location along the biosynthetic pathway. To the best of our knowledge, this is the first study to demonstrate a temporal difference between the accumulation of antioxidants and the induction of genes related to the synthesis of this compound in UV-B-treated canola plants. Our results demonstrated that short-term UV-B irradiation could augment antioxidant biosynthesis in canola without sacrificing crop yield or quality.
Entrepreneurs’ Felt Responsibility for Constructive Change and Entrepreneurial Performance: A Moderated Mediation Model of Technology Action and Market Orientation
Authors: Du Yuechao , Hu Honghao , Wang Zhongming
Published: December 2021

Drawing on self-determination theory, we examine the mechanism through which entrepreneurs’ felt responsibility for constructive change affects entrepreneurial performance and how market orientation affects the influencing mechanism. A questionnaire survey was conducted with 424 entrepreneurs in China. The results show that entrepreneurs’ felt responsibility for constructive change is positively related to technology action and entrepreneurial performance, and technology action mediates the relationship between entrepreneurs’ felt responsibility for constructive change and entrepreneurial performance. In addition, market orientation moderates the relationship between technology action and entrepreneurial performance such that the relationship is stronger when the market orientation is higher. Our findings suggest that when entrepreneur feel responsible for constructive change, they tend to take technology actions to achieve their goals and improve the long-term development of ventures. It is also important for entrepreneurs to hold a market orientation, which helps them be aware of changes in customer needs rather than blindly focusing on the use of the latest technologies. Our study is pioneering in exploring entrepreneurs’ felt responsibility for constructive change in the entrepreneurial context, advancing the research on entrepreneurship psychology.
Sibling, Peer, and Cyber Bullying Among Children and Adolescents: Co-occurrence and Implications for Their Adjustment
Authors: Dantchev Slava , Zemp Martina
Published: December 2021

Bullying across the sibling, peer, and cyber context has consistently been associated with a range of long-term health and well-being consequences for children and adolescents. Although research examining different bullying forms simultaneously in the same study are emerging, it remains unclear to what extend sibling, peer, and cyber bullying co-occur and in what ways they are associated. Moreover, previous work has demonstrated that children and adolescents who experience multiple forms of victimization are at a particular risk of adverse outcomes. However, whether different constellations of co-occurring bullying forms have differential impacts has not yet been investigated sufficiently. The aim of the present study was to examine the frequencies of isolated and co-occurring sibling, peer, and cyber bullying as well as to explore their independent and cumulative relationships with child adjustment. This study was based on a sample of 329 children and adolescents aged between 9 and 15. Bullying experiences across the sibling, peer, and cyber context in the previous 6 months were assessed via self-report. Youth further reported on emotional problems, conduct problems, sleep problems, and academic achievement via an online questionnaire. Sibling, peer, and cyber bullying were uniquely associated with child outcomes. A cumulative relationship between bullying victimization across contexts and emotional problems, conduct problems, and sleep problems could be identified, while bullying perpetration across contexts was only linked to more conduct problems in a cumulative manner. The findings have important practical implications arguing for the adoption of a holistic approach toward bullying in prevention and intervention.
The Cassandra Experience: A Mixed Methods Study on the Intragroup Cognitive Dissonance of Italian Expatriates During the First Wave of COVID-19
Authors: Di Domenico Rossella , Cannata Davide , Mancini Tiziana
Published: December 2021

In March 2020, Italy was the first European country to be hit severely by the first wave of coronavirus disease 2019 (COVID-19) and to put in place moderate-high containment measures. 594 Italian expatriates participated in a cross-sectional mixed-methods survey focusing on the period that goes from the beginning of March 2020 to the beginning of April 2020. The survey aimed to describe the experiences of participants when it comes to conflicting beliefs and behavior with the Italian or host country communities in relation to COVID-19, using the Intragroup Cognitive Dissonance (ICD) framework. We explored: (1) COVID-19 risk perception (assessed for themselves, the Italian community, and the host country community); (2) COVID-19 risk meta-perception (participants’ perception of the Italian and host country communities’ risk perception); (3) intensity of emotions (assessed for themselves); (4) national group identification (assessed for themselves in relation to the Italian and host country communities) before and after the first wave of COVID-19 in Italy. An inductive thematic analysis of three open-ended questions allowed an in-depth understanding of the experiences of Italian expatriates. Results describe the ICD of participants with the Italian or host country communities, expressed as a difference between COVID-19 risk-perception and risk meta-perception. ICD predicts that when a dissonance of beliefs and behavior is experienced within an individual’s group, a shift in identification with another more consonant group will happen, if identity enhancing strategies with the dissonant group are unsuccessful. Our findings showed that when the ICD was experienced with the host country community, this was solved through a disidentification strategy and mediated by negative emotions. Identity enhancing strategies with the host country community were unsuccessfully enacted as described by the qualitative answers of participants referring to episodes of racism, ridicule, and to a Cassandra experience: predicting a catastrophic future without being believed. Unexpectedly, participants experiencing the ICD with the Italian community did not enact a disidentification strategy. An increase in virtual contacts, enhanced sense of belonging, a stronger identification baseline, and different features of the two ICDs can be responsible for these results. This study sheds light on the relevance of ICD in natural settings and on international communities, during global crises.
Two Waves of COVID-19 in University Setting: Mental Health and Underlying Risk Factors
Authors: Křeménková Lucie , Novotný Jan Sebastian , Kvintová Jana
Published: December 2021

The aim of the paper was to assess the differences in the mental distress of university students in the first and second waves of COVID-19, to compare these levels with that of the general population as well as to identify the risk factors associated with the changes in mental health. A total of 2,025 university students in core psychology courses in all years of study at the Faculty of Education at Palacký University Olomouc were approached via e-mail. Of this number of students, 800 students took part in the study, divided into two groups from the spring (N = 438) and autumn (N = 362) pandemic waves. The data were collected online via Google Forms using a battery of questionnaires and analyzed using the Wilcoxon–Mann–Whitney test, One-Sample Wilcoxon Signed Rank Test and binary logistic regression. The results showed a high prevalence of depressive symptoms (38.4 and 51.4%), significant anxiety (43.8 and 37%), and high stress (19.9 and 22.9%) among students in both waves of the pandemic. Depression and stress also increased significantly during the second wave compared with the first one (r = 0.18 [0.12, 0.25] and r = 0.08 [0.01, 0.14]). Finally, university students showed significantly higher levels of mental distress than the general population in all of the variables and in both waves (r = 0.42–0.86). A variety of factors influenced different aspects of mental distress in the spring and autumn pandemic waves. Emotion regulation emerged as the most significant and pervasive factor, both influencing all of the three indicators of mental distress and being a significant predictor in both waves.
Using Trauma Informed Principles in Health Communication: Improving Faith/Science/Clinical Collaboration to Address Addiction
Authors: Clements Andrea D. , Cyphers Natalie A. , Whittaker Deborah L. , Hamilton Bridget , McCarty Brett
Published: December 2021

Problematic substance use is a pressing global health problem, and dissemination and implementation of accurate health information regarding prevention, treatment, and recovery are vital. In many nations, especially the US, many people are involved in religious groups or faith communities, and this offers a potential route to positively affect health through health information dissemination in communities that may have limited health resources. Health information related to addiction will be used as the backdrop issue for this discussion, but many health arenas could be substituted. This article evaluates the utility of commonly used health communication theories for communicating health information about addiction in religious settings and identifies their shortcomings. A lack of trusting, equally contributing, bidirectional collaboration among representatives of the clinical/scientific community and religious/faith communities in the development and dissemination of health information is identified as a potential impediment to effectiveness. The Substance Abuse and Mental Health Services Administration’s (SAMHSA) tenets of trauma-informed practice, although developed for one-on-one use with those who have experienced trauma or adversity, are presented as a much more broadly applicable framework to improve communication between groups such as organizations or communities. As an example, we focus on health communication within, with, and through religious groups and particularly within churches.