bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Evidence of Vestibular Dysregulation in Colicky Babies Before and After Chiropractic Treatment vs. Non-colicky Babies
Authors: Hoeve Jan
Published: May 2021

Background:To date, after 65 years of research that was primarily directed at differentiating between normal and colicky crying, the cause of infantile colic remains elusive and no definitive cure has been found. Given the general absence of pathology, colicky crying is widely considered the extreme end of a spectrum of normal crying behavior. However, evidence gleaned from scattered sources throughout the literature suggests that infantile colic may be the behavioral expression of physiological brainstem dysregulation, particularly of the vestibular and autonomic systems. The purpose of this study is to present a five-point clinical index of vestibular (hyper) activity and its application to investigate vestibular dysregulation in colicky and non-colicky babies.

Methods:One hundred and twenty consecutive colicky babies were evaluated using this index, before and after a very gentle vibratory treatment, and compared to 117 non-colicky babies.

Results:Before treatment, of 120 colicky babies only 2 (1.7%) scored 0, whereas 118 (98.3%) scored 1–5. Of 117 non-colicky babies 89 (76.1%) scored 0 and 28 (23.9%) scored 1–3, none scored 4–5. The odds ratio is OR (CI 95%) 187.54 (43.52–808.09). After treatment 111 (92.5%) scored 0 and 9 (7.5%) scored 1–3, none scored 4–5. A McNemar test showed the difference before and after to be significant (χ2= 109.00,p< 0.001). For colicky babies the mean vestibular score is 2.88 (SD 1.22), compared to 0.37 (SD 0.73) for non-colicky babies, a difference of 87.2%. After treatment the score decreased from 2.88 (SD 1.12) to 0.10 (SD 0.40), or 96.5%.

Conclusion:Colicky babies are not just infants who cry a lot. They also show clinical evidence of vestibular dysregulation. Treatment aimed at relaxing tight sub-occipital musculature by means of gentle vibrational stimulation may be effective in decreasing vestibular hyperactivity, signifying an improvement in brainstem regulation. The vestibular index opens the prospect for development into a tool toward an objective and practical clinical diagnosis of infantile colic.
Case Report: Somatic Symptoms Veiling Gender Dysphoria in an Adolescent
Authors: Morabito Giuliana , Cosentini Dora , Tornese Gianluca , Gortani Giulia , Pastore Serena , Genovese Maria Rita Lucia , Cozzi Giorgio
Published: May 2021

Background: Somatic symptom disorder is common in children and adolescents; usually, it is an expression of a mental health problem or other conditions that lead to psychosocial impairment and suffering. Among these, in pubertal age, gender dysphoria should be considered.

Case Presentation: We present the case of a 15-year-old girl admitted to the hospital because of a 2-month history of scattered arthralgia and myalgia, headache, and fatigue, with repeated visits to the emergency room. The physical exam was unremarkable, except for step walking and pain. Repeated diagnostic tests were normal, and consecutive psychological interviews disclosed intense suffering due to a gender incongruence. Referral to the hospital gender service was offered and refused by the parents.

Conclusions: In pubertal age, gender dysphoria may be expressed through somatoform symptoms. Diagnosis is challenging to accept for the parents even in the presence of adequate multi-disciplinary hospital services.
Anti–SARS-CoV-2 Natural Products as Potentially Therapeutic Agents
Authors: Kim Cheorl-Ho
Published: May 2021

Severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2), a β-coronavirus, is the cause of the recently emerged pandemic and worldwide outbreak of respiratory disease. Researchers exchange information on COVID-19 to enable collaborative searches. Although there is as yet no effective antiviral agent, like tamiflu against influenza, to block SARS-CoV-2 infection to its host cells, various candidates to mitigate or treat the disease are currently being investigated. Several drugs are being screened for the ability to block virus entry on cell surfaces and/or block intracellular replication in host cells. Vaccine development is being pursued, invoking a better elucidation of the life cycle of the virus. SARS-CoV-2 recognizes O-acetylated neuraminic acids and also several membrane proteins, such as ACE2, as the result of evolutionary switches of O-Ac SA recognition specificities. To provide information related to the current development of possible anti–SARS-COV-2 viral agents, the current review deals with the known inhibitory compounds with low molecular weight. The molecules are mainly derived from natural products of plant sources by screening or chemical synthesis via molecular simulations. Artificial intelligence–based computational simulation for drug designation and large-scale inhibitor screening have recently been performed. Structure–activity relationship of the anti–SARS-CoV-2 natural compounds is discussed.
Doxorubicin/Nucleophosmin Binding Protein-Conjugated Nanoparticle Enhances Anti-leukemia Activity in Acute Lymphoblastic Leukemia Cells in vitro and in vivo
Authors: Gan Donghui , Chen Yuwen , Wu Zhengjun , Luo Liping , Yirga Shimuye Kalayu , Zhang Na , Ye Fu , Chen Haijun , Hu Jianda , Chen Yingyu
Published: May 2021

Acute lymphoblastic leukemia (ALL) is an aggressive malignancy. Adults with ALL have more than 50% relapse rates. We have previously validated that overexpression of nucleophosmin (NPM) is involved in the multidrug resistance (MDR) development during ALL; and a synthetically engineered recombinant NPM binding protein (NPMBP) has been developed in our group; NPMBP and doxorubicin (DOX) can be conjugated in a nanoparticle-based drug delivery system named DOX-PMs-NPMBP to counteract MDR during ALL. Here, we evaluated the antileukemia potential of DOX-PMs-NPMBP in resistant ALL cells. This study demonstrates that DOX-PMs-NPMBP significantly enhances chemosensitivity to DOX in ALL cells. Despite at variable concentrations, both resistant and primary ALL cells from relapsed patients were sensitive to DOX-PMs-NPMBP. In detail, the half maximal inhibitory concentration (IC50) values of DOX-PMs-NPMBP were between 1.6- and 7.0-fold lower than those of DOX in cell lines and primary ALL cells, respectively; and apoptotic cells ratio was over 2-fold higher in DOX-PMs-NPMBP than DOX. Mechanistically, p53-driven apoptosis induction and cell cycle arrest played essential role in DOX-PMs-NPMBP-induced anti-leukemia effects. Moreover, DOX-PMs-NPMBP significantly inhibited tumor growth and prolonged mouse survival of ALL xenograft models; and no systemic toxicity occurrence was observed after treatment during follow-up. In conclusion, these data indicate that DOX-PMs-NPMBP may significantly exert growth inhibition and apoptosis induction, and markedly improve DOX antileukemia activity in resistant ALL cells. This novel drug delivery system may be valuable to develop as a new therapeutic strategy against multidrug resistant ALL.
Case Report of Novel Genetic Variant in KCNT1 Channel and Pharmacological Treatment With Quinidine. Precision Medicine in Refractory Epilepsy
Authors: Kravetz M. C. , Viola M. S. , Prenz J. , Curi M. , Bramuglia G. F. , Tenembaum S.
Published: May 2021

Case introduction: In this work we present a female infant patient with epilepsy of infancy with migrating focal seizures (EIMFS). Although many pharmacological schemes were attempted, she developed an encephalopathy with poor response to antiepileptic drugs and progressive cerebral dysfunction.

Aim: To present the pharmacological response and therapeutic drug monitoring of a paediatric patient with a severe encephalopathy carrying a genetic variant in KCNT1 gene, whose identification led to include quinidine (QND) in the treatment regimen as an antiepileptic drug.

Case report: Patient showed slow rhythmic activity (theta range) over left occipital areas with temporal propagation and oculo-clonic focal seizures and without tonic spasms three months after birth. At the age of 18 months showed severe impairments of motor and intellectual function with poor eye contact. When the patient was 4 years old, a genetic variant in the exon 24 of the KCNT1 gene was found. This led to the diagnosis of EIMFS. Due to antiepileptic treatment failed to control seizures, QND a KCNT1 blocker, was introduced as a therapeutic alternative besides topiramate (200 mg/day) and nitrazepam (2 mg/day). Therapeutic drug monitoring (TDM) of QND plasma levels needed to be implemented to establish individual therapeutic range and avoid toxicity. TDM for dose adjustment was performed to establish the individual therapeutic range of the patient. Seizures were under control with QND levels above 1.5 mcg/ml (65–70 mg/kg q. i.d). In addition, QND levels higher than 4.0 mcg/ml, were related to higher risk of suffering arrhythmia due to prolongation of QT segment. Despite initial intention to withdrawal topiramate completely, QND was no longer effective by itself and failed to maintain seizures control. Due to this necessary interaction between quinidine and topiramate, topiramate was stablished in a maintenance dose of 40 mg/day.

Conclusion: The implementation of Precision Medicine by using tools such as Next Generation Sequencing and TDM led to diagnose and select a targeted therapy for the treatment of a KCNT1-related epilepsy in a patient presented with EIMFS in early infancy and poor response to antiepileptic drugs. QND an old antiarrhythmic drug, due to its activity as KCNT1 channel blocker, associated to topiramate resulted in seizures control. Due to high variability observed in QND levels, TDM and pharmacokinetic characterization allowed to optimize drug regimen to maintain QND concentration between the individual therapeutic range and diminish toxicity.
Traditional Chinese Medicine Oral Liquids Combined With Azithromycin for Mycoplasma pneumoniae Pneumonia in Children: A Bayesian Network Meta-Analysis
Authors: Chen Zhe , Shi Qingyang , Peng Yingying , Chen Yongjie , Cao Lujia , Pang Bo , Ji Zhaochen , Liu Chunxiang , Zhang Junhua
Published: May 2021

Background:Mycoplasma pneumoniae pneumonia (MPP) causes flu-like symptoms in children, increasing the burden on the health and education systems. In China, traditional Chinese medicine oral liquids (TCMOLs) combined with azithromycin (TCMOLs + Azithromycin) is commonly used to treat MPP in children. However, TCMOLs with the optimal clinical applicability remain unknown. Here, we evaluated the clinical effectiveness and safety of TCMOLs + Azithromycin in children with MPP.

Methods: We searched PubMed, Embase, Cochrane Library, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP information resource integration service platform databases for eligible randomized controlled trials (RCTs) published from database inception to October 2020. Two reviewers independently performed data extraction and risk of bias assessment. After Bayesian random effect modeling and surface under the cumulative ranking curve (SUCRA) scoring, we ranked each intervention. We assessed heterogeneity using multivariate meta-regression for potential modifiers and used the Grading of Recommendations, Assessment, Development, and Evaluation to rate pooled evidence’s certainty.

Results: In the 63 included RCTs with 6,410 children, five different TCMOLs were combined with azithromycin. TCMOLs + Azithromycin had significantly better primary outcomes than did azithromycin alone. Of all TCMOLs, Xiaoer Xiaoji Zhike (XEXJZK)+Azithromycin showed the best effectiveness with respect to the response rate (odds ratio [OR] = 6.5, 95% credible interval [CrI] = 4.3–10; low certainty) and pulmonary rales disappearance time (mean difference [MD] = −2.1, 95% CrI: −2.9 to −1.2; low certainty) with SUCRA 85 and 80%, respectively. Pudilan Xiaoyan + Azithromycin showed the highest effectiveness with respect to cough disappearance time (MD = −2.6, 95% CrI: −3.4 to −1.7; very low certainty) and fever disappearance time (MD = −1.8, 95% CrI: −2.3 to −1.3; very low certainty) with SUCRA 87 and 87%, respectively. The difference in the adverse effects between TCMOLs + Azithromycin and azithromycin alone was nonsignificant.

Conclusion: Of the different TCMOLs, XEXJZK may be the best option to combine with azithromycin to treat children with MPP. However, our results should be interpreted with caution due to the low certainty of evidence. In general, TCMOLs’ safety remains unclear because of a lack of evidence. More high-quality RCTs are needed to further evaluate efficacy and safety of these TCMOLs.
Kun-Dan Decoction Ameliorates Insulin Resistance by Activating AMPK/mTOR-Mediated Autophagy in High-Fat Diet-Fed Rats
Authors: Su Zuqing , Zeng Kexue , Feng Bing , Tang Lipeng , Sun Chaoyue , Wang Xieqi , Li Caiyun , Zheng Guangjuan , Zhu Ying
Published: May 2021

Background:Metabolic syndrome is characterized by central obesity, hyperglycemia and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been applied to treat patients with metabolic syndrome for over ten years. It is increasingly recognized that autophagy deficiency is the key cause of metabolic syndrome. Therefore, we aimed to explore whether KD can activate autophagy to improve metabolic syndrome.

Methods:Network pharmacology was used to explore the underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral glucose tolerance test and insulin tolerance test, obesity and histological examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-Ⅱ/Ⅰ were examined in rats and LO2 cells. Moreover, autophagy activator rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 were utilized to verify the role of autophagy in the treatment of metabolic syndrome by KD in oleic acid-induced LO2 cells.

Results:Results from network pharmacology indicated that targeted insulin resistance might be the critical mechanism of KD in the treatment of metabolic syndrome. We found that KD significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. Western blot showed that KD could enhance autophagy to increase the insulin sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse the protective effect of KD on LO2 cells. However, rapamycin could cooperate with KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells.

Conclusion:The induction of autophagy may be the major mechanism for KD to improve insulin resistance and metabolic syndrome.
New Viscoelastic Hydrogel Hymovis MO.RE. Single Intra-articular Injection for the Treatment of Knee Osteoarthritis in Sportsmen: Safety and Efficacy Study Results
Authors: Bernetti Andrea , Agostini Francesco , Alviti Federica , Giordan Nicola , Martella Federica , Santilli Valter , Paoloni Marco , Mangone Massimiliano
Published: May 2021

Viscosupplementation by hyaluronic acid (HA) is recommended for non-surgical management of knee osteoarthritis (OA). This study investigated the efficacy and safety of a single i.a. (32 mg/4 ml) Hymovis MO.RE. injection, a new HA derivative hydrogel, for the treatment of adult regular sports players affected by knee OA arising from overuse injuries. Patients were prospectively enrolled if regularly practicing sports and diagnosed with Kellgren-Lawrence grade I-III OA. They received a single Hymovis MO.RE. intra-articular (i.a.) injection and were evaluated 30, 90, 180, and 360 days thereafter. The assessment involved measuring changes in knee function, pain, the activity of daily living (ADL), and quality of life (QOL) by using the Knee injury and Osteoarthritis Outcome Score (KOOS), GAIT analysis, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for knee pain (WOMAC A) and function (WOMAC C), and a visual analogue scale (VAS) pain score. The study involved thirty-one patients, 23 women and eight men, whose median age was 49. KOOS function subscore, as well as GAIT cadence and velocity, showed a statistically significant increase at each time-point after injection (p< 0.0001). WOMAC, KOOS pain, symptoms, ADL, and QOL scores also significantly improved at all control visits. No severe adverse events or treatment-related events were detected. A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection provides a rapid, lasting, and safe response in regular sports players affected by knee OA, possibly representing a viable therapeutic option for this demanding patient subgroup. Further investigations are necessary to confirm these findings.
The Mechanisms of Yu Ping Feng San in Tracking the Cisplatin-Resistance by Regulating ATP-Binding Cassette Transporter and Glutathione S-Transferase in Lung Cancer Cells
Authors: Du Yingqing , Zheng Yuzhong , Yu Ciel Xiaomei , Zhong Lishan , Li Yafang , Wu Baomeng , Hu Weihui , Zhu Elsa Wanyi , Xie Venus Wei , Xu Qitian , Zhan Xingri , Huang Yamiao , Zeng Liyi , Zhang Zhenxia , Liu Xi , Yin Jiachuan , Zha Guangcai , Chan Kelvin , Tsim Karl Wah Keung
Published: May 2021

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs.
Apelin Does Not Impair Coronary Artery Relaxation Mediated by Nitric Oxide-Induced Activation of BKCa Channels
Authors: Mughal Amreen , Sun Chengwen , O’Rourke Stephen T.
Published: May 2021

Apelin-APJ receptor signaling regulates vascular tone in cerebral and peripheral arteries. We recently reported that apelin inhibits BKCa channel function in cerebral arteries, resulting in impaired endothelium-dependent relaxations. In contrast, apelin causes endothelium-dependent relaxation of coronary arteries. However, the effects of apelin on BKCa channel function in coronary arterial myocytes have not yet been explored. We hypothesized that apelin-APJ receptor signaling does not have an inhibitory effect on coronary arterial BKCa channels and hence does not alter nitric oxide (NO)-dependent relaxation of coronary arteries. Patch clamp recording was used to measure whole cell K+ currents in freshly isolated coronary smooth muscle cells. Apelin had no effect on the increases in current density in response to membrane depolarization or to NS1619 (a BKCa channel opener). Moreover, apelin did not inhibit NO/cGMP-dependent relaxations that required activation of BKCa channels in isolated coronary arteries. Apelin-APJ receptor signaling caused a marked increase in intracellular Ca2+ levels in coronary arterial smooth muscle cells, but failed to activate PI3-kinase to increase phosphorylation of Akt protein. Collectively, these data provide mechanistic evidence that apelin has no inhibitory effects on BKCa channel function in coronary arteries. The lack of inhibitory effect on BKCa channels makes it unlikely that activation of APJ receptors in coronary arteries would adversely affect coronary flow by creating a vasoconstrictive environment. It can be expected that apelin or other APJ receptor agonists in development will not interfere with the vasodilator effects of endogenous BKCa channel openers.
Ligustrazine Alleviate Acute Lung Injury Through Suppressing Pyroptosis and Apoptosis of Alveolar Macrophages
Authors: Jiang Rundong , Xu Jiaqi , Zhang Yuezhong , Zhu Xuanmeng , Liu Jiachen , Tan Yurong
Published: May 2021

Ligustrazine (Tetramethylpyrazine, TMP) is an active substance extracted from the Umbelliferae plant Ligusticum chuanxiong. It has been proven to have antioxidant and inflammation effects. The study was designed to explore the efficacy and specific mechanism of TMP for ALI/ARDS treatment. Here, we confirmed that TMP decreased the infiltration of inflammatory cells in alveoli and the secretion of pro-inflammatory factors, which is comparable to glucocorticoids in vivo. In vitro, TMP inhibited the polarization of M1-type macrophages, and to a certain extent, promoted M2-type repolarization, thus reducing LPS-induced massive transcription and secretion of IL-1β, IL-18, TNF-ɑ and other inflammatory factors. Besides, TMP reduced expression of NLRP3, inhibited the formation of inflammasome complexes, and decreased the cleavage of caspase-1, leading to reduced cell pyroptosis and accompanying inflammation. TMP also inhibited apoptosis through caspase-8/caspase-3 signaling pathways. Our study indicates that TMP improved ALI through inhibiting the TLR4/TRAF6/NFκB/NLRP3/caspase-1 and TLR4/caspase-8/caspase-3 signaling pathways, which reversed macrophages polarization, reduced cell pyroptosis and apoptosis, which provides a theoretical basis of using TMP in treating ALI in the future.
Optimal Design of Negative Stiffness Devices for Highway Bridges Using Performance-Based Genetic Algorithm
Authors: Tong Sun , Tianqi Zhu , Li Sun , Hao Zhang
Published: May 2021

Parameter optimization analysis on the negative stiffness device (NSD) installed in the benchmark highway bridge is carried out in this study. Key parameters and constrain conditions are determined in accordance with the characteristics of NSD, and an objective function is designed with safety and comfort being considered. Individual fitness value–related cross and mutation operators are designed to protect excellent chromosome and improve the efficiency and convergence of computation. The genetic algorithm is used to realize parameter optimization of the NSD used in a benchmark highway bridge. Dynamic responses of structure without NSD, with random NSD, and with optimal designed NSD are compared. By analyzing the time history of displacement and acceleration, it can be concluded that dynamic responses of the structure decrease obviously when the NSD is added, and a better seismic reduction effect can be reached when the NSD is designed optimally in accordance with the optimization method and different earthquake excitations have slight influence on the optimization results.
Current Understanding of the Right Ventricle Structure and Function in Pulmonary Arterial Hypertension
Authors: Sharifi Kia Danial , Kim Kang , Simon Marc A.
Published: May 2021

Pulmonary arterial hypertension (PAH) is a disease resulting in increased right ventricular (RV) afterload and RV remodeling. PAH results in altered RV structure and function at different scales from organ-level hemodynamics to tissue-level biomechanical properties, fiber-level architecture, and cardiomyocyte-level contractility. Biomechanical analysis of RV pathophysiology has drawn significant attention over the past years and recent work has found a close link between RV biomechanics and physiological function. Building upon previously developed techniques, biomechanical studies have employed multi-scale analysis frameworks to investigate the underlying mechanisms of RV remodeling in PAH and effects of potential therapeutic interventions on these mechanisms. In this review, we discuss the current understanding of RV structure and function in PAH, highlighting the findings from recent studies on the biomechanics of RV remodeling at organ, tissue, fiber, and cellular levels. Recent progress in understanding the underlying mechanisms of RV remodeling in PAH, and effects of potential therapeutics, will be highlighted from a biomechanical perspective. The clinical relevance of RV biomechanics in PAH will be discussed, followed by addressing the current knowledge gaps and providing suggested directions for future research.
The Optimal Ambient Conditions for World Record and World Class Performances at the Berlin Marathon
Authors: Scheer Volker , Valero David , Villiger Elias , Alvero Cruz José Ramón , Rosemann Thomas , Knechtle Beat
Published: May 2021

The “Berlin Marathon” is the fastest marathon racecourse in the world and has witnessed 11 world records (WRs; eight in men and three in women). Weather conditions can have an important impact on race time and we therefore examined the influence of environmental conditions (i.e., temperature, sunshine, precipitation, barometric pressure, and cloud cover) on WRs and elite (i.e., winner, top three and top 10 finishers) marathon performances of men and women at the “Berlin Marathon” between 1974 and 2019. Average world record marathon times in men were 2:03:52 ± 0:01:19 h:min:s and 2:25:05 ± 0:08:25 h:min:s in females (p < 0.05). Male competitions were held 44 times (mean winning time: 2:09:48 ± 0:09:15 h:min:s) and female competitions 41 times (mean winning time: 02:30:35 ± 0:19:09 h:min:s; p < 0.05). World record performances were set at mean temperatures of 18.61 ± 2.59°C for men and 13.07 ± 4.01°C for women (p > 0.05). The ideal environmental conditions for world record performances for men were temperatures of 18.61°C (p > 0.05), sunny, mostly dry days, with higher atmospheric pressure and little cloud cover (all p > 0.05). In women, ideal conditions for world records performances were temperatures of 13.07°C (p > 0.05), with low atmospheric pressure (p > 0.05), but significantly more rain (p < 0.05), and with no sunshine (p < 0.05) and cloud cover (p < 0.05). With elite performances, the ideal temperatures were of 17.36 ± 4.33°C for men and 17.93 ± 4.07°C for women (p > 0.05), with little to no rain, and moderate cloud cover and sunshine (p > 0.05). In summary, novel findings are, that environmental conditions in world records performances differ between men and women, with women obtaining world records in bad weather (with rain, cloud cover, and no sunshine) and men in good weather (sunny, mostly dry days, with little cloud cover). Larger sample sizes are needed to examine sex differences and environmental conditions on world record marathon performances.
De novo Explorations of Sarcopenia via a Dynamic Model
Authors: Tao Kuan , Duan Yushuang , Wang Huohuo , Zeng Dan , Fang Zilong , Yan Huiping , Lu Yifan
Published: May 2021

Background:The cause of sarcopenia has been observed over decades by clinical trials, which, however, are still insufficient to systematically unravel the enigma of how resistance exercise mediates skeletal muscle mass.

Materials and Methods:Here, we proposed a minimal regulatory network and developed a dynamic model to rigorously investigate the mechanism of sarcopenia. Our model is consisted of eight ordinary differential equations and incorporates linear and Hill-function terms to describe positive and negative feedbacks between protein species, respectively.

Results:A total of 720 samples with 10 scaled intensities were included in simulations, which revealed the expression level of AKT (maximum around 3.9-fold) and mTOR (maximum around 5.5-fold) at 3, 6, and 24 h at high intensity, and non-monotonic relation (ranging from 1.2-fold to 1.7-fold) between the graded intensities and skeletal muscle mass. Furthermore, continuous dynamics (within 24 h) of AKT, mTOR, and other proteins were obtained accordingly, and we also predicted the delaying effect with the median of maximized muscle mass shifting from 1.8-fold to 4.6-fold during a 4-fold increase of delay coefficient.

Conclusion:Thede novomodeling framework sheds light on the interdisciplinary methodology integrating computational approaches with experimental results, which facilitates the deeper understandings of exercise training and sarcopenia.
Limited Effect of 60-Days Strict Head Down Tilt Bed Rest on Vascular Aging
Authors: Möstl Stefan , Orter Stefan , Hoffmann Fabian , Bachler Martin , Hametner Bernhard , Wassertheurer Siegfried , Rabineau Jérémy , Mulder Edwin , Johannes Bernd , Jordan Jens , Tank Jens
Published: May 2021

Background

Cardiovascular risk may be increased in astronauts after long term space flights based on biomarkers indicating premature vascular aging. We tested the hypothesis that 60 days of strict 6° head down tilt bed rest (HDTBR), an established space analog, promotes vascular stiffening and that artificial gravity training ameliorates the response.

Methods

We studied 24 healthy participants (8 women, 24–55 years, BMI = 24.3 ± 2.1 kg/m2) before and at the end of 60 days HDTBR. 16 subjects were assigned to daily artificial gravity. We applied echocardiography to measure stroke volume and isovolumetric contraction time (ICT), calculated aortic compliance (stroke volume/aortic pulse pressure), and assessed aortic distensibility by MRI. Furthermore, we measured brachial-femoral pulse wave velocity (bfPWV) and pulse wave arrival times (PAT) in different vascular beds by blood pressure cuffs and photoplethysmography. We corrected PAT for ICT (cPAT).

Results

In the pooled sample, diastolic blood pressure (+8 ± 7 mmHg, p < 0.001), heart rate (+7 ± 9 bpm, p = 0.002) and ICT (+8 ± 13 ms, p = 0.036) increased during HDTBR. Stroke volume decreased by 14 ± 15 ml (p = 0.001). bfPWV, aortic compliance, aortic distensibility and all cPAT remained unchanged. Aortic area tended to increase (p = 0.05). None of the parameters showed significant interaction between HDTBR and artificial gravity training.

Conclusion

60 days HDTBR, while producing cardiovascular deconditioning and cephalad fluid shifts akin to weightlessness, did not worsen vascular stiffness. Artificial gravity training did not modulate the response.
Identification and Analysis of bZIP Family Genes in Potato and Their Potential Roles in Stress Responses
Authors: Wang Qi , Guo Cun , Li Zhiyuan , Sun Jinhao , Wang Dong , Xu Liangtao , Li Xiaoxu , Guo Yongfeng
Published: May 2021

The bZIP proteins comprise one of the largest transcription factor families and play important roles in plant growth and development, senescence, metabolic reactions, and stress responses. In this study, 49 bZIP transcription factor-encoding genes (StbZIP genes) on the potato genome were identified and analyzed. The 49 StbZIP genes, which are located on 12 chromosomes of the potato genome, were divided into 11 subgroups together with their Arabidopsis homologs based on the results of phylogenetic analysis. Gene structure and protein motif analysis revealed that members from the same subgroup often possessed similar exon/intron structures and motif organizations, further supporting the results of the phylogenetic analysis. Syntenic analysis indicated the existence of gene duplication events, which might play an important role in the expansion of the bZIP gene family in potato. Expressions of the StbZIP genes were analyzed in a variety of tissues via RNA-Seq data, suggesting functional diversity. Several StbZIP genes were found to be induced by different stress conditions. For example, the expression of StbZIP25, the close homolog of AtbZIP36/ABF2, was significantly upregulated by salt stress treatments. The StbZIP25 protein was found to be located in the nucleus and function as a transcriptional activator. Overexpression of StbZIP25 enhanced salt tolerance in Arabidopsis. The results from this study imply potential roles of the bZIP family genes in the stress response of potato.
A VHH-Fc Fusion Targeted to the Chloroplast Thylakoid Lumen Assembles and Neutralizes Enterohemorrhagic E. coli O157:H7
Authors: Chin-Fatt Adam , Menassa Rima
Published: May 2021

Chimeric fusion proteins comprising a single domain antibody (VHH) fused to a crystallizable fragment (Fc) of an immunoglobulin are modular glycoproteins that are becoming increasingly in demand because of their value as diagnostics, research reagents and passive immunization therapeutics. Because ER-associated degradation and misfolding may potentially be limiting factors in the oxidative folding of VHH-Fc fusion proteins in the ER, we sought to explore oxidative folding in an alternative sub-compartment, the chloroplast thylakoid lumen, and determine its viability in a molecular farming context. We developed a set of in-house expression vectors for transient transformation ofNicotiana benthamianaleaves that target a VHH-Fc to the thylakoid lumen via either secretory (Sec) or twin-arginine translocation (Tat) import pathways. Compared to stromal [6.63 ± 3.41 mg/kg fresh weight (FW)], cytoplasmic (undetectable) and Tat-import pathways (5.43 ± 2.41 mg/kg FW), the Sec-targeted VHH-Fc showed superior accumulation (30.56 ± 5.19 mg/kg FW), but was less than that of the ER (51.16 ± 9.11 mg/kg FW). Additionally, the introduction of a rationally designedde novodisulfide bond enhancesin plantaaccumulation when introduced into the Sec-targeted Fc fusion protein from 50.24 ± 4.08 mg/kg FW to 110.90 ± 6.46 mg/kg FW.In vitroimmunofluorescent labeling assays on VHH-Fc purified from Sec, Tat, and stromal pathways demonstrate that the antibody still retains VHH functionality in binding EscherichiacoliO157:H7 and neutralizing its intimate adherence to human epithelial type 2 cells. These results overall provide a proof of concept that the oxidative folding environment of the thylakoid lumen may be a viable compartment for stably folding disulfide-containing recombinant VHH-Fc proteins.
Female Entrepreneurial Intentions in Pakistan: A Theory of Planned Behavior Perspective
Authors: Sarwar Ambreen , Ahsan Qurratulain , Rafiq Nazia
Published: May 2021

With theoretical underpinnings in the theory of planned behavior, this research aims at investigating how women's entrepreneurial intentions might develop in Pakistan. The survey of 216 female students revealed that psychological capital plays an important role in shaping women's entrepreneurial commitment which in turn results in increased intentions to opt for entrepreneurship as a career. Additionally, it was observed that social support moderates the indirect relation in such a way that in the presence of high social support, the association between psychological capital and intentions via commitment is further strengthened. Because women face comparatively more barriers in paid career, therefore it was necessary to study the mechanism and driver that can improve their entrepreneurial intentions, since they represent an untapped resource that might be utilized to improve the economic prospects of a country. The study bridges a significant knowledge gap in utilizing psychological capital to enhance female's entrepreneurial intentions, who are under constant pressure of juggling multiple roles at work and home.
Predicting Regional Variations in Nationalism With Online Expression of Disgust in China
Authors: Gao Shuqing , Chen Hao , Lai Kaisheng , Qian Weining
Published: May 2021

Disgust is one of the basic emotions and is part of the behavioral immune system, which evolutionarily protects humans from toxic substances as well as from contamination threats by outgroup members. Previous works reveal that disgust not only activates humans’ defense against potential individual and collective threats, but also leads to severe moral judgments, negative intergroup attitudes, and even conservative political orientations. As is already known, nationalism is an ideology that features both negative feelings toward outgroups and beliefs about native superiority or privileges. Evidence from previous studies suggests that disgust is related to nationalism’s several components but lacks direct research on nationalism and disgust. The current study examines the relationship between disgust and nationalism in China at both individual and regional levels. In study 1, participants temporally induced disgust (vs. control) increasing the adoption of nationalism. In Study 2, we analyzed covariation in disgust expression in the Chinese micro-blog Weibo and the nationalism index as part of an online large-scale political survey http://zuobiao.me/ at the province level across Mainland China. The results show that online expression of disgust positively predicts nationalistic orientation at the regional level. Finally, we discuss how the findings shed light on research concerning online emotion expression and potential future directions.
Perception and Evaluation of 23 Positive Emotions in Hong Kong and the Netherlands
Authors: Sun Rui , Hou Wai Kai , Hui Bryant P. H. , Siu Nicolson Yat-Fan , Engels Tiarah , Sauter Disa A.
Published: May 2021

Positive emotions are linked to numerous benefits, but not everyone appreciates the same kinds of positive emotional experiences. We examine how distinct positive emotions are perceived and whether individuals’ perceptions are linked to how societies evaluate those emotions. Participants from Hong Kong and Netherlands rated 23 positive emotions based on their individual perceptions (positivity, arousal, and socially engaging) and societal evaluations (appropriate, valued, and approved of). We found that (1) there were cultural differences in judgments about all six aspects of positive emotions; (2) positivity, arousal, and social engagement predicted emotions being positively regarded at the societal level in both cultures; and (3) that positivity mattered more for the Dutch participants, although arousal and social engagement mattered more in Hong Kong for societal evaluations. These findings provide a granular map of the perception and evaluation of distinct positive emotions in two cultures and highlight the role of cultures in the understanding how positive emotions are perceived and evaluated.
Emotions in Intergroup Contact: Incidental and Integral Emotions' Effects on Interethnic Bias Are Moderated by Emotion Applicability and Subjective Agency
Authors: Paolini Stefania , Harwood Jake , Logatchova Aleksandra , Rubin Mark , Mackiewicz Matylda
Published: May 2021

This research draws from three distinct lines of research on the link between emotions and intergroup bias as springboard to integrative, new hypotheses. Past research suggests that emotions extrinsic to the outgroup (or “incidental”), and intrinsic to the outgroup (or “integral”), produce valence-congruent effects on intergroup bias when relevant or “applicable” to the outgroup (e.g., incidental/integral anger and ethnic outgroups). These emotions produce valenceincongruent effects when irrelevant or “non-applicable” to the outgroup (e.g., incidental/integral sadness and happiness, and ethnic outgroups). Internally valid and ecologically sound tests of these contrasting effects are missing; hence we examined them experimentally in meaningful settings of interethnic contact. To this end, we hybridized established research paradigms in mood and intergroup contact research; this approach enabled us to use same materials and induction methods to instigate incidental and integral emotions in a single research design. In Experiment 1, White Australian students (N= 93) inin vivoreal face-to-face contact with an ethnic tutor in their classroom displayed less interethnic bias when incidentally sad (vs. happy) or integrally happy (vs. sad). In Experiment 2, White American males' (N= 492) anti-Arab bias displayed divergent effects under incidental vs. integral (non-applicable) sadness/happiness and similar effects under incidental vs. integral (applicable) anger. The role of perceptions of agency in the emotion-inducing situation is also explored, tested, and explained drawing from mainstream emotion theory. As expected, integral and incidentalapplicableemotions caused valence congruent effects, at the opposite sides of the subjective agency spectrum, by encouraging the generalization of dislike from the outgroup contact partner to the outgroup as a whole. On the other hand, incidental-non-applicable emotions caused valence-incongruent effects on bias, under high agency conditions, by encouraging (non-partner-centered) heuristic processing. Because of the improved methodology, these effects can be regarded as genuine and not the byproduct of methodological artifacts. This theory-driven and empirically sound analysis of the interplay between emotion source, emotion applicability and subjective agency in intergroup contact can increase the precision of emotion-based bias reduction strategies by deepening understanding of the emotion conditions that lead to intergroup bias attenuation vs. exacerbation.
Would You Rather Be Safe or Free? Motivational and Behavioral Aspects in COVID-19 Mitigation
Authors: Costantini Giulio , Di Sarno Marco , Preti Emanuele , Richetin Juliette , Perugini Marco
Published: May 2021

This work investigates the relationship between goals and mitigation behaviors during the COVID-19 pandemic in Italy. Study 1 (pilot) identified goals ascribed to following and violating mitigation-related indications. Study 2 investigated the structure of and link between COVID-related goals and behaviors in a large community sample (N = 995, 301 men). Our results showed substantial relationships between goals and behaviors. Goals were best described by a bi-dimensional structure (being safe vs. being free), whereas behaviors clustered into a three-component structure (hygiene, distancing, going out). Hierarchical multiple regressions demonstrated the incremental validity of goals in the prediction of behaviors. Network analysis suggested that goals imbued with social content were more directly related to both risky and preventive behaviors. Motivational aspects emerged as important contributors to the organization of behaviors in the context of the COVID-19 pandemic.
Adaptation in Predictive Prosodic Processing in Bilinguals
Authors: Foltz Anouschka
Published: May 2021

Native language listeners engage in predictive processing in many processing situations and adapt their predictive processing to the statistics of the input. In contrast, second language listeners engage in predictive processing in fewer processing situations. The current study uses eye-tracking data from two experiments in bilinguals’ native language (L1) and second language (L2) to explore their predictive processing based on contrastive pitch accent cues, and their adaptation in the face of prediction errors. The results of the first experiment show inhibition effects for unpredicted referents in both the L1 and the L2 that can be modeled with a Bayesian adaptation model, suggesting that bilinguals adapt their prediction in the face of prediction errors in a way that is compatible with the model. In contrast, the results of the second experiment, after a training phase that increased the predictive validity of the cue, show inhibition effects for unpredicted referents only in the L1, but not in the L2. In addition, the Bayesian adaptation model significantly predicts only the L1, but not the L2 data. The results are discussed with respect to adaptation to the statistical properties of the input.
Reducing Objectification Could Tackle Stigma in the COVID-19 Pandemic: Evidence From China
Authors: Chen Youli , Jin Jiahui , Zhang Xiangyang , Zhang Qi , Dong Weizhen , Chen Chun
Published: May 2021

Stigmatization associated with the coronavirus disease 2019 (COVID-19) is expected to be a complex issue and to extend into the later phases of the pandemic, which impairs social cohesion and relevant individuals' well-being. Identifying contributing factors and learning their roles in the stigmatization process may help tackle the problem. This study quantitatively assessed the severity of stigmatization against three different groups of people: people from major COVID-19 outbreak sites, those who had been quarantined, and healthcare workers; explored the factors associated with stigmatization within the frameworks of self-categorization theory and core social motives; and proposed solutions to resolve stigma. The cross-sectional online survey was carried out between April 21 and May 7, 2020, using a convenience sample, which yielded 1,388 valid responses. Employing data analysis methods like multivariate linear regression and moderation analysis, this study yields some main findings: (1) those from major COVID-19 outbreak sites received the highest level of stigma; (2) factors most closely associated with stigmatization, in descending order, are objectification and epidemic proximity in an autonomic aspect and fear of contracting COVID-19 in a controllable aspect; and (3) superordinate categorization is a buffering moderator in objectification–stigmatization relationship. These findings are important for further understanding COVID-19-related stigma, and they can be utilized to develop strategies to fight against relevant discrimination and bias. Specifically, reinforcing superordinate categorization by cultivating common in-group identity, such as volunteering and donating for containment of the pandemic, could reduce objectification and, thus, alleviate stigma.
Dimensions and Clusters of Aesthetic Emotions: A Semantic Profile Analysis
Authors: Beermann Ursula , Hosoya Georg , Schindler Ines , Scherer Klaus R. , Eid Michael , Wagner Valentin , Menninghaus Winfried
Published: May 2021

Aesthetic emotions are elicited by different sensory impressions generated by music, visual arts, literature, theater, film, or nature scenes. Recently, the AESTHEMOS scale has been developed to facilitate the empirical assessment of such emotions. In this article we report a semantic profile analysis of aesthetic emotion terms that had been used for the development of this scale, using the GRID approach. This method consists of obtaining ratings of emotion terms on a set of meaning facets (features) which represent five components of the emotion process (appraisal, bodily reactions, action tendencies, expression, and feelings). The aims here were (a) to determine the dimensionality of the GRID features when applied to aesthetic emotions and compare it to published results for emotion terms in general, and (b) to examine the internal organization of the domain of aesthetic emotion terms in order to identify salient clusters of these items based on the similarity of their feature profiles on the GRID. Exploratory Principal Component Analyses suggest a four-dimensional structure of the semantic space consisting of valence, power, arousal, and novelty, converging with earlier GRID studies on large sets of standard emotion terms. Using cluster analyses, 15 clusters of aesthetic emotion terms with similar GRID feature profiles were identified, revealing the internal organization of the aesthetic emotion terms domain and meaningful subgroups of aesthetic emotions. While replication for further languages is required, these findings provide a solid basis for further research and methodological development in the realm of aesthetic emotions.