bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Phenotyping of Headache in Hospitalized COVID-19 Patients via Principal Component Analysis
Authors: Planchuelo-Gómez Álvaro , Trigo Javier , de Luis-García Rodrigo , Guerrero Ángel L. , Porta-Etessam Jesús , García-Azorín David
Published: January 2021

Objectives: Headache is a common symptom in systemic infections, and one of the symptoms of the novel coronavirus disease 2019 (COVID-19). The objective of this study was to characterize the phenotype of COVID-19 headache via machine learning.

Methods: We performed a cross-sectional study nested in a retrospective cohort. Hospitalized patients with COVID-19 confirmed diagnosis who described headache were included in the study. Generalized Linear Models and Principal Component Analysis were employed to detect associations between intensity and self-reported disability caused by headache, quality and topography of headache, migraine features, COVID-19 symptoms, and results from laboratory tests.

Results: One hundred and six patients were included in the study, with a mean age of 56.6 ± 11.2, including 68 (64.2%) females. Higher intensity and/or disability caused by headache were associated with female sex, fever, abnormal platelet count and leukocytosis, as well as migraine symptoms such as aggravation by physical activity, pulsating pain, and simultaneous photophobia and phonophobia. Pain in the frontal area (83.0% of the sample), pulsating quality, higher intensity of pain, and presence of nausea were related to lymphopenia. Pressing pain and lack of aggravation by routine physical activity were linked to low C-reactive protein and procalcitonin levels.

Conclusion: Intensity and disability caused by headache attributed to COVID-19 are associated with the disease state and symptoms. Two distinct headache phenotypes were observed in relation with COVID-19 status. One phenotype seems to associate migraine symptoms with hematologic and inflammatory biomarkers of severe COVID-19; while another phenotype would link tension-type headache symptoms to milder COVID-19.
Different Targets of Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders: A Meta-Analysis Evidenced From Randomized Controlled Trials
Authors: Xue Tao , Yu Jiahao , Chen Shujun , Wang Zilan , Yang Yanbo , Chen Zhouqing , Wang Zhong
Published: January 2021

Background: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune inflammatory disorder of the central nervous system, often leads to vision loss or paralysis. This meta-analysis focused on the assessment of the monoclonal antibody therapy in NMOSD and compared different targets of monoclonal antibodies with each other in terms of efficacy and safety outcomes.

Method: We searched through the databases of MEDLINE, EMBASE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov for randomized controlled trials (RCTs) evaluating monoclonal antibody therapy in NMOSD up to April 2020.

Results: We identified seven randomized controlled trials (RCTs), including 775 patients (monoclonal antibody group, n = 485 and placebo group, n = 290). Monoclonal antibody therapy decreased relapse risk (RR 0.33, 95% CI 0.21–0.52, P < 0.00001), annualized relapse rate (ARR) (mean −0.28, 95% CI −0.35−0.20, P < 0.00001), expanded disability status scale score (EDSS) (mean −0.19, 95% CI −0.32−0.07, P = 0.002) and serious adverse events (RR 0.78, 95% CI 0.61–1.00, P = 0.05). However, we did not observe any significant difference in terms of adverse events or mortality. Further, the subgroup analysis demonstrated that the anti-complement protein C5 monoclonal antibody (eculizumab) might have a lower relapse risk (RR 0.07, 95% CI 0.02–0.23, P < 0.0001) in the AQP4 seropositive patients, and anti-interleukin-6 receptor monoclonal antibodies (satralizumab and tocilizumab) showed decreased EDSS score (mean −0.17, 95% CI −0.31−0.02, P = 0.02) more effectively than other monoclonal antibodies.

Conclusions: Monoclonal antibodies were effective and safe in NMOSD. Different targets of monoclonal antibodies might have their own advantages.
Dance on the Brain: Enhancing Intra- and Inter-Brain Synchrony
Authors: Basso Julia C. , Satyal Medha K. , Rugh Rachel
Published: January 2021

Dance has traditionally been viewed from a Eurocentric perspective as a mode of self-expression that involves the human body moving through space, performed for the purposes of art, and viewed by an audience. In this Hypothesis and Theory article, we synthesize findings from anthropology, sociology, psychology, dance pedagogy, and neuroscience to propose The Synchronicity Hypothesis of Dance, which states that humans dance to enhance both intra- and inter-brain synchrony. We outline a neurocentric definition of dance, which suggests that dance involves neurobehavioral processes in seven distinct areas including sensory, motor, cognitive, social, emotional, rhythmic, and creative. We explore The Synchronicity Hypothesis of Dance through several avenues. First, we examine evolutionary theories of dance, which suggest that dance drives interpersonal coordination. Second, we examine fundamental movement patterns, which emerge throughout development and are omnipresent across cultures of the world. Third, we examine how each of the seven neurobehaviors increases intra- and inter-brain synchrony. Fourth, we examine the neuroimaging literature on dance to identify the brain regions most involved in and affected by dance. The findings presented here support our hypothesis that we engage in dance for the purpose of intrinsic reward, which as a result of dance-induced increases in neural synchrony, leads to enhanced interpersonal coordination. This hypothesis suggests that dance may be helpful to repattern oscillatory activity, leading to clinical improvements in autism spectrum disorder and other disorders with oscillatory activity impairments. Finally, we offer suggestions for future directions and discuss the idea that our consciousness can be redefined not just as an individual process but as a shared experience that we can positively influence by dancing together.
Nitric Oxide Is Essential for Generating the Minute Rhythm Contraction Pattern in the Small Intestine, Likely via ICC-DMP
Authors: Parsons Sean P. , Huizinga Jan D.
Published: January 2021

Nitrergic nerves have been proposed to play a critical role in the orchestration of peristaltic activities throughout the gastrointestinal tract. In the present study, we investigated the role of nitric oxide, using spatiotemporal mapping, in peristaltic activity of the wholeex vivomouse intestine. We identified a propulsive motor pattern in the form of propagating myogenic contractions, that are clustered by the enteric nervous system into a minute rhythm that is dependent on nitric oxide. The cluster formation was abolished by TTX, lidocaine and nitric oxide synthesis inhibition, whereas the myogenic contractions, occurring at the ICC-MP initiated slow wave frequency, remained undisturbed. Cluster formation, inhibited by block of nitric oxide synthesis, was fully restored in a highly regular rhythmic fashion by a constant level of nitric oxide generated by sodium nitroprusside; but the action of sodium nitroprusside was inhibited by lidocaine indicating that it was relying on neural activity, but not rhythmic nitrergic nerve activity. Hence, distention-induced activity of cholinergic nerves and/or a co-factor within nitrergic nerves such as ATP is also a requirement for the minute rhythm. Cluster formation was dependent on distention but was not evoked by a distention reflex. Block of gap junction conductance by carbenoxolone, dose dependently inhibited, and eventually abolished clusters and contraction waves, likely associated, not with inhibition of nitrergic innervation, but by abolishing ICC network synchronization. An intriguing feature of the clusters was the presence of bands of rhythmic inhibitions at 4–8 cycles/min; these inhibitory patches occurred in the presence of tetrodotoxin or lidocaine and hence were not dependent on nitrergic nerves. We propose that the minute rhythm is generated by nitric oxide-induced rhythmic depolarization of the musculature via ICC-DMP.
Theacrine From Camellia kucha and Its Health Beneficial Effects
Authors: Sheng Yue-Yue , Xiang Jing , Wang Ze-Shi , Jin Jing , Wang Ying-Qi , Li Qing-Sheng , Li Da , Fang Zhou-Tao , Lu Jian-Liang , Ye Jian-Hui , Liang Yue-Rong , Zheng Xin-Qiang
Published: January 2021

Theacrine, i.e., 1,3,7,9-tetramethyluric acid, is one of the major purine alkaloids found in leaf of a wild tea plant species Camellia kucha Hung T. Chang. Theacrine has been attracted great attentions academically owing to its diverse health benefits. Present review examines the advances in the research on the health beneficial effects of theacrine, including antioxidant effect, anti-inflammatory effect, locomotor activation and reducing fatigue effects, improving cognitive effect, hypnotic effect, ameliorating lipid metabolism and inhibiting breast cancer cell metastasis effect. The inconsistent results in this research field and further expectations were also discussed.
Interaction Effect Between Copy Number Variation in Salivary Amylase Locus (AMY1) and Starch Intake on Glucose Homeostasis in the Malmö Diet and Cancer Cohort
Authors: Hamid Aida Koder , Andersson-Assarsson Johanna , Ericson Ulrika , Sonestedt Emily
Published: January 2021

Salivary amylase initiates the digestion of starch and it has been hypothesized that salivary amylase may play a role in the development of insulin resistance and type 2 diabetes. The aim was to examine the interaction between copy number variation in the salivary amylase gene AMY1 and starch intake. We studied 3,624 adults without diabetes or elevated blood glucose in the Malmö Diet Cancer cohort. We assessed the associations and interactions between starch intake, AMY1 copies and glucose homeostasis traits (i.e., fasting plasma glucose, insulin and HOMA-IR) and risk of type 2 diabetes over an average of 18 follow-up years. AMY1 copy number was not associated with glucose, insulin or HOMA-IR. We observed a significant interaction between starch intake and AMY1 copies on insulin and HOMA-IR after adjusting for potential confounders (p < 0.05). The inverse association between starch intake and insulin and HOMA-IR was stronger in the group with 10 or more copies (Ptrend < 0.001). In addition, we observed an inverse association between starch intake and type 2 diabetes in the group with 10 or more copies (ptrend = 0.003), but not in the other groups. This cross-sectional observational study suggests that AMY1 copy numbers might interact with starch intake on glucose homeostasis traits. Interventional studies are required to determine whether individuals with high AMY1 copy numbers may benefit from a high starch intake.
Poor Lymphocyte Infiltration to Primary Tumors in Acral Lentiginous Melanoma and Mucosal Melanoma Compared to Cutaneous Melanoma
Authors: Nakamura Yoshiyuki , Zhenjie Zhu , Oya Kazumasa , Tanaka Ryota , Ishitsuka Yosuke , Okiyama Naoko , Watanabe Rei , Fujisawa Yasuhiro
Published: January 2021

Recent clinical trials have demonstrated the efficacy of immune checkpoint inhibitors (ICIs) for treating melanoma. However, these previous studies comprised mainly Caucasian populations, in which cutaneous melanoma (CM) is the major clinical type. In contrast, Asian populations have a distinct profile of melanoma and show much higher frequencies of acral lentiginous melanoma (ALM) and mucosal melanoma (MCM). Compared with CM, ALM and MCM show poorer response to ICIs, but the mechanisms have not been fully understood. To evaluate the immune status in each melanoma subtype, we examined the number of total tumor-infiltrating lymphocytes (TILs), CD4+ TILs, CD8+ TILs, and tumor-infiltrating FoxP3+ regulatory T cells (Tregs) to evaluate the immune status in each melanoma subtype using data from 137 patients with melanoma. Total TIL numbers in ALM and MCM were significantly lower than that in CM. CD4+ TIL number in MCM was also lower than CM although CD4+ TIL number in ALM was comparable with CM. In contrast, CD8+ TIL numbers in both ALM and MCM were significantly lower than that in CM. Although number of tumor-infiltrating Tregs was comparable among the 3 subtypes, the proportion of tumor-infiltrating Tregs in CD4+ T cells in MCM was significantly higher than in CM and ALM. Multivariate regression analysis revealed that ALM and MCM were significantly associated with a lower total TIL number, but only MCM was significantly associated with a lower CD4+ TIL number. Multivariate regression analysis also revealed that both ALM and MCM were significantly associated with a lower CD8+ TIL number. Our results suggest that both ALM and MCM are independent factors of lower total TIL number, which may be associated with poorer responses to ICIs in ALM and MCM.
Targeting NAT10 Induces Apoptosis Associated With Enhancing Endoplasmic Reticulum Stress in Acute Myeloid Leukemia Cells
Authors: Zi Jie , Han Qi , Gu Siyu , McGrath Mary , Kane Shriya , Song Chunhua , Ge Zheng
Published: January 2021

N-acetyltransferase 10 (NAT10) has oncogenic properties in many tumors through its role in different cellular biological processes. NAT10 is also a potential biomarker in acute myeloid leukemia (AML); however, the mechanisms underlying NAT10’s contribution to disease states and the effect of targeting NAT10 as a therapeutic target remain unclear. NAT10 was found to be highly expressed in patients with AML, and increased NAT10 expression was associated with poor outcomes. Additionally, targeting NAT10 via the shRNA knockdown and its pharmacotherapeutic inhibitor resulted in inhibition of cell proliferation, induction of cell cycle arrest in the G1 phase, and apoptosis in AML cells. Moreover, NAT10 induces cell cycle arrest by decreasing expression of CDK2, CDK4, CyclinD1, Cyclin E while simultaneously increasing the expression of p16 and p21. Targeting NAT10 induces ER stress through the increased expression of GRP78 and the cleavage of caspase 12, which are classical markers of ER stress. This triggered the Unfolded Protein Response (UPR) pathway by consequently increasing IRE1, CHOP, and PERK expression, all of which play crucial roles in the UPR pathway. Targeting NAT10 also activated the classical apoptotic pathway through the upregulation of the Bax/bak and the concurrent downregulation of Bcl-2. In summary, our data indicate that targeting NAT10 promotes ER stress, triggers the UPR pathway, and activates the Bax/Bcl-2 axis in AML cells. Our results thus indicate a novel mechanism underlying the induction of NAT10 inhibition-mediated apoptosis and reveal the potential for the therapeutic effect of a NAT10 specific inhibitor in AML.
Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p
Authors: Liu Xiaoli , Fu Qingfeng , Bian Xuehai , Fu Yantao , Xin Jingwei , Liang Nan , Li Shijie , Zhao Yishen , Fang Li , Li Changlin , Zhang Jiao , Dionigi Gianlorenzo , Sun Hui
Published: January 2021

The principal issue derived from thyroid cancer is its high propensity to metastasize to the lymph node. Aberrant exprssion of long non-coding RNAs have been extensively reported to be significantly correlated with lymphatic metastasis of thyroid cancer. However, the clinical significance and functional role of lncRNA-MAPK8IP1P2 in lymphatic metastasis of thyroid cancer remain unclear. Here, we reported that MAPK8IP1P2 was downregulated in thyroid cancer tissues with lymphatic metastasis. Upregulating MAPK8IP1P2 inhibited, while silencing MAPK8IP1P2 enhanced anoikis resistance in vitro and lymphatic metastasis of thyroid cancer cells in vivo. Mechanistically, MAPK8IP1P2 activated Hippo signaling by sponging miR-146b-3p to disrupt the inhibitory effect of miR-146b-3p on NF2, RASSF1, and RASSF5 expression, which further inhibited anoikis resistance and lymphatic metastasis in thyroid cancer. Importantly, miR-146b-3p mimics reversed the inhibitory effect of MAPK8IP1P2 overexpression on anoikis resistance of thyroid cancer cells. In conclusion, our findings suggest that MAPK8IP1P2 may serve as a potential biomarker to predict lymphatic metastasis in thyroid cancer, or a potential therapeutic target in lymphatic metastatic thyroid cancer.
Effectiveness of Gentle Human Touch for Pain Control During Examination for Retinopathy of Pre-maturity: A Randomized Controlled Trial
Authors: Sun Yongping , Zhang Jinghan , Chen Xu , Yang Yang , Qiu Jie , Lu Ke-yu , Cheng Rui
Published: January 2021

Background: Retinopathy of pre-maturity (ROP) is a disorder of the retinal blood vessels in pre-term infants with low birth weight. It is a leading cause of blindness in children. During ROP screening, the use of mydriatic drops and eyelid openers causes pain and discomfort. Pain management strategies include medications and behavioral interventions. The objectives of this study was to investigate the effects of Gentle Human Touch on pain in pre-term infants undergoing screening for ROP.

Methods: In this randomized controlled trial, 82 infants in the neonatal intensive care unit at Children's Hospital of Nanjing Medical University who met the ROP screening criteria were randomly assigned to experimental and control groups using the random number table. The infants in the experimental group continuously received Gentle Human Touch during screening, while those in the control group were screened according to the routine procedure. All neonates were administered local eye anesthesia before the screening. The degree of pain was assessed using the Pre-mature Infant Pain Profile score. A double-channel near-infrared spectroscopy device was used to monitor regional cerebral oxygen saturation (rScO2), while oxygen saturation (SaO2) and heart rate were measured using pulse oximetry. The Pre-mature Infant Pain Profile score was the primary outcome, while heart rate, SaO2, and rScO2 were the secondary outcomes.

Results: The gestational age, corrected gestational age, birth weight, and Apgar score at examination and the basal heart rate, SaO2, and rScO2 showed no significant intergroup differences (P > 0.05 for all). Both groups demonstrated significant decreases in SaO2 and rScO2 in response to the examination (P < 0.05 for all). During the examination, the Pre-mature Infant Pain Profile score (14.82 ± 3.22 vs. 9.29 ± 2.89, respectively; P < 0.05) was significantly higher in the control group than in the experimental group, while rScO2 (57.61 ± 3.51 vs. 54.76 ± 4.54%, respectively; P < 0.05) and SaO2 (91.89 ± 6.43 vs. 85.68 ± 8.31%; P < 0.05) were significantly higher in the experimental group than in the control group. There was no significant difference in heart rate changes between the two groups before and after the examination (182.60 ± 3.50 vs. 170.80 ± 3.50 time/min; P > 0.05).

Conclusions: The findings of this study suggest that Gentle Human Touch can effectively alleviate pain during ROP screening in pre-mature infants.

Clinical Trial Registration: ISRCTN10976481, Registered 06 March 2020, Retrospectively registered.
Fluorofenidone Alleviates Renal Fibrosis by Inhibiting Necroptosis Through RIPK3/MLKL Pathway
Authors: Dai Qin , Zhang Yan , Liao Xiaohua , Jiang Yupeng , Lv Xin , Yuan Xiangning , Meng Jie , Xie Yanyun , Peng Zhangzhe , Yuan Qiongjing , Tao LiJian , Huang Ling
Published: January 2021

Cell death and sterile inflammation are major mechanisms of renal fibrosis, which eventually develop into end-stage renal disease. “Necroptosis” is a type of caspase-independent regulated cell death, and sterile inflammatory response caused by tissue injury is strongly related to necrosis. Fluorofenidone (AKF-PD) is a novel compound shown to ameliorate renal fibrosis and associated inflammation. We investigated whether AKF-PD could alleviate renal fibrosis by inhibiting necroptosis. Unilateral ureteral obstruction (UUO) was used to induce renal tubulointerstitial fibrosis in C57BL/6J mice. AKF-PD (500 mg/kg) or necrostatin-1 (Nec-1; 1.65 mg/kg) was administered simultaneously for 3 and 7 days. Obstructed kidneys and serum were harvested after euthanasia. AKF-PD and Nec-1 ameliorated renal tubular damage, inflammatory-cell infiltration, and collagen deposition, and the expression of proinflammatory factors (interlukin-1β, tumor necrosis factor [TNF]-α) and chemokines (monocyte chemoattractant protein-1) decreased. AKF-PD or Nec-1 treatment protected renal tubular epithelial cells from necrosis and reduced the release of lactate dehydrogenase in serum. Simultaneously, production of receptor-interacting protein kinase (RIPK)3 and mixed lineage kinase domain-like protein (MLKL) was also reduced 3 and 7 days after UUO. AKF-PD and Nec-1 significantly decreased the percentage of cell necrosis, inhibiting the phosphorylation of MLKL and RIPK3 in TNF-α- and Z-VAD–stimulated human proximal tubular epithelial (HK-2) cells. In conclusion, AKF-PD and Nec-1 have effective anti-inflammatory and antifibrotic activity in UUO-induced renal tubulointerstitial fibrosis, potentially mediated by the RIPK3/MLKL pathway.
Physiologically-Based Pharmacokinetic-Pharmacodynamics Model Characterizing CYP2C19 Polymorphisms to Predict Clopidogrel Pharmacokinetics and Its Anti-Platelet Aggregation Effect Following Oral Administration to Coronary Artery Disease Patients With or Without Diabetes
Authors: Xu Ru-jun , Kong Wei-min , An Xiao-fei , Zou Jian-jun , Liu Li , Liu Xiao-dong
Published: January 2021

Background and Objective: Clopidogrel (CLOP) is commonly used in coronary artery disease (CAD) patients with or without diabetes (DM), but these patients often suffer CLOP resistance, especially those with diabetes. This study was aimed to develop a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to describe the pharmacokinetics and pharmacodynamics of clopidogrel active metabolite (CLOP-AM) in CAD patients with or without DM.

Methods: The PBPK-PD model was first established and validated in healthy subjects and then in CAD patients with or without DM. The influences of CYP2C19, CYP2C9, CYP3A4, carboxylesterase 1 (CES1), gastrointestinal transit rates (Kt,i) and platelets response to CLOP-AM (kirre) on predicted pharmacokinetics and pharmacodynamics were investigated, followed with their individual and integrated effects on CLOP-AM pharmacokinetics due to changes in DM status.

Results: Most predictions fell within 0.5–2.0 folds of observations, indicating successful predictions. Sensitivity analysis showed that contributions of interested factors to pharmacodynamics were CES1> kirre> Kt,i> CYP2C19 > CYP3A4> CYP2C9. Mimicked analysis showed that the decreased exposure of CLOP-AM by DM was mainly attributed to increased CES1 activity, followed by decreased CYP2C19 activity.

Conclusion: The pharmacokinetics and pharmacodynamics of CLOP-AM were successfully predicted using the developed PBPK-PD model. Clopidogrel resistance by DM was the integrated effects of altered Kt,i, CYP2C19, CYP3A4, CES1 and kirre.
Coherent Anti-Stokes Raman Scattering Microscopy and Its Applications
Authors: Li Shaowei , Li Yanping , Yi Rongxing , Liu Liwei , Qu Junle
Published: January 2021

Coherent anti-Stokes Raman scattering (CARS) microscopy can provide high resolution, high speed, high sensitivity, and non-invasive imaging of specific biomolecules without labeling. In this review, we first introduce the principle of CARS microscopy, and then discuss its configuration, including that of the laser source and the multiplex CARS system. Finally, we introduce the applications of CARS in biomedicine and materials, and its future prospects.
Linking ADHD and Behavioral Assessment Through Identification of Shared Diagnostic Task-Based Functional Connections
Authors: McNorgan Chris , Judson Cary , Handzlik Dakota , Holden John G.
Published: January 2021

A mixed literature implicates atypical connectivity involving attentional, reward and task inhibition networks in ADHD. The neural mechanisms underlying the utility of behavioral tasks in ADHD diagnosis are likewise underexplored. We hypothesized that a machine-learning classifier may use task-based functional connectivity to compute a joint probability function that identifies connectivity signatures that accurately predict ADHD diagnosis and performance on a clinically-relevant behavioral task, providing an explicit neural mechanism linking behavioral phenotype to diagnosis. We analyzed archival MRI and behavioral data of 80 participants (64 male) who had completed the go/no-go task from the longitudinal follow-up of the Multimodal Treatment Study of ADHD (MTA 168) (mean age = 24 years). Cross-mutual information within a functionally-defined mask measured functional connectivity for each task run. Multilayer feedforward classifier models identified the subset of functional connections that predicted clinical diagnosis (ADHD vs. Control) and split-half performance on the Iowa Gambling Task (IGT). A sample of random models trained on functional connectivity profiles predicted validation set clinical diagnosis and IGT performance with 0.91 accuracy and d′ > 2.9, indicating very high sensitivity and specificity. We identified the most diagnostic functional connections between visual and ventral attentional networks and the anterior default mode network. Our results show that task-based functional connectivity is a biomarker of ADHD. Our analytic framework provides a template approach that explicitly ties behavioral assessment measures to both clinical diagnosis, and functional connectivity. This may differentiate otherwise similar diagnoses, and promote more efficacious intervention strategies.
The Role of Carotid Sinus Nerve Input in the Hypoxic-Hypercapnic Ventilatory Response in Juvenile Rats
Authors: Getsy Paulina M. , Coffee Gregory A. , Lewis Stephen J.
Published: January 2021

In juvenile rats, the carotid body (CB) is the primary sensor of oxygen (O2) and a secondary sensor of carbon dioxide (CO2) in the blood. The CB communicates to the respiratory pattern generator via the carotid sinus nerve, which terminates within the commissural nucleus tractus solitarius (cNTS). While this is not the only peripheral chemosensory pathway in juvenile rodents, we hypothesize that it has a unique role in determining the interaction between O2and CO2, and consequently, the response to hypoxic-hypercapnic gas challenges. The objectives of this study were to determine (1) the ventilatory responses to a poikilocapnic hypoxic (HX) gas challenge, a hypercapnic (HC) gas challenge or a hypoxic-hypercapnic (HH) gas challenge in juvenile rats; and (2) the roles of CSN chemoafferents in the interactions between HX and HC signaling in these rats. Studies were performed on conscious, freely moving juvenile (P25) male Sprague Dawley rats that underwent sham-surgery (SHAM) or bilateral transection of the carotid sinus nerves (CSNX) 4 days previously. Rats were placed in whole-body plethysmographs to record ventilatory parameters (frequency of breathing, tidal volume and minute ventilation). After acclimatization, they were exposed to HX (10% O2, 90% N2), HC (5% CO2, 21% O2, 74% N2) or HH (5% CO2, 10% O2, 85% N2) gas challenges for 5 min, followed by 15 min of room-air. The major findings were: (1) the HX, HC and HH challenges elicited robust ventilatory responses in SHAM rats; (2) ventilatory responses elicited by HX alone and HC alone were generally additive in SHAM rats; (3) the ventilatory responses to HX, HC and HH were markedly attenuated in CSNX rats compared to SHAM rats; and (4) ventilatory responses elicited by HX alone and HC alone were not additive in CSNX rats. Although the rats responded to HX after CSNX, CB chemoafferent input was necessary for the response to HH challenge. Thus, secondary peripheral chemoreceptors do not compensate for the loss of chemoreceptor input from the CB in juvenile rats.
Serum MG53/TRIM72 Is Associated With the Presence and Severity of Coronary Artery Disease and Acute Myocardial Infarction
Authors: Xie Hongyang , Wang Yaqiong , Zhu Tianqi , Feng Shuo , Yan Zijun , Zhu Zhengbin , Ni Jingwei , Ni Jun , Du Run , Zhu Jinzhou , Ding Fenghua , Liu Shengjun , Han Hui , Zhang Hang , Zhao Jiaxin , Zhang Ruiyan , Quan Weiwei , Yan Xiaoxiang
Published: January 2021

Background: Mitsugumin 53 or Tripartite motif 72 (MG53/TRIM72), a myokine/cardiokine belonging to the tripartite motif family, can protect the heart from ischemic injury and regulate lipid metabolism in rodents. However, its biological function in humans remains unclear. This study sought to investigate the relationship between circulating MG53 levels and coronary artery disease (CAD).

Methods: The concentration of MG53 was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 639 patients who underwent angiography, including 205 controls, 222 patients with stable CAD, and 212 patients with acute myocardial infarction (AMI). Logistic and linear regression analyses were used to analyze the relationship between MG53 and CAD.

Results: MG53 levels were increased in patients with stable CAD and were highest in patients with AMI. Additionally, patients with comorbidities, such as chronic kidney disease (CKD) and diabetes also had a higher concentration of MG53. We found that MG53 is a significant diagnostic marker of CAD and AMI, as analyzed by logistic regression models. Multivariate linear regression models revealed that serum MG53 was significantly corelated positively with SYNTAX scores. Global Registry of Acute Coronary Events (GRACE) scores also correlated with serum MG53 levels, indicating that MG53 levels were associated with the severity of CAD and AMI after adjusting for multiple risk factors and clinical biomarkers.

Conclusion: MG53 is a valuable diagnostic marker whose serum levels correlate with the presence and severity of stable CAD and AMI, and may represent a novel biomarker for diagnosing CAD and indicating the severity of CAD.
Symbiotic Performances of Three Mesorhizobium huakuii Strains Inoculated to Chinese Milk Vetch Varieties
Authors: Liu Fang , Yi Mingxuan , Liu Xinbao , Shen Yixin , Li Jianlong , Wang Hui , Yang Dianlin , Sun Zhengguo
Published: January 2021

In this experiment, 4 varieties of Chinese milk vetch (Xinyang, Minzi No. 6, Minzi 8487711, and Shishou) were used as host plants and inoculated with 3 strains of rhizobium (CCBAU 2609, M. h 93, and 7653R). The differences in their morphology, yield, and nodule characteristics at different growth stages were studied and the reasons for these differences were analyzed to explore the exclusivity between different varieties of Chinese milk vetch and strains of rhizobium. Results showed no significant difference in plant height and whole-plant dry weight at seedling stage under different treatments but significant differences in these characteristics at full flowering stage. The results indicated that Minzi 8487711 and Shishou were significantly better than the other varieties. During the whole growth period, the growth indexes and nodule characteristics of the 4 varieties inoculated with strain 7653R were better than those of the varieties inoculated with other strains. At full flowering stage, compared with that of the control group, the biomasses of Xinyang, Minzi No.6, Minzi 8487711, and Shishou had increased by 2.04, 2.84, 1.56, and 2.69-fold, respectively, and nitrogenase activities increased by 3.82, 9.60, 6.21, and 15.18%, respectively. Significant differences in the exclusivity between varieties and strains were observed. Minzi No.6–7653R and Shishou variety–7653R had the strongest exclusivity. The results showed that 7653R was a broad-spectrum and high-efficiency rhizobium strain. 7653R is recommended to be used in combination with Chinese milk vetch varieties, such as Minzi 8487711 and Shishou, to obtain advantages in yield and nitrogen fixation in production.
Clubroot Symptoms and Resting Spore Production in a Doubled Haploid Population of Oilseed Rape (Brassica napus) Are Controlled by Four Main QTLs
Authors: Botero-Ramírez Andrea , Laperche Anne , Guichard Solenn , Jubault Mélanie , Gravot Antoine , Strelkov Stephen E. , Manzanares-Dauleux Maria J.
Published: January 2021

Clubroot, caused byPlasmodiophora brassicaeWoronin, is one of the most important diseases of oilseed rape (Brassica napusL.). The rapid erosion of monogenic resistance in clubroot-resistant (CR) varieties underscores the need to diversify resistance sources controlling disease severity and traits related to pathogen fitness, such as resting spore production. The genetic control of disease index (DI) and resting spores per plant (RSP) was evaluated in a doubled haploid (DH) population consisting of 114 winter oilseed rape lines, obtained from the cross ‘Aviso’ × ‘Montego,’ inoculated withP. brassicaeisolate “eH.” Linkage analysis allowed the identification of three quantitative trait loci (QTLs) controlling DI (PbBn_di_A02, PbBn_di_A04, and PbBn_di_C03). A significant decrease in DI was observed when combining effects of the three resistance alleles at these QTLs. Only one QTL, PbBn_rsp_C03, was found to control RSP, reducing resting spore production by 40%. PbBn_rsp_C03 partially overlapped with PbBn_di_C03 in a nucleotide-binding leucine-rich repeat (NLR) gene-containing region. Consideration of both DI and RSP in breeding for clubroot resistance is recommended for the long-term management of this disease.
Understanding the Better Than Average Effect on Altruism
Authors: Xiao Yunyu , Wong Kelly , Cheng Qijin , Yip Paul S. F.
Published: January 2021

Prior research suggests that most people perceive themselves to be more altruistic than the average population, an observation known as the better-than-average (BTA) effect. Understanding the BTA effect carries significant public health implications, as self-perceived altruism is closely related to altruistic behaviors, which plays a significant role in individual and societal well-being. However, little is known about whether subpopulations with specific sociodemographic profiles are more likely to hold BTA altruistic self-perceptions, making it difficult to design targeted programs based on multiple sociodemographic characteristics to promote altruistic behaviors. This study addresses this gap by identifying the sociodemographic profiles of populations who are more likely to exhibit BTA effects on trait altruism. Data were derived from a representative sample of Hong Kong citizens (n= 1,185) in the 2017 Hong Kong Altruism Survey. A latent class analysis was performed using four domains of sociodemographic characteristics: sex, age, religion, and socioeconomic status. Multivariate multinomial logistic regressions were conducted to examine associations between class membership, BTA effect, and altruistic behaviors. The results yielded four classes of sociodemographic profiles. Middle-aged, Christian/Catholic, highly educated, and high-income individuals (Class 4, 17.8%) were most likely to exhibit BTA effects and behave altruistically; Class 3 (14.0%) were older, male, no/other religious belief, low education, and least likely to exhibit BTA effects and behave altruistically. Findings improve the understanding of the sociodemographic profiles of people showing BTA effects and facilitate targeted policy development to effectively promote altruism.
A Minimal Setup for Spontaneous Smile Quantification Applicable for Valence Detection
Authors: Nascimben Mauro , Ramsøy Thomas Zoëga
Published: January 2021

Tracking emotional responses as they unfold has been one of the hallmarks of applied neuroscience and related disciplines, but recent studies suggest that automatic tracking of facial expressions have low validation. In this study, we focused on the direct measurement of facial muscles involved in expressions such as smiling. We used single-channel surface electromyography (sEMG) to evaluate the muscular activity from the Zygomaticus Major face muscle while participants watched music videos. Participants were then tasked with rating each video with regard to their thoughts and responses to each of them, including their judgment of emotional tone (“Valence”), personal preference (“Liking”) and rating of whether the video displayed strength and impression (“Dominance”). Using a minimal recording setup, we employed three ways to characterize muscular activity associated with spontaneous smiles. The total time spent smiling (ZygoNum), the average duration of smiles (ZygoLen), and instances of high valence (ZygoTrace). Our results demonstrate that Valence was the emotional dimension that was most related to the Zygomaticus activity. Here, the ZygoNum had higher discriminatory power than ZygoLen for Valence quantification. An additional investigation using fractal properties of sEMG time series confirmed previous studies of the Facial Action Coding System (FACS) documenting a smoother contraction of facial muscles for enjoyment smiles. Further analysis using ZygoTrace responses over time to the video events discerned “high valence” stimuli with a 76% accuracy. Additional validation of this approach came against previous findings on valence detection using features derived from a single channel EEG setup. We discuss these results in light of both the recent replication problems of facial expression measures, and in relation to the need for methods to reliably assess emotional responses in more challenging conditions, such as Virtual Reality, in which facial expressions are often covered by the equipment used.
Together Against COVID-19 Concerns: The Role of the Dyadic Coping Process for Partners’ Psychological Well-Being During the Pandemic
Authors: Donato Silvia , Parise Miriam , Pagani Ariela Francesca , Lanz Margherita , Regalia Camillo , Rosnati Rosa , Iafrate Raffaella
Published: January 2021

The situation caused by the 2019 coronavirus disease (COVID-19) has been representing a great source of concern and a challenge to the psychological well-being of many individuals around the world. For couples in particular, this extraordinary rise in concern, combined with the stress posed by the virus containment measures, such as prolonged cohabitation and lack of support networks, may have increased the likelihood of couple problems. At the same time, however, COVID-19 concerns may have been a stimulus to activate couples’ stress management processes. A couple’s resource, which may have an important role in dealing with COVID-19 concerns and stress, is dyadic coping, i.e., the process through which partners face stress together. Drawing on a sample of 1,823 Italian individuals involved in a couple relationship, the current study tested a serial mediation model in which concerns about COVID-19 predicted psychological well-being, through both explicit stress communication and perceived partner dyadic coping responses. In addition, the study explored whether this dyadic coping process functioned the same way in satisfied and dissatisfied couples. Results showed that concerns about the situation related to COVID-19 significantly threatened individuals’ psychological well-being. However, these concerns positively predicted explicit stress communication, which in turn positively predicted perceived partner’s dyadic coping responses, which finally positively predicted psychological well-being. In addition, in the group of dissatisfied individuals, the association between explicit stress communication and perceived partners’ dyadic coping responses was not significant. The present study adds to the research on couples’ coping by testing for the first time the whole theoretical model of dyadic coping and does so during a global emergency situation. The study also suggests key components of preventive interventions for individuals in couples.
Working With Infertile Couples Seeking Assisted Reproduction: An Interpretative Phenomenological Study With Infertility Care Providers
Authors: Facchin Federica , Leone Daniela , Tamanza Giancarlo , Costa Mauro , Sulpizio Patrizia , Canzi Elena , Vegni Elena
Published: January 2021

Although most studies investigated the impact of infertility and its treatment on the couple, a small body of evidence suggested that infertility care providers may experience different sources of stress related for instance to excessive workload, the complexity of the technique, and relational difficulties with patients. The current study aimed at providing further insight into the understanding of the subjective experience of infertility care providers by highlighting their feelings and emotions, personal meanings, challenges, and opportunities. Following the methodological guidelines of Interpretative Phenomenological Analysis, we conducted individual semi-structured interviews with 23 members of two different fertility units. Interviews were audiotaped and transcribed verbatim. Textual analysis was then conducted to identify emerging dominant themes and subthemes. Three main themes were extracted: (i) dealing with infertile patients and their specificities, (ii) performing assisted reproductive technology (ART), (iii) being part of a team. These themes related to participants experiencing: (i) difficulties in establishing an empathic connection and communicating with couples, such that women were sometimes perceived as “particular patients” and men as poorly involved in the process; (ii) difficulties in dealing with a complex procedure in which errors are not allowed (as reported by embryologists), with a growing number of women aged > 40 seeking assisted reproduction, despite the risks for their health; (iii) being part of a team as a resource, although the huge amount of time spent together can involve conflicts and organizational problems. These findings suggested that patients’ overpersistence (rather than just dropout) represents an important source of stress for infertility care providers. At the same time, the concept of particular or difficult patient derives from the combination of multiple factors, including providers’ own history and subjective experience. The presence of mental health professionals in fertility units is essential to help providers improve the quality of doctor-patient communication and relieve the stress related to organizational issues and conflicts.
The Role of Haptic Expectations in Reaching to Grasp: From Pantomime to Natural Grasps and Back Again
Authors: Whitwell Robert L. , Katz Nathan J. , Goodale Melvyn A. , Enns James T.
Published: January 2021

When we reach to pick up an object, our actions are effortlessly informed by the object’s spatial information, the position of our limbs, stored knowledge of the object’s material properties, and what we want to do with the object. A substantial body of evidence suggests that grasps are under the control of “automatic, unconscious” sensorimotor modules housed in the “dorsal stream” of the posterior parietal cortex. Visual online feedback has a strong effect on the hand’s in-flight grasp aperture. Previous work of ours exploited this effect to show that grasps are refractory to cued expectations for visual feedback. Nonetheless, when we reach out to pretend to grasp an object (pantomime grasp), our actions are performed with greater cognitive effort and they engage structures outside of the dorsal stream, including the ventral stream. Here we ask whether our previous finding would extend to cued expectations for haptic feedback. Our method involved a mirror apparatus that allowed participants to see a “virtual” target cylinder as a reflection in the mirror at the start of all trials. On “haptic feedback” trials, participants reached behind the mirror to grasp a size-matched cylinder, spatially coincident with the virtual one. On “no-haptic feedback” trials, participants reached behind the mirror and grasped into “thin air” because no cylinder was present. To manipulate haptic expectation, we organized the haptic conditions into blocked, alternating, and randomized schedules with and without verbal cues about the availability of haptic feedback. Replicating earlier work, we found the strongest haptic effects with the blocked schedules and the weakest effects in the randomized uncued schedule. Crucially, the haptic effects in the cued randomized schedule was intermediate. An analysis of the influence of the upcoming and immediately preceding haptic feedback condition in the cued and uncued random schedules showed that cuing the upcoming haptic condition shifted the haptic influence on grip aperture from the immediately preceding trial to the upcoming trial. These findings indicate that, unlike cues to the availability of visual feedback, participants take advantage of cues to the availability of haptic feedback, flexibly engaging pantomime, and natural modes of grasping to optimize the movement.
No Effects of Acute Psychosocial Stress on Working Memory in Older People With Type 2 Diabetes
Authors: Vallejo Lorena , Zapater-Fajarí Mariola , Montoliu Teresa , Puig-Perez Sara , Nacher Juan , Hidalgo Vanesa , Salvador Alicia
Published: January 2021

Type 2 diabetes (T2D) has been considered a public health threat due to its growing prevalence, particularly in the older population. It is important to know the effects of psychosocial stress and its potential consequences for some basic cognitive processes that are important in daily life. Currently, there is very little information about how people with T2D face acute psychosocial stressors, and even less about how their response affects working memory (WM), which is essential for their functionality and independence. Our aim was to characterize the response to an acute laboratory psychosocial stressor and its effects on WM in older people with T2D. Fifty participants with T2D from 52 to 77 years old were randomly assigned to a stress (12 men and 12 women) or control (12 men and 14 women) condition. Mood and physiological (cortisol, C, and salivary alpha-amylase, sAA) responses to tasks were measured. In addition, participants completed a WM test before and after the stress or control task. Our results showed that the TSST elicited higher negative affect and greater C and sAA responses than the control task. No significant differences in WM were observed depending on the exposure to stress or the control task. Finally, participants who showed higher C and sAA responses to the stressor had lower WM performance. Our results indicate that medically treated older adults with T2D show clear, typical mood and physiological responses to an acute psychosocial stressor. Finally, the lack of acute psychosocial stress effects on WM suggests that it could be related to aging and not to this disease, at least when T2D is adequately treated.
Identifying Rewards Over Difficulties Buffers the Impact of Time in COVID-19 Lockdown for Parents in Australia
Authors: Herbert Jane S. , Mitchell Annaleise , Brentnall Stuart J. , Bird Amy L.
Published: January 2021

Objective

Physical isolation measures, known as lockdown or shelter-in-place, experienced during coronavirus disease 2019 (COVID-19) have the potential to cause psychological distress. This study was conducted to examine parents’ perceived stress and whether reports of rewards and challenges during lockdown impact stress.

Methods

Data were collected using a cross-sectional online survey in New South Wales, Australia, across the 4-week lockdown. The survey was completed by 158 parents of children aged under 6 years. Stress was measured using the short form of the Perceived Stress Scale (PSS-4). Rewards and challenges were reported in response to two open-ended questions.

Results

There was a weak negative correlation between PSS-4 scores and days in isolation (r = −0.167, p = 0.022), with parents who had spent longer in isolation reporting fewer stress symptoms. The relationship between time in isolation and stress was moderated by the degree to which parents described more rewards than challenges: parents who perceived high rewards and low challenges reported lower PSS-4 scores with more days in lockdown, whereas parents who perceived low rewards and high challenges reported higher PSS-4 scores with more days in lockdown. The moderation model examining associations between time in isolation and rewards ratio explained 13% of the variance in PSS-4 scores.

Conclusion

Lockdowns are not uniformly or consistently negative experiences for parents. Identifying positive aspects of the experience may serve to buffer negative mental health risks across time. Understanding resilience strategies is critical for supporting current psychological wellbeing and to adequately prepare for future pandemic experiences.