bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Low-Level Maternal Mosaicism of a Novel CREBBP Variant Causes Recurrent Rubinstein-Taybi Syndrome in Two Siblings of a Chinese Family
Authors: Lin Shaobin , He Zhiming , Huang Linhuan , Liu Jialiu , Lei Ting , Wu Jianzhu , Huang Peizhi , Zhou Yi , Luo Yanmin
Published: March 2021

Familial Rubinstein-Taybi syndrome (RSTS) with recurrent RSTS siblings and apparently unaffected parents is rare; such cases might result from parental somatic and/or germline mosaicism. Parental low-level (<10%) germline mosaicism in the CREBBP-associated RSTS family has not been reported. Here, we present our studies of a Chinese family with two RSTS siblings and apparently unaffected parents. We detected the apparent de novo variant (DNV) c.3235C>T (p.Gln1079*) in CREBBP in the siblings via trio whole-exome sequencing. High-depth next-generation sequencing (NGS) for the parents revealed a low-level (<10%) mosaic variant in both the peripheral blood (3.64%) and buccal mucosa (1.94%) of the unaffected mother, indicating maternal somatic and germline mosaicism. Peripheral blood RNA-sequencing analysis for the patients and normal individuals indicated that the c.3235C>T (p.Gln1079*) non-sense variant did not trigger nonsense-mediated mRNA decay to reduce CREBBP mRNA levels. Transcriptome analysis revealed 151 downregulated mRNAs and 132 upregulated mRNAs between the patients and normal individuals. This study emphasizes that high-depth NGS using multiple specimens might be applied for a family with an affected sibling caused by an apparent CREBBP DNV to identify potential low-level parental mosaicism and provide an assessment of recurrence risk.
Agonistic Anti-CD40 Antibody Triggers an Acute Liver Crisis With Systemic Inflammation in Humanized Sickle Cell Disease Mice
Authors: Yalamanoglu Ayla , Dubach Irina L. , Schulthess Nadja , Ingoglia Giada , Swindle Delaney C. , Humar Rok , Schaer Dominik J. , Buehler Paul W. , Irwin David C. , Vallelian Florence
Published: March 2021

Sickle cell disease (SCD) is an inherited hemolytic disorder, defined by a point mutation in the β-globin gene. Stress conditions such as infection, inflammation, dehydration, and hypoxia trigger erythrocyte sickling. Sickled red blood cells (RBCs) hemolyze more rapidly, show impaired deformability, and increased adhesive properties to the endothelium. In a proinflammatory, pro-coagulative environment with preexisting endothelial dysfunction, sickled RBCs promote vascular occlusion. Hepatobiliary involvement related to the sickling process, such as an acute sickle hepatic crisis, is observed in about 10% of acute sickle cell crisis incidents. In mice, ligation of CD40 with an agonistic antibody leads to a macrophage activation in the liver, triggering a sequence of systemic inflammation, endothelial cell activation, thrombosis, and focal ischemia. We found that anti-CD40 antibody injection in sickle cell mice induces a systemic inflammatory and hemodynamic response with accelerated hemolysis, extensive vaso-occlusion, and large ischemic infarctions in the liver mimicking an acute hepatic crisis. Administration of the tumor necrosis factor-α (TNF-α) blocker, etanercept, and the heme scavenger protein, hemopexin attenuated end-organ damage. These data collectively suggest that anti-CD40 administration offers a novel acute liver crisis model in humanized sickle mice, allowing for evaluation of therapeutic proof-of-concept.
ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus
Authors: Jia Xin , Dai Meng-Han , Ren An-Jing , Wang Ting-Ting , Zhang Weiping J. , Zhang Ling
Published: March 2021

Recent studies have shown that ZBTB20, a zinc-finger protein containing transcription factor, is highly expressed in small-diameter primary sensory neurons in mice, and modulates pain through regulating TRP channels. However, whether ZBTB20 regulates itch sensation has not been demonstrated. In this study, small-diameter primary sensory neuron-specific ZBTB20 knockout (PN-ZB20KO) mice were used to investigate the role of ZBTB20 in the regulation of itch sensation. First, both histamine-dependent and non-histamine-dependent itch behaviors induced by injection of histamine and chloroquine (CQ) into the cheek were significantly diminished in PN-ZB20KO mice. Second, double immunohistochemistry showed that ZBTB20 was mainly expressed in CGRP-labeled small peptidergic neurons and was expressed at low levels in IB4-labeled small non-peptidergic and NF200-labeled large neurons in the trigeminal ganglia (TG). ZBTB20 was also expressed in most TRPV1+ and TRPA1+ neurons and to a lesser extent in TRPM8+ neurons in the TG. Furthermore, cheek injection of histamine and CQ enhanced the mRNA expression of TRPV1 and TRPA1 but not TRPM8 in the TG. Moreover, TRPV1 and TRPA1 knockout (KO) mice exhibited attenuation of itch behavior induced by histamine and CQ, respectively. Finally, silencing endogenous ZBTB20 with recombinant lentivirus expressing a short hairpin RNA against ZBTB20 (LV-shZBTB20) in TG neurons attenuated histamine- and non-histamine-induced itch and downregulated TRP channels in the TG. Our study suggests that ZBTB20 plays an important role in mediating itch in small primary sensory neurons.
The Spectrum of PRRT2-Associated Disorders: Update on Clinical Features and Pathophysiology
Authors: Landolfi Annamaria , Barone Paolo , Erro Roberto
Published: March 2021

Mutations in the PRRT2 (proline-rich transmembrane protein 2) gene have been identified as the main cause of an expanding spectrum of disorders, including paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy, which places this gene at the border between epilepsy and movement disorders. The clinical spectrum has largely expanded to include episodic ataxia, hemiplegic migraine, and complex neurodevelopmental disorders in cases with biallelic mutations. Prior to the discovery of PRRT2 as the causative gene for this spectrum of disorders, the sensitivity of paroxysmal kinesigenic dyskinesia to anticonvulsant drugs regulating ion channel function as well as the co-occurrence of epilepsy in some patients or families fostered the hypothesis this could represent a channelopathy. However, recent evidence implicates PRRT2 in synapse functioning, which disproves the “channel hypothesis” (although PRRT2 modulates ion channels at the presynaptic level), and justifies the classification of these conditions as synaptopathies, an emerging rubric of brain disorders. This review aims to provide an update of the clinical and pathophysiologic features of PRRT2-associated disorders.
Identification of Five Glycolysis-Related Gene Signature and Risk Score Model for Colorectal Cancer
Authors: Zhu Jun , Wang Shuai , Bai Han , Wang Ke , Hao Jun , Zhang Jian , Li Jipeng
Published: March 2021

Metabolic changes, especially in glucose metabolism, are widely established during the occurrence and development of tumors and regarded as biological markers of pan-cancer. The well-known ‘Warburg effect’ demonstrates that cancer cells prefer aerobic glycolysis even if there is sufficient ambient oxygen. Accumulating evidence suggests that aerobic glycolysis plays a pivotal role in colorectal cancer (CRC) development. However, few studies have examined the relationship of glycolytic gene clusters with prognosis of CRC patients. Here, our aim is to build a glycolysis-associated gene signature as a biomarker for colorectal cancer. The mRNA sequencing and corresponding clinical data were downloaded from TCGA and GEO databases. Gene set enrichment analysis (GSEA) was performed, indicating that four gene clusters were significantly enriched, which revealed the inextricable relationship of CRC with glycolysis. By comparing gene expression of cancer and adjacent samples, 236 genes were identified. Univariate, multivariate, and LASSO Cox regression analyses screened out five prognostic-related genes (ENO3, GPC1, P4HA1, SPAG4, and STC2). Kaplan–Meier curves and receiver operating characteristic curves (ROC, AUC = 0.766) showed that the risk model could become an effective prognostic indicator (P < 0.001). Multivariate Cox analysis also revealed that this risk model is independent of age and TNM stages. We further validated this risk model in external cohorts (GES38832 and GSE39582), showing these five glycolytic genes could emerge as reliable predictors for CRC patients’ outcomes. Lastly, based on five genes and risk score, we construct a nomogram model assessed by C-index (0.7905) and calibration plot. In conclusion, we highlighted the clinical significance of glycolysis in CRC and constructed a glycolysis-related prognostic model, providing a promising target for glycolysis regulation in CRC.
Inhibition of HMGB1 Suppresses Hepatocellular Carcinoma Progression via HIPK2-Mediated Autophagic Degradation of ZEB1
Authors: Zhu Wei , Li Jun , Zhang Yuheng , Zhu Zhengyi , Liu Hanyi , Lin Yunzhen , Hu Anyin , Zhou Jingchao , Ren Haozhen , Shi Xiaolei
Published: March 2021

Autophagy is a conserved catabolic process maintaining cellular homeostasis and reportedly plays a critical role in tumor progression. Accumulating data show that autophagic activity is inhibited in hepatocellular carcinoma. However, the underlying molecular basis of impaired autophagy in HCC remains unclear. In this study, we revealed that autophagic activity was suppressed by HMGB1 in a HIPK2-dependent way. Targeting HMGB1 could inhibit the degradation of HIPK2, as a result of which, autophagic degradation of ZEB1 was enhanced by reprogramming glucose metabolism/AMPK/mTOR axis. Moreover, we demonstrated that selectively degradation of ZEB1 was responsible for HCC growth inhibition in HMGB1 deficient cells. Lastly, we found the combination therapy of HMGB1 inhibitor and rapamycin achieved a better anti-HCC effect. These results demonstrate that impaired autophagy is controlled by HMGB1 and targeting HMGB1 could suppress HCC progression via HIPK2-mediated autophagic degradation of ZEB1.
A Rare Case of Acute Liver Failure Secondary to Diffuse Hepatic Infiltration of Small Cell Neuroendocrine Carcinoma
Authors: Yan Ping , Liu Yu , Wang Qing , Chen Xia
Published: March 2021

Background

Malignant liver infiltration is an uncommon cause of acute liver failure (ALF) and has rarely been reported.

Case Presentation

We present a patient with progressive jaundice and dissociation of bilirubin and aminotransferases, who had no history of relevant liver diseases or tumor except the use of Chinese traditional drugs for a cold. An abdominal computed tomography (CT) scan showed ascites without hepatic focal lesions. Laboratory studies revealed no evidence of hepatitis or underlying autoimmune disorders. Following 8 days of conservative management ALF rapidly worsened. Contrast-enhanced CT revealed diffuse regenerative nodules in the liver. The patient underwent liver biopsy, which demonstrated that the liver was infiltrated by pulmonary neuroendocrine tumor classified as small cell lung cancer. The patient died 13 days after diagnosis.

Discussion and Conclusions

This case represents a rare cause of ALF induced by pulmonary neuroendocrine tumor of small cell type and illustrates the importance of prompt biopsy in an unknown cause of ALF.
Distinct Characteristics of COVID-19 Infection in Children
Authors: Han Xuejiao , Li Xuemei , Xiao Yinan , Yang Ruoning , Wang Yang , Wei Xiawei
Published: March 2021

SARS-CoV-2, a member of the family coronaviridae, has triggered a lethal pandemic termed coronavirus disease 2019 (COVID-19). Pediatric patients, mainly from families with a cluster of infection or a history of exposure to epidemic areas, get infected via direct contacts or air-borne droplets. Children (aged below 18 years) are susceptible to COVID-19, with an average incubation period of about 6.5 days. Most cases present asymptomatic or common cold symptoms such as fever, cough, and myalgia or fatigue, which is milder than adult patients. Besides, most abnormal laboratory and radiologic findings in children with COVID-19 are non-specific. Since no specific chemotherapeutic agents have been approved for children, timely preventive methods could effectively forestall the transmission of SARS-CoV-2. To date, mostly studied cases have been adults with COVID-19, whereas data on pediatrics patients remain poorly defined. We herein conducted a literature review for papers published in PubMed and medRxiv (preprints) between December 2019 and December 2020 that reported on pediatrics patients (aged below 18 years) with a confirmed COVID-19 diagnosis. In this review, we summarized and discussed the pathogenesis, epidemiology, and clinical management of COVID-19 in pediatrics patients to improve our understanding of this new disease in children.
Network Pharmacology and Pharmacological Evaluation Reveals the Mechanism of the Sanguisorba Officinalis in Suppressing Hepatocellular Carcinoma
Authors: Jiang Nan , Li Hong , Sun Yueshan , Zeng Jing , Yang Fei , Kantawong Fahsai , Wu Jianming
Published: March 2021

Background:Sanguisorba Officinalis L. (SO) is a well-known traditional Chinese medicine (TCM), commonly applied to treat complex diseases, such as anticancer, antibacterial, antiviral, anti-inflammatory, anti-oxidant and hemostatic effects. Especially, it has been reported to exert anti-tumor effect in various human cancers. However, its effect and pharmacological mechanism on hepatocellular carcinoma (HCC) remains unclear.

Methods: In this study, network pharmacology approach was applied to characterize the underlying mechanism of SO on HCC. Active compounds and potential targets of SO, as well as related genes of HCC were obtained from the public databases, the potential targets and signaling pathways were determined by protein-protein interaction (PPI), gene ontology (GO) and pathway enrichment analyses. And the compound-target and target-pathway networks were constructed. Subsequently, in vitro experiments were also performed to further verify the anticancer effects of SO on HCC.

Results: By using the comprehensive network pharmacology analysis, 41 ingredients in SO were collected from the corresponding databases, 12 active ingredients screened according to their oral bioavailability and drug-likeness index, and 258 potential targets related to HCC were predicted. Through enrichment analysis, SO was found to show its excellent therapeutic effects on HCC through several pathways, mainly related to proliferation and survival via the EGFR, PI3K/AKT, NFκB and MAPK signaling pathways. Additionally, in vitro, SO was found to inhibit cell proliferation, induce apoptosis and down-regulate cell migration and invasion in various HCC cells. Moreover, western blot analysis showed that SO treatment down-regulated the expression of p-EGFR, p-PI3K, p-AKT, p-NFκB and p-MAPK proteins in HepG2 cells. These results validated that SO exerted its therapeutic effects on HCC mainly by the regulation of cell proliferation and survival via the EGFR/MAPK and EGFR/PI3K/AKT/NFκB signaling pathways.

Conclusion: Taken together, this study, revealed the anti-HCC effects of SO and its potential underlying therapeutic mechanisms in a multi-target and multi-pathway manner.
The Effects of Apelin and Elabela Ligands on Apelin Receptor Distinct Signaling Profiles
Authors: Jiang Yunlu , Yan Maocai , Wang Chunmei , Wang Qinqin , Chen Xiaoyu , Zhang Rumin , Wan Lei , Ji Bingyuan , Dong Bo , Wang Huiyun , Chen Jing
Published: March 2021

Apelin and Elabela are endogenous peptide ligands for Apelin receptor (APJ), a widely expressed G protein-coupled receptor. They constitute a spatiotemporal dual ligand system to control APJ signal transduction and function. We investigated the effects of Apelin-13, pGlu1-apelin-13, Apelin-17, Apelin-36, Elabela-21 and Elabela-32 peptides on APJ signal transduction. Whether different ligands are biased to different APJ mediated signal transduction pathways was studied. We observed the different changes of G protein dependent and β-arrestin dependent signaling pathways after APJ was activated by six peptide ligands. We demonstrated that stimulation with APJ ligands resulted in dose-dependent increases in both G protein dependent [cyclic AMP (cAMP), Ca2+ mobilization, and the early phase extracellular related kinase (ERK) activation] and β-arrestin dependent [GRKs, β-arrestin 1, β-arrestin 2, and β2 subunit of the clathrin adaptor AP2] signaling pathways. However, the ligands exhibited distinct signaling profiles. Elabela-32 showed a >1000-fold bias to the β-statin-dependent signaling pathway. These data provide that Apelin-17 was biased toward β-arrestin dependent signaling. Eabela-21 and pGlu1-Apelin-13 exhibited very distinct activities on the G protein dependent pathway. The activity profiles of these ligands could be valuable for the development of drugs with high selectivity for specific APJ downstream signaling pathways.
Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease
Authors: Soattin Luca , Borbas Zoltan , Caldwell Jane , Prendergast Brian , Vohra Akbar , Saeed Yawer , Hoschtitzky Andreas , Yanni Joseph , Atkinson Andrew , Logantha Sunil Jit , Borbas Balint , Garratt Clifford , Morris Gwilym Matthew , Dobrzynski Halina
Published: March 2021

Background

The sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases.

Methods

A goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques.

Results

When the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT).

Conclusions

SAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker.
Dynamic Function and Composition Shift in Circulating Innate Immune Cells in Hibernating Garden Dormice
Authors: Huber Nikolaus , Vetter Sebastian , Stalder Gabrielle , Gerritsmann Hanno , Giroud Sylvain
Published: March 2021

Hibernation is characterized by successive torpor bouts during which metabolic rate is down-regulated to 2–4% of euthermic levels along with core body temperatures (Tb) ranging between 0 and 10°C. One characteristic of the torpid state, which is periodically interrupted by a few hours of euthermic phases or arousals during hibernation, resides in an overall impairment of the immune system. The most striking change during torpor is the reduction of circulating white blood cells up to 90%, while their numbers rise to near summer euthermic level upon rewarming. However, potential changes in responsiveness and function of neutrophil granulocytes, accounting for the primary cellular innate immune defense, are unknown. Here we present the first data on shifts in oxidative burst capacity, i.e., the ability to produce reactive oxygen species (ROS), of neutrophils during hibernation. Using a chemiluminescence assay, we measured real-time ROS production in whole blood of hibernating garden dormice (Eliomys quercinus) in early or late torpor, and upon arousals. Accounting for changes in neutrophil numbers along the torpor-arousal cycle, we found significant differences, between torpid and euthermic states, in the neutrophil oxidative burst capacity (NOC), with shallow cell responses during torpor and a highly significant increase by up to 30-fold during arousals. Further, we observed a significant reduction of NOC from aroused animals with euthermic Tbof 36.95 ± 0.37°C, when tested at 6°C, whereas no change occurred in NOC from torpid individuals reaching constant Tbof 4.67 ± 0.42°C, when measured at 35°C. This dynamic indicates that the reduction in NOC during torpor may be temperature-compensated. These results linked to the understanding of immune function during the torpor-arousal cycle might have clinical relevance in the context of therapeutic hypothermia and reperfusion injury.
The Bibliometric Analysis of the Sustainable Influence of Physical Education for University Students
Authors: Xu Dekai , Zheng Yingying , Jia Yunli
Published: March 2021

With the awakening of people's health consciousness, the concept and practice of health promotion has become the main target of health policies throughout the world. In this study, the relationship between physical education and health promotion was examined. Art students from a university in Taoyuan were selected for research, and a total of 320 questionnaires were issued. Invalid and incomplete questionnaires were eliminated, with a total of 227 valid questionnaires. Finally, the LISREL (Linear Structural Relations) model was used to analyze the correlation between various factors and health promotion. The results of the model analysis show that in terms of basic fit, the three factors of physical education (course design, teaching content, and activity design) have a high correlation with the influence of physical education, reaching a significant level (t > 1.96, p < 0.05). In terms of influence on sports participation, the three factors (physiological factors, psychological factors, social factors) of sports participation reached a significant level (t > 1.96, p < 0.05). The two factors of health promotion (physiological health, and mental health and practical ideas) have a high correlation with the influence of health promotion, reaching a significant level (t > 1.96, p < 0.05). In terms of overall mode fit, the overall mode fit standard χ2/Df was 1.344, less than the standard value of 3 or less, and the RMR value was 0.007, indicating that the χ2/DF and RMR result standards were appropriate, and the chi-square value was very sensitive to the sample size. Therefore, there was a positive correlation among physical education, sports participation, and health promotion. In conclusion, physical activities can improve the human body's immune function, reduce the symptoms of chronic diseases, and positively promote health. The research result is important for emphasizing the benefit of sports to art students, and provides reference for improving the quality of school physical education, and the physical and mental health level of people in Taiwan.
Gender Differences in the Distribution of Creativity Scores: Domain-Specific Patterns in Divergent Thinking and Creative Problem Solving
Authors: He Wu-jing , Wong Wan-chi
Published: March 2021

The present study examined gender differences in the distribution of creative abilities through the lens of the greater male variability hypothesis, which postulated that men showed greater interindividual variability than women in both physical and psychological attributes (Ellis, 1894/1934). Two hundred and six (51.9% female) undergraduate students in Hong Kong completed two creativity measures that evaluated different aspects of creativity, including: (a) a divergent thinking test that aimed to assess idea generation and (b) a creative problem-solving test that aimed to assess restructuring ability. The present findings extended the research of greater male variability in creativity by showing that men generally exhibited greater variance than women in the overall distribution of the creativity scores in both divergent thinking and creative problem solving, despite trivial gender differences in mean scores. The findings further enriched the discourse of the greater male variability hypothesis by showing interesting domain-specific gendered patterns: (1) greater male variability was more likely to occur in figural forms of creativity, with larger effect sizes, when compared to the variability in verbal forms of creativity; and (2) mixed gendered patterns were found in the upper tails of the creativity score distribution with respect to the verbal domain but not the figural one, despite greater male representation being consistently observed in the lower tail of the distribution. Possible underlying mechanisms and implications were discussed.
Storytelling on Oral Grounds: Viewpoint Alignment and Perspective Taking in Narrative Discourse
Authors: van Krieken Kobie , Sanders José
Published: March 2021

In this paper, we seek to explain the power of perspective taking in narrative discourse by turning to research on the oral foundations of storytelling in human communication and language. We argue that narratives function through a central process of alignment between the viewpoints of narrator, hearer/reader, and character and develop an analytical framework that is capable of generating general claims about the processes and outcomes of narrative discourse while flexibly accounting for the great linguistic variability both across and within stories. The central propositions of this viewpoint alignment framework are that the distance between the viewpoints of participants in the narrative construal – narrator, character, reader – is dynamic and regulated by linguistic choices as well as contextual factors. Fundamentally, viewpoint alignment is grounded in oral narrative interaction and, from this conversation, transferred to the written narrative situation, varying between demonstration and invasion of the narrative subjects and guiding readers’ route of processing the narrative (experientialversusreflective). Our claim is that variations in viewpoint alignment are functional to the communicative context and intended outcomes of narratives. This is illustrated with the analysis of a corporate journalistic narrative that comprises both interactional and non-interactional aspects of storytelling. The concept of viewpoint alignment further explains the oral fundaments of narrative discourse in conversational storytelling and poses new questions on the relation between the dynamic processing of stories on the one hand and their static outcomes on the other.
Spillover Effects When Taking Turns in Dyadic Coping: How Lingering Negative Affect and Perceived Partner Responsiveness Shape Subsequent Support Provision
Authors: Pauw Lisanne S. , Hoogeveen Suzanne , Breitenstein Christina J. , Meier Fabienne , Rauch-Anderegg Valentina , Neysari Mona , Martin Mike , Bodenmann Guy , Milek Anne
Published: March 2021

When experiencing personal distress, people usually expect their romantic partner to be supportive. However, when put in a situation to provide support, people may at times (still) be struggling with issues of their own. This interdependent nature of dyadic coping interactions as well as potential spillover effects is mirrored in the state-of-the-art research method to behaviorally assess couple’s dyadic coping processes. This paradigm typically includes two videotaped 8-min dyadic coping conversations in which partners swap roles as sharer and support provider. Little is known about how such dyadic coping interactions may feed back into one another, impacting the motivation and ability to be a responsive support provider. In three behavioral studies, we examined how sharers’ experiences may spill over to affect their own support provision in a subsequent dyadic coping interaction. We hypothesized that the extent to which sharers perceive their partner as responsive to their self-disclosure increases the quality of their own subsequent support provision (Hypothesis 1), whereas sharers’ lingering negative affect reduces the quality of their own subsequent support provision (Hypothesis 2). In line with our first hypothesis, perceived partner responsiveness predicted the provision of higher-quality support, though primarily as perceived by the partner. Sharers who perceived their partner to have been more responsive were somewhat more likely to subsequently engage in positive dyadic coping and were rated as more responsive by their partners. Negative dyadic coping behavior was unaffected. Evidence for our second hypothesis was mixed. While lingering negative affect did not affect positive dyadic coping behavior or perceived support, it did increase the chances of negative dyadic coping behavior. However, given the very low occurrences of negative affect and negative dyadic coping, these findings should be interpreted with caution. Taken together, these findings suggest that support interactions may feed back into one another, highlighting the complex and interdependent nature of dyadic coping. The strongest and most consistent findings concerned the spillover effect of perceived partner responsiveness on subsequent perceived support quality, speaking to the key role of believing that one’s partner is responsive to one’s needs in promoting healthy relationship functioning.
An Update on Advances in COVID-19 Laboratory Diagnosis and Testing Guidelines in India
Authors: Kumar K. S. Rajesh , Mufti Suhail Sayeed , Sarathy Vinu , Hazarika Diganta , Naik Radheshyam
Published: March 2021

The declaration of COVID-19 as a global pandemic has warranted the urgent need for technologies and tools to be deployed for confirming diagnosis of suspected cases. Diagnostic testing for COVID-19 is critical for understanding epidemiology, contract-tracing, case management, and to repress the transmission of the SARS-CoV-2. Currently, the Nucleic Acid Amplification Test (NAAT)-based RT-PCR technique is a gold standard test used for routine diagnosis of COVID-19 infection. While there are many commercially available RT-PCR assay kits available in the market, selection of highly sensitive, specific, and validated assays is most crucial for the accurate diagnosis of COVID-19 infection. Laboratory diagnosis of SARS-CoV-2 is extremely important in the disease and outbreak management. Development of rapid point of care tests with better sensitivity and specificity is the critical need of the hour as this will help accurate diagnosis and aid in containing the spread of SARS-CoV-2 infection. Early detection of viral infection greatly enhances implementation of specific public health intervention, such as infection control, environmental decontamination, and the closure of specific high-risk zones. Large-scale sequencing of SARS-CoV-2 genome isolated from affected populations across the world needs to be carried to monitor mutations that might affect performance of molecular tests. Creation of genome repositories and open-source genetic databases for use by global researchers is clearly the way forward to manage COVID-19 outbreak and accelerate vaccine development. This review summarizes various molecular diagnostics methods, technical guidelines, and advanced testing strategies adopted in India for laboratory diagnosis of COVID-19.
Health Literacy and Health Behavior Among Women in Ghazni, Afghanistan
Authors: Harsch Stefanie , Jawid Asadullah , Jawid Ebrahim , Saboga-Nunes Luis , Sørensen Kristine , Sahrai Diana , Bittlingmayer Uwe H.
Published: March 2021

Background:Health literacy is a determinant of health and assessed globally to inform the development of health interventions. However, little is known about health literacy in countries with one of the poorest health indicators worldwide, such as Afghanistan. Studies worldwide demonstrate that women play a key role in developing health literacy. Hence, this study's purpose is to explore health literacy of women in Afghanistan and the associated factors.

Methods:From May to June 2017, we randomly recruited 7–10 women per day at the hospital in Ghazni, a representative province of Afghanistan. Two trained female interviewers interviewed 322 women (15–61 years old) orally in Dari or Pashto on a voluntary basis and assessed their health literacy using the HLS-EU-Q16, associated socio-demographics, and health behavior.

Results:Health literacy of women (among educated and illiterates) is low even compared to other Asian countries. Health literacy is linked to age and education. We found mixed evidence of the relationship between health literacy and contextual factors, help-seeking, and health-related behavior.

Conclusion:This study provides novel data on health literacy and astonishing insights into its association with health behavior of women in Afghanistan, thus contributing to health status. The study calls for recognition of health literacy as a public health challenge be addressed in Afghanistan and other low-income countries affected by crises.
Cost Analysis of Health Examination Screening Program for Ischemic Heart Disease in Active-Duty Military Personnel in the Middle-Income Country
Authors: Simic Radoje , Ratkovic Nenad , Dragojevic Simic Viktorija , Savkovic Zorica , Jakovljevic Mihajlo , Peric Vitomir , Pandrc Milena , Rancic Nemanja
Published: March 2021

Cardiovascular diseases, including ischemic heart disease, are the most common causes of morbidity and death in the world, including Serbia, as a middle-income European country. The aim of the study was to determine the costs of preventive examinations for ischemic heart disease in active-duty military personnel, as well as to assess whether this was justified from the point of view of the limited health resources allocated for the treatment of the Republic of Serbia population. This is a retrospective cost-preventive study which included 738 male active-duty military personnel, aged from 23 to 58. The costs of primary prevention of ischemic heart disease in this population were investigated. Out of 738 subjects examined, arterial hypertension was detected in 101 subjects (in 74 of them, arterial hypertension was registered for the first time, while 27 subjects were already subjected to pharmacotherapy for arterial hypertension). Average costs of all services during the periodic-health-examination screening program were €76.96 per subject. However, average costs of all services during the periodic-health-examination screening program for patients with newfound arterial hypertension and poorly regulated arterial hypertension were €767.54 per patient and €2,103.63 per patient, respectively. Since periodic-health-examination screening program in military personnel enabled not only discovery of patient with newfound arterial hypertension but also regular monitoring of those who are already on antihypertensive therapy, significant savings of €690.58 per patient and €2,026.67 per patient can be achieved, respectively. As financial resources for providing health care in Serbia, as a middle-income country, are limited, further efforts should be put on screening programs for ischemic heart disease due to possible significant savings.
Inter-evaluator and Intra-evaluator Reliability of a Software Program Used to Extract Kinematic Variables Obtained by an Extremity-Mounted Inertial Measurement Unit System in Sound Horses at the Trot Under Soft and Hard Ground Conditions and Treadmill Exercise
Authors: Schwarz Julia , Vidondo Beatriz , Maninchedda Ugo E. , Sprick Miriam , Schöpfer Melina C. , Cruz Antonio M.
Published: March 2021

Objective:To assess the inter-evaluator and intra-evaluator reliability of a software program used to extract kinematic variables by a commercially available extremity-mounted inertial measurement unit system in sound horses at the trot under soft and hard ground conditions and treadmill exercise.

Animals:Thirty adult, sound and healthy French Montagne stallions.

Procedures:Data collection was performed with six IMUs strapped to the distal, metacarpal, metatarsal and tibial regions of every horse. Per surface (treadmill, soft and hard ground) 10 stallions were trotted three times. Prior to the analysis done by six evaluators (three experienced, three inexperienced) the data was blinded and copied three times. For every analysis a minimum of five strides had to be selected. To assess the intra- and inter-evaluator reliability a selection of gait variables was used to calculate intra and inter correlation coefficients (ICCs) as well as variance partitioning coefficients (VPCs).

Results:All of the tested gait variables showed high levels of reliability. There was no mentionable difference considering the correlation coefficients between the intra and inter reliability as well as between the three different surfaces. VPCs showed that the factor horse is by far the most responsible for any appearing variance. The experience of the evaluator had no influence on the results.

Conclusions and Clinical Relevance:The software program tested in this study has a high inter- and intra-evaluator reliability under the chosen conditions for the selected variables and acts independent of the ground situation and the experience of the evaluator. On the condition of a correct application it has the potential to become a clinically relevant and reliable gait analysis tool.
Role of Tumor-Associated Macrophages in Sarcomas
Authors: Fujiwara Tomohiro , Healey John , Ogura Koichi , Yoshida Aki , Kondo Hiroya , Hata Toshiaki , Kure Miho , Tazawa Hiroshi , Nakata Eiji , Kunisada Toshiyuki , Fujiwara Toshiyoshi , Ozaki Toshifumi
Published: March 2021

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.
Prognostic Value of Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA 19-9) in Gallbladder Cancer; 65 IU/mL of CA 19-9 Is the New Cut-Off Value for Prognosis
Authors: Kim Myongjin , Kim Hongbeom , Han Youngmin , Sohn Heeju , Kang Jae Seung , Kwon Wooil , Jang Jin-Young
Published: March 2021

Due to the lack of appropriate tumor markers with optimal cut-off values to predict the prognosis of gallbladder cancer (GBC), this study aimed to demonstrate the relationship between prognosis and the levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), and to determine optimal thresholds. In total, 539 patients diagnosed with GBC were examined. The relationship between tumor marker levels and overall survival (OS) was analyzed. The C-tree method was used to suggest tumor marker thresholds, and multivariate analysis was conducted to identify prognostic factors for overall survival. The mean age of the patients was 65.3 years, and the 5-year overall survival rate in all patients was 68.9%. Following the C-tree method, the optimal cut-off value was set at 5 IU/mL for CEA and at 65 IU/mL for CA 19-9. Multivariate analysis revealed that age, CA 19-9 level, operative method, T stage, and N stage were significant prognostic factors for OS. Consequently, CA 19-9 had a stronger association with prognosis than CEA, and 65 IU/mL for CA 19-9 may be suggestive in evaluating the prognosis of GBC. Moreover, it could be an effective indicator for determining the surgical extent necessary and the need for adjuvant treatment.
How Should We Respond to the Global Pandemic: The Need for Cultural Change
Authors: Gray Ben
Published: March 2021

The Covid pandemic has had a terrible effect on the world and government responses have been described as “Catastrophic Moral Failure”. The approach of bioethics of developing “normative ethics” has provided frameworks on how to act but despite the fact that we knew what to do to prevent the pandemic, we did not do it. In this paper I argue that ethics is culture bound: it is the stories that “we” live by. I illustrate this with examples of cultures with differing values that were developed as a result of the particular circumstances of those cultures. I then argue that after World War 2 in response to the risks of further large wars and atrocities, work was done to further establish a “global culture” and a detailed normative ethical framework was developed by negotiation through the United Nations for that “culture”. Whilst this approach has been necessary, it has not been sufficient. I argue that we need to reframe the approach as one of achieving cultural change rather than complying with ethical norms. Some societies that were unable to adapt to changed circumstances failed to survive, others failed to thrive. A similar fate awaits the whole planet if we cannot change the stories we live by.
A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea)
Authors: Hodgin Kathleen S. , Donovan Emily K. , Kekes-Szabo Sophia , Lin Joanne C. , Feick Joseph , Massey Rebecca L. , Ness Timothy J. , Younger Jarred W.
Published: March 2021

A chronic multi-symptom illness of unknown etiology, Gulf War Illness (GWI) affects 175,000 to 250,000 veterans of the Gulf War. Because inflammation has suspected involvement in the pathophysiology of GWI, botanical treatments that target inflammation may be beneficial in reducing symptoms. No FDA-approved treatments currently exist for GWI, and rapid prioritization of agents for future efficacy testing is important. This study is part of a larger project that screened nine different botanical compounds with purported anti-inflammatory properties for potential treatment of GWI. We tested three botanicals (resveratrol [Polygonum cuspidatum], luteolin, and fisetin [Rhus succedanea]) on symptom severity of GWI in this placebo-controlled, pseudo-randomized clinical trial. Twenty-one male veterans with GWI completed the study protocol, which consisted of 1 month (30 days ± 3) of baseline symptom reports, 1 month of placebo, 1 month of lower-dose botanical, and 1 month of higher-dose botanical. Participants completed up to 3 different botanicals, repeating the placebo, lower-dose, and higher-dose cycle for each botanical assigned. Linear mixed models were used for analyses. Resveratrol reduced GWI symptom severity significantly more than placebo at both the lower (p = 0.035) and higher (p = 0.004) dosages. Luteolin did not decrease symptom severity more than placebo at either the lower (p = 0.718) or higher dosages (p = 0.492). Similarly, fisetin did not reduce symptom severity at either the lower (p = 0.504) or higher (p = 0.616) dosages. Preliminary findings from this screening study suggest that resveratrol may be beneficial in reducing symptoms of GWI and should be prioritized for future testing. Larger trials are required to determine efficacy, response rates, durability of effects, safety, and optimal dosage. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.
Test–Retest Reliability of an iPhone® Inclinometer Application to Assess the Lumbar Joint Repositioning Error in Non-Specific Chronic Low Back Pain
Authors: Caña-Pino Alejandro , Espejo-Antúnez Luís , Adsuar José Carmelo , Apolo-Arenas María Dolores
Published: March 2021

Background: The joint position sense (JPS) has been used as an indirect marker of proprioception in subjects with non-specific chronic low back pain (NSCLBP), showing impairment in previous studies. It seems necessary to devise reliable tests to measure proprioceptive deficits in subjects with NSLBP. The objective of this study was to analyse the test–retest reliability and smallest real difference (SRD) of lumbar proprioception through the JPS indicator in a sample of patients with NSCLBP. Methods: Fifty participants with NSCLBP performed three repetitions of 30° lumbar flexion while standing and sitting using the iPhone® inclinometer application to measure the lumbar joint repositioning error. For the reliability analysis, we performed an intra-session test–retest. Results: The total sample ICC values were excellent for standing (0.96) and sitting (0.93) 30° lumbar flexion. In addition, our results showed that, for the total sample, an SRD < 12% can be considered as a true change in proprioception concerning this procedure. On the other hand, men have better reliability than women in both standing and sitting positions. Additionally, the sitting position has better reliability than the standing position. The standard error of measurement (SEM) percentage was 4.2 for standing and 3.8 for sitting. The SRD percentage was 11.6 for standing and 10.4 for sitting. Conclusions: The iPhone® inclinometer seems reliable for assessing proprioceptive ability through the lumbar joint repositioning error in subjects with NSCLBP in both standing (ICC = 0.96) and sitting (ICC = 0.93) positions. This technological device showed a lower measurement error for sitting position (SRD < 12%).
Pattern Recognition of the COVID-19 Pandemic in the United States: Implications for Disease Mitigation
Authors: Wu Jianyong , Sha Shuying
Published: March 2021

The novel coronavirus (COVID-19) pandemic presents a severe threat to human health worldwide. The United States (US) has the highest number of reported COVID-19 cases, and over 16 million people were infected up to the 12 December 2020. To better understand and mitigate the spread of the disease, it is necessary to recognize the pattern of the outbreak. In this study, we explored the patterns of COVID-19 cases in the US from 1 March to 12 December 2020. The county-level cases and rates of the disease were mapped using a geographic information system (GIS). The overall trend of the disease in the US, as well as in each of its 50 individual states, were analyzed by the seasonal-trend decomposition. The disease curve in each state was further examined using K-means clustering and principal component analysis (PCA). The results showed that three clusters were observed in the early phase (1 March–31 May). New York has a unique pattern of the disease curve and was assigned one cluster alone. Two clusters were observed in the middle phase (1 June–30 September). California, Texas and Florida were assigned in the same cluster, which has the pattern different from the remaining states. In the late phase (1 October–12 December), California has a unique pattern of the disease curve and was assigned a cluster alone. In the whole period, three clusters were observed. California, Texas and Florida still have similar patterns and were assigned in the same cluster. The trend analysis consolidated the patterns identified from the cluster analysis. The results from this study provide insight in making disease control and mitigation strategies.