bluuebunny/crossref_metadata_2025 huggingface dataset:
No Difference in Arousal or Cognitive Demands Between Manual and Partially Automated Driving: A Multi-Method On-Road Study
Authors: Lohani Monika , Cooper Joel M. , Erickson Gus G. , Simmons Trent G. , McDonnell Amy S. , Carriero Amanda E. , Crabtree Kaedyn W. , Strayer David L.
Published: June 2021

Introduction

Partial driving automation is not always reliable and requires that drivers maintain readiness to take over control and manually operate the vehicle. Little is known about differences in drivers’ arousal and cognitive demands under partial automation and how it may make it difficult for drivers to transition from automated to manual modes. This research examined whether there are differences in drivers’ arousal and cognitive demands during manual versus partial automation driving.

Method

We compared arousal (using heart rate) and cognitive demands (using the root mean square of successive differences in normal heartbeats; RMSSD, and Detection Response Task; DRT) while 39 younger (M= 28.82 years) and 32 late-middle-aged (M= 52.72 years) participants drove four partially automated vehicles (Cadillac, Nissan Rogue, Tesla, and Volvo) on interstate highways. If compared to manual driving, drivers’ arousal and cognitive demands were different under partial automation, then corresponding differences in heart rate, RMSSD, and DRT would be expected. Alternatively, if drivers’ arousal and cognitive demands were similar in manual and partially automated driving, no difference in the two driving modes would be expected.

Results

Results suggest no significant differences in heart rate, RMSSD, or DRT reaction time performance between manual and partially automated modes of driving for either younger or late-middle-aged adults across the four test vehicles. A Bayes Factor analysis suggested that heart rate, RMSSD, and DRT data showed extreme evidence in favor of the null hypothesis.

Conclusion

This novel study conducted on real roads with a representative sample provides important evidence of no difference in arousal and cognitive demands. Younger and late-middle-aged motorists who are new to partial automation are able to maintain arousal and cognitive demands comparable to manual driving while using the partially automated technology. Drivers who are more experienced with partially automated technology may respond differently than those with limited prior experience.
Disruptions of Circadian Rhythms and Thrombolytic Therapy During Ischemic Stroke Intervention
Authors: Liu Jennifer A. , Walton James C. , DeVries A. Courtney , Nelson Randy J.
Published: June 2021

Several endogenous and exogenous factors interact to influence stroke occurrence, in turn contributing to discernable daily distribution patterns in the frequency and severity of cerebrovascular events. Specifically, strokes that occur during the morning tend to be more severe and are associated with elevated diastolic blood pressure, increased hospital stay, and worse outcomes, including mortality, compared to strokes that occur later in the day. Furthermore, disrupted circadian rhythms are linked to higher risk for stroke and play a role in stroke outcome. In this review, we discuss the interrelation among core clock genes and several factors contributing to ischemic outcomes, sources of disrupted circadian rhythms, the implications of disrupted circadian rhythms in foundational stroke scientific literature, followed by a review of clinical implications. In addition to highlighting the distinct daily pattern of onset, several aspects of physiology including immune response, endothelial/vascular and blood brain barrier function, and fibrinolysis are under circadian clock regulation; disrupted core clock gene expression patterns can adversely affect these physiological processes, leading to a prothrombotic state. Lastly, we discuss how the timing of ischemic onset increases morning resistance to thrombolytic therapy and the risk of hemorrhagic transformation.
Psychosocial Determinants of Vegetable Intake Among Nepalese Young Adults: An Exploratory Survey
Authors: Pandey Sujita , Budhathoki Mausam , Yadav Dipendra Kumar
Published: June 2021

Background: Adequate intake of vegetables facilitates a healthy lifestyle. However, the majority of Nepalese young adults consume inadequate amount of vegetables per day.

Objectives: We explored psychosocial determinants of daily intake of two or more servings of vegetables among Nepalese young adults using attitude, social influence, and self-efficacy (ASE) as a theoretical framework, extended with measures of habit and self-identity as additional constructs.

Methods/Participants: A cross-sectional study through a web-based questionnaire survey was conducted among 461 Nepalese young adults aged 18–35 years old. Participants were recruited through convenience (snowball) sampling. A factor-based partial least square structural equation modelling was used for analysis.

Results: The findings indicated that attitudes (β = 0.09, p = 0.029), social influence (β = 0.17, p < 0.001), habit (β = 0.24, p < 0.001) and self-identity (β = 0.30, p < 0.001) were significant factors influencing intention to eat two or more servings of vegetables per day. Further, self-efficacy (β = 0.10, p = 0.011), habit (β = 0.08, p = 0.034), diet (β = −0.10, p = 0.014), and place of residence (β = 0.11, p = 0.007) significantly influenced behaviour to eat two or more servings of vegetables per day. However, self-efficacy (β = 0.07, p = 0.062) did not significantly influence intention and self-identity (β = 0.06, p = 0.083), age (β = −0.02, p = 0.328), gender (β = 0.02, p = 0.350), and body mass index (β = −0.04, p = 0.209) did not significantly influence behaviour to eat two or more servings of vegetables per day.

Conclusion: The study shows that attitudes, social influence, habit, and self-identity were significant factors influencing intention to eat two or more servings of vegetables per day. Further, self-efficacy and habit significantly influenced behaviour to eat two or more servings of vegetables per day. However, self-efficacy did not significantly influence intention and self-identity did not significantly influence behaviour to eat two or more servings of vegetables per day.
The Correlation Between SPP1 and Immune Escape of EGFR Mutant Lung Adenocarcinoma Was Explored by Bioinformatics Analysis
Authors: Zheng Yi , Hao Shiying , Xiang Cheng , Han Yaguang , Shang Yanhong , Zhen Qiang , Zhao Yiyi , Zhang Miao , Zhang Yan
Published: June 2021

Background

Immune checkpoint inhibitors have achieved breakthrough efficacy in treating lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR), leading to the revision of the treatment guidelines. However, most patients with EGFR mutation are resistant to immunotherapy. It is particularly important to study the differences in tumor microenvironment (TME) between patients with and without EGFR mutation. However, relevant research has not been reported. Our previous study showed that secreted phosphoprotein 1 (SPP1) promotes macrophage M2 polarization and PD-L1 expression in LUAD, which may influence response to immunotherapy. Here, we assessed the role of SPP1 in different populations and its effects on the TME.

Methods

We compared the expression of SPP1 in LUAD tumor and normal tissues, and in samples with wild-type and mutant EGFR. We also evaluated the influence of SPP1 on survival. The LUAD data sets were downloaded from TCGA and CPTAC databases. Clinicopathologic characteristics associated with overall survival in TCGA were assessed using Cox regression analysis. GSEA revealed that several fundamental signaling pathways were enriched in the high SPP1 expression group. We applied CIBERSORT and xCell to calculate the proportion and abundance of tumor-infiltrating immune cells (TICs) in LUAD, and compared the differences in patients with high or low SPP1 expression and wild-type or mutant EGFR. In addition, we explored the correlation between SPP1 and CD276 for different groups.

Results

SPP1 expression was higher in LUAD tumor tissues and in people with EGFR mutation. High SPP1 expression was associated with poor prognosis. Univariate and multivariate cox analysis revealed that up-regulated SPP1 expression was independent indicator of poor prognosis. GSEA showed that the SPP1 high expression group was mainly enriched in immunosuppressed pathways. In the SPP1 high expression group, the infiltration of CD8+ T cells was lower and M2-type macrophages was higher. These results were also observed in patients with EGFR mutation. Furthermore, we found that the SPP1 expression was positively correlated with CD276, especially in patients with EGFR mutation.

Conclusion

SPP1 levels might be a useful marker of immunosuppression in patients with EGFR mutation, and could offer insight for therapeutics.
Articles That Use Artificial Intelligence for Ultrasound: A Reader’s Guide
Authors: Kuang Ming , Hu Hang-Tong , Li Wei , Chen Shu-Ling , Lu Xiao-Zhou
Published: June 2021

Artificial intelligence (AI) transforms medical images into high-throughput mineable data. Machine learning algorithms, which can be designed for modeling for lesion detection, target segmentation, disease diagnosis, and prognosis prediction, have markedly promoted precision medicine for clinical decision support. There has been a dramatic increase in the number of articles, including articles on ultrasound with AI, published in only a few years. Given the unique properties of ultrasound that differentiate it from other imaging modalities, including real-time scanning, operator-dependence, and multi-modality, readers should pay additional attention to assessing studies that rely on ultrasound AI. This review offers the readers a targeted guide covering critical points that can be used to identify strong and underpowered ultrasound AI studies.
Classifying Medulloblastoma Subgroups Based on Small, Clinically Achievable Gene Sets
Authors: Gershanov Sivan , Madiwale Shreyas , Feinberg-Gorenshtein Galina , Vainer Igor , Nehushtan Tamar , Michowiz Shalom , Goldenberg-Cohen Nitza , Birger Yehudit , Toledano Helen , Salmon-Divon Mali
Published: June 2021

As treatment protocols for medulloblastoma (MB) are becoming subgroup-specific, means for reliably distinguishing between its subgroups are a timely need. Currently available methods include immunohistochemical stains, which are subjective and often inconclusive, and molecular techniques—e.g., NanoString, microarrays, or DNA methylation assays—which are time-consuming, expensive and not widely available. Quantitative PCR (qPCR) provides a good alternative for these methods, but the current NanoString panel which includes 22 genes is impractical for qPCR. Here, we applied machine-learning–based classifiers to extract reliable, concise gene sets for distinguishing between the four MB subgroups, and we compared the accuracy of these gene sets to that of the known NanoString 22-gene set. We validated our results using an independent microarray-based dataset of 92 samples of all four subgroups. In addition, we performed a qPCR validation on a cohort of 18 patients diagnosed with SHH, Group 3 and Group 4 MB. We found that the 22-gene set can be reduced to only six genes (IMPG2, NPR3, KHDRBS2, RBM24, WIF1, and EMX2) without compromising accuracy. The identified gene set is sufficiently small to make a qPCR-based MB subgroup classification easily accessible to clinicians, even in developing, poorly equipped countries.
A Key Pathway to Cancer Resilience: The Role of Autophagy in Glioblastomas
Authors: Jandrey Elisa Helena Farias , Bezerra Marcelle , Inoue Lilian Tiemi , Furnari Frank B. , Camargo Anamaria Aranha , Costa Érico Tosoni
Published: June 2021

There are no effective strategies for the successful treatment of glioblastomas (GBM). Current therapeutic modalities effectively target bulk tumor cells but leave behind marginal GBM cells that escape from the surgical margins and radiotherapy field, exhibiting high migratory phenotype and resistance to all available anti-glioma therapies. Drug resistance is mostly driven by tumor cell plasticity: a concept associated with reactivating transcriptional programs in response to adverse and dynamic conditions from the tumor microenvironment. Autophagy, or “self-eating”, pathway is an emerging target for cancer therapy and has been regarded as one of the key drivers of cell plasticity in response to energy demanding stress conditions. Many studies shed light on the importance of autophagy as an adaptive mechanism, protecting GBM cells from unfavorable conditions, while others recognize that autophagy can kill those cells by triggering a non-apoptotic cell death program, called ‘autophagy cell death’ (ACD). In this review, we carefully analyzed literature data and conclude that there is no clear evidence indicating the presence of ACD under pathophysiological settings in GBM disease. It seems to be exclusively induced by excessive (supra-physiological) stress signals, mostly from in vitro cell culture studies. Instead, pre-clinical and clinical data indicate that autophagy is an emblematic example of the ‘dark-side’ of a rescue pathway that contributes profoundly to a pro-tumoral adaptive response. From a standpoint of treating the real human disease, only combinatorial therapy targeting autophagy with cytotoxic drugs in the adjuvant setting for GBM patients, associated with the development of less toxic and more specific autophagy inhibitors, may inhibit adaptive response and enhance the sensibility of glioma cells to conventional therapies.
Integrative Multi-Omics Analysis of Identified NUF2 as a Candidate Oncogene Correlates With Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer
Authors: Chen Mengqing , Li Shangkun , Liang Yuling , Zhang Yue , Luo Dan , Wang Wenjun
Published: June 2021

Background

Lung cancer is one of the most common malignant tumors and the leading causes of cancer-related deaths worldwide. As a component of the nuclear division cycle 80 complex, NUF2 is a part of the conserved protein complex related to the centromere. Although the high expression of NUF2 has been reported in many different types of human cancers, the multi-omics analysis in non-small cell lung cancer (NSCLC) of NUF2 remains to be elucidated.

Methods

In this analysis, NUF2 expression difference analysis in non-small cell lung cancer was evaluated by Oncomine, TIMER, GEO, and TCGA database. And the prognosis analysis of NUF2 based on Kaplan-Meier was performed. R language was used to analyze the differential expression genes, functional annotation and protein-protein interaction (PPI). GSEA analysis of differential expression genes was also carried out. Mechanism analysis about exploring the characteristic of NUF2, multi-omics, and correlation analysis was carried out using UALCAN, cBioportal, GEPIA, TIMER, and TISIDB, respectively.

Results

The expression of NUF2 in NSCLC, both lung adenocarcinoma (LUAD) and squamous lung cancer (LUSC), was significantly higher than that in normal tissues. The analysis of UALCAN database samples proved that NUF2 expression was connected with stage and smoking habits. Meanwhile, the overall survival curve also validated that high expression of NUF2 has a poorer prognosis in NSCLC. GO, KEGG, GSEA, subcellular location from COMPARTMENTS indicated that NUF2 may regulate the cell cycle. Correlation analysis also showed that NUF2 was mainly positively associated with cell cycle and tumor-related genes. NUF2 altered group had a poorer prognosis than unaltered group in NSCLC. Immune infiltration analysis showed that the NUF2 expression mainly have negatively correlation with immune cells and immune subtypes in LUAD and LUSC. Furthermore, quantitative PCR was used to validate the expression difference of NUF2 in LUAD and LUSC.

Conclusion

Our findings elucidated that NUF2 may play an important role in cell cycle, and significantly associated with tumor-related gene in NSCLC; we consider that NUF2 may be a prognostic biomarkers in NSCLC.
N6-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1
Authors: Huang Chunxian , Liang Jinxiao , Lin Shaodan , Wang Dongyan , Xie Qingsheng , Lin Zhongqiu , Yao Tingting
Published: June 2021

Objective

Cervical cancer is a frequently encountered gynecological malignancy as a major contributor to cancer-related deaths in women. This study focuses on how miR-193b promotes cervical cancer aggressiveness as well as the role of m6A in miR-193b silencing.

Methods

Cervical cancer samples and the matching adjacent normal cervical tissues were used to determine the significance of miR-193b in cervical cancer. The CCK-8 assay, cell cycle analysis, qRT-PCR, Western blot assay, IHC, RIP, and xenograft models were utilized to explore the impact of miR-193b in cervical cancer and how m6A regulates miR-193b expression. Luciferase reporter assays, qRT-PCR, and Western blotting were enlisted to study the interaction between miR-193b and CCND1.

Results

Our study suggested that lower miR-193b expressions were strongly linked to more advanced cervical cancer stages and the presence of deeper stromal invasion. miR-193b functions as a tumor suppressor that is regulated by m6A methylation in cervical tumors. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting.

Conclusions

m6A associated downregulation of miR-193b promotes cervical cancer aggressiveness by targeting CCND1.
Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
Authors: Trojaniello Claudia , Luke Jason J. , Ascierto Paolo A.
Published: June 2021

Melanoma is the most fatal skin cancer. In the early stages, it can be safely treated with surgery alone. However, since 2011, there has been an important revolution in the treatment of melanoma with new effective treatments. Targeted therapy and immunotherapy with checkpoint inhibitors have changed the history of this disease. To date, more than half of advanced melanoma patients are alive at 5 years; despite this breakthrough, approximately half of the patients still do not respond to treatment. For these reasons, new therapeutic strategies are required to expand the number of patients who can benefit from immunotherapy or combination with targeted therapy. Current research aims at preventing primary and acquired resistance, which are both responsible for treatment failure in about 50% of patients. This could increase the effectiveness of available drugs and allow for the evaluation of new combinations and new targets. The main pathways and molecules under study are the IDO inhibitor, TLR9 agonist, STING, LAG-3, TIM-3, HDAC inhibitors, pegylated IL-2 (NKTR-214), GITR, and adenosine pathway inhibitors, among others (there are currently about 3000 trials that are evaluating immunotherapeutic combinations in different tumors). Other promising strategies are cancer vaccines and oncolytic viruses. Another approach is to isolate and remove immune cells (DCs, T cells, and NK cells) from the patient’s blood or tumor infiltrates, add specific gene fragments, expand them in culture with growth factors, and re-inoculate into the same patient. TILs, TCR gene transfer, and CAR-T therapy follow this approach. In this article, we give an overview over the current status of melanoma therapies, the clinical rationale for choosing treatments, and the new immunotherapy approaches.
The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase-2, Promotes Epithelial-Mesenchymal Transition
Authors: Gómez-Valenzuela Fernán , Escobar Enrico , Pérez-Tomás Ricardo , Montecinos Viviana P.
Published: June 2021

The tumor microenvironment (TME) corresponds to a complex and dynamic interconnection between the extracellular matrix and malignant cells and their surrounding stroma composed of immune and mesenchymal cells. The TME has constant cellular communication through cytokines that sustain an inflammatory profile, which favors tumor progression, angiogenesis, cell invasion, and metastasis. Although the epithelial-mesenchymal transition (EMT) represents a relevant metastasis-initiating event that promotes an invasive phenotype in malignant epithelial cells, its relationship with the inflammatory profile of the TME is poorly understood. Previous evidence strongly suggests that cyclooxygenase-2 (COX-2) overexpression, a pro-inflammatory enzyme related to chronic unresolved inflammation, is associated with common EMT-signaling pathways. This review article summarizes how COX-2 overexpression, within the context of the TME, orchestrates the EMT process and promotes initial metastatic-related events.
Telehealth for Children With Epilepsy Is Effective and Reduces Anxiety Independent of Healthcare Setting
Authors: Klotz Kerstin Alexandra , Borlot Felippe , Scantlebury Morris H. , Payne Eric T. , Appendino Juan Pablo , Schönberger Jan , Jacobs Julia
Published: June 2021

Objectives: The use of telemedicine has grown exponentially as an alternative to providing care to patients with epilepsy during the pandemic. We investigated the impact of the current pandemic among children with epilepsy from two distinct pediatric epilepsy centers. We also compared perceptions among those who received telemedicine against those who did not.

Methods: We developed a questionnaire and invited families followed in Freiburg, Germany, and Calgary, Alberta, Canada, to participate during the initial 9 months of the pandemic. The survey contained 32 questions, 10 of which were stratified according to telemedicine exposure.

Results: One hundred twenty-six families (80 in Freiburg, 46 in Calgary) participated, and 40.3% received telemedicine care. Most children (mean age 10.4 years, SD 5.1) had chronic epilepsy but poorly controlled seizures. Negative impacts were reported by 36 and 65% of families who had to reschedule appointments for visits and diagnostics, respectively. Nearly two-thirds of families reported no change in seizure frequency, while 18.2% reported either worsening or improvement of seizures. Although most families did not note behavioral changes, 28.2% reported behavior worsening. Families who received telemedicine care had a statistically significant reduction of parental self-reported anxiety level after virtual visits compared to those who did not experience telemedicine. Families with telemedicine consultations were more likely to consider future virtual care (84 vs. 65.2% of those without), even after the pandemic. Patient data safety, easy access to specialized services, and consistency with the same healthcare provider were graded as important in both centers, while a shorter waiting time was most relevant in Calgary.

Conclusion: In our cohort, some children with epilepsy experienced increased seizures and worsening behavior during the first 9 months of the current pandemic. In addition, our data suggest that telemedicine might reduce parental anxiety symptoms, and families who experienced telehealth were more positive and open to similar appointments in the future.
Fecal High-Mobility Group Box 1 as a Marker of Early Stage of Necrotizing Enterocolitis in Preterm Neonates
Authors: Vitali Roberta , Terrin Gianluca , Palone Francesca , Laudadio Ilaria , Cucchiara Salvatore , Boscarino Giovanni , Di Chiara Maria , Stronati Laura
Published: June 2021

Introduction:An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis. We evaluated whether fecal high-mobility group box protein 1 (HMGB1) may early identify preterms at risk of developing NEC.

Materials and Methods:A case-control study including neonates admitted at the Neonatal Intensive Care Unit (NICU) of the Sapienza University Hospital “Umberto I” in Rome, from July 2015 to December 2016. Stool samples obtained from cases (preterm newborns with NEC) and controls (newborns without NEC) were collected at the enrolment (T0) and within 7–14 days after the first sample collection (T1). HMGB1, extracted and measured with western blot, was reported as densitometry units (DUS).

Results:HMGB1 levels in 30 cases (n= 28—Bell stage 1,n= 2 Bell stage 2) were higher [T0: 21,462 DUS (95% CI, 16,370–26,553 DUS)—T1: 17,533 DUS (95% CI, 13,052–22,014 DUS)] than in 30 preterm controls [T0: 9,446 DUS (95% CI, 6,147–12,746 DUS)—T1: 9,261 DUS (95% CI, 5,126–13,396 DUS),p< 0.001). Preterm newborns showed significant higher levels of HMGB1 (15,690 DUS (95% CI, 11,929–19,451 DUS)] in comparison with 30 full-term neonates with birth weight >2,500 g [6,599 DUS (95% CI, 3,141–10,058 DUS),p= 0.003]. Multivariate analysis showed that the risk of NEC was significantly (p= 0.012) related to the HMGB1 fecal levels at T0.

Conclusions:We suggest fecal HMGB1 as a reliable marker of early NEC in preterm neonates. This study supports further investigation on the role of fecal HMGB1 assessment in managing preterm newborns at risk of NEC. Further studies are advocated to evaluate diagnostic accuracy of this marker in more severe forms of the disease.
Noncanonical NF-κB Signaling Upregulation in Inflammatory Bowel Disease Patients is Associated With Loss of Response to Anti-TNF Agents
Authors: Nguyen Vu Q. , Eden Kristin , Morrison Holly A. , Sammons Megan B. , Knight Kristin K. , Sorrentino Siena , Brock Rebecca M. , Grider Douglas J. , Allen Irving C. , Sorrentino Dario
Published: June 2021

Objectives: Targeting tumor necrosis factor (TNF) with biologic agents, such as infliximab and adalimumab, is a widely used and effective therapeutic strategy in inflammatory bowel disease (IBD). Unfortunately, a significant number of patients fail to respond or lose response over time to these agents. Previous studies have defined multiple complex roles for canonical NF-κB signaling in the pathogenesis of IBD. However, preliminary evidence suggests that the lesser defined noncanonical NF-κB signaling pathway also contributes to disease pathogenesis and response to anti-TNF agents. The objective of this study was to evaluate this hypothesis in Crohn’s disease (CD) and ulcerative colitis (UC) patients.

Design: A total of 27 subjects with IBD (19 with CD and 8 with UC) and 15 control subjects were tested. Clinical criteria, patient history, and endoscopic disease activity were factors used to categorize patients and define therapeutic response. Biopsy specimens were collected during colonoscopy and expression was determined for 88 target genes known to be associated with noncanonical NF-κB signaling and IBD.

Results: Noncanonical NF-κB signaling was significantly upregulated in IBD patients and was associated with increased gastrointestinal inflammation, epithelial cell death, lymphocyte migration, and Nod-like receptor signaling. Furthermore, noncanonical NF-κB signaling was further upregulated in patients unresponsive to anti-TNF agents and was suppressed in responsive patients. MAP3K14, NFKB2, CCL19, CXCL12, and CXCL13 were significantly dysregulated, as were genes that encode pathway regulators, such as CYLD, NLRP12, and BIRC2/3.

Conclusion: Our study identifies a previously uncharacterized role for the understudied noncanonical NF-κB signaling pathway in the pathogenesis of IBD and anti-TNF therapy responsiveness. The genes and pathways identified may ultimately prove useful in IBD management and could potentially be used as biomarkers of drug response.
Chinese Herbal Medicine for the Treatment of Children and Adolescents With Refractory Mycoplasma Pneumoniae Pneumonia: A Systematic Review and a Meta-Analysis
Authors: Ling Xiaoying , Sun Xun , Kong Huimin , Peng Shanshan , Yu Zheng , Wen Jiali , Yuan Bin
Published: June 2021

Objectives: Chinese herb medicine (CHM) is one of the most popular complementary and alternative therapies, which has been widely used to treat Refractory Mycoplasma Pneumoniae Pneumonia (RMPP). However, the effect and safety of CHM remain controversial. Hence, we conducted this meta-analysis to evaluate whether CHM combination therapy could bring benefits to children and adolescents with RMPP.

Methods: Seven databases were used for data searching through November 11, 2020 following the PRISMA checklist generally. Review Manager 5.3, Trial sequential analysis 0.9.5.10 Beta software and Stata16.0 were applied to perform data analyses. Mean difference or risk ratio was adopted to express the results, where a 95% confidence interval (CI) was applied.

Results: In general, this research enrolled 17 trials with 1,451 participants. The overall pooled results indicated that CHM was beneficial for children and adolescents with RMPP by improving the clinical efficacy rate [RR = 1.20, 95% CI (1.15, 1.25), p < 0.00001], shortening antipyretic time [MD = −2.60, 95% CI (−3.06, −2.13), p < 0.00001], cough disappearance time [MD = −2.77, 95% CI (−3.12, −2.42), p < 0.00001], lung rale disappearance time [MD = −2.65, 95% CI (−3.15, −2.15), p < 0.00001], lung X-ray infiltrates disappearance time [MD = −2.75, 95% CI (−3.33, −2.17), p < 0.00001], reducing TNF-α level [MD = −5.49, 95% CI (−7.21, −3.77), p < 0.00001]. Moreover, subgroup results suggested that removing heat-phlegm and toxicity therapy had more advantages in shortening antipyretic time, cough disappearance time, lung X-ray infiltrates disappearance time and reducing TNF-α level. Meanwhile promoting blood circulation therapy seemed to be better at relieving lung rale. However, regarding adverse events, the two groups displayed no statistical difference [RR = 0.97, 95% CI (0.60, 1.57), p = 0.91].

Conclusion: Despite of the apparently positive results in relieving clinical symptoms, physical signs and reducing inflammation, it is premature to confirm the efficacy of CHM in treating RMPP because of the limitation of quality and the number of the included studies. More large-scale, double-blind, well-designed, randomized controlled trials are needed in future research.
Variation of Two S3b Residues in KV4.1–4.3 Channels Underlies Their Different Modulations by Spider Toxin κ-LhTx-1
Authors: Xiao Zhen , Zhao Piao , Wu Xiangyue , Kong Xiangjin , Wang Ruiwen , Liang Songping , Tang Cheng , Liu Zhonghua
Published: June 2021

The naturally occurred peptide toxins from animal venoms are valuable pharmacological tools in exploring the structure-function relationships of ion channels. Herein we have identified the peptide toxin κ-LhTx-1 from the venom of spider Pandercetes sp (the Lichen huntsman spider) as a novel selective antagonist of the KV4 family potassium channels. κ-LhTx-1 is a gating-modifier toxin impeded KV4 channels’ voltage sensor activation, and mutation analysis has confirmed its binding site on channels’ S3b region. Interestingly, κ-LhTx-1 differently modulated the gating of KV4 channels, as revealed by toxin inhibiting KV4.2/4.3 with much more stronger voltage-dependence than that for KV4.1. We proposed that κ-LhTx-1 trapped the voltage sensor of KV4.1 in a much more stable resting state than that for KV4.2/4.3 and further explored the underlying mechanism. Swapping the non-conserved S3b segments between KV4.1(280FVPK283) and KV4.3(275VMTN278) fully reversed their voltage-dependence phenotypes in inhibition by κ-LhTx-1, and intensive mutation analysis has identified P282 in KV4.1, D281 in KV4.2 and N278 in KV4.3 being the key residues. Furthermore, the last two residues in this segment of each KV4 channel (P282/K283 in KV4.1, T280/D281 in KV4.2 and T277/N278 in KV4.3) likely worked synergistically as revealed by our combinatorial mutations analysis. The present study has clarified the molecular basis in KV4 channels for their different modulations by κ-LhTx-1, which have advanced our understanding on KV4 channels’ structure features. Moreover, κ-LhTx-1 might be useful in developing anti-arrhythmic drugs given its high affinity, high selectivity and unique action mode in interacting with the KV4.2/4.3 channels.
Case Report: Chronic Bacterial Prostatitis Treated With Phage Therapy After Multiple Failed Antibiotic Treatments
Authors: Johri Apurva Virmani , Johri Pranav , Hoyle Naomi , Pipia Levan , Nadareishvili Lia , Nizharadze Dea
Published: June 2021

Background: Chronic Bacterial Prostatitis (CBP) is an inflammatory condition caused by a persistent bacterial infection of the prostate gland and its surrounding areas in the male pelvic region. It is most common in men under 50 years of age. It is a long-lasting and debilitating condition that severely deteriorates the patient’s quality of life. Anatomical limitations and antimicrobial resistance limit the effectiveness of antibiotic treatment of CBP. Bacteriophage therapy is proposed as a promising alternative treatment of CBP and related infections. Bacteriophage therapy is the use of lytic bacterial viruses to treat bacterial infections. Many cases of CBP are complicated by infections caused by both nosocomial and community acquired multidrug resistant bacteria. Frequently encountered strains include Vancomycin resistant Enterococci, Extended Spectrum Beta Lactam resistant Escherichia coli, other gram-positive organisms such as Staphylococcus and Streptococcus, Enterobacteriaceae such as Klebsiella and Proteus, and Pseudomonas aeruginosa, among others.

Case Presentation: We present a patient with the typical manifestations of CBP. The patient underwent multiple courses of antibiotic treatment without any long-term resolution of his symptoms. Testing of prostatic secretion and semen samples revealed pathogenic bacteria in each case, which collectively included members of the Staphylococcal species such as Methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus haemolyticus, Enterococcus faecalis, and Streptococcus mitis, among others.

Methods and Outcome: Bacteriophage preparations from the Eliava Institute were used to treat the patient after establishing phage sensitivity to the pathogenic bacteria. Significant improvements in symptoms and re-testing of samples after bacteriophage treatment indicated a reduction in the bacterial load and resolution of the infection.

Discussion: The patient saw significant improvement of symptoms, and positive dynamics in bacterial titers and ultrasound controls after phage therapy. The failure of antibiotic therapy and subsequent success of bacteriophage therapy in treating chronic bacterial prostatitis shows the effectiveness of bacteriophages in controlling chronic infections in areas of low vascularity and anatomical complexity. These cases also highlight the efficacy of phages in overcoming antibiotic-resistant infections as well as biofilm infections.
A Combined Morphological and Molecular Evolutionary Analysis of Karst-Environment Adaptation for the Genus Urophysa (Ranunculaceae)
Authors: Xie Deng-Feng , Cheng Rui-Yu , Fu Xiao , Zhang Xiang-Yi , Price Megan , Lan Yan-Ling , Wang Chang-Bao , He Xing-Jin
Published: June 2021

The karst environment is characterized by low soil water content, periodic water deficiency, and poor nutrient availability, which provides an ideal natural laboratory for studying the adaptive evolution of its inhabitants. However, how species adapt to such a special karst environment remains poorly understood. Here, transcriptome sequences of two Urophysa species (Urophysa rockii and Urophysa henryi), which are Chinese endemics with karst-specific distribution, and allied species in Semiaquilegia and Aquilegia (living in non-karst habitat) were collected. Single-copy genes (SCGs) were extracted to perform the phylogenetic analysis using concatenation and coalescent methods. Positively selected genes (PSGs) and clusters of paralogous genes (Mul_genes) were detected and subsequently used to conduct gene function annotation. We filtered 2,271 SCGs and the coalescent analysis revealed that 1,930 SCGs shared the same tree topology, which was consistent with the topology detected from the concatenated tree. Total of 335 PSGs and 243 Mul_genes were detected, and many were enriched in stress and stimulus resistance, transmembrane transport, cellular ion homeostasis, calcium ion transport, calcium signaling regulation, and water retention. Both molecular and morphological evidences indicated that Urophysa species evolved complex strategies for adapting to hostile karst environments. Our findings will contribute to a new understanding of genetic and phenotypic adaptive mechanisms of karst adaptation in plants.
G3BPs in Plant Stress
Authors: Abulfaraj Aala A. , Hirt Heribert , Rayapuram Naganand
Published: June 2021

The sessile nature of plants enforces highly adaptable strategies to adapt to different environmental stresses. Plants respond to these stresses by a massive reprogramming of mRNA metabolism. Balancing of mRNA fates, including translation, sequestration, and decay is essential for plants to not only coordinate growth and development but also to combat biotic and abiotic environmental stresses. RNA stress granules (SGs) and processing bodies (P bodies) synchronize mRNA metabolism for optimum functioning of an organism. SGs are evolutionarily conserved cytoplasmic localized RNA-protein storage sites that are formed in response to adverse conditions, harboring mostly but not always translationally inactive mRNAs. SGs disassemble and release mRNAs into a translationally active form upon stress relief. RasGAP SH3 domain binding proteins (G3BPs or Rasputins) are “scaffolds” for the assembly and stability of SGs, which coordinate receptor mediated signal transduction with RNA metabolism. The role of G3BPs in the formation of SGs is well established in mammals, but G3BPs in plants are poorly characterized. In this review, we discuss recent findings of the dynamics and functions of plant G3BPs in response to environmental stresses and speculate on possible mechanisms such as transcription and post-translational modifications that might regulate the function of this important family of proteins.
Transcriptome-Wide Analysis of RNA m6A Methylation and Gene Expression Changes Among Two Arabidopsis Ecotypes and Their Reciprocal Hybrids
Authors: Xu Zhihui , Shi Xiaobo , Bao Mengmei , Song Xiaoqian , Zhang Yuxia , Wang Haiyan , Xie Hairong , Mao Fei , Wang Shuai , Jin Hongmei , Dong Suomeng , Zhang Feng , Wu Zhe , Wu Yufeng
Published: June 2021

The remodeling of transcriptome, epigenome, proteome, and metabolome in hybrids plays an important role in heterosis. N(6)-methyladenosine (m6A) methylation is the most abundant type of post-transcriptional modification for mRNAs, but the pattern of inheritance from parents to hybrids and potential impact on heterosis are largely unknown. We constructed transcriptome-wide mRNA m6A methylation maps of Arabidopsis thaliana Col-0 and Landsberg erecta (Ler) and their reciprocal F1 hybrids. Generally, the transcriptome-wide pattern of m6A methylation tends to be conserved between accessions. Approximately 74% of m6A methylation peaks are consistent between the parents and hybrids, indicating that a majority of the m6A methylation is maintained after hybridization. We found a significant association between differential expression and differential m6A modification, and between non-additive expression and non-additive methylation on the same gene. The overall RNA m6A level between Col-0 and Ler is clearly different but tended to disappear at the allelic sites in the hybrids. Interestingly, many enriched biological functions of genes with differential m6A modification between parents and hybrids are also conserved, including many heterosis-related genes involved in biosynthetic processes of starch. Collectively, our study revealed the overall pattern of inheritance of mRNA m6A modifications from parents to hybrids and a potential new layer of regulatory mechanisms related to heterosis formation.
Price Attractiveness and Price Complexity: Why People Prefer Level-Payment Loans
Authors: Lu Yang , Wang Jian , Li Chenyang , Huang Haoya , Zhuang Xintian
Published: June 2021

The improving sequence effect suggests that in choices between a rising earning and any other sequences, participants prefer the rising earning. Recent studies show that the improving sequence effect also exists in a loan context. As consumers have a strong preference for falling loan profiles, banks may consider to offer loans in which the loan repayments concentrate at the beginning of the loan term. In this paper, we examined the improving sequence effect in context of a car loan with three repayment plans expressed in temporally reframed prices (TRP). By regressing the evaluation of loan profiles on the perceived price attractiveness, price complexity, TRP and the interaction terms, we find that (1) the perceived price attractiveness and price complexity significantly predict the loan evaluation, and they also explain a significant proportion of variance in loan evaluation; (2) the TRP effect interacts with the improving sequence effect. Specifically, with the introduction of TRP, respondents prefer constant profiles over falling profiles. TRP may explain why level-payment loans are still popular in real world, though the improving sequence effect suggests otherwise.
Personalized Adaptive Training Improves Performance at a Professional First-Person Shooter Action Videogame
Authors: Neri Francesco , Smeralda Carmelo Luca , Momi Davide , Sprugnoli Giulia , Menardi Arianna , Ferrone Salvatore , Rossi Simone , Rossi Alessandro , Di Lorenzo Giorgio , Santarnecchi Emiliano
Published: June 2021

First-Person Shooter (FPS) game experience can be transferred to untrained cognitive functions such as attention, visual short-term memory, spatial cognition, and decision-making. However, previous studies have been using off-the-shelf FPS games based on predefined gaming settings, therefore it is not known whether such improvement of in game performance and transfer of abilities can be further improved by creating a in-game, adaptive in-game training protocol. To address this question, we compared the impact of a popular FPS-game (Counter-Strike:Global-Offensive–CS:GO) with anad hocversion of the game based on a personalized, adaptive algorithm modifying the artificial intelligence of opponents as well as the overall game difficulty on the basis of individual gaming performance. Two groups of FPS-naïve healthy young participants were randomly assigned to playing one of the two game versions (11 and 10 participants, respectively) 2 h/day for 3 weeks in a controlled laboratory setting, including daily in-game performance monitoring and extensive cognitive evaluations administered before, immediately after, and 3 months after training. Participants exposed to the adaptive version of the game were found to progress significantly faster in terms of in-game performance, reaching gaming scenarios up to 2.5 times more difficult than the group exposed to standard CS:GO (p< 0.05). A significant increase in cognitive performance was also observed. Personalized FPS gaming can significantly speed-up the learning curve of action videogame-players, with possible future applications for expert-video-gamers and potential relevance for clinical-rehabilitative applications.
Drive and Instinct—How They Produce Relatedness and Addiction
Authors: Ringwood Thomas , Cox Lindsay , Felldin Breanna , Kirsch Michael , Johnson Brian
Published: June 2021

Addictive drugs are responsible for mass killing. Neither persons with addiction nor the general populace seem conscious of the malevolence of governments and drug dealers working together. How could this be? What is the place of psychoanalysis in thinking about deaths from addiction and in responding to patients with addiction? To answer these questions, we revise concepts of SEEKING, drive, instinct, pleasure, and unpleasure as separable. We review the neurobiological mechanism of cathexis. We discuss how addictive drugs take over the will by changing the SEEKING system. We review how opioid tone in the central nervous system regulates human relationships and how this endogenous hormonal system is modified by external opioid administration. We differentiate the pleasure of relatedness from the unpleasure of urgent need including the urgent need for drugs. We show how addictive drug-induced changes in the SEEKING system diminish dopaminergic tone, reducing the motivation to engage in the pursuit of food, water, sex, sleep, and relationships in favor of addictive drugs. With this neuropsychoanalytic understanding of how drugs work, we become more confidently conscious of our ability to respond individually and socially.
The Effect of Psychological Contract Combined With Stress and Health on Employees’ Management Behavior
Authors: Cheng Yueyuan
Published: June 2021

In order to effectively manage employees and improve their work enthusiasm, based on the theoretical basis of project team members’ psychological contract, the status quo of employees’ psychological contract, stress and health status are investigated and analyzed. The differences of employees’ psychological contract are analyzed through the questionnaire. A total of 400 questionnaires are distributed and 365 are returned. The method of one-way ANOVA is used to study the psychological contract status of project members from four aspects: gender, education background, position level, and working years, and obtain the results of difference analysis in four aspects. Functional magnetic resonance imaging (FMRI) is used to evaluate the work stress of employees. The results show that gender, education background, position level and working years have different effects on employees’ psychological contract. Moreover, if employees continue to bear high-intensity work stress, a series of psychological and physical health problems will appear, such as difficulty in concentration. For enterprises, the poor psychological and physical conditions of employees will make the overall work inefficient and the working atmosphere dull. Therefore, enterprises should control employees’ work stress within a reasonable range, and should not blindly impose high-intensity work stress on employees. This exploration demonstrates the way to realize the psychological contract construction of project team members, and targeted employee management countermeasures are put forward.
Designing “Safer Water.” A Virtual Reality Tool for the Safety and the Psychological Well-Being of Citizens Exposed to the Risk of Natural Disasters
Authors: Gamberini Luciano , Bettelli Alice , Benvegnù Giulia , Orso Valeria , Spagnolli Anna , Ferri Michele
Published: June 2021

Virtual Reality (VR) is a popular technology to recreate reality-like scenarios, including dangerous ones, in a realistic but safe way. Because of this potential, VR based research has been applied in psychology studies to provide training and education about how to behave in emergencies such as fires, earthquakes, floods, or typhoons. All these different virtual scenarios have been built to observe how people react to emergencies, what behaviors they adopted, what level of stress is generated, and finally, how to increase citizens' safety. However, there is still little research that shows how Virtual Environment (VE) should be designed to convey appropriate social and psychological “cues” to participants. In this work, we present the result of a series of co-design sessions aiming to bring experts to collaborate in setting up virtual scenarios to increase the quality of life, safety perception, and risk awareness in people living in the proximity of a river. Floods are one of the most threatening climate events, and because of climate change, they are expected to become even more frequent. These disasters have a devastating impact on communities, increasing anxiety and stress levels in citizens living close to rivers. We involved relevant stakeholders to design “Safer Water,” an immersive, interactive, virtual experience to support citizens in psychologically and behaviorally managing pre and post riverbank breakdown situations. HCI experts, hydrogeological and hydraulic engineers, psychologists, and VEs designers took part in affinity diagram and brainstorming activities. Results show how the adopted method was able to generate suitable virtual scenarios, to highlight and classify relevant design requirements, and to find strategies that could improve the quality of life and psychological well-being in “risk-exposed citizens.” The discussion includes a set of open-access guidelines derived from the co-design activities, to support the design of VE for the purposes discussed in the paper.