bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Characteristics of New-Onset Epilepsy in the Elderly and Risk Factors for Treatment Outcomes of Antiseizure Medications
Authors: Qi Jing , Liu Xiao , Xu Na , Wang Qun
Published: February 2022

Objective

To describe the clinical characteristics of elderly patients with new-onset epilepsy in a Class A tertiary comprehensive hospital in north China and evaluate the treatment outcomes of antiseizure medications (ASMs). This study focuses on investigating the factors affecting the treatment outcomes, guiding the drug treatment, and judging the prognosis of elderly epilepsy patients.

Methods

We included patients aged 60 years or older at the time of their first seizure between January 2014 and August 2020. Demographic characteristics, effects of ASM, and the proportion of 1-year and long-term seizure freedom were reported. The univariate analysis and binary logistic regression were used to identify factors potentially influencing treatment outcomes.

Results

A total of 326 patients (median age 65 years, 67.2% men) were included. Moreover, 185 (56.7%) patients who received the first ASM monotherapy achieved 1 year of seizure freedom in the early stage. Compared with structural etiology, unknown etiology was associated with a higher likelihood of early seizure freedom (odds ratio [OR] = 0.545; p < 0.05). Conversely, comorbid intracranial malignant tumors, taking carbamazepine (CBZ), and sodium valproate (VPA) were associated with a lower likelihood of seizure freedom (OR = 3.527 vs. 6.550 vs. 8.829; p < 0.05). At long-term follow-up, 263 (80.6%) patients achieved seizure freedom, with 79.8% on monotherapy.

Conclusions

Elderly patients with new-onset epilepsy responded well to the initial ASMs treatment. Patients with intracranial malignant tumors and prescribed VPA and CBZ were less likely to achieve early seizure freedom, while those with unknown etiology had higher probabilities of achieving early seizure freedom than those with structural etiology.
Exercise Intensity and Brain Plasticity: What’s the Difference of Brain Structural and Functional Plasticity Characteristics Between Elite Aerobic and Anaerobic Athletes?
Authors: Zhang Keying , Jan Yih-Kuen , Liu Yu , Zhao Tao , Zhang Lingtao , Liu Ruidong , Liu Jianxiu , Cao Chunmei
Published: February 2022

This study investigated the differences in morphometry and functional plasticity characteristics of the brain after long-term training of different intensities. Results showed that an aerobic group demonstrated higher gray matter volume in the cerebellum and temporal lobe, while an anaerobic group demonstrated higher gray matter volume in the region of basal ganglia. In addition, the aerobic group also showed significantly higher fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC) in the motor area of the frontal lobe and parietal lobe, and the frontal gyrus, respectively. At the same time, the anaerobic group demonstrated higher fALFF and DC in the cerebellum posterior lobe (family-wise error corrected,p< 0.01). These findings may further prove that different brain activation modes respond to different intensities of physical activity and may help to reveal the neural mechanisms that can classify athletes from different intensity sports.
Identifying Boys With Autism Spectrum Disorder Based on Whole-Brain Resting-State Interregional Functional Connections Using a Boruta-Based Support Vector Machine Approach
Authors: Zhao Lei , Sun Yun-Kai , Xue Shao-Wei , Luo Hong , Lu Xiao-Dong , Zhang Lan-Hua
Published: February 2022

An increasing number of resting-state functional magnetic resonance neuroimaging (R-fMRI) studies have used functional connections as discriminative features for machine learning to identify patients with brain diseases. However, it remains unclear which functional connections could serve as highly discriminative features to realize the classification of autism spectrum disorder (ASD). The aim of this study was to find ASD-related functional connectivity patterns and examine whether these patterns had the potential to provide neuroimaging-based information to clinically assist with the diagnosis of ASD by means of machine learning. We investigated the whole-brain interregional functional connections derived from R-fMRI. Data were acquired from 48 boys with ASD and 50 typically developing age-matched controls at NYU Langone Medical Center from the publicly available Autism Brain Imaging Data Exchange I (ABIDE I) dataset; the ASD-related functional connections identified by the Boruta algorithm were used as the features of support vector machine (SVM) to distinguish patients with ASD from typically developing controls (TDC); a permutation test was performed to assess the classification performance. Approximately, 92.9% of participants were correctly classified by a combined SVM and leave-one-out cross-validation (LOOCV) approach, wherein 95.8% of patients with ASD were correctly identified. The default mode network (DMN) exhibited a relatively high network degree and discriminative power. Eight important brain regions showed a high discriminative power, including the posterior cingulate cortex (PCC) and the ventrolateral prefrontal cortex (vlPFC). Significant correlations were found between the classification scores of several functional connections and ASD symptoms (p < 0.05). This study highlights the important role of DMN in ASD identification. Interregional functional connections might provide useful information for the clinical diagnosis of ASD.
Systematic Review: Sleep Disorders Based on Objective Data in Children and Adolescents Treated for a Brain Tumor
Authors: Helligsoe Anne Sophie Lind , Weile Kathrine Synne , Kenborg Line , Henriksen Louise Tram , Lassen-Ramshad Yasmin , Amidi Ali , Wu Lisa Maria , Winther Jeanette Falck , Pickering Line , Mathiasen René
Published: February 2022

Background

Tumors of the central nervous system (CNS) are the most common solid childhood malignancy. Over the last decades, treatment developments have strongly contributed to the improved overall 5-year survival rate, which is now approaching 75%. However, children now face significant long-term morbidity with late-effects including sleep disorders that may have detrimental impact on everyday functioning and quality of life. The aims of this study were to (1) describe the symptoms that lead to polysomnographic evaluation; (2) describe the nature of sleep disorders diagnosed in survivors of childhood CNS tumor using polysomnography (PSG); and (3) explore the association between tumor location and diagnosed sleep disorder.

Methods

An extensive literature search following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (PRISMA) was conducted. Inclusion criteria were children and adolescents diagnosed with a CNS tumor age <20 years having a PSG performed after end of tumor treatment. The primary outcome was sleep disorder confirmed by PSG.

Results

Of the 1,658 studies identified, 11 met the inclusion criteria. All the included articles were appraised for quality and included in the analysis. Analyses indicated that sleep disorders commonly occur among childhood CNS tumor survivors. Symptoms prior to referral for PSG were excessive daytime sleepiness (EDS), fatigue, irregular breathing during sleep and snoring. The most common sleep disorders diagnosed were sleep-related breathing disorders (i.e., obstructive sleep apnea) and central disorders of hypersomnolence (i.e., narcolepsy).

Conclusion

Our findings point to the potential benefit of systematically registering sleep disorder symptoms among CNS tumor patients together with tumor type and treatment information, so that at-risk patients can be identified early. Moreover, future rigorous and larger scale controlled observational studies that include possible modifiable confounders of sleep disorders such as fatigue and obesity are warranted.

Clinical Trial Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021243866, identifier [CRD42021243866].
Joint Effect of Beer, Spirits Intake, and Excess Adiposity on Hyperuricemia Among Chinese Male Adults: Evidence From the China National Health Survey
Authors: He Huijing , Pan Li , Ren Xiaolan , Wang Dingming , Du Jianwei , Cui Ze , Zhao Jingbo , Wang Hailing , Wang Xianghua , Liu Feng , Pa Lize , Peng Xia , Yu Chengdong , Wang Ye , Shan Guangliang
Published: February 2022

Alcohol intake and excess adiposity are associated with serum uric acid (SUA), but their interaction effect on hyperuricemia (HUA) remains unclear. Using data from the China National Health Survey (CNHS) (2012–2017), we analyzed the additive interaction of beer, spirits intake, excess adiposity [measured by body mass index (BMI), body fat percentage (BFP), and visceral fat index (VFI)] with HUA among male participants aged 20–80 from mainland China. The relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (SI) were calculated to assess the interaction effect on the additive scale. Both RERI and AP larger than 0 and SI larger than 1 indicate a positive additive interaction. Among 12,592 male participants, the mean SUA level was 367.1 ± 85.5 μmol/L and 24.1% were HUA. Overweight/obese men who were presently drinking spirits had an odds ratio (OR) of 3.20 (95%CI: 2.71–3.79) than the never drink group, with RERI, AP, and SI of 0.45 (95%CI: 0.08–0.81), 0.14 (95%CI: 0.03–0.25), and 1.25 (95%CI: 1.02–1.54), respectively. However, although combined exposures on beer intake and excess adiposity had the highest OR compared with no beer intake and nonobese participants, there was no additive interaction, with RERI, AP, and SI in the overweight/obesity and the beer intake group of 0.58 (−0.41–1.57), 0.17 (−0.08–0.41), and 1.30 (0.85–1.97), respectively. Other excess adiposity indexes revealed similar estimates. Our findings suggested that the exposures of both excess adiposity and alcohol drink could result in an additive interaction effect on HUA: the combined risk of excess adiposity with spirits intake but not with beer was greater than the sum of the effects among Chinese male adults.
Case Report: An “Immune-Cold” EGFR Mutant NSCLC With Strong PD-L1 Expression Shows Resistance to Chemo-Immunotherapy
Authors: Zhao Qian , Zhang Xue , Ma Qiang , Luo Nuo , Liu Zhulin , Wang Renyuan , He Yong , Li Li
Published: February 2022

Long-term survival benefit has been noticed in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), such as PD-1 inhibitors. However, it is still controversial whether patients with EGFR-activating mutations may benefit from ICIs. Recently, in stage IIIA NSCLC, chemo-immunotherapy has led to significant pathological response, yet patients with the presence of known EGFR mutations were excluded from some randomized trials of neoadjuvant therapy. Herein, we report a case of a 50-year-old female patient, who was initially diagnosed as stage IIIA lung squamous cell carcinoma. Immunohistochemistry analysis showed that the patient presented with high PD-L1 expression. Then, chemo-immunotherapy was given to the patient but the disease progressed quickly with distant metastasis. A re-biopsy revealed a poorly differentiated lung adenocarcinoma together with EGFR p.L858R mutation. Then the patient received gefitinib, which resulted in significant regression of primary lung lesion. A detailed examination of pre-treatment tumor sections demonstrated rare infiltration of CD8+ T cells, indicating that the current patient presented with an “immune-cold” microenvironment, which might explain the primary resistance to chemo-immunotherapy. Taken together, our case indicated that comprehensive detection of PD-L1 expression, driver gene status, together with tumor immune microenvironment, may offer a better prediction of treatment efficacy.
Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma
Authors: Yan Qing , Lin Hao-Ming , Zhu Ke , Cao Yi , Xu Xiao-Lin , Zhou Zi-Yu , Xu Lei-bo , Liu Chao , Zhang Rui
Published: February 2022

LAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role in the inhibition of T cells. However, the FGL1 expression in circulating tumor cells (CTCs) and its clinical significance in hepatocellular carcinoma (HCC) remain unclear. Therefore, this bioinformatics analysis was performed to assess the expression of FGL1 in various tumors and its association with immune infiltration. After that, CTCs from 109 HCC patients were detected and the immunofluorescence staining was performed (CD45, EpCAM, CK8/18/19, Vimentin, Twist, DAPI and FGL1). Then, we investigated FGL1 expression and EMT of CTCs and analyzed its relationship with patient survival and clinical relevance. Bioinformatic results showed that FGL1 expression was abnormal in various tumor and it was correlated with the infiltration level of several immune cells. FGL1 expression was detected in CTCs of 40 patients (36.7%). The proportion of advanced TNM stage (P<0.001) and distant metastasis(P=0.020) in FGL1 positive patients was higher than that of FGL1 negative patients. In addition, patients with FGL1 positive circulating tumor cells had worse postoperative survival than FGL1 negative patients (p=0.0297). The mixed phenotypic CTC presented a higher level of FGL1 expression than any other types, the number of which also predicted worse prognosis(p=0.0443). We also found that the expression of FGL1 on CTCs was associated with the level of FGL1 in tumor tissues. Of 12 patients receiving PD-1/PD-L1 blockade in a total of 109 cases, 8 out of 10 patients with FGL1 positive CTC showed immunotherapy resistance. It is the first study that suggested FGL1 expression in CTCs as an indicator of the poor prognosis in HCC patients. CTC detection may serve as a promising replacement for determination of tumor tissue FGL1 expression and provide evidence for the application of immunotherapy.
Targeting Mcl-1 by AMG-176 During Ibrutinib and Venetoclax Therapy in Chronic Lymphocytic Leukemia
Authors: Yi Xue , Jain Nitin , Iles LaKesla R. , Ayres Mary L. , Wierda William G. , Gandhi Varsha
Published: February 2022

B-cell receptor (BCR) signaling pathway and Bcl-2 family prosurvival proteins, specifically Bcl-2 and Mcl-1, are functional in the pathobiology of chronic lymphocytic leukemia (CLL). A pivotal and apical molecule in the BCR pathway is Bruton’s tyrosine kinase (BTK). Together, BTK, Bcl-2, and Mcl-1 participate in the maintenance, migration, proliferation, and survival of CLL cells. Several ongoing and published clinical trials in CLL reported high rates of remission, namely, undetectable measurable residual disease (u-MRD) status with combined BTK inhibitor ibrutinib and Bcl-2 antagonist, venetoclax. While the majority of patients achieve complete remission with undetectable-measurable residual disease, at least one third of patients do not achieve this milestone. We hypothesized that cells persistent during ibrutinib and venetoclax therapy may be sensitive to combined venetoclax and Mcl-1 inhibitor, AMG-176. To test this hypothesis, we took peripheral blood samples at baseline, after Cycle 1 and Cycle 3 of ibrutinib monotherapy, after one week and 1 cycle of ibrutinib plus venetoclax therapy. These serial samples were tested for pharmacodynamic changes and treated in vitro with AMG-176 or in combination with venetoclax. Compared to C1D1 cells, residual cells during ibrutinib and venetoclax treatment were inherently resistant to endogenous cell death. Single agent exposure induced some apoptosis but combination of 100 nM venetoclax and 100 or 300 nM of AMG-176 resulted in 40–100% cell death in baseline samples. Cells obtained after four cycles of ibrutinib and one cycle of venetoclax, when treated with such concentration of venetoclax and AMG-176, showed 10–80% cell death. BCR signaling pathway, measured as autophosphorylation of BTK was inhibited throughout therapy in all post-therapy samples. Among four anti-apoptotic proteins, Mcl-1 and Bfl-1 decreased during therapy in most samples. Proapoptotic proteins decreased during therapy. Collectively, these data provide a rationale to test Mcl-1 antagonists alone or in combination in CLL during treatment with ibrutinib and venetoclax.
Fetal Tracheal Occlusion Increases Lung Basal Cells via Increased Yap Signaling
Authors: Serapiglia Vincent , Stephens Chad A. , Joshi Rashika , Aydin Emrah , Oria Marc , Marotta Mario , Peiro Jose L. , Varisco Brian M.
Published: February 2022

Fetal endoscopic tracheal occlusion (FETO) is an emerging surgical therapy for congenital diaphragmatic hernia (CDH). Ovine and rabbit data suggested altered lung epithelial cell populations after tracheal occlusion (TO) with transcriptomic signatures implicating basal cells. To test this hypothesis, we deconvolved mRNA sequencing (mRNA-seq) data and used quantitative image analysis in fetal rabbit lung TO, which had increased basal cells and reduced ciliated cells after TO. In a fetal mouse TO model, flow cytometry showed increased basal cells, and immunohistochemistry demonstrated basal cell extension to subpleural airways. Nuclear Yap, a known regulator of basal cell fate, was increased in TO lung, and Yap ablation on the lung epithelium abrogated TO-mediated basal cell expansion. mRNA-seq of TO lung showed increased activity of downstream Yap genes. Human lung specimens with congenital and fetal tracheal occlusion had clusters of subpleural basal cells that were not present in the control. TO increases lung epithelial cell nuclear Yap, leading to basal cell expansion.
Case Report: A Novel KMT2E Splice Site Variant as a Cause of O'Donnell-Luria-Rodan Syndrome in a Male Patient
Authors: Cao Zixuan , Wang Chunli , Chen Jing , Guo Hu , Wu Chunfeng , Zhang Gang , Ding Le
Published: February 2022

Background

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant systemic disorder characterized by global developmental delay caused by mutations in the KMT2E gene. The aim of this study was to investigate the role of KMT2E mutations as a cause of ODLURO syndrome in a Chinese boy.

Methods

We reported the clinical course of a Chinese boy who was diagnosed with ODLURO syndrome by the whole exome sequencing. We extracted genomic DNA of the proband and parents, gene variations were screened using whole-exome sequencing, followed by validation using direct Sanger sequencing. The effect of mRNA splicing variants were analyzed through a minigene splice assay and in vitro reverse transcription PCR (RT-PCR).

Results

The proband presented with recurrent seizures and developmental delay. Using genetic analysis, we identified that the proband carried a de novo heterozygous splicing variant (c.1248+1G>T) in the KMT2E gene. In vivo transcript analysis showed that the proband did not carry any KMT2E mRNA transcript, while a specific exon11-exon13 (440 bp) transcript was detected in the unaffected parents. The in vitro minigene splice assay conducted in HEK293 cells confirmed that the c.1248+1G>T variant resulted in exon 12 skipping, which in turn caused an alteration in KMT2E mRNA splicing. The mutant transcript created a premature stop codon at the 378 amino acid position that could have been caused nonsense-mediated mRNA decay (NMD).

Conclusion

We verified the pathogenic effect of the KMT2E c.1248+1G>T splicing variant, which disturbed normal mRNA splicing and caused mRNA decay. Our findings suggest that splice variants play an important role in the molecular basis of ODLURO, and that careful molecular profiling of these patients could play an essential role in tailoring of personalized treatment options soon.
Chinese Medicinal Herb-Derived Carbon Dots for Common Diseases: Efficacies and Potential Mechanisms
Authors: Li Dan , Xu Kun-yan , Zhao Wei-peng , Liu Ming-feng , Feng Rui , Li De-qiang , Bai Jing , Du Wen-li
Published: February 2022

The management of hemorrhagic diseases and other commonly refractory diseases (including gout, inflammatory diseases, cancer, pain of various forms and causes) are very challenging in clinical practice. Charcoal medicine is a frequently used complementary and alternative drug therapy for hemorrhagic diseases. However, studies (other than those assessing effects on hemostasis) on charcoal-processed medicines are limited. Carbon dots (CDs) are quasi-spherical nanoparticles that are biocompatible and have high stability, low toxicity, unique optical properties. Currently, there are various studies carried out to evaluate their efficacy and safety. The exploration of using traditional Chinese medicine (TCM) -based CDs for the treatment of common diseases has received great attention. This review summarizes the literatures on medicinal herbs-derived CDs for the treatment of the difficult-to-treat diseases, and explored the possible mechanisms involved in the process of treatment.
Expression and Functions of the CB2 Receptor in Human Leukocytes
Authors: Simard Mélissa , Rakotoarivelo Volatiana , Di Marzo Vincenzo , Flamand Nicolas
Published: February 2022

The cannabinoid CB2 receptor was cloned from the promyeloid cell line HL-60 and is notably expressed in most, if not all leukocyte types. This relatively restricted localization, combined to the absence of psychotropic effects following its activation, make it an attractive drug target for inflammatory and autoimmune diseases. Therefore, there has been an increasing interest in the past decades to identify precisely which immune cells express the CB2 receptor and what are the consequences of such activation. Herein, we provide new data on the expression of both CB1 and CB2 receptors by human blood leukocytes and discuss the impact of CB2 receptor activation in human leukocytes. While the expression of the CB2 mRNA can be detected in eosinophils, neutrophils, monocytes, B and T lymphocytes, this receptor is most abundant in human eosinophils and B lymphocytes. We also review the evidence obtained from primary human leukocytes and immortalized cell lines regarding the regulation of their functions by the CB2 receptor, which underscore the urgent need to deepen our understanding of the CB2 receptor as an immunoregulator in humans.
Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines
Authors: Ragone Angela , Salzillo Alessia , Spina Annamaria , Naviglio Silvio , Sapio Luigi
Published: February 2022

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers. Albeit its incidence does not score among the highest in cancer, PDAC prognosis is tremendously fatal. As a result of either aggressiveness or metastatic stage at diagnosis, chemotherapy constitutes the only marginally effective therapeutic approach. As gemcitabine (Gem) is still the cornerstone for PDAC management, the low response rate and the onset of resistant mechanisms claim for additional therapeutic strategies. The first synthetic orally active adiponectin receptor agonist AdipoRon (AdipoR) has recently been proposed as an anticancer agent in several tumors, including PDAC. To further address the AdipoR therapeutic potential, herein we investigated its pharmacodynamic interaction with Gem in human PDAC cell lines. Surprisingly, their simultaneous administration revealed a more effective action in contrasting PDAC cell growth and limiting clonogenic potential than single ones. Moreover, the combination AdipoR plus Gem persisted in being effective even in Gem-resistant MIA PaCa-2 cells. While a different ability in braking cell cycle progression between AdipoR and Gem supported their cooperating features in PDAC, mechanistically, PD98059-mediated p44/42 MAPK ablation hindered combination effectiveness. Taken together, our findings propose AdipoR as a suitable partner in Gem-based therapy and recognize the p44/42 MAPK pathway as potentially involved in combination outcomes.
Improving the Performance of Reputation Evaluation by Combining a Network Structure With Nonlinear Recovery
Authors: Li Meng , Han Chengyuan , Jiang Yuanxiang , Di Zengru
Published: February 2022

Characterizing the reputation of an evaluator is particularly significant for consumers to obtain useful information from online rating systems. Furthermore, overcoming the difficulties of spam attacks on a rating system and determining the reliability and reputation of evaluators are important topics in the research. We have noticed that most existing reputation evaluation methods rely only on using the evaluator’s rating information and abnormal behaviour to establish a reputation system, which disregards the systematic aspects of the rating systems, by including the structure of the evaluator-object bipartite network and nonlinear effects. In this study, we propose an improved reputation evaluation method by combining the structure of the evaluator-object bipartite network with rating information and introducing penalty and reward factors. The proposed method is empirically analyzed on a large-scale artificial data set and two real data sets. The results have shown that this method has better performance than the original correlation-based and IARR2 in the presence of spamming attacks. Our work contributes a new idea to build reputation evaluation models in sparse bipartite rating networks.
Between-Subject and Within-Subject Variation of Muscle Atrophy and Bone Loss in Response to Experimental Bed Rest
Authors: Böcker Jonas , Schmitz Marie-Therese , Mittag Uwe , Jordan Jens , Rittweger Jörn
Published: February 2022

To improve quantification of individual responses to bed rest interventions, we analyzed peripheral quantitative computer tomography (pQCT) datasets of the lower leg of 76 participants, who took part in eight different bed rest studies. A newly developed statistical approach differentiated measurement uncertainty UMeas from between-subject-variation (BSV) and within-subject variation (WSV). The results showed that UMeas decreased 59.3% to 80% over the two decades of bed rest studies (p < 0.01), and that it was higher for muscles than for bones. The reduction of UMeas could be explained by improved measurement procedures as well as a higher standardization. The majority (59.1%) of the individual responses pci exceeded the 95% confidence interval defined by UMeas, indicating significant and substantial BSV, which was greater for bones than for muscles, especially at the diaphyseal measurement sites. Non-significant to small positive inter-site correlations between bone sites, but very large positive inter-site correlation between muscle sites suggests that substantial WSV exists in the tibia bone, but much less so in the calf musculature. Furthermore, endocortical circumference, an indicator of the individual’s bone geometry could partly explain WSV and BSV. These results demonstrate the existence of substantial bone BSV, and that it is partly driven by WSV, and likely also by physical activity and dietary habits prior to bed rest. In addition, genetic and epigenetic variation could potentially explain BSV, but not WSV. As to the latter, differences of bone characteristics and the bone resorption process could offer an explanation for its existence. The study has also demonstrated the importance of duplicate baseline measurements. Finally, we provide here a rationale for worst case scenarios with partly effective countermeasures in long-term space missions.
The Role of the Endogenous Opioid System in the Vocal Behavior of Songbirds and Its Possible Role in Vocal Learning
Authors: Singh Utkarsha A. , Iyengar Soumya
Published: February 2022

The opioid system in the brain is responsible for processing affective states such as pain, pleasure, and reward. It consists of three main receptors, mu- (μ-ORs), delta- (δ-ORs), and kappa- (κ-ORs), and their ligands – the endogenous opioid peptides. Despite their involvement in the reward pathway, and a signaling mechanism operating in synergy with the dopaminergic system, fewer reports focus on the role of these receptors in higher cognitive processes. Whereas research on opioids is predominated by studies on their addictive properties and role in pain pathways, recent studies suggest that these receptors may be involved in learning. Rodents deficient in δ-ORs were poor at recognizing the location of novel objects in their surroundings. Furthermore, in chicken, learning to avoid beads coated with a bitter chemical from those without the coating was modulated by δ-ORs. Similarly, μ-ORs facilitate long term potentiation in hippocampal CA3 neurons in mammals, thereby having a positive impact on spatial learning. Whereas these studies have explored the role of opioid receptors on learning using reward/punishment-based paradigms, the role of these receptors in natural learning processes, such as vocal learning, are yet unexplored. In this review, we explore studies that have established the expression pattern of these receptors in different brain regions of birds, with an emphasis on songbirds which are model systems for vocal learning. We also review the role of opioid receptors in modulating the cognitive processes associated with vocalizations in birds. Finally, we discuss the role of these receptors in regulating the motivation to vocalize, and a possible role in modulating vocal learning.
A Continuous Assay Set to Screen and Characterize Novel Protein N-Acetyltransferases Unveils Rice General Control Non-repressible 5-Related N-Acetyltransferase2 Activity
Authors: Asensio Thomas , Dian Cyril , Boyer Jean-Baptiste , Rivière Frédéric , Meinnel Thierry , Giglione Carmela
Published: February 2022

Protein N-acetyltransferases (NATs) belong to the general control non-repressible 5 (Gcn5)-related N-acetyltransferases (GNATs) superfamily. GNATs catalyze the transfer of acetyl from acetyl-CoA to the reactive amine moiety of a wide range of acceptors. NAT sequences are difficult to distinguish from other members of the GNAT superfamily and there are many uncharacterized GNATs. To facilitate the discovery and characterization of new GNATs, we have developed a new continuous, non-radioactive assay. This assay is virtually independent of the substrate and can be used to get substrate specificity hints. We validated first the assay with the well-characterizedSchizosaccharomyces pombeNatA (SpNatA). The SpNatA kinetic parameters were determined with various peptides confirming the robustness of the new assay. We reveal that the longer the peptide substrate the more efficient the enzyme. As a proof of concept of the relevance of the new assay, we characterized a NAA90 member from rice (Oryza sativa), OsGNAT2. We took advantage of anin vivomedium-scale characterization of OsGNAT2 specificity to identify and then validatein vitroseveral specific peptide substrates. With this assay, we reveal long-range synergic effects of basic residues on OsGNAT2 activity. Overall, this new, high-throughput assay allows better understanding of the substrate specificity and activity of any GNAT.
Emerging Issues and Potential Opportunities in the Rice–Wheat Cropping System of North-Western India
Authors: Dhanda Sachin , Yadav Ashok , Yadav Dharam Bir , Chauhan Bhagirath Singh
Published: February 2022

The rice–wheat cropping system (RWCS) is the backbone of Indian farming, especially in the north-western region. But continuous adoption of the RWCS in northwest India has resulted in major challenges and stagnation in the productivity of this system. Additionally, the Indo-Gangetic Plains of Pakistan, Nepal, and Bangladesh are also facing similar challenges for sustainable production of the RWCS. Several emerging problems, such as the exhausting nutrient pool in soil, deteriorating soil health, groundwater depletion, escalating production cost, labor scarcity, environmental pollution due to crop residue burning and enhanced greenhouse gas emissions, climatic vulnerabilities, and herbicide resistance in weed species, are a few major threats to its sustainability. To address these challenges, a wide range of sustainable intensification technologies have been developed to reduce the irrigation and labor requirements, tillage intensity, and straw burning. Awareness and capacity building of the stakeholders and policy matching/advocacy need to be prioritized to adopt time- and need-based strategies at the ground level to combat these challenges. This review summarizes the current status and challenges of the RWCS in the northwest region of the country and also focuses on the precision management options for achieving high productivity, profitability, and sustainability.
Effects of South-to-North Water Diversion Project Cascade Dams on Riparian Vegetation Along the Middle and Lower Reaches of the Hanjiang River, China
Authors: Yang Jiao , Li En-Hua , Yang Chao , Xia Ying , Zhou Rui
Published: February 2022

The influence of the construction of dams for water diversion on the ecological environment has attracted recent widespread attention. Over time, dams have emerged as one of the most important factors affecting the vegetation along the riparian zones of rivers. To elucidate the effects of cascade dams on riparian vegetation along the middle and lower reaches of the Hanjiang River, we examined riparian vegetation types upstream and downstream from dams. A total of 14 sample sites and 131 quadrats perpendicular to the river were investigated in June 2019, and 14 sample sites and 134 quadrats were investigated in October 2019. The riparian vegetation was divided into 15 (in June) and 11 (in October) vegetation types by two-way indicator species analysis (TWINSPAN). Significant differences were found between the vegetation types upstream and downstream of dams. Redundancy analysis (RDA) showed that soil moisture content, distance from the water, altitude and soil total nitrogen (TN) were the main environmental factors affecting plants distributions, and soil moisture content was the main factor affecting the zonal distribution of vegetation. By analyzing the impact of cascade dams on the hydrological regime, we found that the construction of cascade dams led to the differentiation of vegetation types upstream and downstream of the dam, and the riparian habitats were fragmented by these dams. This study provides both an important reference for the protection of riparian vegetation and riparian ecosystems and a basis for the management and restoration of river ecosystems after the construction of cascade dams.
The Association Between Sociability and COVID-19 Pandemic Stress
Authors: Luo Peihao , LaPalme Matthew L. , Cipriano Christina , Brackett Marc A.
Published: February 2022

The COVID-19 pandemic threatened our physical health, alongside our mental and social wellbeing. Social distancing requirements, which are necessary to mitigate the spread of COVID-19, increased social isolation by limiting social interactions that are an essential part of human wellbeing. In this study, we examined the stress caused by COVID-19 early on in the pandemic through the lens of sociability among a large sample of preservice educators (N = 2,183). We found that individuals who have higher sociability (including deriving joy from social interactions and using social support to manage emotions) experienced greater COVID-19 stress. This study also contributed to prior literature which has sought to relate pandemic-related stress to demographic group differences. We found no significant relationship between demographic membership (gender, race, and sexual orientation) and COVID-19 stress. This study is among the first, however, to demonstrate that vulnerability to pandemic stress varies as a function of sociability. Implications of these findings and ways people can better cope with pandemic isolation are discussed.
China's SMEs Developed Characteristics and Countermeasures in the Post-epidemic Era
Authors: Su Wunhong , Guo Xiaohan , Ling Yunxia , Fan Yi-Hao
Published: February 2022

Due to the COVID-19 outbreak, a series of chain reactions, like international trade breakdown, stock market collapse, and crude oil's collapse, have adversely affected the global economy, particularly small and medium-sized enterprises (SMEs). As a result, the Chinese government issued many fiscal and financial policies to support SMEs. This paper analyzes SMEs' coping methods and conceptual changes affected by the epidemic and distinguishes “victims” and “beneficiaries.” Subsequently, based on extensive international experience and local government experience, it provides effective suggestions for the Chinese government to deal with the post-epidemic era's economic changes, policy suggestions, and coping strategies for SMEs' short-term and long-term sustainable development.
The Construction of Interactive Teaching Quality Monitoring System From the Perspective of Psychology
Authors: Chen Kewei
Published: February 2022

The article first proposes a reflection on the status quo of classroom teaching in public universities, selects a large number of educational scenes, and analyzes these selected educational concepts in detail from a theoretical perspective. Through the establishment of a teaching quality monitoring system based on careful observation and analysis, several major problems in public university classrooms have been discovered: poor classroom interaction mode, single classroom interaction mode, low classroom interaction efficiency, and inefficient classroom interaction feedback. Specific manifestations include the alienation of teacher–student relationship, insufficient student coverage, lack of interaction channels, lack of interaction context, only formalized teacher–student interaction, low impact, and simplification of teacher–student interaction. Summarizing the causes of classroom interaction problems, the article summarizes three factors: teachers, students, and the macro environment. In the experiment, 85% of the students thought that the teacher–student relationship was relatively ordinary. Among the 11 students who participated in the experiment, 60% of the students were very active in interactive classroom discussions. Therefore, based on the analysis of problems and factors, the article puts forward an optimization strategy to create a classroom interaction atmosphere, improve classroom interaction mode, improve classroom interaction efficiency, and strengthen classroom interaction feedback. In particular, it promotes the integration of teacher–student relationship, emphasizes the role of students, improves the level of classroom interaction, creates conditions for classroom interaction, improves teacher–student interaction control ability, enhances student interactive speech ability, strengthens error correction and feedback, and increases multiple feedback methods.
Associations Between Household Pesticide Exposure, Smoking and Hypertension
Authors: Chen Haiyan , Liang Xiaohua , Chen Li , Zuo Lei , Chen Kuncai , Wei Yuehong , Chen Shouyi , Hao Guang
Published: February 2022

This analysis aims to investigate the association between household pesticide exposure and hypertension risk, and to determine whether smoking plays a role in this association. We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999–2014, including a total of 32,309 U.S. adult participants who were 20 years or older. Smoking status and pesticide exposure were self-reported. Blood pressure was measured by trained personnel using a mercury sphygmomanometer, according to a standardized protocol. We observed an increased risk of hypertension (OR [odds ratio] = 1.10, 95% confidence intervals [CI]: 1.01–1.18) in participants with exposure to household pesticides. Moreover, a significant interaction between smoking status and pesticide exposure on hypertension was observed (P = 0.022). Stratified analysis showed that household pesticide exposure was associated with a 29% higher risk of hypertension (OR = 1.29, 95% CI: 1.08–1.53) in smokers. However, for non-smokers, this association was not significant. Similar trends were found for systolic and diastolic blood pressures. In addition, we investigated the associations between pesticide metabolites in urine/serum and hypertension and found that several metabolites of dioxins, furans, and coplanar polychlorinated biphenyls were significantly associated with a higher risk of hypertension. This study suggests that household pesticide exposure is associated with an elevated risk of hypertension. We also report that smoking may accentuate the effect of pesticide exposure on hypertension.
Engaging Native American High School Students in Public Health Career Preparation Through the Indigenous Summer Enhancement Program
Authors: Dreifuss Heather M. , Belin Kalvina L. , Wilson Jamie , George Shawndeena , Waters Amber-Rose , Kahn Carmella B. , Bauer Mark C. , Teufel-Shone Nicolette I.
Published: February 2022

Native American1 populations are systematically marginalized in the healthcare and public health workforce. One effective approach to reduce health disparities and improve health care delivery among Indigenous populations is to train more Native American health professionals who integrate academic and cultural knowledge to understand and influence health behaviors and perspectives. Diné College partnered with Northern Arizona University to develop the Navajo Native American Research Center for Health (NARCH) Partnership, funded by the National Institutes of Health. The high school component of the Navajo NARCH Partnership created the Indigenous Summer Enhancement Program (ISEP), a 1-week summer training program providing exposure to health careers and mentorship in pursuing public health careers for Native American high school students. ISEP utilizes the Diné Educational Philosophy (DEP), a Navajo conceptual framework to serve as the foundation of the program. In 2020–2021, due to COVID-19 restrictions, the DEP model had to be incorporated in the Navajo NARCH high school virtual program activities. ISEP used 2018 and 2019 past program evaluation data to inform the virtual programming. Students' perception of the program was collected using an online Qualtrics evaluation questionnaire. Students stated appreciation for program staff, fellow students, peer mentors and culturally relevant learning experiences in both virtual and in-person environments. Recommendations included: expanding the length of ISEP and continuing the hands-on activities and Public Health Leadership series.
Health Literacy Needs Among Unemployed Persons: Collating Evidence Through Triangulation of Interview and Scoping Review Data
Authors: Samkange-Zeeb Florence , Singh Hunny , Lakeberg Meret , Kolschen Jonathan , Schüz Benjamin , Christianson Lara , De Santis Karina Karolina , Brand Tilman , Zeeb Hajo
Published: February 2022

Background

Unemployed persons are at high risk for low health literacy. Most studies addressing health literacy of unemployed persons focus on risk factors for low health literacy or correlates of health literacy, but studies on needs of unemployed persons regarding health literacy are scarce. We aimed to obtain better understanding of health literacy needs of unemployed adults by triangulating the results from a scoping review on health literacy needs in unemployed adults and additional in-depth qualitative interviews.

Methods

Scoping review: We searched six databases up to January 2021 as well as gray literature for relevant studies following PRISMA-ScR guidelines. Titles, abstracts, and full texts were screened independently by two researchers. Qualitative study: Ten participants of a job-reintegration program in Germany were interviewed following a guideline covering topics including health issues of interest to the participants, their sources of health-related information and the barriers/facilitators they experience when accessing health services.

Results

Scoping review: After screening 2,966 titles and abstracts, 36 full texts were considered, and five articles fulfilled the inclusion criteria. Four focused on mental health literacy and outcomes, while the fifth assessed information-seeking practices. One additional report on health literacy was identified via the gray literature search. Awareness of one's condition was identified as a facilitator for mental health help-seeking, while fear of harmful effects of medication prevented help-seeking. Qualitative study: Participants were interested in and were generally well-informed about health topics such as nutrition and physical activity. The main challenge perceived was translating the knowledge into practice in daily life. GPs and the social services providers played an important role as a source of health information and advice. Regarding mental health, similar barriers, facilitators and needs were identified through triangulation of findings of the scoping review with those of the interviews.

Conclusions

There is need to address health literacy needs of long-term unemployed persons that go beyond mental health literacy. Public health interventions should not only aim at improving health literacy scores, but also focus on how to help participants translate health literacy into practice. Population groups of interest should also be involved in all processes of designing interventions.
Safety and Efficacy of a MEURI Program for the Use of High Dose Ivermectin in COVID-19 Patients
Authors: Mayer Marcos Alejandro , Krolewiecki Alejandro , Ferrero Alejandro , Bocchio Marcelo , Barbero Juan , Miguel Marcos , Paladini Ariel , Delgado Carlos , Ojeda Juan Ramón , Elorza Claudia , Bertone Ana , Fleitas Pedro Emanuel , Vera Gustavo , Kohan Mario Rubén
Published: February 2022

Background

In the absence of antiviral alternatives, interventions under research for COVID-19 might be offered following guidelines from WHO for monitored emergency use of unregistered and experimental interventions (MEURI). Ivermectin is among several drugs explored for its role against SARS-CoV-2, with a well-known safety profile but conflicting data regarding clinical utility for COVID-19. The aim of this report is to inform on the results of a MEURI Program of high-dose ivermectin in COVID-19 carried out by the Ministry of Health of the Province of La Pampa, Argentina.

Methods

COVID-19 subjects, within 5 days of symptoms onset were invited to participate in the program, which consisted in the administration of ivermectin 0.6 mg/kg/day for 5 days plus standard of care. Active pharmacosurveillance was performed for 21 days, and hepatic laboratory assessments were performed in a subset of patients. Frequency of Intensive Care Unit (ICU) admission and COVID-19-related mortality of subjects in the ivermectin intention to treat group were compared with that observed in inhabitants of the same province during the same period not participating in the program.

Results

From 21,232 subjects with COVID-19, 3,266 were offered and agreed to participate in the ivermectin program and 17,966 did not and were considered as controls. A total of 567 participants reported 819 adverse events (AEs); 3.13% discontinued ivermectin due to adverse events. ICU admission was significantly lower in the ivermectin group compared to controls among participants ≥40 year-old (1.2 vs. 2.0%, odds ratio 0.608; p = 0.024). Similarly, mortality was lower in the ivermectin group in the full group analysis (1.5 vs. 2.1%, odds ratio 0.720; p = 0.029), as well as in subjects ≥ 40 year- old (2.7 vs. 4.1%, odds ratio 0.655; p = 0.005).

Conclusions

This report highlights the safety and possible efficacy of high dose ivermectin as a potentially useful intervention deserving public health-based consideration for COVID-19 patients.