bluuebunny/crossref_metadata_2025 huggingface dataset:
Fusion Gene Detection Using Whole-Exome Sequencing Data in Cancer Patients
Authors: Deng Wenjiang , Murugan Sarath , Lindberg Johan , Chellappa Venkatesh , Shen Xia , Pawitan Yudi , Vu Trung Nghia
Published: February 2022

Several fusion genes are directly involved in the initiation and progression of cancers. Numerous bioinformatics tools have been developed to detect fusion events, but they are mainly based on RNA-seq data. The whole-exome sequencing (WES) represents a powerful technology that is widely used for disease-related DNA variant detection. In this study, we build a novel analysis pipeline called Fuseq-WES to detect fusion genes at DNA level based on the WES data. The same method applies also for targeted panel sequencing data. We assess the method to real datasets of acute myeloid leukemia (AML) and prostate cancer patients. The result shows that two of the main AML fusion genes discovered in RNA-seq data, PML-RARA and CBFB-MYH11, are detected in the WES data in 36 and 63% of the available samples, respectively. For the targeted deep-sequencing of prostate cancer patients, detection of the TMPRSS2-ERG fusion, which is the most frequent chimeric alteration in prostate cancer, is 91% concordant with a manually curated procedure based on four other methods. In summary, the overall results indicate that it is challenging to detect fusion genes in WES data with a standard coverage of ∼ 15–30x, where fusion candidates discovered in the RNA-seq data are often not detected in the WES data and vice versa. A subsampling study of the prostate data suggests that a coverage of at least 75x is necessary to achieve high accuracy.
Coping With Stress: The Mitokine GDF-15 as a Biomarker of COVID-19 Severity
Authors: Ahmed Darakhshan Sohail , Isnard Stéphane , Berini Carolina , Lin John , Routy Jean-Pierre , Royston Léna
Published: February 2022

Growth differentiation factor 15 (GDF-15) is a transforming growth factor (TGF)-β superfamily cytokine that plays a central role in metabolism regulation. Produced in response to mitochondrial stress, tissue damage or hypoxia, this cytokine has emerged as one of the strongest predictors of disease severity during inflammatory conditions, cancers and infections. Reports suggest that GDF-15 plays a tissue protective role via sympathetic and metabolic adaptation in the context of mitochondrial damage, although the exact mechanisms involved remain uncertain. In this review, we discuss the emergence of GDF-15 as a distinctive marker of viral infection severity, especially in the context of COVID-19. We will critically review the role of GDF-15 as an inflammation-induced mediator of disease tolerance, through metabolic and immune reprogramming. Finally, we discuss potential mechanisms of GDF-15 elevation during COVID-19 cytokine storm and its limitations. Altogether, this cytokine seems to be involved in disease tolerance to viral infections including SARS-CoV-2, paving the way for novel therapeutic interventions.
Performance, Rumen Microbial Community and Immune Status of Goat Kids Fed Leucaena leucocephala Post-weaning as Affected by Prenatal and Early Life Nutritional Interventions
Authors: Artiles-Ortega Einar , Portal Orelvis , Jeyanathan Jeyamalar , Reguera-Barreto Beydis , de la Fé-Rodríguez Pedro Yoelvys , Lima-Orozco Raciel , Fievez Veerle
Published: February 2022

Leucaena leucocephala represents a local protein source in tropical ruminant diets. However, its full exploitation is impaired by mimosine, unless it is degraded by the rumen microbial community. Recently, the ruminal bacterial communities of newborns were persistently modified through prenatal or postnatal dietary interventions. Such early-life interventions might enhance adaptation of ruminants to Leucaena leucocephala, which was investigated using a 2 × 2 factorial design trial that tested both supplementation of L. leucocephala in the late pregnancy diet of goat does, and supplementation of live yeast to their newborns. The composition of ruminal bacteria, immune status, as well as organic matter digestibility (OMD) and performance of kids were studied during and after the intervention. Ten pregnant goats were divided into two groups: the D+ and D– groups, which either received or did not receive 30 g of L. leucocephala forage meal during the last 7 ± 0.5 weeks of gestation. Twins from each goat were divided into the K+ and K– group (supplemented with or without 0.2 g/d of live yeast from day 3 until weaning at 8 weeks). Rumen samples were collected from 4-, 8-, 14-, and 20-weeks old kids to assess the bacterial community, while immune parameters (white blood cells, immunoglobulin M and G, and chitotriosidase activity) were measured in blood and saliva sampled at 4-, 8-, and 20-weeks. We found a stimulatory effect of the prenatal exposure on the post-weaning dry matter intake of the L. leucocephala supplemented diet, resulting in a higher daily gain and final body weight at 20 weeks in the D+ vs. D– group (406 vs. 370 g DM/d, 85.4 vs. 78.6 g/d, and 15.2 vs. 13.8 kg, respectively). Moreover, Ruminococcus represented a greater proportion of the rumen bacterial community of the D+ vs. D– kids (5.1 vs. 1.6%). Differences in the immune status were relatively small and not thought to be a driving factor of differences in animal performance. Furthermore, postnatal supplementation of live yeast favored maturation of the rumen bacterial community (i.e., greater abundance of Bacteroidetes, in particular Prevotella, and reduced abundance of Firmicutes) and protozoa colonization. Concomitantly, OMD was enhanced post-weaning, suggesting effects of the early-life intervention persisted and could have affected animal performance.
Enrofloxacin Promotes Plasmid-Mediated Conjugation Transfer of Fluoroquinolone-Resistance Gene qnrS
Authors: Zhao Yue , Cao Zhengzheng , Cui Luqing , Hu Tianyu , Guo Kaixuan , Zhang Fan , Wang Xiangru , Peng Zhong , Liu Quan , Dai Menghong
Published: February 2022

This study aimed to determine the effect of enrofloxacin (ENR) on the transfer of the plasmid-mediated quinolone resistance (PMQR) gene qnrS from opportunistic pathogen Escherichia coli (E2) to Salmonella Enteritidis (SE211) and to analyze the resistance characteristics of SE211-qnrS isolates. The plasmid carrying qnrS gene of E2 was sequenced by Oxford Nanopore technology. The plasmid carrying qnrS gene belonged to incompatibility group IncY. In vitro, the transfer experiment of IncY plasmid was performed by the liquid medium conjugation method. The conjugation transfer frequency of the IncY plasmid was 0.008 ± 0.0006 in the absence of ENR, 0.012 ± 0.003 in 1/32 MICENR, 0.01 ± 0.008 in 1/8 MICENR, and 0.03 ± 0.015 (Mean±SD) in 1/2 MICENR, respectively. After inoculation of E. coli E2 and SE211, chickens were treated with different doses of ENR (3.03, 10, and 50 mg/kg b.w.) for 7 days consecutively. To screen the SE211-qnrS strains from intestinal tract of chickens, the resistance genes and susceptibility of isolates were identified. The amount of E. coli E2 and the copy number of qnrS gene in the chicken intestinal tract were determined by colony counting and qPCR, respectively. In vivo, more SE211-qnrS strains were isolated from the treated group compared with the untreated group. SE211-qnrS strains not only obtained IncY plasmid, but also showed similar resistance phenotype as E2. In conclusion, ENR treatment can promote the spread of a IncY-resistance plasmid carrying the qnrS fluoroquinolone-resistance gene in Escherichia coli and the development of drug-resistant bacteria.
Multi-Omics Analysis After Vaginal Administration of Bacteroides fragilis in Chickens
Authors: Chen Lu , Yang Maosen , Zhu Wei , Su Yuan , Li Diyan , Wang Tao
Published: February 2022

The reproductive tract of chickens is an important organ for egg formation. The vagina is in close contact with the external environment, which may lead to the invasion of a variety of pathogenic bacteria, affect the internal and external quality of eggs, and even increase mortality and cause economic loss. In recent years, probiotics as a substitute for antibiotics have brought economic benefits in livestock and poultry production. In the present study, we investigated the effects of vaginal administration of Bacteroides fragilis on the cloacal microbiota, vaginal transcriptome and metabolomics of chickens and evaluated the beneficial potential of B. fragilis. The results showed that B. fragilis treatment could affect the microbial composition of the cloaca. Transcriptome analysis found that the immune-related genes CCN3, HAS2, and RICTOR were upregulated, that the inflammatory genes EDNRB, TOX, and NKX2-3 were downregulated, and that DEGs were also enriched in the regulation of the inflammatory response, cellular metabolism, and synaptic response pathways. In addition, the differential metabolites were mainly related to steroid hormone biosynthesis, unsaturated fatty acid biosynthesis, and arachidonic acid metabolism, and we identified associations between specific differential metabolites and genes. Overall, this study provides a theoretical basis for the application of B. fragilis as a potential probiotic in livestock and poultry production.
Altered Global Signal Topography in Alcohol Use Disorders
Authors: Duan Ranran , Jing Lijun , Li Yanfei , Gong Zhe , Yao Yaobing , Wang Weijian , Zhang Yong , Cheng Jingliang , Peng Ying , Li Li , Jia Yanjie
Published: February 2022

The most common symptom of patients with alcohol use disorders (AUD) is cognitive impairment that negatively affects abstinence. Presently, there is a lack of indicators for early diagnosis of alcohol-related cognitive impairment (ARCI). We aimed to assess the cognitive deficits in AUD patients with the help of a specific imaging marker for ARCI. Data-driven dynamic and static global signal topography (GST) methods were applied to explore the cross-talks between local and global neuronal activities in the AUD brain. Twenty-six ARCI, 54 AUD without cognitive impairment (AUD-NCI), and gender/age-matched 40 healthy control (HC) subjects were recruited for this study. We found that there was no significant difference with respect to voxel-based morphometry (VBM) and static GST between AUD-NCI and ARCI groups. And in dynamic GST measurements, the AUD-NCI patients had the highest coefficient of variation (CV) at the right insula, followed by ARCI and the HC subjects. In precuneus, the order was reversed. There was no significant correlation between the dynamic GST and behavioral scores or alcohol consumption. These results suggested that dynamic GST might have potential implications in understanding AUD pathogenesis and disease management.
Etiology and Clinical Features of Diplopia in South China: Analysis of 303 Cases
Authors: Wang Zhonghao , Zhu Binbin , Fu Licheng , Yan Jianhua
Published: February 2022

Purpose

To provide a new classification system for diplopia and evaluate the etiology and clinical features of diplopia subtypes in south China.

Methods

In this retrospective study, all patients presenting with diplopia over the period from 2012 to 2014 in south China were reviewed. Patients were categorized into 3 groups according to their extraocular muscle (EOM) dysfunction: single EOM (sEOM), multiple EOMs (mEOMs), and a comitant strabismus group. Clinical data evaluated included age, sex, medical history, etiology and duration of diplopia, ocular alignment, and ocular motility.

Results

A total of 303 patients were enrolled. The most common type of EOM dysfunction was sEOM (158 cases, 52.1%), followed by mEOMs (n = 119, 39.3%), and finally the comitant strabismus group (n = 26, 8.6%). Overall, the most common cause of diplopia involved orbital diseases. Within the sEOM group, microangiopathy (n = 42, 26.6%) and trauma (n = 41, 25.9%) were the major etiologies, with the lateral rectus (LR) (n = 86, 54.4%) being the most frequently involved. There were 12 (4.0%) patients who were considered as nasopharyngeal carcinoma (NPC)-associated diplopia (10 caused by radiation neuropathy following radiation therapy). Thyroid associated ophthalmopathy (TAO, 56 cases, 47.1%) was the predominant etiology found in the mEOMs group. Acute acquired comitant esotropia (AACE, 14 cases, 53.9%) was the most common etiology in the comitant strabismus group.

Conclusions

This new classification system for assessing diplopia as based on EOM dysfunction represents an easy-to-follow approach that can be readily adapted for the clinical use. While microangiopathy and trauma represent common etiologies of diplopia, both orbital diseases and NPC-associated diplopia also warrant special attention when assessing diplopia within patients in south China.
Similarities Between Somatosensory Cortical Responses Induced via Natural Touch and Microstimulation in the Ventral Posterior Lateral Thalamus in Macaques
Authors: Francis Joseph Thachil , Rozenboym Anna , von Kraus Lee , Xu Shaohua , Chhatbar Pratik , Semework Mulugeta , Hawley Emerson , Chapin John
Published: February 2022

Lost sensations, such as touch, could be restored by microstimulation (MiSt) along the sensory neural substrate. Such neuroprosthetic sensory information can be used as feedback from an invasive brain-machine interface (BMI) to control a robotic arm/hand, such that tactile and proprioceptive feedback from the sensorized robotic arm/hand is directly given to the BMI user. Microstimulation in the human somatosensory thalamus (Vc) has been shown to produce somatosensory perceptions. However, until recently, systematic methods for using thalamic stimulation to evoke naturalistic touch perceptions were lacking. We have recently presented rigorous methods for determining a mapping between ventral posterior lateral thalamus (VPL) MiSt, and neural responses in the somatosensory cortex (S1), in a rodent model (Choi et al., 2016; Choi and Francis, 2018). Our technique minimizes the difference between S1 neural responses induced by natural sensory stimuli and those generated via VPL MiSt. Our goal is to develop systems that know what neural response a given MiSt will produce and possibly allow the development of natural “sensation.” To date, our optimization has been conducted in the rodent model and simulations. Here, we present data from simple non-optimized thalamic MiSt during peri-operative experiments, where we used MiSt in the VPL of macaques, which have a somatosensory system more like humans, as compared to our previous rat work (Li et al., 2014; Choi et al., 2016). We implanted arrays of microelectrodes across the hand area of the macaque S1 cortex as well as in the VPL. Multi and single-unit recordings were used to compare cortical responses to natural touch and thalamic MiSt in the anesthetized state. Post-stimulus time histograms were highly correlated between the VPL MiSt and natural touch modalities, adding support to the use of VPL MiSt toward producing a somatosensory neuroprosthesis in humans.
Oxysterols as Reliable Markers of Quality and Safety in Cholesterol Containing Food Ingredients and Products
Authors: Canzoneri Federico , Leoni Valerio , Rosso Ginevra , Risso Davide , Menta Roberto , Poli Giuseppe
Published: February 2022

Cholesterol is a lipid of high nutritional value that easily undergoes oxidation through enzymatic and non-enzymatic pathways, leading to a wide variety of cholesterol oxidation products (COPs), more commonly named oxysterols. The major oxysterols found in animal products are 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, 5α,6α-epoxycholesterol, 5β,6β-epoxycholesterol, cholestan-3β,5α,6β-triol, and 25-hydroxycholesterol. They are all produced by cholesterol autoxidation, thus belonging to the non-enzymatic oxysterol subfamily, even if 7α-hydroxycholesterol and 25-hydroxycholesterol are, in part, generated enzymatically as well. A further oxysterol of the full enzymatic origin has recently been detected for the first time in milk of both human and bovine origin, namely 27-hydroxycholesterol. Nowadays, gas or liquid chromatography combined to mass spectrometry allows to measure all these oxysterols accurately in raw and in industrially processed food. While non-enzymatic oxysterols often exhibitedin vitrorelevant cytotoxicity, above all 7β-hydroxycholesterol and 7-ketocholesterol, 27-hydroxycholesterol, as well as 25-hydroxycholesterol, shows a broad spectrumin vitroantiviral activity, inhibition of SARS-CoV-2 included, and might contribute to innate immunity. Quantification of oxysterols was afforded over the years, almost always focused on a few family's compounds. More comprehensive COPs measurements, also including oxysterols of enzymatic origin, are, nowadays, available, which better display the many advantages of systematically adopting this family of compounds as markers of quality, safety, and nutritional value in the selection of ingredients in processing and storage. Regarding foodstuff shelf life, COPs monitoring already provided useful hints for more suitable packaging. The identification of a subset of non-enzymatic and enzymatic oxysterols to be routinely assessed in food production and storage is proposed.
The Sensitivity of Diagnostic Criteria of Marais S, et al. in Confirmed Childhood Tuberculous Meningitis
Authors: Wang Mao-Shui , Wang Jun-Li , Liu Xin-Jie , Zhang Yan-An
Published: February 2022

Background

To establish the sensitivity of the diagnostic criteria published by Marais and co-workers in 2010 for childhood tuberculous meningitis (TBM), a retrospective study on children with confirmed TBM was conducted.

Methods

Between January 2006 and December 2019, children consecutively diagnosed with TBM were recruited retrospectively at our center. TBM was defined in cases where any of the following criteria were met: the presence of acid-fast bacilli (AFB) in cerebrospinal fluid (CSF) microscopy, CSF nucleic acid amplification test (NAAT, +), or M.tuberculosis cultured from CSF. The demographic and clinical features of all enrolled patients were recorded including clinical characteristics, CSF findings, cerebral imaging features, and other evidence of TB.

Results

A total of 30 children with confirmed diagnosis of TBM over an 14-year period were recruited. The mean age of patients was 7.2 ± 5.1 years and 16 (53.3%) were male. The estimated mean diagnostic score was 12.7 ± 2.4. Twenty-three (76.7%; 95% CI: 59.1–88.2%) patients were classified as “probable TBM” according to the Marais criteria and 7 (23.3%; 95% CI: 11.8–40.9%) as “possible TBM.” Further statistical analysis revealed significant differences in CSF scores between probable and possible TBM groups. Other variables reported at a relatively low frequency, such as symptoms and imaging features, made little contribution to TBM diagnosis according to the Marais criteria.

Conclusion

Childhood TBM could be effectively identified by the criteria defined by Marais et al. However, further revision is required to ensure that the system is more sensitive and easier to perform in practice.
Sorafenib-Induced Autophagy Promotes Glycolysis by Upregulating the p62/HDAC6/HSP90 Axis in Hepatocellular Carcinoma Cells
Authors: Yan Xiaoyu , Tian Rui , Sun Jicheng , Zhao Yuanxin , Liu Buhan , Su Jing , Li Minghua , Sun Wei , Xu Xuesong
Published: February 2022

Sorafenib has attracted much attention as the first drug approved by the FDA for the treatment of advanced hepatocellular carcinoma (HCC). Because of the drug tolerance, the overall outcomes were far from satisfactory. Current studies suggest that changes in glucose metabolism induced by sorafenib are the pivotal resistant mechanism of HCC cells, but the specific regulatory mechanism remains unclear, which makes it difficult to increase drug sensitivity by targeting glycolysis. As a metabolic-recycling pathway, autophagy regulates multiple important pathways involved in cell survival and death. In this study, we found the expression of key autophagy proteins were closely related to the prognosis and progression of HCC patients. Based on in vitro experiments, our studies showed sorafenib induced autophagy in HCC cells. Inhibition of autophagy by chloroquine could significantly increase the sensitivity of HCC cells to sorafenib and reverse the enhancement of glycolysis. Furthermore, sorafenib-induced autophagy promoted the deacetylase activity of HDAC6 by degrading p62, which promoted the activity of PKM2 by regulating the acetylation of its critical substrate HSP90. In this study, we investigated the role of autophagy-induced HDAC6 in regulating the key glycolytic enzyme PKM2, which may be helpful to clarify the relationship between autophagy and glycolysis in a sorafenib-resistant mechanism. Targeting p62/HDAC6/HSP90 could herald a potential improvement in HCC therapy.
The Binding Mode to Orthosteric Sites and/or Exosites Underlies the Therapeutic Potential of Drugs Targeting Cannabinoid CB2 Receptors
Authors: Franco Rafael , Morales Paula , Navarro Gemma , Jagerovic Nadine , Reyes-Resina Irene
Published: February 2022

The classical terms agonists and antagonists for G protein coupled receptors (GPCRs) have often become misleading. Even the biased agonism concept does not describe all the possibilities already demonstrated for GPCRs. The cannabinoid CB2 receptor (CB2R) emerged as a promising target for a variety of diseases. Reasons for such huge potential are centered around the way drugs sit in the orthosteric and/or exosites of the receptor. On the one hand, a given drug in a specific CB2R conformation leads to a signaling cascade that differs qualitatively and/or quantitatively from that triggered by another drug. On the other hand, a given drug may lead to different signaling outputs in two different tissues (or cell contexts) in which the conformation of the receptor is affected by allosteric effects derived from interactions with other proteins or with membrane lipids. This highlights the pharmacological complexity of this receptor and the need to further unravel the binding mode of CB2R ligands in order to fine-tune signaling effects and therapeutic propositions.
The Effect of University Students’ Emotional Intelligence, Learning Motivation and Self-Efficacy on Their Academic Achievement—Online English Courses
Authors: Chang Yuan-Cheng , Tsai Yu-Ting
Published: February 2022

The COVID-19 pandemic has had a significant impact on education worldwide. The disease first hit China and numerous Chinese cities then started to conduct online courses. Therefore, this study aims to explore the effect of the Shanghai students’ emotional intelligence, learning motivation, and self-efficacy on their academic achievement when they participated in online English classes during the latter phase of the pandemic in China. Furthermore, the research also examines whether the students’ emotional intelligence can influence their academic achievement through the mediation effect of their learning motivation and self-efficacy. Social Cognitive Theory (SCT) and the social cognitive Expectancy-Value Model were employed to build the research framework, and the method of structural equation modeling (SEM) was utilized to conduct the model verification. Ten universities in Shanghai, China were selected for sampling. In total, 450 students were surveyed of which 404 questionnaires were valid. The results show that the students’ emotional intelligence did not directly affect their academic achievement. Nevertheless, the students’ emotional intelligence had a positive effect on their learning motivation and self-efficacy. In addition, mediation analysis showed that the relation between emotional intelligence and academic achievement was sequentially mediated by learning motivation and self-efficacy.
Resilience and Anxiety Among Healthcare Workers During the Spread of the SARS-CoV-2 Delta Variant: A Moderated Mediation Model
Authors: Liu Ying , Hou Tianya , Gu Hongjuan , Wen Jing , Shao Xiaoqin , Xie Yawei , Deng Wenxi , Dong Wei
Published: February 2022

Introduction

The B.1.617.2 (Delta) variant of SARS-COV-2 has caused a surge in COVID-19 cases worldwide, placing a great burden on the health care system under the zero-tolerance epidemic prevention policy in China. The present study aimed to investigate the prevalence of anxiety among health care workers during the spread of the SARS-CoV-2 Delta variant, and to discuss the mediating role of positive coping style between resilience and anxiety, and the moderating role of general self-efficacy.

Method

Connor-Davidson Resilience scale (CD-RISC), Generalized Anxiety Disorder Scale (GAD-7), General Self-efficacy Scale (GSES) and Simplified Coping Style Questionnaire (SCSQ) were used in this cross-sectional study among 390 healthcare workers in Jiangsu Province, China. Mackinnon's four-step procedure was applied to test the mediation effect, and Hayes PROCESS macro was conducted to examine the moderated mediation model.

Results

The prevalence of anxiety among Chinese healthcare workers during the spread of the SARS-CoV-2 Delta variant was 41.8%. Male, unmarried, childless and younger subjects reported higher levels of anxiety. Positive coping partially mediated the effect of resilience on anxiety among healthcare workers and the indirect effect was stronger with the increase of general self-efficacy.

Conclusions

Anxiety was prevalent among healthcare workers during the spread of SARS-CoV-2 Delta variant. This research sheds new light on the potential mechanism underlying the association between resilience and anxiety and provides new insight into the prevention of anxiety among healthcare workers during the spread of the SARS-CoV-2 Delta variant.
Health of International Migrant Workers During the COVID-19 Pandemic: A Scoping Review
Authors: Oliva-Arocas Adriana , Benavente Pierina , Ronda Elena , Diaz Esperanza
Published: February 2022

Background

The coronavirus (COVID-19) pandemic and control measures adopted have had a disproportionate impact on workers, with migrants being a group specifically affected but poorly studied. This scoping review aims to describe the evidence published on the impact of the COVID-19 pandemic on the physical and mental health of migrant workers.

Methods

Papers written in English covering physical and mental health among international migrant workers during the COVID-19 pandemic, retrieved from six electronic databases searched on July 31, 2021, were included. A total of 1,096 references were extracted, of which 26 studies were finally included.

Results

Most of the migrant populations studied were born in Asia (16 of 26) and Latin America (8 of 26) and were essential workers (15 of 26). Few studies described the length of stay in the host country (9 of 26), the legal status of the migrant population (6 of 26), or established comparison groups (7 of 26). Ten studies described COVID-19 outbreaks with high infection rates. Fourteen studies evaluated mental health (anxiety, depression, worries, fears, stress, and post-traumatic stress disorder). Three of the 26 studies presented collateral positive effects of the COVID-19 pandemic because of improved hygiene.

Conclusion

There is a limited number of original publications related to the impact of the COVID-19 pandemic on the physical and mental health of migrant workers around the world. These publications mainly focus on migrants born in Asia and Latin America. The physical, long-term impact of the COVID-19 pandemic has, so far, not been evaluated. The positive collateral effects of improving healthcare conditions for migrant workers should also be further investigated.
Estimation of Relative Risk of Mortality and Economic Burden Attributable to High Temperature in Wuhan, China
Authors: Chen Si , Zhao Junrui , Lee Soo-Beom , Kim Seong Wook
Published: February 2022

In the context of climate change, most of the global regions are facing the threat of high temperature. Influenced by tropical cyclones in the western North Pacific Ocean, high temperatures are more likely to occur in central China, and the economic losses caused by heat are in urgent need of quantification to form the basis for health decisions. In order to study the economic burden of high temperature on the health of Wuhan residents between 2013 and 2019, we employed meta-analysis and the value of statistical life (VSL) approach to calculate the relative risk of high temperature health endpoints, the number of premature deaths, and the corresponding economic losses in Wuhan City, China. The results suggested that the pooled estimates of relative risk of death from high temperature health endpoints was 1.26 [95% confidence interval (CI): 1.15, 1.39]. The average number of premature deaths caused by high temperature was estimated to be 77,369 (95% CI: 48,906–105,198) during 2013–2019, and the induced economic losses were 156.1 billion RMB (95% CI: 92.28–211.40 billion RMB), accounting for 1.81% (95% CI: 1.14–2.45%) of Wuhan's annual GDP in the seven-year period. It can be seen that high temperature drives an increase in the premature deaths, and the influence of high temperature on human health results in an economic burden on the health system and population in Wuhan City. It is necessary for the decision-makers to take measures to reduce the risk of premature death and the proportion of economic loss of residents under the impacts of climate change.
Conveying Intention by Motions With Awareness of Information Asymmetry
Authors: Fukuchi Yosuke , Osawa Masahiko , Yamakawa Hiroshi , Takahashi Tatsuji , Imai Michita
Published: February 2022

Humans sometimes attempt to infer an artificial agent’s mental state based on mere observations of its behavior. From the agent’s perspective, it is important to choose actions with awareness of how its behavior will be considered by humans. Previous studies have proposed computational methods to generate such publicly self-aware motion to allow an agent to convey a certain intention by motions that can lead a human observer to infer what the agent is aiming to do. However, little consideration has been given to the effect of information asymmetry between the agent and a human, or to the gaps in their beliefs due to different observations from their respective perspectives. This paper claims that information asymmetry is a key factor for conveying intentions with motions. To validate the claim, we developed a novel method to generate intention-conveying motions while considering information asymmetry. Our method utilizes a Bayesian public self-awareness model that effectively simulates the inference of an agent’s mental states as attributed to the agent by an observer in a partially observable domain. We conducted two experiments to investigate the effects of information asymmetry when conveying intentions with motions by comparing the motions from our method with those generated without considering information asymmetry in a manner similar to previous work. The results demonstrate that by taking information asymmetry into account, an agent can effectively convey its intention to human observers.
Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Predict the Cardiotoxicity Potential of Next Generation Nicotine Products
Authors: Simms Liam , Yu Fan , Palmer Jessica , Rudd Kathryn , Sticken Edgar Trelles , Wieczorek Roman , Chapman Fiona , Czekala Lukasz , Stevenson Matthew , O’Connell Grant
Published: February 2022

Combustible cigarette smoking is an established risk factor for cardiovascular disease. By contrast, the cardiotoxicity potential of non-combustible next generation nicotine products (NGPs), which includes heated tobacco products (HTPs) and electronic vaping products (EVPs), and how this compares relative to combustible cigarettes is currently an area of scientific exploration. As such, there is a need for a rapid screening assay to assess this endpoint. The Cardio quickPredict is a metabolomics biomarker-based assay that uses human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to screen for potential structural and functional cardiac toxicants based on the changes of four metabolites, lactic acid, arachidonic acid, thymidine, and 2′-deoxycytidine. The study aims were to investigate the cardiotoxicity potential of NGPs compared to cigarettes, in addition to nicotine. To accomplish this, hiPSC-CM were exposed to smoke or aerosol bubbled PBS samples: reference cigarette (1R6F); three variants of HTP; and three EVP variants. The 1R6F bPBS was the most active, having cardiotoxic potential at 0.3–0.6% bPBS (0.4–0.9 μg/mL nicotine), followed by HTP, which displayed cardiotoxic potential at a 10 times higher concentration, 3.3% bPBS (4.1 μg/mL nicotine). Both 1R6F and HTP bPBS (at 10-fold higher concentration than 1R6F) affected all four predictive metabolites, whereas none of the EVP bPBS samples were active in the assay up to the maximal concentration tested (10% bPBS). Nicotine tested on its own was predicted to have cardiotoxic potential at concentrations greater than 80 μg/mL, which is higher than expected physiological levels associated with combustible cigarette smoking. The application of this rapid screening assay to NGP research and the associated findings adds to the weight-of-evidence indicating that NGPs have a tobacco harm reduction potential when compared to combustible cigarettes. Additionally, this technique was shown to be sensitive and robust for the assessment of different NGPs and may be considered as part of a larger overall scientific framework for NGP assessments.
Screening and Validation of p38 MAPK Involved in Ovarian Development of Brachymystax lenok
Authors: Huang Tianqing , Gu Wei , Liu Enhui , Zhang Lanlan , Dong Fulin , He Xianchen , Jiao Wenlong , Li Chunyu , Wang Bingqian , Xu Gefeng
Published: February 2022

Brachymystax lenok (lenok) is a rare cold-water fish native to China that is of high meat quality. Its wild population has declined sharply in recent years, and therefore, exploring the molecular mechanisms underlying the development and reproduction of lenoks for the purposes of artificial breeding and genetic improvement is necessary. The lenok comparative transcriptome was analyzed by combining single molecule, real-time, and next generation sequencing (NGS) technology. Differentially expressed genes (DEGs) were identified in five tissues (head kidney, spleen, liver, muscle, and gonad) between immature [300 days post-hatching (dph)] and mature [three years post-hatching (ph)] lenoks. In total, 234,124 and 229,008 full-length non-chimeric reads were obtained from the immature and mature sequencing data, respectively. After NGS correction, 61,405 and 59,372 non-redundant transcripts were obtained for the expression level and pathway enrichment analyses, respectively. Compared with the mature group, 719 genes with significantly increased expression and 1,727 genes with significantly decreased expression in all five tissues were found in the immature group. Furthermore, DEGs and pathways involved in the endocrine system and gonadal development were identified, and p38 mitogen-activated protein kinases (MAPKs) were identified as potentially regulating gonadal development in lenok. Inhibiting the activity of p38 MAPKs resulted in abnormal levels of gonadotropin-releasing hormone, follicle-stimulating hormone, and estradiol, and affected follicular development. The full-length transcriptome data obtained in this study may provide a valuable reference for the study of gene function, gene expression, and evolutionary relationships in B. lenok and may illustrate the basic regulatory mechanism of ovarian development in teleosts.
Programmed Cell Death in Cystinosis
Authors: Ames Elizabeth G. , Thoene Jess G.
Published: February 2022

Cystinosis is a lethal autosomal recessive disease that has been known clinically for over 100 years. There are now specific treatments including dialysis, renal transplantation and the orphan drug, cysteamine, which greatly improve the duration and quality of patient life, however, the cellular mechanisms responsible for the phenotype are unknown. One cause, programmed cell death, is clearly involved. Study of extant literature via Pubmed on “programmed cell death” and “apoptosis” forms the basis of this review. Most of such studies involved apoptosis. Numerous model systems and affected tissues in cystinosis have shown an increased rate of apoptosis that can be partially reversed with cysteamine. Proposed mechanisms have included changes in protein signaling pathways, autophagy, gene expression programs, and oxidative stress.
Research on Electromagnetic Susceptibility of Electronic Modules in Component-Level HEMP PCI Test
Authors: Du Chuanbao , Xia Dewei , Huang Quan , Mao Congguang , Cui Zhitong , Fang Wenxiao , Nie Xin
Published: February 2022

The study of electromagnetic sensitivity of electronic modules is crucial for the selection of a component-level pulse current injection (PCI) waveform, which will determine whether a component-level PCI test is equivalent to a system-level pulse illumination test of the system to which the electronic module belongs. For electromagnetic sensitivity analysis, the equivalence between the injection waveform and a typical high-altitude electromagnetic pulse (HEMP) conducted disturbance waveform in a component-level PCI test is studied. Based on an RF low noise amplifier (LNA) test board, component-level PCI tests were performed using 20 ns/500 ns double exponential wave and square-wave pulse with multiple pulse-widths. The damage threshold was analyzed and determined by using vector norm and its internal damage was observed and validated by optical microscopic analysis. The conclusions are demonstrated as follows: first, during square-wave PCI tests of RF LNA, the electromagnetic sensitive parameter action is divided into three regions by pulse-width range, called ∞-norm, 2-norm and competitive failure-dominating regions; second, the electromagnetic damage effect of the RF LNA is mainly caused by the burning of its two cascaded transistors, forming a pulse energy transmission channel with short-circuit impedance from the input port to the ground; third, the 100 ns-width square waveform can be determined as the equivalent injection waveform of a HEMP conducted waveform, and the pulse peak value of injected current is determined as the electromagnetic sensitive parameter for square-wave PCI tests of the RF LNA. The conclusions verified the feasibility of establishing the equivalence between different pulse waveforms according to the electromagnetic sensitivity analysis based on the vector norm theory and effect mechanism analysis.
Cartography and Art: A Comparative Study Based on Color
Authors: Stamou Leda
Published: February 2022

Color occupies a prominent place in the bibliography of cartography, as it is an important element in the formation of cartographic symbolization. Apart from the technical issues of its application to maps, color theory is one of the elements that connect maps with art. In this paper various cartographic trends and their origins are examined and correlated with the artistic periods in which they were developed in order to investigate and document the extent to which maps follow the artistic movements and, particularly in the art of painting, concerning the form and the content of the maps and whether color can be used as an identification element of the art trend and the corresponding period. The research spans from the end of the Middle Ages to the 21st century and is referred spatially in Western Europe, including Italy. The comparison of colors is made in both descriptive and quantitative terms through the commentary of hue, brightness, and saturation, as well as through plotting them in the color wheel, a process that allows an overview of the range and location of color sequences. Concluding, the paintings and maps that were selected and examined in detail support the effect of painting on maps, without implying that it is intentional.
Respect in the Eyes of Non-Urban Elders: Using Qualitative Interviews to Distinguish Community Elders’ Perspective of Respect in General and Healthcare Services
Authors: Tseng Yu-Hsien , Li Yu-Ling , Luu Shyuemeng , Luh Dih-Ling
Published: February 2022

This study aimed to describe the connotation of respect for community elders in daily situations, and discuss the elderly’s views on respect for healthcare services. A qualitative research design was conducted to interview elders from a non-urban area in Changhua, Taiwan. Study sites were Lukang and Ershui. A total of 52 people were interviewed, with an average age of 75 years old. Based on Grounded theory, the thematic analysis method was used to analyze data. This study found that respect from the perspective of the elderly can be divided into three categories: (1) verbal expression, (2) non-verbal behavior, and (3) behavior combined with appropriate language. We found that elders use the performance of healthcare service providers to discuss respect in the field of healthcare services. Respect can also be shown in the physical environment in healthcare settings. This study found that, for the community elders, respect is an individual’s subjective feelings regarding the process of interpersonal interaction. Compared to daily life, the respect of the elderly for the healthcare setting has increased the element of the environment. In addition, it was found that elderly people have lower expectations and requirements for respect in healthcare settings.
N-Acetylcysteine and Aripiprazole Improve Social Behavior and Cognition and Modulate Brain BDNF Levels in a Rat Model of Schizophrenia
Authors: Rogóż Zofia , Kamińska Kinga , Lech Marta Anna , Lorenc-Koci Elżbieta
Published: February 2022

Treatment of negative symptoms and cognitive disorders in patients with schizophrenia is still a serious clinical problem. The aim of our study was to compare the efficacy of chronic administration of the atypical antipsychotic drug aripiprazole (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl] butoxy}-3,4-dihydro-2(1H)-quinolinone; ARI) and the well-known antioxidant N-acetylcysteine (NAC) both in alleviating schizophrenia-like social and cognitive deficits and in reducing the decreases in the levels of the brain-derived neurotrophic factor (BDNF) in the prefrontal cortex (PFC) and hippocampus (HIP) of adult Sprague-Dawley rats, that have been induced by chronic administration of the model compound L-buthionine-(S, R)-sulfoximine (BSO) during the early postnatal development (p5–p16). ARI was administered at doses of 0.1 and 0.3 mg/kg while NAC at doses of 10 and 30 mg/kg, alone or in combination. Administration of higher doses of ARI or NAC alone, or co-treatment with lower, ineffective doses of these drugs significantly improved social and cognitive performance as assessed in behavioral tests. Both doses of NAC and 0.3 mg/kg of ARI increased the expression of BDNF mRNA in the PFC, while all doses of these drugs and their combinations enhanced the levels of BDNF protein in this brain structure. In the HIP, only 0,3 mg/kg ARI increased the levels of both BDNF mRNA and its protein. These data show that in the rat BSO-induced neurodevelopmental model of schizophrenia, ARI and NAC differently modulated BDNF levels in the PFC and HIP.
Distinct Cold Acclimation of Productivity Traits in Arabidopsis thaliana Ecotypes
Authors: Demmig-Adams Barbara , Polutchko Stephanie K. , Baker Christopher R. , Stewart Jared J. , Adams III William W.
Published: February 2022

Improvement of crop climate resilience will require an understanding of whole-plant adaptation to specific local environments. This review places features of plant form and function related to photosynthetic productivity, as well as associated gene-expression patterns, into the context of the adaptation of Arabidopsis thaliana ecotypes to local environments with different climates in Sweden and Italy. The growth of plants under common cool conditions resulted in a proportionally greater emphasis on the maintenance of photosynthetic activity in the Swedish ecotype. This is compared to a greater emphasis on downregulation of light-harvesting antenna size and upregulation of a host of antioxidant enzymes in the Italian ecotype under these conditions. This differential response is discussed in the context of the climatic patterns of the ecotypes’ native habitats with substantial opportunity for photosynthetic productivity under mild temperatures in Italy but not in Sweden. The Swedish ecotype’s response is likened to pushing forward at full speed with productivity under low temperature versus the Italian ecotype’s response of staying safe from harm (maintaining redox homeostasis) while letting productivity decline when temperatures are transiently cold. It is concluded that either strategy can offer directions for the development of climate-resilient crops for specific locations of cultivation.
Modulation of miR-204 Expression during Chondrogenesis
Authors: Dalle Carbonare Luca , Bertacco Jessica , Minoia Arianna , Cominacini Mattia , Bhandary Lekhana , Elia Rossella , Gambaro Giovanni , Mottes Monica , Valenti Maria Teresa
Published: February 2022

RUNX2 and SOX9 are two pivotal transcriptional regulators of chondrogenesis. It has been demonstrated that RUNX2 and SOX9 physically interact; RUNX2 transactivation may be inhibited by SOX9. In addition, RUNX2 exerts reciprocal inhibition on SOX9 transactivity. Epigenetic control of gene expression plays a major role in the alternative differentiation fates of stem cells; in particular, it has been reported that SOX9 can promote the expression of miRNA (miR)-204. Our aim was therefore to investigate the miR-204-5p role during chondrogenesis and to identify the relationship between this miR and the transcription factors plus downstream genes involved in chondrogenic commitment and differentiation. To evaluate the role of miR-204 in chondrogenesis, we performed in vitro transfection experiments by using Mesenchymal Stem Cells (MSCs). We also evaluated miR-204-5p expression in zebrafish models (adults and larvae). By silencing miR-204 during the early differentiation phase, we observed the upregulation of SOX9 and chondrogenic related genes compared to controls. In addition, we observed the upregulation of COL1A1 (a RUNX2 downstream gene), whereas RUNX2 expression of RUNX2 was slightly affected compared to controls. However, RUNX2 protein levels increased in miR-204-silenced cells. The positive effects of miR204 silencing on osteogenic differentiation were also observed in the intermediate phase of osteogenic differentiation. On the contrary, chondrocytes’ maturation was considerably affected by miR-204 downregulation. In conclusion, our results suggest that miR-204 negatively regulates the osteochondrogenic commitment of MSCs, while it positively regulates chondrocytes’ maturation.
Whole Genome Analysis of 335 New Bacterial Species from Human Microbiota Reveals a Huge Reservoir of Transferable Antibiotic Resistance Determinants
Authors: Khabthani Sami , Rolain Jean-Marc , Merhej Vicky
Published: February 2022

Background: The emergence and diffusion of strains of pathogenic bacteria resistant to antibiotics constitutes a real public health challenge. Antibiotic resistance genes (ARGs) can be carried by both pathogenic and non-pathogenic bacteria, including commensal bacteria from the human microbiota, which require special monitoring in the fight against antimicrobial resistance. Methods: We analyzed the proteomes of 335 new bacterial species from human microbiota to estimate its whole range of ARGs using the BLAST program against ARGs reference databases. Results: We found 278 bacteria that harbor a total of 883 potential ARGs with the following distribution: 264 macrolides-lincosamides-streptogramin, 195 aminoglycosides, 156 tetracyclines, 58 β-lactamases, 58 fosfomycin, 51 glycopeptides, 36 nitroimidazoles, 33 phenicols and 32 rifamycin. Furthermore, evolutionary analyses revealed the potential horizontal transfer with pathogenic bacteria involving mobile genetic elements such as transposase and plasmid. We identified many ARGs that may represent new variants in fosfomycin and β-lactams resistance. Conclusion: These findings show that new bacterial species from human microbiota should be considered as an important reservoir of ARGs that can be transferred to pathogenic bacteria. In vitro analyses of their phenotypic potential are required to improve our understanding of the functional role of this bacterial community in the development of antibiotic resistance.