bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Profiles of IncRNA and mRNA Highlight the Role of Ferroptosis in Chronic Neuropathic Pain With Memory Impairment
Authors: Tang Yidan , Liu Changliang , Zhu Tao , Chen Hai , Sun Yalan , Zhang Xueying , Zhao Qi , Wu Jiahui , Fei Xuejie , Ye Shixin , Chen Chan
Published: April 2022

Background: Chronic neuropathic pain is commonly associated with memory loss, which increases the risk of dementia, lowers life quality and spending. On the other hand, the molecular processes are unknown, and effective therapies have yet to be discovered. Long non-coding RNAs (lncRNAs) are emerging potential therapeutic targets for chronic pain, but their role in chronic pain-induced memory impairment is unknown.

Methods: We established a CCI-induced memory impairment rat model. To investigate and validate the gene expression alterations in the hippocampus of CCI-induced memory impairment, we used RNA-Seq, bioinformatics analysis, qRT-PCR, western blot, immunostaining, Nissl staining, and Diaminobenzidine-enhanced Perls’ stain.

Results: CCI rats displayed long-term memory deficits in the Y maze and novel objective recognition tests, and chronic mechanical and thermal pain hypersensitivity in the hind paws. We found a total of 179 differentially expressed mRNAs (DEmRNAs) (81 downregulated and 98 upregulated) and 191 differentially expressed long noncoding RNAs (DElncRNAs) (87 downregulated and 105 upregulated) between the hippocampus CA1 of CCI-induced memory impairment model and the sham control, using RNA-Seq expression profiles. The most enriched pathways involving oxidation and iron metabolism were explored using a route and function pathway analysis of DEmRNAs and DElncRNAs. We also discovered that ATF3 was considerably overexpressed in the hippocampal CA1 area, and gene markers of ferroptosis, such as GPX4, SLC7A11, SLC1A5, and PTGS2, were dysregulated in the CCI-induced memory impairment paradigm. Furthermore, in the hippocampus CA1 of CCI-induced memory impairment, lipid peroxidation and iron overload were considerably enhanced. Fer-1 treatment reversed ferroptosis damage of CCI with memory impairment model. Finally, in CCI-induced memory impairment, a competing RNA network analysis of DElncRNAs and DEmRNAs was performed to investigate the putative regulatory link of DElncRNAs on DEmRNAs via miRNA sponging.

Conclusion: Using RNA-Seq, we created a genome-wide profile of the whole hippocampus of a rat model of CCI-induced memory impairment. In the hippocampus, pathways and function analyses revealed numerous intriguing genes and pathways involved in ferroptosis and memory impairment in response to chronic pain stress. As a result, our research may aid in the identification of potential and effective treatments for CCI-induced memory impairment.
Intense Laser Pulse Interaction With Graphene and Graphene Ribbons
Authors: Faisal F. H. M.
Published: April 2022

In this work we investigate quantum mechanically the interaction of an intense ultrashort laser pulse with the graphene monolayer as well as with the armchair graphene ribbons of different widths. We consider a tight binding (TB) Hamiltonian of the monolayer graphene and give two rules for deriving the dispersion relations of the armchair graphene ribbons of any width, N, from the TB eigenvalues of the monolayer. The band structure of the monolayer and the armchair ribbons of different widths are discussed with illustrations. The time-dependent wavefunctions of the systems and the expectation values of interest are determined by solving the coupled equations of the band amplitudes “exactly” (numerically). First, simulations are made for the population excitation in the conduction band (CB) from the valence band (BV), the VB-CB interband correlation (or “coherence”), the intraband, the interband and the total currents in the monolayer graphene. The graphene currents are compared with the corresponding currents induced in an armchair ribbon (width, N = 3). The change from the 2D monolayer to the 1D ribbon shows a remarkable transition of the dominance of the intraband current that leads to a near steady total current in the monolayer, to a dominance of the interband current in the ribbon that induces an oscillatory current in the ribbon beyond the pulse duration. The difference observed might be a combined effect of the “confinement” in one dimention and a finite band-gap minimum in the case of the ribbon. However, this transition should be further investigated for better clarity. A brief comparison of the radiation spectra emitted from the monolayer and from the ribbon is also made. They show a grossly similar structure and a relative insensitivity with respect to the detailed structure of the targets chosen. This might be due to the dominance of virtual continuum-continuum transitions, to and from the bands states, that lie behind the fundamental quantum process of high harmonic emissions. Lastly, the dependence of the charge currents, induced in a ribbon of unit width (N = 1), on the carrier-envelope-phase (CEP) of the incident laser pulse is investigated. It is seen that the shape of the main part of the current produced in the ribbon can be fully reversed by changing the CEP of the ultrashort laser pulse from 0 to π. More generally, it is suggested that the pulse shape of the charge carriers in the ribbon could be designed by similarly tailoring the form of the vector potential of the incident laser pulse.
Analyzing the Macro-Economic and Employment Implications of Ambitious Mitigation Pathways and Carbon Pricing
Authors: Fragkos Panagiotis , Fragkiadakis Kostas
Published: April 2022

The recent EU Green Deal puts forward ambition climate targets aiming to make the EU the first climate neutral continent by mid-century while ensuring a just transition. This requires a large-scale transformation of the EU and global energy and economic systems induced by both regulatory and market-based policies, in particular carbon pricing. Macro-economic models currently used for the analysis of climate policy impacts need improvements to consistently capture the transition dynamics and challenges. The study presents the methodological enhancements realized in general equilibrium model GEM-E3-FIT (including enhanced energy system representation, low-carbon innovation, clean energy markets, technology progress, policy instruments) to improve the simulation of the impacts of ambitious climate policies. The model-based analysis shows that high carbon pricing has limited negative impacts on the EU GDP and consumption, while leading to an economy transformation toward a capital-intensive structure triggered by increased investment in low-carbon technologies and energy efficient equipment. Global decarbonization to achieve the well-below 2°C goal of the Paris Agreement will modestly impact total employment, but its effects are pronounced on specific sectors which are impacted either negatively (e.g., supply of fossil fuels, energy intensive industries) or positively by creating additional jobs (e.g., low-carbon manufacturing, electricity sector).
Biomarkers of Cardiac Injury, Renal Injury, and Inflammation Are Strong Mediators of Sex-Associated Death in COVID-19
Authors: Lumish Heidi S. , Kim Eunyoung , Selvaggi Caitlin , Cao Tingyi , Gupta Aakriti , Foulkes Andrea S. , Reilly Muredach P.
Published: April 2022

Background

Studies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality.

Methods

Patients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine.

Results

In the CUIMC/NYPH cohort (n = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, p = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine (p < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer.

Conclusions

This study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases.
Risk of Stroke Among Different Metabolic Obesity Phenotypes: A Systematic Review and Meta-Analysis
Authors: Meng Miaomiao , Guo Yixin , Kuang Zhuoran , Liu Lingling , Cai Yefeng , Ni Xiaojia
Published: April 2022

Background and Purpose

Overweight/obesity is a modified risk factor for stroke. This systematic review and meta-analysis aimed to assess the impact of different obesity phenotypes on stroke risk in adults.

Methods

The PubMed, Embase, and Cochrane Library databases were searched from their inception to 7 March 2021 to identify the prospective cohort studies investigating stroke risk among different metabolic overweight/obesity phenotypes. The methodological quality of the included studies was evaluated using the Newcastle–Ottawa Scale. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

A total of eleven prospective cohorts (n = 5,609,945 participants) were included in the systematic review, nine of which were included in the meta-analysis. All metabolically unhealthy phenotypes had a higher risk of stroke than the metabolically healthy normal-weight phenotypes, including metabolically unhealthy normal weight (HR = 1.63, 95% CI: 1.41–1.89, I2 = 89.74%, n = 7 cohort studies, 1,042,542 participants), metabolically unhealthy overweight (HR = 1.94, 95% CI: 1.58–2.40, I2 = 91.17%, n = 4 cohort studies, 676,166 participants), and metabolically unhealthy obese (HR = 1.99, 95% CI: 1.66–2.40, I2 = 93.49%, n = 6 cohort studies, 1,035,420 participants) phenotypes. However, no risk of stroke was observed in the populations with metabolically healthy overweight (MHOW) (HR = 1.07, 95% CI: 1.00–1.14, I2 = 69.50%, n = 5 studies, 4,171,943 participants) and metabolically healthy obese (MHO) (HR = 1.07, 95% CI: 0.99–1.16, I2 = 54.82%, n = 8 studies, 5,333,485 participants) phenotypes. The subgroup analyses for the MHO studies suggested that the risk of stroke increased only when the MHO participants were mainly females, from North America, and when the World Health Organization standard was applied to define obesity. In the subgroup analysis of the risk of stroke in MHOW, a longer follow-up duration was also associated with a higher risk of stroke.

Conclusion

The risk of stroke increase for all metabolically unhealthy phenotypes irrespective of the body mass index (BMI). The associated risk of stroke with metabolic health but high BMI shows substantial heterogeneity, which requires future research considering the impact of sex and transition of the metabolic status on the risk of stroke.

Systematic Review Registration

The study protocol was prospectively registered in PROSPERO (No. CRD42021251021).
Perceptions of Assessment: An Interview Study of Participants’ Perceptions of Being Assessed in Swedish Adult Education Colleges
Authors: Jönsson Anders
Published: April 2022

Assessments have been shown to influence students’ learning and motivation. To avoid negative consequences, different strategies have been proposed, such as making a more distinct separation between assessments for summative and formative purposes. In this way, situations are created that are exclusively formative, where students may focus on learning without worrying about test scores or grades. This study has investigated perceptions of such a context, where grading is kept apart from assessment for formative purposes. Semi-structured interviews have been performed with 19 participants at five so called “adult education colleges.” At these colleges, students’ “grades” are determined as a joint decision by all the teachers together at the end of the academic year, and no grades are communicated to the participants beforehand. Data from the interviews was analyzed with qualitative thematic analysis, identifying four themes relating to participants’ perceptions of assessment. Findings suggest that participants perceive that there is a lack of feedback on overall progress, limiting their possibilities to regulate their learning. Findings also suggest that the participants do not always know when, or on what grounds, they are being summatively assessed, leading to less productive study strategies. The consequences of this particular assessment context thereby seem similar in several respects, as compared to those reported from the ordinary Swedish school system, even though the latter is greatly influenced by numerous summative assessment events.
Design and Analysis of a Resistive Sensor Interface With Phase Noise-Energy-Resolution Scalability for a Time-Based Resistance-to-Digital Converter
Authors: Seo Dong-Hyun , Chatterjee Baibhab , Scott Sean M. , Valentino Daniel J. , Peroulis Dimitrios , Sen Shreyas
Published: April 2022

This article presents the design and analysis of a resistive sensor interface with three different designs of phase noise-energy-resolution scalability in time-based resistance-to-digital converters (RDCs), including test chip implementations and measurements, targeted toward either minimizing the energy/conversion step or maximizing bit-resolution. The implemented RDCs consist of a three-stage differential ring oscillator, which is current starved using the resistive sensor, a differential-to-single-ended amplifier, and digital modules and serial interface. The first RDC design (baseline) included the basic structure of time-based RDC and targeted low-energy/conversion step. The second RDC design (goal: higher-resolution) aimed to improve the rms jitter/phase noise of the oscillator with help of speed-up latches, to achieve high bit-resolution as compared to the first RDC design. The third RDC design (goal: process portability) reduced the power consumption by scaling the technology with the improved phase-noise design, achieving 1-bit better resolution as that of the second RDC design. Using time-based implementation, the RDCs exhibit energy-resolution scalability and consume a measured power of 861 nW with 18-bit resolution in design 1 in TSMC 0.35 μm technology (with 10 ms read-time, with one readout every second). Measurements of designs 2 and 3 demonstrate power consumption of 19.2 μW with 20-bit resolution using TSMC 0.35μm and 17.6 μW with 20-bit resolution using TSMC 0.18μm, respectively (both with 10 ms read-time, repeated every second). With 30 ms read-time, design 3 achieves 21-bit resolution, which is the highest resolution reported for a time-based ADC. The 0.35-μm time-based RDC is the lowest-power time-based ADC reported, while the 0.18-μm time-based RDC with speed-up latch offers the highest resolution. The active chip-area for all three designs is less than 1.1 mm2.
Thermal Management and Dynamic Performance of a Cooler Design for the Supercritical CO2 Turbine Shaft Cooling
Authors: Li Jun , Gurgenci Hal , Guan Zhiqiang , Li Jishun , Xue Yujun , Li Lun
Published: April 2022

This paper presents the results of a numerical study on a supercritical CO2 (SCO2) turboshaft cooling device by considering heat transfer and hydrodynamics. A micro-cooling device with a radius clearance of 50 micron and a nozzle diameter of 4 mm was designed and used to investigate the heat transfer characteristics of a micro-spacing impinging and gas film dynamics. Sixteen nozzles (N = 16) are equally spaced around the shaft in single or double rows. Investigations include journal speed- and eccentricity-dependent forward and cross-coupled force coefficients, and the effects of nozzle layouts and mass flow rate on the heat transfer efficiency. Analysis of the correlation coefficient shows that the gas density in the radial clearance is the dominant factor affecting the convective heat transfer performance, while the fluid velocity is a secondary factor. And the cooling efficiency (mass flow utilization rate) at low cooling pressure (ps < 0.7 MPa) is significantly greater than that at high cooling pressure (ps > 0.7 MP). In addition, considering the structure alone, a dual-row cooler exhibits a higher average Nusselt number, also registers a higher mass flow rate at the same pressure. Once the shaft is heated only one end, the difference in effectiveness between single- and dual-row cooling is not significant, so coolers with a single-row configuration should be preferred. Then, experimental values for the temperature of the heated rotor are provided under specific cooling airflow conditions. Dynamic analysis results show that the force coefficient of the single-row configuration is more dependent on the journal rotation speed and eccentricity ratio, and exhibits a negative direct stiffness coefficient at higher inlet pressure and journal rotation speed. Moreover, cross-coupled terms (stiffness coefficient) generally have a more explicit variation tendency than direct terms, and are more sensitive to changes in shaft speed and eccentricity. Small clearance cooling is a relatively complex technology aimed to improve heat dissipation efficiency in gas cooling devices while minimizing the effect of hydrodynamic pressure. Comparing the gas force coefficients of different journal speeds reveals a drastic increase in the effect of hydrodynamic pressure when the journal is eccentric. The cooler may be considered for operation with compliant support (such as bump foil) to generate additional damping and appropriately compensate for the eccentricity of the rotor.
Bald Eagle Search Algorithm for Parameter Identification of Proton Exchange Membrane Fuel Cell
Authors: Yang Bo , Li Danyang , Zeng Chunyuan , Han Yiming , Li Junhui
Published: April 2022

A precise and reliable proton exchange membrane fuel cell (PEMFC) parameter identification performs an essential function in simulation analysis, optimal control, and performance research of actual PEMFC systems. Unfortunately, achieving an accurate, efficient, and stable parameter identification can sometimes be problematic for traditional optimization methods, owing to its strong coupling, inherent nonlinear, and multi-variable characteristics. Therefore, an advanced bald eagle search (BES) algorithm is designed to dependably identify the unknown parameters of the electrochemical PEMFC model in this work. For evaluating and analyzing the overall optimization performance of the BES comprehensively, it is compared with the genetic algorithm (GA) based on MATLAB under three cases. According to the simulation results, the optimum root mean square error (RMSE) achieved by BES is 96.27% less than that achieved by GA in parameter identification, which fully indicates that the precision, accuracy, and stability of the optimization results can be remarkably improved via the application of BES.
Does Qatar Face a Trade-off Between Economic Growth and CO2 Emissions?
Authors: Shannak Sa'd , Contestabile Marcello
Published: April 2022

Driven by the development of the oil and gas sector, Qatar has made remarkable economic achievements over the past few decades. However, Qatar’s high dependence on fossil fuels has resulted in a rapid increase in its CO2 emissions. As such, the country may be facing a trade-off between achieving continued economic growth and carbon emissions reductions. This study empirically analyzes the relationship between economic growth and carbon emissions in Qatar, using annual data of income and CO2 emissions from 1970 to 2018. The analysis was conducted by employing the Environmental Kuznets Curve (EKC) framework and the Decoupling Index (DI) approach. The EKC was evaluated using the Fully Modified Ordinary Least Squares cointegration method. Additionally, a robustness check was conducted by Canonical Cointegrating Regression (CCR) cointegration method to confirm the results attained by FMOLS. The findings support the evidence of an N-shaped relationship and suggest that the country is currently undergoing expanding relative decoupling. Although findings show that Qatar’s per capita emissions have been declining over the last few years, additional measures such as energy conservation, energy efficiency and renewable energy are required to allow cost-effective carbon emission reductions.
How to Improve Environment Performance? The Comparison of Stakeholder Perceptions on How to Improve Air Quality in China
Authors: Liu Hehe
Published: April 2022

The air quality and carbon neutrality strategies in China has attracted the growing concern of multiple stakeholders. Through face-to-face surveys conducted in five major cities in North China, we compared the stakeholders’ perceptions. Our research reveals conflicting perceptions among stakeholders. On the one hand, local authorities and academics prefer to focus on market-based regulation to prevent air pollution. Enterprise managers, however, do not want to be regulated. On the other hand, social groups expect more information about air pollution to be released, but local authorities do not see releasing that information as a top priority. These differences of perceptions can actually be useful in terms of policymaking.
Threshold Effects of Urban Population Size and Industrial Structure on CO2 Emissions in China
Authors: Zhao Xiaojing , Xi Yanling
Published: April 2022

Population and industry are closely related to CO2 emissions in Cities. However, few studies have explored the joint influence of population size and industrial structure on CO2 emissions. This paper examined the nonlinear influence of population size and industrial structure on CO2 emissions by using a threshold-STIRPAT model with the latest available data in 2001–2017 from 255 cities in China. Results indicated that the promotion effect of urban population size on CO2 emissions increased in the first two stages and then decreased in the third stage when the industrial structure exceeded the threshold value of 1.22. Meanwhile, the industrial structure had a positive impact on CO2 emissions if the urban population was less than 1.38 million. However, the previous promotional effect became an inhibitory effect when the urban population exceeded 1.38 million. According to the above findings, it is necessary to find a reasonable match between urban population size and industrial structure. Specifically, China should formulate differentiated urban population policies in cities with different industrial structures. In addition, for cities with a population size of more than 1.38 million, adjusting the industrial structure to give priority to the tertiary industry will be an effective way to reduce CO2 emissions.
A Comparative Analysis of the Chloroplast Genomes of Four Polygonum Medicinal Plants
Authors: Guo Shuai , Liao Xuejiao , Chen Shiyu , Liao Baosheng , Guo Yiming , Cheng Ruiyang , Xiao Shuiming , Hu Haoyu , Chen Jun , Pei Jin , Chen Yangjin , Xu Jiang , Chen Shilin
Published: April 2022

Polygonum is a generalized genus of the Polygonaceae family that includes various herbaceous plants. In order to provide aid in understanding the evolutionary and phylogenetic relationship in Polygonum at the chloroplast (cp) genome-scale level, we sequenced and annotated the complete chloroplast genomes of four Polygonum species using next-generation sequencing technology and CpGAVAS. Then, repeat sequences, IR contractions, and expansion and transformation sites of chloroplast genomes of four Polygonum species were studied, and a phylogenetic tree was built using the chloroplast genomes of Polygonum. The results indicated that the chloroplast genome construction of Polygonum also displayed characteristic four types of results, comparable to the published chloroplast genome of recorded angiosperms. The chloroplast genomes of the four Polygonum plants are highly consistent in genome size (159,015 bp–163,461 bp), number of genes (112 genes, including 78 protein-coding genes, 30 tRNA genes, and 4 rRNA genes), gene types, gene order, codon usage, and repeat sequence distribution, which identifies the high preservation among the Polygonum chloroplast genomes. The Polygonum phylogenetic tree was recreated by a full sequence of the chloroplast genome, which illustrates that the P. bistorta, P. orientale, and P. perfoliatum are divided into the same branch, and P. aviculare belongs to Fallopia. The precise system site of lots base parts requires further verification, but the study would provide a basis for developing the available genetic resources and evolutionary relationships of Polygonum.
FGFR2–BRD4 Axis Regulates Transcriptional Networks of Histone 3 Modification and Synergy Between Its Inhibitors and PD-1/PD-L1 in a TNBC Mouse Model
Authors: Lei Josh Haipeng , Zhang Lei , Wang Zhenyi , Peltier Raoul , Xie Yusheng , Chen Ganchao , Lin Shiqi , Miao Kai , Deng Chu-Xia , Sun Hongyan
Published: April 2022

Epigenetic reprogramming is an independent mode of gene expression that often involves changes in the transcription and chromatin structure due to tumor initiation and development. In this study, we developed a specifically modified peptide array and searched for a recognized epigenetic reader. Our results demonstrated that BRD4 is not only an acetylation reader but of propionylation as well. We also studied the quantitative binding affinities between modified peptides and epigenetic regulators by isothermal titration calorimetry (ITC). Furthermore, we introduced the Fgfr2-S252W transgenic mouse model to confirm that this acetylation is associated with the activation of c-Myc and drives tumor formation. Targeted disruption of BRD4 in Fgfr2-S252W mouse tumor cells also confirmed that BRD4 is a key regulator of histone 3 acetylation. Finally, we developed a tumor slice culture system and demonstrated the synergy between immune checkpoint blockade and targeted therapy in triple-negative breast cancer (TNBC). These data extend our understanding of epigenetic reprogramming and epigenetics-based therapies.
Chagas Disease Expands Its Epidemiological Frontiers From Rural to Urban Areas
Authors: Alarcón de Noya Belkisyole , Díaz-Bello Zoraida , Ruiz-Guevara Raiza , Noya Oscar
Published: April 2022

The infection with the hemoflagellate parasiteTrypanosoma cruzioriginates from America where the wildlife cycle remains to alternate between mammals and hematophagous triatomines. Transmission through contamination of the bite site by vector feces containing highly infectious forms of parasite or direct ingestion ofT. cruzi-infected triatomines appear to be the dominant transmission mechanisms. Man joins the transmission when he enters this wild environment or takes the leaves of palms carrying vectors to build houses. Rural Chagas disease develops associated with populations of low economic resources, with infection and reinfection of vector bites since childhood, and the consequent evolution toward chronic cases in adults, when there is little therapeutic benefit to infected people. The progressive migration of people from rural to urban areas and the adaptation of vectors to the peripheries of cities due to displacement caused by deforestation or urbanization that has favored the presence of enzootic cycles withPanstrongylus geniculatusas the most widely distributed species and mammals (synanthropic and domestic) allow vector transmission by ingestion of food contaminated with excrements containing infectious trypomastigotes as the dominant transmission mechanism in the urban environment. Human-to-human transmissions through vertical mother–child infection, transfusions, organ transplants, and the possibility of sexual transmission, transform the epidemiology and the clinical evolution of Chagas disease in the urban environment. Vectors of American trypanosomiasis are no longer restricted to the endemic area, but its presence has been demonstrated in nonendemic areas of the United States, Asia, and other latitudes. The worldwide plague of bedbugs (Cimex lectularius) threatens the possibility of expansion of transmission since they are vectors susceptible to infection, transmission to mammals, trans-stadial penetration, and not being affected byT. cruziinfection at least experimentally. These factors, added to the presence of an unknown number of migrating Latin American asymptomatic carriers together with the presence of triatomines in other continents, have initiated the globalization of a pathology originating in the American continent. Only with an integrative approach, based on new and better tolerated and efficient drugs, vaccines and residual action insecticides, all of them included in an epidemiological surveillance program.
Intrapleural Perfusion With Staphylococcal Enterotoxin C for Malignant Pleural Effusion: A Clustered Systematic Review and Meta-Analysis
Authors: Jiang Hong , Yang Xue-Mei , Wang Cheng-Qiong , Xu Jiao , Huang Jun , Feng Ji-Hong , Chen Xiao-Fan , Chen Kai , Zhan Lin , Xiao Xue , Xiao Zheng
Published: April 2022

Introduction

The staphylococcal enterotoxin C (SEC), a commercially available bio-product from Staphylococcus aureus (S. aureus), has been widely used to control MPE.

Objectives

We designed and performed a new systematic review (SR) and meta-analysis to clarify the perfusion protocols with SEC, determine their clinical effectiveness and safety, and reveal the indication and optimum usage for achieving the desired responses.

Methodology

All randomized controlled trials (RCTs) about SEC for MPE were collected from electronic databases (from inception until July 2021), and clustered into multiple logical topics. After evaluating their methodological quality, we pooled the data from each topic using the meta-analysis or descriptive analysis, and summarized the evidence quality using the grading of recommendation assessment, development, and evaluation (GRADE) approach.

Results

All 114 studies were clustered into SEC perfusion alone or plus chemical agents. The SEC alone showed a better complete response (CR), a lower pleurodesis failure, and adverse drug reactions (ADRs), and a higher fever than cisplatin (DDP) alone. The SEC and chemical agents developed 10 perfusion protocols. Among them, only SEC and DDP perfusion showed a better CR, a lower failure, disease progression and ADRs, and a higher fever than DDP alone. The SEC (100–200 ng per time, one time a week for one to four times) with DDP (30–40 mg, or 50–60 mg each time) significantly improved clinical responses for patients with moderate to large volume, Karnofsky performance status (KPS) scores ≥40, ≥50, or ≥60, and anticipated survival time (AST) ≥2 or 3 months. Most results were moderate to low quality.

Conclusion

Current pieces of evidence indicate that super-antigen SEC is a pleurodesis agent, which provides an attractive alternative to existing palliative modalities for patients with MPE. Among 10 protocols, the SEC and DDP perfusion is a most commonly used, which shows a significant improvement in clinical responses with low ADRs. These findings also provide a possible indication and optimal usage for SEC and DDP perfusion.
Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020
Authors: Xie Ming-Zhu , Chen Lin-Yi , Yang Yan-Na , Cui Yan , Zhang Si-Hui , Zhao Tian-Shuo , Zhang Wan-Xue , Du Juan , Cui Fu-Qiang , Lu Qing-Bin
Published: April 2022

Background

The changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China.

Method

From January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes.

Result

A total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world.

Conclusions

The predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.
Pathology Assessments of Multiple Organs in Fatal COVID-19 in Intensive Care Unit vs. Non-intensive Care Unit Patients
Authors: Zerbib Yoann , Guilain Nelly , Eymieux Sébastien , Uzbekov Rustem , Castelain Sandrine , Blanchard Emmanuelle , François Catherine , Chatelain Denis , Brault Clément , Maizel Julien , Roingeard Philippe , Slama Michel
Published: April 2022

Purpose

The objective of the present study was to provide a detailed histopathological description of fatal coronavirus disease 2019 (COVID 19), and compare the lesions in Intensive Care Unit (ICU) and non-ICU patients.

Methods

In this prospective study we included adult patients who died in hospital after presenting with confirmed COVID-19. Multiorgan biopsies were performed. Data generated with light microscopy, transmission electron microscopy (TEM) and RT-PCR assays were reviewed.

Results

20 patients were enrolled in the study and the main pulmonary finding was alveolar damage, which was focal in 11 patients and diffuse in 8 patients. Chronic fibrotic and inflammatory lesions were observed in 18 cases, with acute inflammatory lesions in 12 cases. Diffuse lesions, collapsed alveoli and dystrophic pneumocytes were more frequent in the ICU group (62.5%, vs. 25%; 63%, vs. 55%; 87.5%, vs. 54%). Acute lesions (82%, vs. 37.5%; p = 0.07) with neutrophilic alveolitis (63.6% vs. 0%, respectively; p = 0.01) were observed more frequently in the non-ICU group. Viral RNA was detected in 12 lung biopsies (60%) up to 56 days after disease upset. TEM detected viral particles in the lung and kidney biopsy samples up to 27 days after disease upset. Furthermore, abundant networks of double-membrane vesicles (DMVs, a hallmark of viral replication) were observed in proximal tubular epithelial cells.

Conclusion

Lung injury was different in ICU and non-ICU patients. Extrapulmonary damage consisting in kidney and myocardial injury were more frequent in ICU patients. Our TEM experiments provided the first description of SARS-CoV-2-induced DMVs in kidney biopsy samples—a sign of intense viral replication in this organ.
Efficacy of Huangqi Injection in the Treatment of Hypertensive Nephropathy: A Systematic Review and Meta-Analysis
Authors: Xu ZhongChi , Qian LiChao , Niu RuGe , Yang Ying , Liu ChunLing , Lin Xin
Published: April 2022

Background

Huangqi injection (HQI) is the extract of Astragalus membranaceus (Fisch.) Bunge, which is widely used in the treatment of a variety of diseases in China. It is supposed to be an important adjuvant therapy for hypertensive nephropathy.

Objective

To evaluate the efficacy of HQI combined with antihypertensive drugs in the treatment of hypertensive nephropathy.

Materials and Methods

We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang Knowledge Service Platform (WanfangData), Chinese Biomedical Database (CBM), EMBASE, PubMed and Cochrane Library from their inception to April 23st, 2021. All studies were independently screened by two auditors according to the inclusion and exclusion criteria. Randomized controlled trials comparing HQI in combination with antihypertensive drugs vs. antihypertensive drugs alone were extracted.

Results

The meta-analysis included 15 studies involving 1,483 participants.The effect of HQI combined with antihypertensive drugs is better than that of antihypertensive drugs alone in regulating hypertensive nephropathy for reducing 24-h urinary total protein (24 h UTP) [WMD=-0.29, 95% CI (−0.40, −0.18), P = 0.000], microalbuminuria (mALB) [WMD = −17.04, 95% CI (−23.14, −10.94), P = 0.000], serum creatinine (SCr) [WMD = −40.39, 95% CI (−70.39, −10.39), P = 0.008], systolic blood pressure (SBP) [WMD = −9.50, 95% CI (−14.64, −4.37), P = 0.000], diastolic blood pressure (DBP) [WMD = −4.588, 95% CI (−6.036, −3.140), P = 0.000], cystatin-C (Cys-c) [WMD = −0.854, 95% CI (−0.99, −0.72), P = 0.000], blood urea nitrogen (BUN) [WMD = −4.155, 95% CI (−6.152, −2.157), P = 0.000].

Conclusion

The combination of HQI and antihypertensive drugs is more efficient in improving the related indexes of patients with hypertensive nephropathy than using antihypertensive drugs alone, and a moderate dose of HQI (no more than 30 mL) may benefit more. However, the quality of the methodology is low and the number of samples is small, the results need to be confirmed by more stringent randomized controlled trials.
Vitrectomy and All-Cause and Cause-Specific Mortality in Elderly Patients With Vitreoretinal Diseases: A Nationwide Cohort Study
Authors: Kim Yoon Jeon , Lee Ji Sung , Lee Yunhan , Lee Hun , Kim Jae Yong , Tchah Hungwon
Published: April 2022

Purpose

To determine the all-cause and cause-specific mortality in elderly patients with vitreoretinal diseases based on vitrectomy status.

Methods

Elderly patients (aged ≥ 60 years) diagnosed with vitreoretinal diseases between 2003 and 2012 using the Korean National Health Insurance Service-Senior cohort (2002–2015) were included in this nationwide population-based retrospective cohort study. The exposure of interest was vitrectomy, and information on mortality from patient inclusion until December 2015 was obtained. Cox regression modeling was used to assess the association between vitrectomy and mortality. An additional subgroup analysis was performed to investigate the effects of the underlying retinal disease characteristics and comorbidities on mortality.

Results

The study cohort included 152,283 patients (3,313 and 148,970 in the vitrectomy and non-vitrectomy groups, respectively). The adjusted model showed vitrectomy was associated with a decreased risk of pulmonary-cause mortality [hazard ratio (HR), 0.51; P < 0.001]; however, no association was observed for all-cause mortality (HR, 0.93; P = 0.325). Vitrectomy was associated with increased mortality risk (all-cause: HR, 1.26; P < 0.001 and vascular causes: HR, 1.41; P = 0.003) among patients with retinal vascular diseases and decreased mortality risk (all-cause: HR, 0.64; P < 0.001 and pulmonary causes: HR, 0.35; P = 0.011) among patients with macular diseases. There were significant interactions between age and vitrectomy with respect to all-cause mortality among patients with either vitreoretinal disease.

Conclusions

In elderly patients with retinal diseases, the vitrectomy group showed the lower mortality from pulmonary causes with no association for all-cause mortality.
Medical Student Experiences of Uncertainty Tolerance Moderators: A Longitudinal Qualitative Study
Authors: Stephens Georgina C. , Sarkar Mahbub , Lazarus Michelle D.
Published: April 2022

Introduction

Uncertainty tolerance (UT), a construct explicating individuals' response to perceived uncertainty, is increasingly considered a competency for effective medical practice. Lower UT among physicians is linked with negative outcomes, including less favorable attitudes toward patient-centered care, and increased burnout risk. Despite decades of research, as yet few have engaged methodological approaches aiming to understand the factors that may influence medical students' UT (so-called moderators). Such knowledge, though, could inform teaching practices for fostering learners' skills for managing uncertainties. Accordingly, we asked “What factors do medical students in their clinical years perceive as moderating their perceptions of, and responses to, uncertainty?”

Methods

We conducted a qualitative study with forty-one medical students in clinical years at an Australian medical school, with data collected throughout 2020. Participants described their experiences of uncertainty through both in-semester reflective diary entries (n= 230) and end of semester group or individual semi-structured interviews (n= 40). Data were analyzed using a team-based framework analysis approach.

Results

Four major themes of UT moderators were identified: (1) Individual factors, (2) Sociocultural factors, (3) Academic factors and (4) Reflective learning. Aspects of individual, sociocultural and academic factors were perceived as having either positive or negative influences on students' perceptions of uncertainty. By contrast, reflective learning was described as having a predominantly positive influence on students' perceptions of uncertainty, with students noting learning opportunities and personal growth afforded through uncertain experiences.

Conclusions

As healthcare becomes increasingly complex, a future challenge is equipping our medical students with strategies and skills to manage uncertainties. Our study identified multiple moderators of medical students' UT, key among them being reflective learning. We also identified UT moderators that contemporary and future medical educators may be able to harness in order to develop learner UT as a healthcare graduate attribute, especially through teaching practices such as intellectual candor. Further research is now required to evaluate the impact of proposed educational interventions, and to develop effective assessments of students' skills for managing clinical uncertainties.
Selective Maternal Seeding and Rearing Environment From Birth to Weaning Shape the Developing Piglet Gut Microbiome
Authors: Chen Wei , Ma Jingyun , Jiang Yiming , Deng Li , Lv Ning , Gao Jinming , Cheng Jian , Liang Juan Boo , Wang Yan , Lan Tian , Liao Xindi , Mi Jiandui
Published: April 2022

The acquisition and development of the mammalian microbiome early in life are critical to establish a healthy host-microbiome symbiosis. Despite recent advances in understanding microbial sources in infants, the relative contribution of various microbial sources to the colonization of the gut microbiota in pigs remains unclear. Here, we longitudinally sampled the microbiota of 20 sow-piglet pairs (three piglets per sow) reared under identical conditions from multiple body sites and the surrounding weaning environment from birth to 28 days postpartum (1,119 samples in total). Source-tracking analysis revealed that the contribution of various microbial sources to the piglet gut microbiome gradually changed over time. The neonatal microbiota was initially sparsely populated, and the predominant contribution was from the maternal vaginal microbiota that increased gradually from 69.0% at day 0 to 89.3% at day 3 and dropped to 0.28% at day 28. As the piglets aged, the major microbial community patterns were most strongly associated with the sow feces and slatted floor, with contributions increasing from 0.52 and 9.6% at day 0 to 62.1 and 33.8% at day 28, respectively. The intestinal microbial diversity, composition, and function significantly changed as the piglets aged, and 30 age-discriminatory bacterial taxa were identified with distinctive time-dependent shifts in their relative abundance, which likely reflected the effect of the maternal and environmental microbial sources on the selection and adaptation of the piglet gut microbiota. Overall, these data demonstrate that the vaginal microbiota is the primary source of the gut microbiota in piglets within 3 days after birth and are gradually replaced by the sow fecal and slatted floor microbiota over time. These findings may offer novel strategies to promote the establishment of exogenous symbiotic microbes to improve piglet gut health.
Diet Type Impacts Production Performance of Fattening Lambs by Manipulating the Ruminal Microbiota and Metabolome
Authors: Li Siqi , Du Meiyu , Zhang Chongyu , Wang Yun , Lee Yunkyoung , Zhang Guiguo
Published: April 2022

The pelleted total mixed ration (PTMR) has a positive effect on the productivity of fattening lambs. However, whether the beneficial effects are underpinned by altering the rumen microbiota and metabolome that remain unclear. This study aimed to investigate correlations among growth performance, ruminal microbiota, and ruminal metabolome of lambs fed PTMR diet. A total of 100 crossbred (Dorper sheep × Fine-wool sheep) ram lambs at 55 days of age with similar body weight (BW) (13.2 ± 0.5 kg) were randomly allocated to 10 pens that were fed either PTMR (PTMR group) or unpelleted total mixed ration (UPTMR group) with the same dietary ingredients and nutritional contents. The average daily gain (ADG) and average daily feed intake (ADFI) were determined during the 62-day experimental period and ruminal pH, volatile fatty acid (VFA) concentrations, microbiota, and metabolome in the rumen of the lambs were examined at the end of the experiment. Compared to those of the UPTMR group, the PTMR group had greater ADFI (P = 0.002), ADG (P = 0.003), and feed efficiency (G/F) (P < 0.05). Similarly, feeding PTMR increased the concentration of total VFA (TVFA) and the molar proportion of propionate, but decreased the proportion of butyrate and acetate to propionate ratio in the rumen of lambs compared to that in lambs from the UPTMR group (P < 0.05). In addition, the PTMR group demonstrated lowered alpha-diversity of the ruminal microbiota and enhanced the relative abundance of Fibrobacter (P < 0.05), Veillonellaceae (P < 0.05), and the abundance of Rikenellaceae (P = 0.064) in the rumen compared with those in the UPTMR group. Feeding lambs with PTMR significantly upregulated the metabolic pathways involving tryptophan, histidine, cysteine and methionine, β-alanine, tyrosine metabolisms, and steroid biosynthesis. Moreover, the abundance of the microbiota strongly correlated with the altered performance, ruminal VFA, metabolites, and metabolic pathways of lambs. Taken together, feeding PTMR shaped the ruminal microbiota of lambs with decreased diversity, while improving relative abundance of some specific microbes and upregulating certain growth-related metabolic pathways, which contributed to the augmented growth performance and G/F of fattening lambs. Thus, feeding PTMR to fattening lambs for superior production performance and G/F is recommended.