bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in the immune system persist after one year of convalescence in severe COVID-19 patients
Authors: Abarca-Zabalía Judith , González-Jiménez Adela , Calle-Rubio Myriam , López-Pastor Andrea R. , Fariña Tomás , Ramos-Acosta Carlos , Anguita Eduardo , Urcelay Elena , Espino-Paisán Laura
Published: February 2023

Introduction

Severe COVID-19 originates a myriad of alterations in the immune system during active disease, especially in the T and NK cell compartments, but several studies in the last year have unveiled some alterations that persist in convalescence. Although most of the studies follow the participants for a short recovery time, studies following patients up to three or six months still find alterations. We aimed at evaluating changes in the NK, T and B cell compartments after severe COVID-19 in participants with a median recovery time of eleven months.

Methods

Eighteen convalescent of severe COVID-19 (CSC), 14 convalescent of mild COVID-19 (CMC) and nine controls were recruited. NKG2A, NKG2C, NKG2D and the activating receptor NKp44 were evaluated in NKbright, NKdim and NKT subpopulations. In addition, CD3 and CD19 were measured and a basic biochemistry with IL-6 levels was obtained.

Results

CSC participants showed lower NKbright/NKdim ratio, higher NKp44 expression in NKbright subpopulations, higher levels of serum IL-6, lower levels of NKG2A+ T lymphocytes and a trend to a lower expression of CD19 in B lymphocytes compared to controls. CMC participants showed no significant alterations in the immune system compared to controls.

Conclusions

These results are concordant with previous studies, which find alterations in CSC weeks or months after resolution of the symptoms, and point to the possibility of these alterations lasting one year or more after COVID-19 resolution.
Improving sustainable practices in tuna purse seine fish aggregating device (FAD) fisheries worldwide through continued collaboration with fishers
Authors: Murua Jefferson , Moreno Gala , Dagorn Laurent , Itano David , Hall Martin , Murua Hilario , Restrepo Victor
Published: February 2023

More than a decade of bottom-up collaborative workshops and research with fishers from the principal tropical tuna purse seine fleets to reduce ecological impacts associated with the use of fish aggregating devices (FADs) has yielded novel improved sustainable fishing practices in all oceans. This integrative effort is founded on participatory knowledge-exchange workshops organized by the International Seafood Sustainability Foundation (ISSF), referred to as “ISSF Skippers Workshops”, where scientists, fishers, and key stakeholders examine and develop together ways and tools to minimize fishery impacts. Workshops organized since 2010 have reached fleet members in 23 countries across Asia, Africa, the Americas, Europe, and Oceania, with over 4,000 attendances, mostly skippers and crew, operating in the Indian, Atlantic, and Pacific oceans. Structured and continued open transparent discussions on ocean-specific options to minimize FAD associated bycatch, ghost fishing and marine pollution have produced an array of novel co-constructed solutions and a better understanding of ecosystem and fishery dynamics. Dedicated at sea research cruises in commercial purse seiners have enabled testing some of the ideas proposed in workshops. Results obtained were then communicated back to fishers for a double loop learning system resulting in solution refinement and/or adoption. Furthermore, fishers’ increased trust and stewardship have stimulated unprecedented large-scale science-industry research projects across oceans, such as multi-fleet biodegradable FAD trials, the adoption and widespread use of non-entangling FADs, and the development and adoption of best practices for the safe handling and release of vulnerable bycatch. This model of collaborative research is broadly applicable to other natural resource conservation fields. Support for long-term inclusive programs enabling harvesters to proactively collaborate in impact mitigation research contributes to improved scientific advice, voluntary compliance, and adaptive management for lasting sustainability trajectories.
Fatigue load model of orthotropic steel deck for port highway in China
Authors: Peng Xi , Wang Kunpeng , Yang Qiuwei , Xu Bin , Di Jin
Published: February 2023

Vehicle load is an important factor for the fatigue damage of the orthotropic steel decks. The traffic vehicles for port highway in China are mainly multi-axle container trucks, which show different characteristics from conventional highways. Based on the multi-period traffic flow data collected by weight-in-motion system of a bridge over the sea in Zhejiang, China, this study has investigated the traffic load characteristics of the port highway bridge. Eight typical vehicles of fatigue load spectrum are classified according to the number of axles and wheelbase. The distribution characteristics of the gross vehicle weight (GVW) and axle weights of typical vehicles are analyzed by lane. Depended on the equivalent fatigue damage principle, the vehicle load spectrum for fatigue evaluation of the port highway bridges is established. The results show that the average proportion of the trucks (weighing greater than 3 tons) in the total traffic flow is 73.2%, and trucks with more than four-axle accounted for 89.0%. Heavy vehicles are mainly concentrated on the outer lanes, and the probability of vehicles driving in the heavy lane increases with the increase of gross vehicle weight. The maximum equivalent gross vehicle weight is 62.5 tons, which appeared in V7 in the exiting island direction. The simplified fatigue vehicle model in the heavy lane for Chinese port highway bridges is proposed, based on the six-axle vehicle which contributed the most fatigue damage. The proposed fatigue load model can better represent the actual traffic load level of port highway bridges in China.
Recent advances in addressing the market failure of new antimicrobials: Learnings from NICE's subscription-style payment model
Authors: Schurer Marieke , Patel Renu , van Keep Marjolijn , Horgan Jake , Matthijsse Suzette , Madin-Warburton Matthew
Published: February 2023

Background

Antimicrobial resistance (AMR) is a growing threat to global health. With pathogenic bacteria inevitably becoming more resistant to existing antimicrobials, mortality and costs due to AMR will significantly increase over the next few decades if adequate action is not taken. A major challenge in addressing AMR is the lack of financial incentives for manufacturers to invest in developing new antimicrobials. This is partly because current approaches in health technology assessment (HTA) and standard modeling methods fail to capture the full value of antimicrobials.

Aim

We explore recent reimbursement and payment frameworks, particularly pull incentives, aimed to address the market failures in antimicrobials. We focus on the “subscription-style” payment model recently used in the UK and discuss the learnings for other European countries.

Methods

A pragmatic literature review was conducted to identify recent initiatives and frameworks between 2012 and 2021, across seven European markets. The National Institute for Health and Care Excellence (NICE) technology appraisals for cefiderocol and for ceftazidime with avibactam were reviewed to evaluate how the new UK model has been applied in practice and identify the key challenges.

Conclusion

The UK and Sweden are the first European countries to pilot the feasibility of implementing pull incentives through fully and partially delinked payment models, respectively. The NICE appraisals highlighted the complexity and large areas of uncertainty of modeling antimicrobials. If HTA and value-based pricing are part of the future in tackling the market failure in AMR, European-level efforts may be needed to overcome some of the key challenges.
Bio-removal of rare earth elements from hazardous industrial waste of CFL bulbs by the extremophile red alga Galdieria sulphuraria
Authors: Singh Anjali , Čížková Mária , Náhlík Vít , Mezricky Dana , Schild Dominik , Rucki Marian , Vítová Milada
Published: February 2023

In recent decades, a shift has been seen in the use of light-emitting diodes over incandescent lights and compact fluorescent lamps (CFL), which eventually led to an increase in wastes of electrical equipment (WEE), especially fluorescent lamps (FLs) and CFL light bulbs. These widely used CFL lights, and their wastes are good sources of rare earth elements (REEs), which are desirable in almost every modern technology. Increased demand for REEs and their irregular supply have exerted pressure on us to seek alternative sources that may fulfill this demand in an eco-friendly manner. Bio-removal of wastes containing REEs, and their recycling may be a solution to this problem and could balance environmental and economic benefits. To address this problem, the current study focuses on the use of the extremophilic red alga, Galdieria sulphuraria, for bioaccumulation/removal of REEs from hazardous industrial wastes of CFL bulbs and the physiological response of a synchronized culture of G. sulphuraria. A CFL acid extract significantly affected growth, photosynthetic pigments, quantum yield, and cell cycle progression of this alga. A synchronous culture was able to efficiently accumulate REEs from a CFL acid extract and efficiency was increased by including two phytohormones, i.e., 6-Benzylaminopurine (BAP - Cytokinin family) and 1-Naphthaleneacetic acid (NAA - Auxin family).
Olfactory function changes and the predictive performance of the Chinese Smell Identification Test in patients with mild cognitive impairment and Alzheimer's disease
Authors: Mi Yan , Ma Xiaojuan , Du Shan , Du Chengxue , Li Xiaobo , Tan Huihui , Zhang Jie , Zhang Qi , Shi Wenzhen , Zhang Gejuan , Tian Ye
Published: February 2023

Objectives

Olfactory disorder is one of the sensory features that reflects a decline in cognitive function. However, olfactory changes and the discernibility of smell testing in the aging population have yet to be fully elucidated. Therefore, this study aimed to examine the effectiveness of the Chinese Smell Identification Test (CSIT) in distinguishing individuals with cognitive decline from those with normal aging and to determine whether the patients with MCI and AD show changes in their olfactory identification abilities.

Methods

This cross-sectional study included eligible participants aged over 50 years between October 2019 and December 2021. The participants were divided into three groups: individuals with mild cognitive impairment (MCI), individuals with Alzheimer's disease (AD), and cognitively normal controls (NCs). All participants were assessed using neuropsychiatric scales, the Activity of Daily Living scale, and the 16-odor cognitive state test (CSIT) test. The test scores and the severity of olfactory impairment were also recorded for each participant.

Results

In total, 366 eligible participants were recruited, including 188 participants with MCI, 42 patients with AD, and 136 NCs. Patients with MCI achieved a mean CSIT score of 13.06 ± 2.05, while patients with AD achieved a mean score of 11.38 ± 3.25. These scores were significantly lower than those of the NC group (14.6 ± 1.57; P < 0.001). An analysis showed that 19.9% of NCs exhibited mild olfactory impairment, while 52.7% of patients with MCI and 69% of patients with AD exhibited mild to severe olfactory impairment. The CSIT score was positively correlated with the MoCA and MMSE scores. The CIST score and the severity of olfactory impairment were identified as robust indicators for MCI and AD, even after adjusting for age, gender, and level of education. Age and educational level were identified as two important confounding factors that influence cognitive function. However, no significant interactive effects were observed between these confounders and CIST scores in determining the risk of MCI. The area under the ROC curve (AUC) generated from the ROC analysis was 0.738 and 0.813 in distinguishing patients with MCI and patients with AD from NCs based on the CIST scores, respectively. The optimal cutoff for distinguishing MCI from NCs was 13, and for distinguishing AD from NCs was 11. The AUC for distinguishing AD from MCI was 0.62.

Conclusions

The olfactory identification function is frequently affected in patients with MCI and patients with AD. CSIT is a beneficial tool for the early screening of cognitive impairment among elderly patients with cognitive or memory issues.
The evolution of social media in nephrology education: A mini-review
Authors: Shankar Mythri , Sparks Matthew A.
Published: February 2023

Social media is defined as “a group of Internet-based applications that build on the ideological and technological foundations of Web 2.0, that allow the creation and exchange of user-generated content”. Social media can be used in medical education to enhance knowledge sharing among peer groups and the public in general. The internet revolutionized learning by allowing easier dissemination of knowledge that did not depend on printing and physical distribution of books, journals, or magazines. According to a report from 2018, 95% of students have access to smartphones and 45% are online at any given time. Social media platforms are powerful tools to spread knowledge by the way of stories, videos, and educational games. Both formal and informal learning can be achieved with the use of social media. The microblogging website Twitter has become a popular social media platform by many in medical education including the nephrology community. Twitter, for example, is used to build communities, discuss journal articles, inform the community of conferences, share infographics and visual abstracts of original research work. As an example, it can be difficult for women in nephrology to connect and travel to make a physical presence. The use of social media allows women to connect via webinars and Women in Nephrology (WIN) India live Twitter chats. Thus, social media can help facilitate networking and collaboration with nephrologists all over the world. Social media has limitations as well. Insensitive posts can have a detrimental effect on one’s career. A survey has shown that increased use of social media can contribute to addiction, anxiety, diminished self-esteem, and even depression. Hence, in order to effectively use social media to contribute positively to one’s career, we recommend considering the positive and negative aspects of social media.This review will discuss the various social media platforms and how they have been applied to nephrology education.
The carotid web: Current research status and imaging features
Authors: Liang Shixiao , Qin Peixin , Xie Lili , Niu Shanshan , Luo Junqi , Chen Fei , Chen Xiangmeng , Zhang Jie , Wang Guojie
Published: February 2023

The carotid web is commonly found in the carotid bulb or the beginning of the internal carotid artery. It presents as a thin layer of proliferative intimal tissue originating from the arterial wall and extending into the vessel lumen. A large body of research has proven that the carotid web is a risk factor for ischemic stroke. This review summarizes the current research status of the carotid web and focuses on its imaging presentation.
The opportunities and challenges for nutritional intervention in childhood cancers
Authors: Wang Kaiyue , Yang Tianyou , Zhang Yubin , Gao Xiang , Tao Ling
Published: February 2023

Diet dictates nutrient availability in the tumor microenvironment, thus affecting tumor metabolic activity and growth. Intrinsically, tumors develop unique metabolic features and are sensitive to environmental nutrient concentrations. Tumor-driven nutrient dependencies provide opportunities to control tumor growth by nutritional restriction or supplementation. This review summarized the existing data on nutrition and pediatric cancers after systematically searching articles up to 2023 from four databases (PubMed, Web of Science, Scopus, and Ovid MEDLINE). Epidemiological studies linked malnutrition with advanced disease stages and poor clinical outcomes in pediatric cancer patients. Experimental studies identified several nutrient dependencies (i.e., amino acids, lipids, vitamins, etc.) in major pediatric cancer types. Dietary modifications such as calorie restriction, ketogenic diet, and nutrient restriction/supplementation supported pediatric cancer treatment, but studies remain limited. Future research should expand epidemiological studies through data sharing and multi-institutional collaborations and continue to discover critical and novel nutrient dependencies to find optimal nutritional approaches for pediatric cancer patients.
Review of biomarkers for response to immunotherapy in HNSCC microenvironment
Authors: Chen Shaoshi , Yang Yifan , He Shizhi , Lian Meng , Wang Ru , Fang Jugao
Published: February 2023

Head and neck squamous cell carcinoma are one of the most common types of cancer worldwide. Although a variety of treatment methods such as surgery, radiotherapy, chemotherapy, and targeted therapy are widely used in diagnosing and treating HNSCC, the survival prognosis of patients has not been significantly improved in the past decades. As an emerging treatment approach, immunotherapy has shown exciting therapeutic effects in R/M HNSCC. However, the current screening methods are still insufficient, and there is a significant need for reliable predictive biomarkers for personalized clinical management and new therapeutic strategies. This review summarized the application of immunotherapy in HNSCC, comprehensively analyzed the existing bioinformatic studies on immunotherapy in HNSCC, evaluated the current methods of tumor immune heterogeneity and immunotherapy, and aimed to screen molecular markers with potential predictive significance. Among them, PD-1 has obvious predictive relevance as the target of existing immune drugs. Clonal TMB is a potential biomarker for HNSCC immunotherapy. The other molecules, including IFN-γ, CXCL, CTLA-4, MTAP, SFR4/CPXM1/COL5A1, TILs, CAFs, exosomes, and peripheral blood indicators, may have suggestive significance for tumor immune microenvironment and prognosis of immunotherapy.
Efficacy and safety of a biomarker-driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with RAS/BRAF wild type tumors at start of first line: The CAPRI 2 GOIM trial
Authors: Martini Giulia , Ciardiello Davide , Napolitano Stefania , Martinelli Erika , Troiani Teresa , Latiano Tiziana Pia , Avallone Antonio , Normanno Nicola , Di Maio Massimo , Maiello Evaristo , Ciardiello Fortunato
Published: February 2023

Background

Monoclonal antibodies targeting EGFR such as cetuximab or panitumumab represent a major step forward in the treatment of RAS wild type (WT) metastatic colorectal cancer (mCRC). Unfortunately, primary and acquired resistance mechanisms occur, with a huge percentage of patients succumbing to the disease. In the last years, RAS mutation has been identified as the main molecular driver that determine resistance to anti-EGFR monoclonal antibodies. Liquid biopsy analysis allows to a dynamic and longitudinal assessment of mutational status during mCRC disease and has provided important information on the use of anti-EGFR drugs beyond progression or as rechallenge strategy in patients with RAS WT tumors.

Methods

The phase II CAPRI 2 GOIM trial investigates the efficacy and safety of a bio-marker-driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with RAS/BRAF WT tumors at start of first line.

Discussion

The aim of the study is to identify patients with RAS/BRAF WT tumors defined as “addicted” to an-anti EGFR based treatment along three lines of therapy. Moreover, the trial will evaluate the activity of cetuximab re-introduction in combination with irinotecan as 3rd line therapy as rechallenge for patients that will be treated in second line with FOLFOX plus bevacizumab, having a RAS/BRAF mutant disease at progression after FOLFIRI plus cetuximab first line. A novel characteristic of this program is that the therapeutic algorithm will be defined at each treatment decision (first line, second line and third line) in a prospective fashion in each patient by a liquid biopsy assessment of RAS/BRAF status by a comprehensive 324 genes Foundation One Liquid assay (Foundation/Roche).

Trial registration

EudraCT Number: 2020-003008-15, ClinicalTrials.gov identifier: NCT05312398.
Analysis of Paediatric Clinical Trial Characteristics and Activity Over 23 Years—Impact of the European Paediatric Regulation on a Single French Clinical Research Center
Authors: Arnadottir Johanna , Luc François , Kaguelidou Florentia , Jacqz-Aigrain Evelyne ,   the Collaborative CIC1426 Investigator Group
Published: February 2023

As unlicensed or off-label drugs are frequently prescribed in children, the European Pediatric Regulation came into force in 2007 to improve the safe use of medicinal products in the pediatric population. This present report analyzes the pediatric research trials over 23 years in a clinical research center dedicated to children and the impact of regulation. The database of trial characteristics from 1998 to 2020 was analyzed. We also searched for differences between two periods (1998–2006 and 2007–2020) and between institutional and industrial sponsors during the whole period (1998–2020). A total of 379 pediatric trials were initiated at our center, corresponding to inclusion of 7955 subjects and 19448 on-site patient visits. The trials were predominantly drug evaluation trials (n = 278, 73%), sponsored by industries (n = 216, 57%) or government/non-profit institutions (n = 163, 43%). All age groups and most subspecialties were concerned. We noted an important and regular increase in the number of trials conducted over the years, with an increased number of multinational, industrially sponsored trials. Based on the data presented, areas of improvement are discussed: (1) following ethical and regulatory approval depending on the sponsor, the mean time needed for administrative and financial agreement, validation of trial procedures allowing trial initiation at the level of the center was 6.3 and 6.5 months (periods 1 and 2, respectively) and should be reduced, (2) availability of expert research teams remain insufficient, time dedicated to research attributed to physicians should be organized and recognition of research nurses is required. The positive impact of the European Pediatric Regulation highlights the need to increase the availability of trained research teams, organized within identified multicenter international pediatric research networks.
Burnout syndrome, doctor-patient relationship and family support of pediatric medical staff during a COVID-19 Local outbreak in Shanghai China: A cross-sectional survey study
Authors: Lyu Baiyu , Xu Meijia , Lu Lijuan , Zhang Xiaoying
Published: February 2023

Objectives

To explore burnout syndrome (BOS) incidence, doctor-patient relationship, and family support on pediatric medical staff in Shanghai comprehensive hospitals during a COVID-19 local outbreak.

Methods

A cross-sectional survey of pediatric medical staff from 7 comprehensive hospitals across Shanghai was conducted from March to July 2022. The survey included BOS, doctor-patient relationships, family support, and the related factors of COVID-19. The T-test, variance, the LSD-t test, Pearson's r correlation coefficient, and multiple regression analyses examined the data.

Results

Using Maslach Burnout Inventory-General Survey (MBI-GS), 81.67% of pediatric medical staff had moderate BOS, and 13.75% were severe. The difficult doctor-patient relationship was positively correlated with emotional exhaustion(EE), cynicism(Cy), and negatively with personal accomplishment(PA). When medical staff need help, the greater the support provided by the family, the lower the EE and CY, and the higher the PA.

Conclusion

“In our study, the pediatric medical staff in Shanghai comprehensive hospitals had significant BOS during a COVID-19 local outbreak.” We provided the potential steps that can be taken to reduce the increasing rate of BOS in pandemics. These measures include increased job satisfaction, psychological support, maintaining good health, increased salary, lower intent to leave the profession, regularly carrying out COVID-19 prevention training, improving doctor-patient relations, and strengthening family support.
Transcriptome sequencing of facial adipose tissue reveals alterations in mRNAs of hemifacial microsomia
Authors: Liu Bingyang , Liu Wei , Zhao Shanbaga , Ma Lunkun , Zang Tianying , Huang Changjin , Shu Kaiyi , Gao Hengbin , Tang Xiaojun
Published: February 2023

Hemifacial microsomia (HFM) is a common congenital malformation of the craniofacial region, including mandibular hypoplasia, microtia, facial palsy and soft tissue deficiencies. However, it remains unclear which specific genes are involved in the pathogenesis of HFM. By identifying differentially expressed genes (DEGs) in deficient facial adipose tissue from HFM patients, we hope to provide a new insight into disease mechanisms from the transcriptome perspective. RNA sequencing (RNA-Seq) was performed with 10 facial adipose tissues from patients of HFM and healthy controls. Differentially expressed genes in HFM were validated by quantitative real-time PCR (qPCR). Functional annotations of the DEGs were analyzed with DESeq2 R package (1.20.0). A total of 1,244 genes were identified as DEGs between HFM patients and matched controls. Bioinformatic analysis predicted that the increased expression of HOXB2 and HAND2 were associated with facial deformity of HFM. Knockdown and overexpression of HOXB2 were achieved with lentiviral vectors. Cell proliferation, migration, and invasion assay was performed with adipose-derived stem cells (ADSC) to confirm the phenotype of HOXB2. We also found that PI3K−Akt signaling pathway and human papillomavirus infection were activated in HFM. In conclusion, we discovered potential genes, pathways and networks in HFM facial adipose tissue, which contributes to a better understanding of the pathogenesis of HFM.
Factors influencing plasma concentration of voriconazole and voriconazole- N-oxide in younger adult and elderly patients
Authors: Cheng Lin , Liang Zaiming , Liu Fang , Lin Ling , Zhang Jiao , Xie Linli , Yu Mingjie , Sun Fengjun
Published: February 2023

Background: Voriconazole (VCZ) metabolism is influenced by many factors. Identifying independent influencing factors helps optimize VCZ dosing regimens and maintain its trough concentration (C0) in the therapeutic window.

Methods: We conducted a prospective study investigating independent factors influencing VCZ C0 and the VCZ C0 to VCZ N-oxide concentration ratio (C0/CN) in younger adults and elderly patients. A stepwise multivariate linear regression model, including the IL-6 inflammatory marker, was used. The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive effect of the indicator.

Results: A total of 463 VCZ C0 were analyzed from 304 patients. In younger adult patients, the independent factors that influenced VCZ C0 were the levels of total bile acid (TBA) and glutamic-pyruvic transaminase (ALT) and the use of proton-pump inhibitors. The independent factors influencing VCZ C0/CN were IL-6, age, direct bilirubin, and TBA. The TBA level was positively associated with VCZ C0 (ρ = 0.176, p = 0.019). VCZ C0 increased significantly when the TBA levels were higher than 10 μmol/L (p = 0.027). ROC curve analysis indicated that when the TBA level ≥4.05 μmol/L, the incidence of a VCZ C0 greater than 5 μg/ml (95% CI = 0.54–0.74) (p = 0.007) increased. In elderly patients, the influencing factors of VCZ C0 were DBIL, albumin, and estimated glomerular filtration rate (eGFR). The independent factors that affected VCZ C0/CN were eGFR, ALT, γ-glutamyl transferase, TBA, and platelet count. TBA levels showed a positive association with VCZ C0 (ρ = 0.204, p = 0.006) and C0/CN (ρ = 0.342, p < 0.001). VCZ C0/CN increased significantly when TBA levels were greater than 10 μmol/L (p = 0.025). ROC curve analysis indicated that when the TBA level ≥14.55 μmol/L, the incidence of a VCZ C0 greater than 5 μg/ml (95% CI = 0.52–0.71) (p = 0.048) increased.

Conclusion: TBA level may serve as a novel marker for VCZ metabolism. eGFR and platelet count should also be considered when using VCZ, especially in elderly patients.
Positive allosteric GABAA receptor modulation counteracts lipotoxicity-induced gene expression changes in hepatocytes in vitro
Authors: Rohbeck Elisabeth , Niersmann Corinna , Köhrer Karl , Wachtmeister Thorsten , Roden Michael , Eckel Jürgen , Romacho Tania
Published: February 2023

Introduction: We have previously shown that the novel positive allosteric modulator of the GABAA receptor, HK4, exerts hepatoprotective effects against lipotoxicity-induced apoptosis, DNA damage, inflammation and ER stress in vitro. This might be mediated by downregulated phosphorylation of the transcription factors NF-κB and STAT3. The current study aimed to investigate the effect of HK4 on lipotoxicity-induced hepatocyte injury at the transcriptional level.

Methods: HepG2 cells were treated with palmitate (200 μM) in the presence or absence of HK4 (10 μM) for 7 h. Total RNA was isolated and the expression profiles of mRNAs were assessed. Differentially expressed genes were identified and subjected to the DAVID database and Ingenuity Pathway Analysis software for functional and pathway analysis, all under appropriate statistical testing.

Results: Transcriptomic analysis showed substantial modifications in gene expression in response to palmitate as lipotoxic stimulus with 1,457 differentially expressed genes affecting lipid metabolism, oxidative phosphorylation, apoptosis, oxidative and ER stress among others. HK4 preincubation resulted in the prevention of palmitate-induced dysregulation by restoring initial gene expression pattern of untreated hepatocytes comprising 456 genes. Out of the 456 genes, 342 genes were upregulated and 114 downregulated by HK4. Enriched pathways analysis of those genes by Ingenuity Pathway Analysis, pointed towards oxidative phosphorylation, mitochondrial dysregulation, protein ubiquitination, apoptosis, and cell cycle regulation as affected pathways. These pathways are regulated by the key upstream regulators TP53, KDM5B, DDX5, CAB39 L and SYVN1, which orchestrate the metabolic and oxidative stress responses including modulation of DNA repair and degradation of ER stress-induced misfolded proteins in the presence or absence of HK4.

Discussion: We conclude that HK4 specifically targets mitochondrial respiration, protein ubiquitination, apoptosis and cell cycle. This not only helps to counteract lipotoxic hepatocellular injury through modification of gene expression, but - by targeting transcription factors responsible for DNA repair, cell cycle progression and ER stress - might even prevent lipotoxic mechanisms. These findings suggest that HK4 has a great potential for the treatment of non-alcoholic fatty liver disease (NAFLD).
An analysis of sugary endosperm in sorghum: Characterization of mutant phenotypes depending on alleles of the corresponding starch debranching enzyme
Authors: Hashimoto Shumpei , Okada Satoshi , Araki-Nakamura Satoko , Ohmae-Shinohara Kozue , Miura Kotaro , Kawaguchi Hideo , Ogino Chiaki , Kasuga Shigemitsu , Sazuka Takashi
Published: February 2023

Sorghum is the fifth most important cereal crop. Here we performed molecular genetic analyses of the ‘SUGARY FETERITA’ (SUF) variety, which shows typical sugary endosperm traits (e.g., wrinkled seeds, accumulation of soluble sugars, and distorted starch). Positional mapping indicated that the corresponding gene was located on the long arm of chromosome 7. Within the candidate region of 3.4 Mb, a sorghum ortholog for maize Su1 (SbSu) encoding a starch debranching enzyme ISA1 was found. Sequencing analysis of SbSu in SUF uncovered nonsynonymous single nucleotide polymorphisms (SNPs) in the coding region, containing substitutions of highly conserved amino acids. Complementation of the rice sugary-1 (osisa1) mutant line with the SbSu gene recovered the sugary endosperm phenotype. Additionally, analyzing mutants obtained from an EMS-induced mutant panel revealed novel alleles with phenotypes showing less severe wrinkles and higher Brix scores. These results suggested that SbSu was the corresponding gene for the sugary endosperm. Expression profiles of starch synthesis genes during the grain-filling stage demonstrated that a loss-of-function of SbSu affects the expression of most starch synthesis genes and revealed the fine-tuned gene regulation in the starch synthetic pathway in sorghum. Haplotype analysis using 187 diverse accessions from a sorghum panel revealed the haplotype of SUF showing severe phenotype had not been used among the landraces and modern varieties. Thus, weak alleles (showing sweet and less severe wrinkles), such as in the abovementioned EMS-induced mutants, are more valuable for grain sorghum breeding. Our study suggests that more moderate alleles (e.g. produced by genome editing) should be beneficial for improving grain sorghum.
Genome-wide identification, expression pattern and genetic variation analysis of SWEET gene family in barley reveal the artificial selection of HvSWEET1a during domestication and improvement
Authors: Yue Wenhao , Cai Kangfeng , Xia Xue , Liu Lei , Wang Junmei
Published: February 2023

SWEET (Sugars Will Eventually be Exported Transporter) proteins, an essential class of sugar transporters, are involved in vital biological processes of plant growth and development. To date, systematical analysis of SWEET family in barley (Hordeum vulgare) has not been reported. In this study, we genome-wide identified 23 HvSWEET genes in barley, which were further clustered into four clades by phylogenetic tree. The members belonging to the same clade showed relatively similar gene structures and conserved protein motifs. Synteny analysis confirmed the tandem and segmental duplications among HvSWEET genes during evolution. Expression profile analysis demonstrated that the patterns of HvSWEET genes varied and the gene neofunctionalization occurred after duplications. Yeast complementary assay and subcellular localization in tobacco leaves suggested that HvSWEET1a and HvSWEET4, highly expressed in seed aleurone and scutellum during germination, respectively, functioned as plasma membrane hexose sugar transporters. Furthermore, genetic variation detection indicated that HvSWEET1a was under artificial selection pressure during barley domestication and improvement. The obtained results facilitate our comprehensive understanding and further functional investigations of barley HvSWEET gene family, and also provide a potential candidate gene for de novo domestication breeding of barley.
Economic, social, and cultural capital and ESQ in academic achievement: A comparison of Afghan and Iranian students
Authors: Pishghadam Reza , Naji Meidani Elham , Momenzadeh Seyed Mohammad Ebrahim , Hasanzadeh Saba , Miri Mir Abdullah
Published: February 2023

The present study aimed to investigate the role of different types of capital, including economic, social, and cultural, as well as emo-sensory intelligence (ESI) in the academic achievement of students in the two contexts of Afghanistan and Iran. For this purpose, 317 students from both countries participated in the study. They were asked to fill out the Social and Cultural Capital Questionnaire (SCCQ) and the Emo-sensory Intelligence Questionnaire (ESI-Q). Their grade point average (GPA) was taken as the indicator of their academic achievement. The findings revealed that students’ level of cultural capital and emo-sensory quotient (ESQ) had a significantly positive role in their academic achievement (p< 0.05). Moreover, significant differences were found between the two contexts in terms of the level of capital, with Afghan students having significantly more cultural capital, and Iranian students having significantly higher economic capital (p< 0.05). Iranian students were also found to have a significantly higher level of ESQ compared to Afghan students (p< 0.05). Finally, the results were discussed, and implications and suggestions for further research were provided.
Satisfaction with online education among students, faculty, and parents before and after the COVID-19 outbreak: Evidence from a meta-analysis
Authors: Xu Tianyuan , Xue Ling
Published: February 2023

The COVID-19 pandemic has presented a unique opportunity for the advancement of online education, as billions of students from 190 countries have been compelled to take classes remotely. The degree of satisfaction is considered one of the major factors in determining the quality of online educational programs. As a result, many empirical studies have been conducted on the level of satisfaction with online education over the last two decades. However, few studies have synthesized previous findings from similar research questions. Therefore, to reinforce statistical power, the study aimed to conduct a meta-analysis to examine satisfaction with online education among students, faculty, and parents before and after the COVID-19 outbreak. A total of 52 studies in English were screened from six academic electronic databases, yielding 57 effect sizes using Comprehensive Meta-Analysis (CMA) software. The results showed that the prevalence of satisfaction with online education among students, faculty, and parents before and after the COVID-19 outbreak was 59.5, 75.3, and 70.7%, respectively, with a significant difference between the satisfaction rates of students and those of their faculty and parents. Besides, we conducted a moderator analysis that found that (1) a significantly higher number of students in the pre-pandemic era in countries with developed digital infrastructure and emergency online learning environments were less satisfied with online education than their counterparts in the post-pandemic era, in countries with developing digital infrastructure, and in non-emergency online learning environments. Additionally, a significantly higher proportion of adult education learners reported being satisfied with online education compared to K-12 and university students. (2) The faculty in the non-emergency situation reported almost double the satisfaction rate of their counterparts in the emergency circumstance. With fewer satisfied remote learning students, efforts could be made by providing well-designed online lessons via faculty and strengthening digital infrastructure via governments to improve student satisfaction.
What does it take to be rigid? Reflections on the notion of rigidity in autism
Authors: Petrolini Valentina , Jorba Marta , Vicente Agustín
Published: February 2023

Characterizations of autism include multiple references to rigid or inflexible features, but the notion of rigidity itself has received little systematic discussion. In this paper we shed some light on the notion of rigidity in autism by identifying different facets of this phenomenon as discussed in the literature, such as fixed interests, insistence on sameness, inflexible adherence to routines, black-and-white mentality, intolerance of uncertainty, ritualized patterns of verbal and non-verbal behavior, literalism, and discomfort with change. Rigidity is typically approached in a disjointed fashion (i.e., facet by facet), although there are recent attempts at providing unifying explanations. Some of these attempts assume that the rigidity facets mainly relate to executive functioning: although such an approach is intuitively persuasive, we argue that there are equally plausible alternative explanations. We conclude by calling for more research on the different facets of rigidity and on how they cluster together in the autistic population, while suggesting some ways in which intervention could benefit from a finer-grained view of rigidity.
Preschool experiences and home learning environments of migrant children in urban China
Authors: Gong Jing , Rao Nirmala
Published: February 2023

Internal migration and urban expansion, hallmarks of rapid urbanization in China, have led to an increasing number of children with diverse backgrounds in cities. Cities now include migrants from rural and urban areas, and children from “urban villages” in addition to “urban locals”. Parents of young children who migrate from rural to urban areas leave their children behind in rural areas (“left-behind” children) or take them along with them. In recent years, increasing parental migration from one urban area to another has also led to children being “left-behind” in urban areas. This study examined the preschool experiences and home learning environments of rural-origin migrants, urban-origin migrants, and rural-origin locals in comparison to urban locals, leveraging data from the nationally representative China Family Panel Studies (2012–2018) with 2,446 3- to 5-year-olds residing in urban areas. Regression model results indicated that children living in cities who held a rural household registration certificate (hukou) were less likely to attend publically funded preschools and experienced less stimulating home learning environments than urban local children. After controlling for family characteristics (i) rural-origin locals remained less likely to participate in preschool and experienced fewer home learning activities than urban locals; and (ii) there were no differences in preschool experiences and home learning environments between rural-origin migrants and urban locals. Mediation analyses suggested that the relation between hukou status and the home learning environment was mediated by parental absence. Implications of the findings are discussed.
Prevalence of psychosocial work factors and stress and their associations with the physical and mental health of hospital physicians: A cross-sectional study in Lithuania
Authors: Zutautiene Rasa , Kaliniene Gintare , Ustinaviciene Ruta , Radisauskas Ricardas
Published: February 2023

Background

A negative psychosocial work environment causes stress to the physicians of healthcare institutions, which affect their physical and mental health. This study aimed to evaluate the prevalence of psychosocial work factors and stress and their associations with the physical and mental health of hospital physicians in the Kaunas region of Lithuania.

Materials and methods

A cross-sectional study was performed. It was based on a questionnaire survey, which contained the Job Content Questionnaire (JCQ), three scales of Copenhagen Psychosocial Questionnaire (COPSOQ), and Medical Outcomes Study Short Form-36 (SF-36) health survey. The study was carried out in 2018. A total of 647 physicians completed the survey. Multivariate logistic regression models were performed by using the stepwise method. In the models potentially, confounding factors such as age and gender were controlled. In our study, the dependent variables were stress dimensions, and the independent variables were psychosocial work factors.

Results

The analysis showed that a quarter of surveyed physicians were classified as having low job skill discretion and decision-making authority, and the support of supervisors was weak. Approximately one-third of the respondents had low decision latitude, low co-worker support, and high job demands, and felt insecure at work. Job insecurity and gender were found to be the strongest independent variables for general and cognitive stress. The support of the supervisor was found as a significant factor in the case of somatic stress. Better evaluation of mental health was related to job skill discretion and co-workers' and supervisors' support, but it did not affect physical health.

Conclusion

The confirmed associations suggest that looking at work organization factors, reducing exposure to stress, and increasing perception of the psychosocial environment can be linked to better subjective health evaluation.
How both positive and burdensome caregiver experiences are associated with care recipient cognitive performance: Evidence from the National Health and Aging Trends Study and National Study of Caregiving
Authors: Wennberg Alexandra M. , Anderson Loretta R. , Cagnin Annachiara , Chen-Edinboro Lenis P. , Pini Lorenzo
Published: February 2023

Introduction

Being an informal caregiver to a person with chronic disease, including persons living with dementia (PLWD), is a big role to take on and many caregivers experience both substantial burden and emotional reward related to caregiving. Care recipient factors (e.g., behavioral symptoms) are associated with caregiver experience. However, the relationship between caregiver and care recipient is bidirectional, so it is likely that caregiver factors impact the care recipient, though few studies have investigated this.

Methods

In the 2017 round of the National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC), we studied 1,210 care dyads-−170 PLWD dyads and 1,040 without dementia dyads. Care recipients completed immediate and delayed word list memory tasks, the Clock Drawing Test, and a self-rated memory rating, while caregivers were interviewed about their caregiving experiences using a 34-item questionnaire. Using principal component analysis, we created a caregiver experience score with three components—Practical Care Burden, Positive Care Experiences, and Emotional Care Burden. We then investigated the cross-sectional association between caregiver experience components and care recipient cognitive test performance using linear regression models adjusted for age, sex, education, race, and depressive and anxiety symptoms.

Results

Among PLWD dyads, a higher caregiver Positive Care Experiences score was associated with better care recipient performance on the delayed word recall (B = 0.20, 95% CI 0.05, 0.36) and Clock Draw (B = 0.12, 95% CI 0.01, 0.24) tests while higher Emotional Care Burden score was associated with worse self-rated memory score (B = −0.19, 95% CI −0.39, −0.003). Among participants without dementia, higher Practical Care Burden score was associated with poorer care recipient performance on the immediate (B = −0.07, 95% CI −0.12, −0.01) and delayed (B = −0.10, 95% CI −0.16, −0.05) word recall tests.

Discussion

These findings support the concept that caregiving is bidirectional within the dyad and that positive variables can positively impact both members of the dyad. This suggests that caregiving interventions should target the caregiver and recipient both individually and as a unit, with the goal of holistically improving outcomes for both.
Moving to a healthier city? An analysis from China's internal population migration
Authors: Gao Ping , Qi Wei , Liu Sheng He , Liu Zhen , Pan Ze Han
Published: February 2023

A healthy urban environment is considered as an important issue for the amenity and equity of migrants. China has one of the largest internal population movements in the world, and the environmental health of its migrants becomes a growing concern. Based on the 1‰ microdata from the 2015 1% population sample survey, this study uses the spatial visualization and spatial econometric interaction model to reveal intercity population migration patterns and the role of environmental health in China. The results are as follows. First, the main direction of population migration is toward economically developed high class cities, especially the eastern coast where the intercity population migration is most active. However, these major destinations are not necessarily the healthiest areas for the environment. Second, environmentally friendly cities are mainly located in the southern region. Among them, the areas with less serious atmospheric pollution are mainly distributed in the south, climate comfort zones are mainly located in the southeastern region, but areas with more urban green space are mainly distributed in the northwestern region. Third, compared with socioeconomic factors, environmental health factors have not yet become a major driver of population migration. Migrants often place higher value on income than on environmental health. The government should focus not only on the public service wellbeing of migrant workers, but also on their environmental health vulnerability.