bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased gene expression and copy number of mutated blaKPC lead to high-level ceftazidime/avibactam resistance in Klebsiella pneumoniae
Authors: Sun Lingxiao , Li Haibo , Wang Qi , Liu Yingmei , Cao Bin
Published: August 2021

Background

Resistance to ceftazidime-avibactam was reported, and it is important to investigate the mechanisms of ceftazidime/avibactam resistance in K. pneumoniae with mutations in blaKPC.

Results

We report the mutated blaKPC is not the only mechanism related to CZA resistance, and investigate the role of outer porin defects, efflux pump, and relative gene expression and copy number of blaKPC and ompk35/36. Four ceftazidime/avibactam-sensitive isolates detected wild type blaKPC-2, while 4 ceftazidime/avibactam-resistant isolates detected mutated blaKPC (blaKPC-51, blaKPC-52, and blaKPC-33). Compared with other ceftazidime/avibactam-resistant isolates with the minimal inhibitory concentration of ceftazidime/avibactam ranging 128–256 mg/L, the relative gene expression and copy number of blaKPC was increased in the isolate which carried blaKPC-51 and also showed the highest minimal inhibitory concentration of ceftazidime/avibactam at 2048 mg/L. The truncated Ompk35 contributes rare to ceftazidime/avibactam resistance in our isolates. No significant difference in minimal inhibitory concentration of ceftazidime/avibactam was observed after the addition of PABN.

Conclusions

Increased gene expression and copy number of mutated blaKPC can cause high-level ceftazidime/avibactam resistance.
The role of the bacterial microbiome in the treatment of cancer
Authors: Yu Zi-Kun , Xie Rui-Ling , You Rui , Liu You-Ping , Chen Xu-Yin , Chen Ming-Yuan , Huang Pei-Yu
Published: August 2021

The human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.
Association of treatment procedures and resilience to symptom load three-years later in a clinical sample of adolescent psychiatric patients
Authors: Gårdvik Kari Skulstad , Rygg Marite , Torgersen Terje , Wallander Jan Lance , Lydersen Stian , Indredavik Marit Sæbø
Published: August 2021

Background

We aimed to examine symptom load in a clinical adolescent population at three-year follow-up and explore associations with standard care treatment procedures and resilience factors upon first presenting at Child and Adolescent Mental Health Services.

Methods

This study is part of a prospective longitudinal cohort study: The Health Survey in Department of Children and Youth, St. Olavs hospital, Norway. A clinical population of 717 (43.5% of eligible) adolescents aged 13–18 years participated in the first study visit (T1, 2009–2011). Of these, 447 adolescents with psychiatric disorders, with treatment history from medical records and self-reported resilience factors (Resilience Scale for Adolescents; READ) at T1, reported symptom load (Achenbach System of Empirically Based Assessment - Youth Self Report; YSR) three years later aged 16–21 years (T2).

Result

At T1, 93.0% received individual treatment. The frequency of psychotherapy and medication varied by disorder group and between genders. Overall, psychotherapy was more frequent among girls, whereas medication was more common among boys. Total READ mean value (overall 3.5, SD 0.8), ranged from patients with mood disorders (3.0, SD 0.7) to patients with Attention Deficit Hyperactivity disorder (3.7, SD 0.7), and was lower for girls than boys in all diagnostic groups. At T2, the YSR Total Problem mean T-score ranged across the diagnostic groups (48.7, SD 24.0 to 62.7, SD 30.2), with highest symptom scores for those with mood disorders at T1, of whom 48.6% had T-scores in the borderline/clinical range (≥60) three years later. Number of psychotherapy sessions was positively associated and Total READ score was negatively associated with the YSR Total Problems T-score (regression coefficient β = 0.5, CI (0.3 to 0.7), p < 0.001 and β = − 15.7, CI (− 19.2 to − 12.1), p < 0.001, respectively). The subscale Personal Competence was associated with the lowest Total Problem score for both genders.

Conclusions

Self-reported symptom load was substantial after three years, despite comprehensive treatment procedures. Higher self-reported resilience characteristics were associated with lower symptom load after three years. These results highlight the burden of adolescent psychiatric disorders, the need for extensive interventions and the importance of resilience factors for a positive outcome.
Exploring the experiences of mental health professionals engaged in the adoption of mobile health technology in Irish mental health services
Authors: Melia Ruth , Monahan Luke , Duggan Jim , Bogue John , O’Sullivan Mary , Young Karen , Chambers Derek , McInerney Shane
Published: August 2021

Background

The World Health Organization report that an estimated 793,000 people died by suicide in 2016 globally. The use of digital technology has been found to be beneficial in the delivery of Web-based suicide prevention interventions. Research on the integration of digital technology within mental health services has indicated that despite the proliferation of technology, engagement by patients and professionals in adopting such technology can be poor.

Objectives

The current study aims to explore the experiences of 15 mental health professionals involved in integrating mobile health technology into their practice. A secondary aim was to identify the drivers and barriers to the adoption of such technology by mental health professionals, and to consider what theoretical models could best account for the data.

Methods

Semi-structured interviews, conducted from July to October 2019, were used to explore the experiences of mental health professionals engaged in the adoption of mobile health technology within mental health services. Mental Health professionals and clinician managers working in HSE Child and Adolescent Mental Health, Adult Mental Health, and Primary Care Psychology services were recruited for the study. Qualitative interview data was transcribed and analysed using NVivo. Thematic Analysis was used to identify themes.

Results

Four major themes were identified: Accessibility, ‘Transitional Object’, Integration, and Trust. Within these 4 major themes, a total of 9 subthemes were identified: Service Accessibility, Immediate Access, Client Engagement, Adjunct-to-therapy, Therapeutic Relationship, Infrastructural Support, Enhancing Treatment, Trust in the Technology, Trust in the Organisation.

Conclusions

Overall, Diffusion of Innovation Theory provides a useful theoretical framework which is consistent with and can adequately account for many of the Major and Subthemes identified in the data. In addition, ‘Transitional Objects’, a key concept within Object Relations Theory, could offer a means of better understanding how patients and professionals engage with digital technology within mental health services particularly.
Adaptive learning and recall of motor-sensory sequences in adult echolocating bats
Authors: Taub Mor , Yovel Yossi
Published: August 2021

Background

Learning to adapt to changes in the environment is highly beneficial. This is especially true for echolocating bats that forage in diverse environments, moving between open spaces to highly complex ones. Bats are known for their ability to rapidly adjust their sensing according to auditory information gathered from the environment within milliseconds but can they also benefit from longer adaptive processes? In this study, we examined adult bats’ ability to slowly adapt their sensing strategy to a new type of environment they have never experienced for such long durations, and to then maintain this learned echolocation strategy over time.

Results

We show that over a period of weeks, Pipistrellus kuhlii bats gradually adapt their pre-takeoff echolocation sequence when moved to a constantly cluttered environment. After adopting this improved strategy, the bats retained an ability to instantaneously use it when placed back in a similarly cluttered environment, even after spending many months in a significantly less cluttered environment.

Conclusions

We demonstrate long-term adaptive flexibility in sensory acquisition in adult animals. Our study also gives further insight into the importance of sensory planning in the initiation of a precise sensorimotor behavior such as approaching for landing.
Post-treatment with the PPAR-γ agonist pioglitazone inhibits inflammation and bacterial growth during Klebsiella pneumonia
Authors: Ramirez-Moral Ivan , Ferreira Bianca Lima , de Vos Alex F. , van der Poll Tom
Published: August 2021

Agonists of peroxisome proliferator-activated receptor (PPAR)-γ have been suggested as potential adjuvant therapy in bacterial pneumonia because of their capacity to inhibit inflammation and enhance bacterial clearance. Previous studies only assessed the effects of pretreatment with these compounds, thereby bearing less relevance for the clinical scenario. Moreover, PPAR-γ agonists have not been studied in pneumonia caused by Klebsiella pneumoniae, a common human respiratory pathogen of which antibiotic treatment is hampered by increasing antimicrobial resistance. Here we show that administration of the PPAR-γ agonist pioglitazone 6 or 8 h after infection of mice with a highly virulent strain of Klebsiella pneumoniae via the airways results in reduced cytokine and myeloperoxidase levels in the lungs at 24 h after infection, as well as reduced bacterial growth in the lungs and decreased dissemination to distant organs at 42 h post-infection. These results suggest that pioglitazone may be an interesting agent in the treatment of Klebsiella pneumonia.
Pseudogene HSPA7 is a poor prognostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) and correlated with immune infiltrates
Authors: Ding Chunjin , He Rundong , Zhang Jinghan , Dong Zhan , Wu Jun
Published: August 2021

Background

Pseudogenes played important roles in tumorigenesis, while there are nearly no reports about the expression and roles of HSPA7 in the cancer.

Methods

Firstly, we used Logistic regression, the KS test, the GEPIA database, UALCAN database and qRT-PCR to analyze the expression level of HSPA7 in KIRC, then we used the Cox regression and the Kaplan–Meier curve to analyze the overall survival (OS) of KIRC patients with different Clinico-pathological parameters. Thirdly, we used the multivariate Cox analysis of influencing factors to compare the correlation between the HSPA7 expression level and the clinical parameters. Finally, we used multi-GSEA analysis and the Tumor Immunoassay Resource (TIMER) database to explore the functional role of HSPA7 in KIRC

Results

The HSPA7 is highly expressed in KIRC tumor tissues, and its expression is related to clinico-pathological features and survival in KIRC patients. GSEA analysis displayed the high expression of HSPA7 in KIRC were related to several tumor-related and immune-related pathways. With the TIMER database analysis we showed that HSPA7 levels were correlated with the CD4+ T cells, neutrophils and Dendritic Cell.

Conclusions

Our study showed that HSPA7 is very important in the tumor progression and may act as a poor prognostic biomarker for KIRC tumor by modulating immune infiltrating cells.
Family planning for urban slums in low- and middle-income countries: a scoping review of interventions/service delivery models and their impact
Authors: Ganle John Kuumuori , Baatiema Leonard , Ayamah Paul , Ofori Charlotte Abra Esime , Ameyaw Edward Kwabena , Seidu Abdul-Aziz , Ankomah Augustine
Published: August 2021

Background

Although evidence suggest that many slum dwellers in low- and middle-income countries have the most difficulty accessing family planning (FP) services, there are limited workable interventions/models for reaching slum communities with FP services. This review aimed to identify existing interventions and service delivery models for providing FP services in slums, and as well examine potential impact of such interventions and service delivery models in low- and middle-income settings.

Methods

We searched and retrieved relevant published studies on the topic from 2000 to 2020 from e-journals, health sources and six electronic databases (MEDLINE, Global Health, EMBASE, CINAHL, PsycINFO and Web of Science). Grey and relevant unpublished literature (e.g., technical reports) were also included. For inclusion, studies should have been published in a low- and middle-income country between 2000 and 2020. All study designs were included. Review articles, protocols or opinion pieces were excluded. Search results were screened for eligible articles and reports using a pre-defined criterion. Descriptive statistics and narrative syntheses were produced to summarize and report findings.

Results

The search of the e-journals, health sources and six electronic databases including grey literature and other unpublished materials produced 1,260 results. Following screening for title relevance, abstract and full text, nine eligible studies/reports remained. Six different types of FP service delivery models were identified: voucher schemes; married adolescent girls’ club interventions; Willows home-based counselling and referral programme; static clinic and satellite clinics; franchised family planning clinics; and urban reproductive health initiatives. The urban reproductive health initiatives were the most dominant FP service delivery model targeting urban slums. As regards the impact of the service delivery models identified, the review showed that the identified interventions led to improved targeting of poor urban populations, improved efficiency in delivery of family planning service, high uptake or utilization of services, and improved quality of family planning services.

Conclusions

This review provides important insights into existing family planning service delivery models and their potential impact in improving access to FP services in poor urban slums. Further studies exploring the quality of care and associated sexual and reproductive health outcomes as a result of the uptake of these service delivery models are essential. Given that the studies were reported from only 9 countries, further studies are needed to advance knowledge on this topic in other low-middle income countries where slum populations continue to rise.
Toolkit for detecting misused epidemiological methods
Authors: Soskolne Colin L. , Kramer Shira , Ramos-Bonilla Juan Pablo , Mandrioli Daniele , Sass Jennifer , Gochfeld Michael , Cranor Carl F. , Advani Shailesh , Bero Lisa A.
Published: August 2021

Background

Critical knowledge of what we know about health and disease, risk factors, causation, prevention, and treatment, derives from epidemiology. Unfortunately, its methods and language can be misused and improperly applied. A repertoire of methods, techniques, arguments, and tactics are used by some people to manipulate science, usually in the service of powerful interests, and particularly those with a financial stake related to toxic agents. Such interests work to foment uncertainty, cast doubt, and mislead decision makers by seeding confusion about cause-and-effect relating to population health. We have compiled a toolkit of the methods used by those whose interests are not aligned with the public health sciences. Professional epidemiologists, as well as those who rely on their work, will thereby be more readily equipped to detect bias and flaws resulting from financial conflict-of-interest, improper study design, data collection, analysis, or interpretation, bringing greater clarity—not only to the advancement of knowledge, but, more immediately, to policy debates.

Methods

The summary of techniques used to manipulate epidemiological findings, compiled as part of the 2020 Position Statement of the International Network for Epidemiology in Policy (INEP) entitled Conflict-of-Interest and Disclosure in Epidemiology, has been expanded and further elucidated in this commentary.

Results

Some level of uncertainty is inherent in science. However, corrupted and incomplete literature contributes to confuse, foment further uncertainty, and cast doubt about the evidence under consideration. Confusion delays scientific advancement and leads to the inability of policymakers to make changes that, if enacted, would—supported by the body of valid evidence—protect, maintain, and improve public health. An accessible toolkit is provided that brings attention to the misuse of the methods of epidemiology. Its usefulness is as a compendium of what those trained in epidemiology, as well as those reviewing epidemiological studies, should identify methodologically when assessing the transparency and validity of any epidemiological inquiry, evaluation, or argument. The problems resulting from financial conflicting interests and the misuse of scientific methods, in conjunction with the strategies that can be used to safeguard public health against them, apply not only to epidemiologists, but also to other public health professionals.

Conclusions

This novel toolkit is for use in protecting the public. It is provided to assist public health professionals as gatekeepers of their respective specialty and subspecialty disciplines whose mission includes protecting, maintaining, and improving the public’s health. It is intended to serve our roles as educators, reviewers, and researchers.
USP10 alleviates sepsis-induced acute kidney injury by regulating Sirt6-mediated Nrf2/ARE signaling pathway
Authors: Gao Fei , Qian Mingjiang , Liu Guoyue , Ao Wanping , Dai Dahua , Yin Cunzhi
Published: August 2021

Background

Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis.

Results

In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury.

Conclusions

This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.
Imaging asparaginyl endopeptidase (AEP) in the live brain as a biomarker for Alzheimer’s disease
Authors: Wang Shan-Shan , Liu Zi-Kai , Liu Jing-Jing , Cheng Qing , Wang Yan-Xia , Liu Yan , Ni Wen-Wen , Chen Hong-Zhuan , Song Mingke
Published: August 2021

Background

Discovery of early-stage biomarkers is a long-sought goal of Alzheimer’s disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn’t proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology.

Results

This AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala–Ala–Asn–Cys–Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg−1, p.o.) reduced production of β-amyloid (Aβ) and ameliorated memory loss. Therefore, elevation of AEP is an early sign of AD onset. Finally, we showed that live animal imaging with this AEP-responsive probe could monitor the up-regulated AEP in the brain of APP/PS1 mice.

Conclusions

The current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD.

Graphical abstract
Quality of life and fear of COVID-19 in 2600 baccalaureate nursing students at five universities: a cross-sectional study
Authors: Beisland E. G. , Gjeilo K. H. , Andersen J. R. , Bratås O. , Bø B. , Haraldstad K. , Hjelmeland I. H. H. , Iversen M. M. , Løyland B. , Norekvål T. M. , Riiser K. , Rohde G. , Urstad K. H. , Utne I. , Flølo T. N. ,   the LIVSFORSK network
Published: August 2021

Background

The COVID-19 pandemic has caused significant disruptions in the implementation of programs across educational institutions. Nursing students, being both young adults and by practical training, part of the health care system, may be particularly vulnerable during the COVID-19 pandemic. The purpose of this study was to explore the associations between self-reported fear of COVID-19, general health, psychological distress and overall quality of life (QoL) in a sample of Norwegian baccalaureate nursing students compared to reference data.

Methods

The survey targeted baccalaureate nursing students from five universities in February 2021. An electronic questionnaire consisted of the Fear of COVID-19 Scale (FCV-19S), the Hopkins Symptom Checklist 5 (SCL-5), one general health and one overall QoL question. The respondents’ mean scores were compared to reference data. Hierarchical regression analyses were conducted, and effect sizes (Cohen’s d) were evaluated.

Results

In total, 2605 out of 6088 (43%) students responded. Their FCV-19S scores (mean 2.45, CI 2.42, 2.48) were significantly higher than those of the reference population (mean 1.8, P < 0.001). Nursing students scores showed significantly lower general health (mean 3.50 ± 0.93 SD, population mean = 3.57, Cohen’s d = 0.07), higher levels of psychological distress (mean 2.68 ± 1.03 SD, population mean = 2.12, Cohen’s d = 0.55) and lower overall QoL (mean 5.50 ± 2.16 SD, population mean = 8.00, Cohen’s d = 1.16) compared to pre-pandemic reference data. FCV-19S scores were significantly associated with levels of general health (Cohen’s d = 0.26), psychological distress (Cohen’s d = 0.76) and overall QoL (Cohen’s d = 0.18).

Conclusions

Baccalaureate nursing students reported worse outcomes during the Covid-19 pandemic on general health, psychological distress and overall QoL compared to the reference population. Level of fear of Covid-19, however, accounted for few of these differences. Other factors related to the pandemic may have reduced nursing students’ overall QoL.
Use of proteomics to identify mechanisms of hepatocellular carcinoma with the CYP2D6*10 polymorphism and identification of ANGPTL6 as a new diagnostic and prognostic biomarker
Authors: Hu Guiming , Gao Fei , Wang Guanzhe , Fang Yan , Guo Yuanyuan , Zhou Jun , Gu Yuhan , Zhang Cunzhen , Gao Na , Wen Qiang , Qiao Hailing
Published: August 2021

Background

Although an association between the cytochrome P4502D6 (CYP2D6) *10 (100C>T) polymorphism and hepatocellular carcinoma (HCC) is known, the mechanism remains unclear. Here we aimed to explore mechanisms of CYP2D6*10 (100C>T) polymorphism conferring to HCC, and screen markers for HCC.

Methods

Label-free global proteome profiling with 34 normal livers and peritumor tissue from 61 HCC patients was performed, and angiopoietin-like protein-6 (ANGPTL6) was evaluated in 2 liver samples validation cohorts and 2 blood specimens validation cohorts.

Results

We found a significantly decreased frequency of TT in HCC patients which reduced HCC susceptibility by 69.2% and was accompanied by lowered enzymatic activity for CYP2D6. Proteomic analysis revealed 1342 differentially expressed proteins (DEPs) that were associated with HCC and 88 DEPs were identified as 100 TT-related proteins, likely underlying the susceptibility to HCC. Twenty-two upregulated DEPs and 66 downregulated DEPs were mainly related to lipid metabolism and the extracellular matrix, respectively. High ANGPTL6 was associated with a higher risk to HCC and worse prognosis. ANGPTL6 was both an independent risk factor and an independent prognostic factor for HCC and exhibited strong potential for predicting HCC occurrence, with comparable AUC values and higher sensitivity compared with alpha-fetoprotein.

Conclusions

The TT genotype-associated decreased risk of HCC appears to be related to lowered CYP2D6 activity and altered protein expression in the tumor microenvironment, and ANGPTL6 is a promising new diagnostic and prognostic biomarker for HCC. Our findings reveal new mechanistic insights for polymorphisms related to HCC risk and provide avenues for screening for HCC.
Antiviral activity of diallyl trisulfide against H9N2 avian influenza virus infection in vitro and in vivo
Authors: Ming Le , Li Zhihui , Li Xiaofang , Tang Ling , He Guimei
Published: August 2021

Background

Diallyl trisulfide (DATS) is a garlic-derived organosulfur compound. As it has been shown to have anti-viral activity, we hypothesized that it may alleviate infections caused by H9N2 avian influenza virus (AIV), which is prevalent in poultry with pandemic potential.

Methods

Human lung A549 epithelial cells were treated with three different concentrations of DATS 24 h before (pre-treatment) or one hour after (post-treatment) H9N2 AIV infection. Culture supernatants were collected 24 h and 48 h post-infection and analyzed for viral titers and levels of inflammatory and anti-viral immune responses. For in vivo experiments, BABL/c mice were administered daily by intraperitoneal injection with DATS (30 mg/kg) for 2 weeks starting 1 day after H9N2 AIV infection. Clinical signs, lung pathology, and inflammatory and anti-viral immune responses were assessed 2, 4, and 6 days after infection.

Results

Both pre-treatment and post-treatment of A549 cells with DATS resulted in reduced viral loads, increased expression of anti-viral genes (RIG-I, IRF-3, and interferon-β), and decreased expression of inflammatory cytokines (TNF-α and IL-6). These effects were also observed in H9N2 AIV-infected mice treated with DATS. Such treatment also reduced lung edema and inflammation in mice.

Conclusions

Results suggest that DATS has anti-viral activity against H9N2 AIV and may be used as an alternative treatment for influenza virus infection.
VariantStore: an index for large-scale genomic variant search
Authors: Pandey Prashant , Gao Yinjie , Kingsford Carl
Published: August 2021

Efficiently scaling genomic variant search indexes to thousands of samples is computationally challenging due to the presence of multiple coordinate systems to avoid reference biases. We present VariantStore, a system that indexes genomic variants from multiple samples using a variation graph and enables variant queries across any sample-specific coordinate system. We show the scalability of VariantStore by indexing genomic variants from the TCGA project in 4 h and the 1000 Genomes project in 3 h. Querying for variants in a gene takes between 0.002 and 3 seconds using memory only 10% of the size of the full representation.
Efficacy of active and passive evidence-based practice training for postgraduate medical residents: a non-randomized controlled trial
Authors: Goodarzi Hassan , Teymourzadeh Ehsan , Rahimi Siyavash , Nasiri Taha
Published: August 2021

Objective

This study examined the effects of two evidence-based practice (EBP) educational programs for postgraduate medical residents on their attitude, behavior, knowledge, outcome, and competencies in EBP.

Results

Forty-five and thirty-five medical residents were recruited in the active and passive educational intervention groups, respectively. Among those, 39 and 30 participants were included in the final analysis. The participants of the active group received 12 h of EBP-structured presentation. The passive educational group received EBP education through their daily rounds, evidence-based journal clubs, and morning reports. Participants were evaluated with EBP-KABQ and ACE tools questionnaires. The active and passive intervention groups were not significantly different from each other at the baseline in the EBP-KABQ questionnaire and ACE tools score (p > 0.05). However, most questions in the EBP-KABQ questionnaire were significantly different from the pre-intervention measurement and the passive intervention group after the educational intervention. Educational intervention in both groups led to a significant difference in ACE tools score between groups (8.86 ± 2.62 vs. 7.31 ± 2.92, p = 0.029, in the active and passive groups, respectively). Paired t-test analysis revealed that our intervention led to a significant increase in ACE tool scores in both groups (p < 0.000, in both groups).
TFCrowd: a blockchain-based crowdsourcing framework with enhanced trustworthiness and fairness
Authors: Li Chunxiao , Qu Xidi , Guo Yu
Published: August 2021

Blockchain technology has attracted considerable attention due to the boom of cryptocurrencies and decentralized applications. Among them, the emerging blockchain-based crowdsourcing is a typical paradigm, which gets rid of centralized cloud-servers and leverages smart contracts to realize task recommendation and reward distribution. However, there are still two critical issues yet to be solved urgently. First, malicious evaluation from crowdsourcing requesters will result in honest workers not getting the rewards they deserve even if they have provided valuable solutions. Second, unfair evaluation and reward distribution can lead to low enthusiasm for work. Therefore, the above problems will seriously hinder the development of blockchain-based crowdsourcing platforms. In this paper, we propose a new blockchain-based crowdsourcing framework with enhanced trustworthiness and fairness, named TFCrowd. The core idea of TFCrowd is utilizing a smart contract of blockchain as a trusted authority to fairly evaluate contributions and allocate rewards. To this end, we devise a reputation-based evaluation mechanism to punish the requester who behaves as “false-reporting” and a Shapley value-based method to distribute rewards fairly. By using our proposed schemes, TFCrowd can prevent malicious requesters from making unfair comments and reward honest workers according to their contributions. Extensive simulations and the experiment results demonstrate that TFCrowd can protect the interests of workers and distribute rewards fairly.
A blockchain-assisted framework for secure and reliable data sharing in distributed systems
Authors: Guo Yu , Wang Shenling , Huang Jianhui
Published: August 2021

The explosive growth of big data is pushing forward the paradigm of cloud-based data store today. Among other, distributed storage systems are widely adopted due to their superior performance and continuous availability. However, due to the potentially wide attacking surfaces of the public cloud, outsourcing data store inevitably raises new concerns on user privacy exposure and unauthorized data access. Besides, directly introducing a centralized third-party authority for query authorization management does not work because it still can be compromised. In this paper, we propose a blockchain-assisted framework that can support trustworthy data sharing services. In particular, data owners allow to outsource their sensitive data to distributed systems in encrypted form. By leveraging smart contracts of blockchain, a data owner can distribute secret keys for authorized users without extra round interaction to generate the permitted search tokens. Meanwhile, such blockchain-assisted framework naturally solves the trust issues of query authorization. Besides, we devise a secure local index framework to support encrypted keyword search with forward privacy and mitigate blockchain overhead. To validate our design, we implement the prototype and deploy it at Amazon Cloud. Extensive experiments demonstrate the security, efficiency, and effectiveness of the blockchain-assisted design.
New general integral transform via Atangana–Baleanu derivatives
Authors: Meddahi M. , Jafari H. , Ncube M. N.
Published: August 2021

The current paper is about the investigation of a new integral transform introduced recently by Jafari. Specifically, we explore the applicability of this integral transform on Atangana–Baleanu derivative and the associated fractional integral. It is shown that by applying specific conditions on this integral transform, other integral transforms are deduced. We provide examples to reinforce the applicability of this new integral transform.
Novel improved fractional operators and their scientific applications
Authors: Hyder Abd-Allah , Barakat M. A.
Published: August 2021

The motivation of this research is to introduce some new fractional operators called “the improved fractional (IF) operators”. The originality of these fractional operators comes from the fact that they repeat the method on general forms of conformable integration and differentiation rather than on the traditional ones. Hence the convolution kernels correlating with the IF operators are served in conformable abstract forms. This extends the scientific application scope of their fractional calculus. Also, some results are acquired to guarantee that the IF operators have advantages analogous to the familiar fractional integral and differential operators. To unveil the inverse and composition properties of the IF operators, certain function spaces with their characterizations are presented and analyzed. Moreover, it is remarkable that the IF operators generalize some fractional and conformable operators proposed in abundant preceding works. As scientific applications, the resistor–capacitor electrical circuits are analyzed under some IF operators. In the case of constant and periodic sources, this results in novel voltage forms. In addition, the overall influence of the IF operators on voltage behavior is graphically simulated for certain selected fractional and conformable parameter values. From the standpoint of computation, the usage of new IF operators is not limited to electrical circuits; they could also be useful in solving scientific or engineering problems.
Experimental colitis promotes sustained, sex-dependent, T-cell-associated neuroinflammation and parkinsonian neuropathology
Authors: Houser Madelyn C. , Caudle W. Michael , Chang Jianjun , Kannarkat George T. , Yang Yuan , Kelly Sean D. , Oliver Danielle , Joers Valerie , Shannon Kathleen M. , Keshavarzian Ali , Tansey Malú Gámez
Published: August 2021

Background

The etiology of sporadic Parkinson’s disease (PD) remains uncertain, but genetic, epidemiological, and physiological overlap between PD and inflammatory bowel disease suggests that gut inflammation could promote dysfunction of dopamine-producing neurons in the brain. Mechanisms behind this pathological gut-brain effect and their interactions with sex and with environmental factors are not well understood but may represent targets for therapeutic intervention.

Methods

We sought to identify active inflammatory mechanisms which could potentially contribute to neuroinflammation and neurological disease in colon biopsies and peripheral blood immune cells from PD patients. Then, in mouse models, we assessed whether dextran sodium sulfate-mediated colitis could exert lingering effects on dopaminergic pathways in the brain and whether colitis increased vulnerability to a subsequent exposure to the dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We assessed the involvement of inflammatory mechanisms identified in the PD patients in colitis-related neurological dysfunction in male and female mice, utilizing mice lacking the Regulator of G-Protein Signaling 10 (RGS10)—an inhibitor of nuclear factor kappa B (NFκB)—to model enhanced NFκB activity, and mice in which CD8+T-cells were depleted.

Results

High levels of inflammatory markers includingCD8Band NFκB p65 were found in colon biopsies from PD patients, and reduced levels of RGS10 were found in immune cells in the blood. Male mice that experienced colitis exhibited sustained reductions in tyrosine hydroxylase but not in dopamine as well as sustained CD8+T-cell infiltration and elevatedIfngexpression in the brain. CD8+T-cell depletion prevented colitis-associated reductions in dopaminergic markers in males. In both sexes, colitis potentiated the effects of MPTP. RGS10 deficiency increased baseline intestinal inflammation, colitis severity, and neuropathology.

Conclusions

This study identifies peripheral inflammatory mechanisms in PD patients and explores their potential to impact central dopaminergic pathways in mice. Our findings implicate a sex-specific interaction between gastrointestinal inflammation and neurologic vulnerability that could contribute to PD pathogenesis, and they establish the importance of CD8+T-cells in this process in male mice.

Graphical abstract
Provenance of Zhou Dynasty bronze vessels unearthed from Zongyang County, Anhui Province, China: determined by lead isotopes and trace elements
Authors: Wang Yanjie , Wei Guofeng , Li Qiang , Zheng Xiaoping , Wang Danchun
Published: August 2021

Thirteen Zhou Dynasty bronze vessels and two slags from Zongyang County along the north bank of the Yangtze River in Anhui were analyzed by LA-MC-ICP-MS and EDXRF. The results of lead isotope analysis showed that there were two kinds of lead materials in the Zongyang bronzes. Vessels in Class I, thought to have originated from the Wannan region were primarily used during the Western Zhou and the following Spring and Autumn period; while those in Class II, possibly from the local mines in Zongyang County, were mainly present during the Warring States period. Such a shift in the ore material sources is also revealed by the trace element analysis of the Zongyang bronzes. With reference to the relevant historical documents, we suggest that the transformation of the bronze material sources might have been associated with the changes of the political situation during the Zhou Dynasty.
Adsorption of Cr(VI) onto cross-linked chitosan-almond shell biochars: equilibrium, kinetic, and thermodynamic studies
Authors: Altun Türkan , Ecevit Hüseyin , Kar Yakup , Çiftçi Birsen
Published: August 2021

In this study, to remove Cr(VI) from the solution environment by adsorption, the almond shell was pyrolyzed at 400 and 500 °C and turned into biochar (ASC400 and ASC500) and composite adsorbents were obtained by coating these biochars with chitosan (Ch-ASC400 and Ch-ASC500). The resulting biochars and composite adsorbents were characterized using Fourier transform infrared (FTIR) spectroscopy; Brunauer, Emmett, and Teller (BET) surface area; scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX); and the point of zero charge pH (pHpzc) analyses. The parameters affecting the adsorption were examined with batch adsorption experiments and the optimum parameters for the efficient adsorption of Cr(VI) in 55 mg L−1 solution were determined as follows; adsorbent dosages: 5 g L−1 for biochars, 1.5 g L−1 for composite adsorbents, contact time: 120 min, pH: 1.5. It was seen that the temperature did not affect the adsorption much. Under optimum conditions, Cr(VI) adsorption capacities of ASC400, ASC500, Ch-ASC400, and Ch-ASC500 adsorbents are 11.33, 11.58, 37.48, and 36.65 mg g−1, respectively, and their adsorption percentages are 95.2%, 97.5%, 94.3%, and 94.0%, respectively. Adsorption data were applied to Langmuir, Freundlich, Scatchard, Dubinin-Radushkevic, and Temkin isotherms and pseudo-first-order kinetic model, pseudo-second-order kinetic model, intra-particle diffusion model, and film diffusion model. The adsorption data fitted well to the Langmuir isotherm and pseudo-second-order kinetic models. From these results, it was determined that chemical adsorption is the dominant mechanism. Also, both intra-particle diffusion and film diffusion is effective in the adsorption rate. For all adsorbents, the Langmuir isotherm proved to be the most appropriate model for adsorption. The maximum monolayer adsorption capacities calculated from this model are 24.15 mg g−1, 27.38 mg g−1, 54.95 mg g−1, and 87.86 mg g−1 for ASC400, ASC500, Ch-ASC400, and Ch-ASC500, respectively. The enthalpy change, entropy change, and free energy changes during the adsorption process were calculated and the adsorption was also examined thermodynamically. As a result, adsorption occurs spontaneously for all adsorbents.
Design, methodology, and baseline of whole city-million scale children and adolescents myopia survey (CAMS) in Wenzhou, China
Authors: Xu Liangde , Zhuang Youyuan , Zhang Guosi , Ma Yunlong , Yuan Jian , Tu Changseng , Li MiaoMiao , Wang Wencan , Zhang Yaru , Lu Xiaoyan , Li Jing , Liu Xinting , Xue Zhengbo , Zhou Meng , Sun Jie , Bao Jinhua , Li Ming , Lu Fan , Wang Hong , Su Jianzhong , Qu Jia
Published: August 2021

Background

Myopia is the most common visual impairment in children and adolescents worldwide. This study described an economical and effective population-based screening pipeline and performed the project of a million scale children and adolescents myopia survey (CAMS), which will shed light on the further study of myopia from the level of epidemiology and precision medicine.

Methods

We developed a novel population-based screening pattern, an intelligent screening process and internet-based information transmission and analysis system to carry out the survey consisting of school children in Wenzhou, China. The examination items include unaided distance visual acuity, presenting distance visual acuity, and non-cycloplegic autorefraction. Myopia and high myopia were defined as spherical equivalent (SE) ≤ − 1.00 diopters (D) and SE ≤ − 6.00 D, respectively. Next, the reports of the vision checking were automatically sent to parents and the related departments. The CAMS project will be done two to four times annually with the support of the government. An online eyesight status information management system (OESIMS) was developed to construct comprehensive and efficient electronic vision health records (EVHRs) for myopia information inquiry, risk pre-warning, and further study.

Results

The CAMS completed the first-round of screening within 30 days for 99.41% of Wenzhou students from districts and counties, in June 2019. A total of 1,060,925 participants were eligible for CAMS and 1,054,251 (99.37% participation rate) were selected through data quality control, which comprised 1305 schools, and 580,609, 251,050 and 170,967 elementary, middle, and high school students. The mean age of participants was 12.21 ± 3.32 years (6–20 years), the female-to-male ratio was 0.82. The prevalence of myopia in elementary, middle, and high school students was 38.16%, 77.52%, and 84.00%, respectively, and the high myopia incidence was 0.95%, 6.90%, and 12.98%.

Conclusions

The CAMS standardized myopia screening model involves automating large-scale information collection, data transmission, data analysis and early warning, thereby supporting myopia prevention and control. The entire survey reduced 90% of staff, cost, and time consumption compared with previous surveys. This will provide new insights for decision support for public health intervention.
Identification of glioblastoma immune subtypes and immune landscape based on a large cohort
Authors: Zhang Huiyuan , Chen Ying
Published: August 2021

Glioblastomas (GBM) are the most common primary brain malignancy and also the most aggressive one. In addition, GBM have to date poor treatment options. Therefore, understanding the GBM microenvironment may help to design immunotherapy treatments and rational combination strategies. In this study, the gene expression profiles and clinical follow-up data were downloaded from TCGA-GBM, and the molecular subtypes were identified using ConsensusClusterPlus. Univariate and multivariate Cox regression were used to evaluate the prognostic value of immune subtypes. The Graph Structure Learning method was used for dimension reduction to reveal the internal structure of the immune system. A Weighted Correlation Network Analysis (WGCNA) was used to identify immune-related gene modules. Four immune subtypes (IS1, IS2, IS3, IS4) with significant prognosis differences were obtained. Interestingly, IS4 had the highest mutation rate. We also found significant differences in the distribution of the four subtypes at immune checkpoints, molecular markers, and immune characteristics. WGCNA identified 11 co-expressed module genes, and there were significant differences among the four subtypes. Finally, CD1A, CD1E, and IL23R genes with significant prognostic significance were selected as the final feature genes in the brown module. Overall, this study provided a conceptual framework for understanding the tumor immune microenvironment of GBM.