bluuebunny/crossref_metadata_2025 huggingface dataset:
GenTB: A user-friendly genome-based predictor for tuberculosis resistance powered by machine learning
Authors: Gröschel Matthias I. , Owens Martin , Freschi Luca , Vargas Roger , Marin Maximilian G. , Phelan Jody , Iqbal Zamin , Dixit Avika , Farhat Maha R.
Published: August 2021

Background

Multidrug-resistant Mycobacterium tuberculosis (Mtb) is a significant global public health threat. Genotypic resistance prediction from Mtb DNA sequences offers an alternative to laboratory-based drug-susceptibility testing. User-friendly and accurate resistance prediction tools are needed to enable public health and clinical practitioners to rapidly diagnose resistance and inform treatment regimens.

Results

We present Translational Genomics platform for Tuberculosis (GenTB), a free and open web-based application to predict antibiotic resistance from next-generation sequence data. The user can choose between two potential predictors, a Random Forest (RF) classifier and a Wide and Deep Neural Network (WDNN) to predict phenotypic resistance to 13 and 10 anti-tuberculosis drugs, respectively. We benchmark GenTB’s predictive performance along with leading TB resistance prediction tools (Mykrobe and TB-Profiler) using a ground truth dataset of 20,408 isolates with laboratory-based drug susceptibility data. All four tools reliably predicted resistance to first-line tuberculosis drugs but had varying performance for second-line drugs. The mean sensitivities for GenTB-RF and GenTB-WDNN across the nine shared drugs were 77.6% (95% CI 76.6–78.5%) and 75.4% (95% CI 74.5–76.4%), respectively, and marginally higher than the sensitivities of TB-Profiler at 74.4% (95% CI 73.4–75.3%) and Mykrobe at 71.9% (95% CI 70.9–72.9%). The higher sensitivities were at an expense of ≤ 1.5% lower specificity: Mykrobe 97.6% (95% CI 97.5–97.7%), TB-Profiler 96.9% (95% CI 96.7 to 97.0%), GenTB-WDNN 96.2% (95% CI 96.0 to 96.4%), and GenTB-RF 96.1% (95% CI 96.0 to 96.3%). Averaged across the four tools, genotypic resistance sensitivity was 11% and 9% lower for isoniazid and rifampicin respectively, on isolates sequenced at low depth (< 10× across 95% of the genome) emphasizing the need to quality control input sequence data before prediction. We discuss differences between tools in reporting results to the user including variants underlying the resistance calls and any novel or indeterminate variants

Conclusions

GenTB is an easy-to-use online tool to rapidly and accurately predict resistance to anti-tuberculosis drugs. GenTB can be accessed online at https://gentb.hms.harvard.edu, and the source code is available at https://github.com/farhat-lab/gentb-site.
Accelerated osteoarthritis in women with polycystic ovary syndrome: a prospective nationwide registry-based cohort study
Authors: Kluzek Stefan , Rubin Katrine Hass , Sanchez-Santos Maria , O’Hanlon Mary S. , Andersen Marianne , Glintborg Dorte , Abrahamsen Bo
Published: August 2021

Background

Osteoarthritis (OA) is the most common form of arthritis with multiple risk factors implicated including female sex and obesity. Metabolic dysregulation associated with obesity leading to metabolic syndrome is a proposed component of that association. Polycystic ovary syndrome (PCOS) commonly affects women of reproductive age and these women are at higher risk of developing metabolic syndrome and thus likely to represent a high-risk group for early OA development. There are no published studies exploring the epidemiology of knee, hip and hand OA in women diagnosed with PCOS.

Study aim

To assess the prevalence and incidence of knee, hip and hand osteoarthritis (OA) in women with polycystic ovary syndrome (PCOS) when compared with age-matched controls.

Methods

Prospective Danish national registry-based cohort study. The prevalence of OA in 2015 and incidence rates of OA over 11.1 years were calculated and compared in more than 75,000 Danish women with either a documented diagnosis of PCOS ± hirsutism (during the period of 1995 to 2012) or age-matched females without those diagnoses randomly drawn from the same population register.

Results

In 2015, the prevalence of hospital treated knee, hip and hand OA was 5.2% in women with PCOS diagnosis. It was 73% higher than that seen in age-matched controls. Significantly higher incidence rates were observed in the PCOS cohort compared with the age-matched controls during the follow-up period (up to 20 years), with the following hazard ratios (HR): 1.9 (95% CI 1.7 to 2.1) for knee, 1.8 (95% CI 1.3–2.4) for hand and 1.3 (95% CI 1.1 to 1.6) for hip OA. After excluding women with obesity, similar associations were observed for knee and hand OA. However, risk of developing hip OA was no longer significant.

Conclusions

In this large prospective study, women with PCOS diagnosis had higher prevalence and accelerated onset of OA of both weight and non-weight bearing joints, when compared with age-matched controls. Further studies are needed to understand the relative effect of metabolic and hormonal changes linked with PCOS and their role in promoting development of OA.
Epidemiology and treatment of Behçet’s disease in the USA: insights from the Rheumatology Informatics System for Effectiveness (RISE) Registry with a comparison with other published cohorts from endemic regions
Authors: Hammam Nevin , Li Jing , Evans Michael , Kay Julia L. , Izadi Zara , Anastasiou Christine , Gianfrancesco Milena A. , Yazdany Jinoos , Schmajuk Gabriela
Published: August 2021

Background

Behçet’s disease (BD), a chronic systemic vasculitis, has distinct geographical and ethnic variation. Data regarding the epidemiology of patients with BD in the U.S. are limited; therefore, we sought to describe BD patient characteristics and medication use in the U.S., and compared them with data from patients from endemic regions.

Methods

We conducted a cross-sectional study using data from the RISE registry (2014–2018). Patients aged ≥ 18 years with BD were included. Sociodemographic and treatment information was extracted. We compared patients from the RISE registry to data from other published studies of patients with BD from endemic areas.

Results

One thousand three hundred twenty-three subjects with BD from the RISE registry were included. Mean age was 48.7 ± 16.3 years, female to male ratio was 3.8:1, and 66.7% were White. The most frequently used medications included glucocorticoids (67.6%) and colchicine (55.0%). Infliximab and adalimumab were the most used biologics (14.5% and 14.1%, respectively); 3.2% of patients used apremilast. The RISE registry had more women (79.3%), and patients were older compared to previously published BD studies from endemic areas. Methotrexate and TNFi were more commonly reported in RISE (21.8% and 29.4%) compared to studies from Egypt and Turkey. Colchicine, cyclosporine, and cyclophosphamide were more commonly used in cohorts from Egypt, Turkey, and Iran.

Conclusions

Findings from the largest BD dataset in the U.S. suggest that BD patients are predominantly female. Further research is needed to explore the reasons for the higher prevalence of BD among women in the U.S. and its possible impact on disease severity and management.
More than a meeting: identifying the needs of the community-based seniors’ services sector as providers of health promotion services
Authors: Tong Catherine E. , Sims-Gould Joanie , Lusina-Furst Sarah , McKay Heather
Published: August 2021

Objective

Many economically developed countries have seen a decline in publicly funded community programming. Within this context, community-based seniors’ service (CBSS) organizations have been increasingly tasked to deliver programs to support the health and wellbeing of older citizens (e.g., home support, physical activity programs, and chronic disease management education). The primary objective of this study was to capture of the current needs of CBSS leaders in British Columbia, Canada, who attended a seminal event in the CBSS sector’s development—the inaugural Summit on Aging.

Results

Our evaluation of the Summit included: pre/post Summit surveys (N = 79/76), ethnographic observations, and follow-up interviews (n = 22). Our detailed evaluation plan may inform others undertaking similar data collection; the most informative results were derived from the follow-up interviews and our findings suggest that interviews may be sufficient for similar evaluations. Summit delegates identified key opportunities to strengthen the CBSS as a sector, including enhanced collaboration; improved mechanisms that foster connecting and collaborating; and more resources, including training and qualified staff, to increase their capacity to deliver community-based health services. These findings echo work already completed in the community-based health promotion sector.
SonoGames: sounds of the right kind introducing gamification into radiology training
Authors: Ali Maria Fatima , Nadeem Naila , Khalid Farah , Anwar Naveed Muhammad , Nabie Ghulam , Docherty Charles
Published: August 2021

Background

Radiology as compared to other fields of medicine has lagged, in incorporating modern training modalities such as gamification and simulation into its teaching curriculum.

Objective

This study aims to evaluate effectiveness of simulation-based teaching in collaboration with gamification. Bandura’s conception of self-efficacy was used to provide qualitative assessment of participants’ learning process through training event. Modified competitive game-based teaching methodology was utilized in an experimental study conducted for radiology residents. Workshop was divided into two sessions, first being three interactive didactic lectures followed by three competitive rounds. All participants were required to fill pre and post-self-efficacy questionnaire along with an activity evaluation form.

Results

Significant self-efficacy scores were calculated for simulation-based stations of knowledge assessment and hands-on stations. Whereas significant association was also found between gender and knowledge assessment in communication skill (0.054), Professionalism (0.004), and general knowledge (0.018). Similarly, noteworthy correlation was found between gender and all hands-on skills. In conclusion, study reported an overall increase in knowledge of post-test scores compared to pre-test scores due to use of gamification in combination with simulation-based teaching which shows a positive role in clinical training. However, further consideration is needed to improve process of integrating simulation in clinical training of participants.
Dynamics of epigenetic regulator gene BCOR mutation and response predictive value for hypomethylating agents in patients with myelodysplastic syndrome
Authors: Li Xiao , Xu Feng , Zhang Zheng , Guo Juan , He Qi , Song Lu-Xi , Wu Dong , Zhou Li-Yu , Su Ji-Ying , Xiao Chao , Chang Chun-Kang , Wu Ling-Yun
Published: August 2021

Background

BCOR (BCL6 corepressor) is an epigenetic regulator gene involved in the specification of cell differentiation and body structure development. Recurrent somatic BCOR mutations have been identified in myelodysplastic syndrome (MDS). However, the clinical impact of BCOR mutations on MDS prognosis is controversial and the response of hypomethylating agents in MDS with BCOR mutations (BCORMUT) remains unknown.

Results

Among 676 MDS patients, 43 patients (6.4%) harbored BCOR mutations. A higher frequency of BCOR mutations (8.7%) was investigated in patients with normal chromosome, compared to 4.2% in patients with abnormal karyotype (p = 0.040). Compared to the BCORWT patients, the BCORMUT patients showed a higher ratio of refractory anemia with excess blasts subset (p = 0.008). The most common comutations with BCOR genes were ASXL1 (p = 0.002), DNMT3A (p = 0.114) and TET2 (p = 0.148). When the hierarchy of somatic mutations was analyzed, BCOR mutations were below the known initial mutations (ASXL1 or TET2) but were above U2AF1 mutations. Transformation-free survival was significantly shorter in BCORMUT patients than that in BCORWT patients (16 vs. 35 months; p = 0.035). RNA-sequencing was performed in bone marrow mononuclear cells from BCORMUT and BCORWT patients and revealed 2030 upregulated and 772 downregulated genes. Importantly, HOXA6, HOXB7, and HOXB9 were significantly over-expressed in BCORMUT patients, compared to BCORWT patients. Eight of 14 BCORMUT patients (57.1%) achieved complete remission (CR) with decitabine treatment, which was much higher than that in BCORWT patients (28.7%, p = 0.036). Paired sequencing results (before and after decitabine) showed three of 6 CR patients lost the mutated BCOR. The median survival of CR patients with a BCORMUT was 40 months, which was significantly longer than that in patients with BCORWT (20 months, p = 0.036). Notably, prolonged survival was observed in three BCORMUT CR patients even without any subsequent therapies.

Conclusions

BCOR mutations occur more frequently in CN MDS patients, predicting higher risk of leukemia transformation. BCORMUT patients showed a better response to decitabine and achieved longer post-CR survival.
The inferior vena cava: anatomical variants and acquired pathologies
Authors: Li Simon J. , Lee Jean , Hall Jonathan , Sutherland Tom R.
Published: August 2021

The inferior vena cava (IVC) is the largest vein in the body, draining blood from the abdomen, pelvis and lower extremities. This pictorial review summarises normal anatomy and embryological development of the IVC. In addition, we highlight a wide range of anatomical variants, acquired pathologies and a common pitfall in imaging of the IVC. This information is essential for clinical decision making and to reduce misdiagnosis.
Predictors and moderators of outcome of psychotherapeutic interventions for mental disorders in adolescents and young adults: protocol for systematic reviews
Authors: Vousoura Eleni , Gergov Vera , Tulbure Bogdan Tudor , Camilleri Nigel , Saliba Andrea , Garcia-Lopez LuisJoaquin , Podina Ioana R. , Prevendar Tamara , Löffler-Stastka Henriette , Chiarenza Giuseppe Augusto , Debbané Martin , Markovska-Simoska Silvana , Milic Branka , Torres Sandra , Ulberg Randi , Poulsen Stig
Published: August 2021

Background

Adolescence and young adulthood is a risk period for the emergence of mental disorders. There is strong evidence that psychotherapeutic interventions are effective for most mental disorders. However, very little is known about which of the different psychotherapeutic treatment modalities are effective for whom. This large systematic review aims to address this critical gap within the literature on non-specific predictors and moderators of the outcomes of psychotherapeutic interventions among adolescents and young adults with mental disorders.

Methods

The protocol is being reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement. PubMed and PsycINFO databases will be searched for randomized controlled and quasi-experimental/naturalistic clinical trials. Risk of bias of all included studies will be assessed by the Mixed Methods Appraisal Tool. The quality of predictor and moderator variables will be also assessed. A narrative synthesis will be conducted for all included studies.

Discussion

This systematic review will strengthen the evidence base on effective mental health interventions for young people, being the first to explore predictors and moderators of outcome of psychotherapeutic interventions for a wide range of mental disorders in young people.

Systematic review registration

PROSPERO CRD42020166756.
Strong convergence for monotone bilevel equilibria with constraints of variational inequalities and fixed points using subgradient extragradient implicit rule
Authors: He Long , Cui Yun-Ling , Ceng Lu-Chuan , Zhao Tu-Yan , Wang Dan-Qiong , Hu Hui-Ying
Published: August 2021

In a real Hilbert space, let GSVI and CFPP represent a general system of variational inequalities and a common fixed point problem of a countable family of nonexpansive mappings and an asymptotically nonexpansive mapping, respectively. In this paper, via a new subgradient extragradient implicit rule, we introduce and analyze two iterative algorithms for solving the monotone bilevel equilibrium problem (MBEP) with the GSVI and CFPP constraints, i.e., a strongly monotone equilibrium problem over the common solution set of another monotone equilibrium problem, the GSVI and the CFPP. Some strong convergence results for the proposed algorithms are established under the mild assumptions, and they are also applied for finding a common solution of the GSVI, VIP, and FPP, where the VIP and FPP stand for a variational inequality problem and a fixed point problem, respectively.
A pooled prevalence of fetal alcohol spectrum disorders in South Africa: a systematic review and meta-analysis protocol
Authors: Adebiyi Babatope O. , Mukumbang Ferdinand C.
Published: August 2021

Background

Fetal Alcohol Spectrum Disorder (FASD) remains a global public health problem. South Africa is estimated to have the highest recorded prevalence of FASD. However, no study has systematically evaluated the available prevalence studies to provide estimates that may facilitate effective planning and delivery of prevention and management services. Therefore, we propose to conduct a systematic review and meta-analysis to report a pooled estimate of the FASD prevalence among children, youth and adults in South Africa.

Methods

We will include quantitative (cohort and cross-sectional) studies that reported on the prevalence of FASD in South Africa. We will search databases such as Academic Search Complete, Education Resource Information Center (ERIC), SocINDEX, Health Source: Nursing/Academic Edition, Cumulative Index of Nursing and Allied Health and PsycARTICLES), Scopus, Science Direct, Springer Link, JSTOR, SAGE journals, PubMed, Web of Science and Sabinet. The references of included studies will be searched for additional studies on the prevalence of FASD. The search will be from inception to October 2021. Screening of (titles, abstracts and full text of the potentially relevant articles) will be done by two independent authors using software. All disagreements will be resolved by discussion. A standardised data extraction form will be designed for the extraction. Two authors will independently extract the data from the selected articles and all disagreements will be resolved by discussion. We will use a tool developed by Munn and colleagues to critically appraise all the included studies. The primary outcome will be the proportion of individuals with FASD in South Africa. We will use the Freeman–Tukey double arcsine transformation to transform the raw prevalence estimates so that the data can follow an approximately normal distribution. We will use random-effects models to calculate 95% confidence intervals and prediction intervals based on multiple meta-analyses with transformed proportions. We will test heterogeneity using Cochran’s Q and describe using the I2 statistic.

Discussion

The pooled prevalence estimate will assist the government and other stakeholders (such as non-profit organisations and researchers) to plan and prioritise prevention and management interventions.

Systematic review registration

The protocol has been registered with PROSPERO (registration number: CRD42020197979).
Admission screening and cohort care decrease carbapenem resistant enterobacteriaceae in Vietnamese pediatric ICU’s
Authors: Garpvall K. , Duong V. , Linnros S. , Quốc T. N. , Mucchiano D. , Modeen S. , Lagercrantz L. , Edman A. , Le N. K. , Huong T. , Hoang N. T. B. , Le H. T. , Khu D. TK. , Tran D. M. , Phuc P. H. , Hanberger H. , Olson L. , Larsson M.
Published: August 2021

Objectives

To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay, mortality, and costs in three Intensive Care Units (ICU’s) at the Vietnamese National Children’s Hospital.

Method

CRE screening using rectal swabs and ChromIDCarbas elective culture at admission and if CRE negative, once weekly. Patients were treated in cohorts based on CRE colonization status.

Results

CRE colonization at baseline point-prevalence screening was 76.9% (103/134). Of 941 CRE screened at admission, 337 (35.8%) were CREpos. 694 patients met inclusion criteria. The 244 patients CRE negative at admission and screened > 2 times were stratified in 8 similar size groups (periods), based on time of admission. CRE acquisition decreased significant (OR − 3.2, p < 0.005) from 90% in period 2 (highest) to 48% in period 8 (last period). Patients with CRE acquisition compared to no CRE acquisition had a significantly higher rate of culture confirmed HAI, n = 20 (14%) vs. n = 2 (2%), longer hospital stays, 3.26 vs. 2.37 weeks, and higher total treatment costs, 2852 vs. 2295 USD.

Conclusion

Admission CRE screening and cohort care in pediatric ICU’s significantly decreased CRE acquisition, cases of HAI and duration of hospital-stay.
Pain and health-related quality of life in adolescents and the mediating role of self-esteem and self-efficacy: a cross-sectional study including adolescents and parents
Authors: Mikkelsen Hilde Timenes , Haraldstad Kristin , Helseth Sølvi , Skarstein Siv , Småstuen Milada Cvancarova , Rohde Gudrun
Published: August 2021

Background

To promote health-related quality of life (HRQOL) in adolescents with pain, it is important to study factors associated with pain. This study aimed to describe selected factors and pain in 14–15-year-old adolescents and their parents, to assess how these factors are associated with adolescent pain groups, and to explore whether the relationship between pain intensity and HRQOL in adolescents with persistent pain is mediated by self-esteem and self-efficacy.

Methods

A cross-sectional study was performed among 508 dyads of adolescents (14–15 years) and parents in a school-based setting. Among these, 148 adolescents had persistent pain. We explored the following variables: HRQOL, pain, self-efficacy, self-esteem, sleep, loneliness, stress and sociodemographic variables. All variables were assessed with well-validated instruments. HRQOL was measured with KIDSCREEN-27. Analyses included Chi-square, ANOVA, Mann–Whitney U tests, Kruskal–Wallis and the PROCESS macro method for mediation analyses.

Results

Adolescents with pain reported significantly higher levels of stress, loneliness and lack of sleep and lower levels of self-efficacy, self-esteem and HRQOL compared to adolescents without pain. More girls than boys reported pain. Adolescents with persistent pain scored significantly worse on self-esteem, stress, loneliness, lack of sleep, school absence, pain and HRQOL compared to adolescents with shorter pain duration. Adolescent pain groups did not differ significantly considering parental factors. However, more adolescents with persistent pain reported that someone in their family had pain. The associations between pain intensity and the HRQOL subscales in adolescents with persistent pain were completely mediated by self-esteem, but not by self-efficacy. The highest degree of mediation was estimated for the HRQOL subscale school environment (indirect effect = 73.5%).

Conclusions

Our findings highlight the complexity within adolescent pain, demonstrating that adolescents with pain differ from adolescents without pain when it comes to gender, school absence, factors within-person and between-persons. Longer pain duration makes adolescents more vulnerable. We confirm the importance of resilience factors for HRQOL but indicate that self-esteem is more important than self-efficacy. To promote HRQOL in adolescents with persistent pain, a strengthening of both their self-esteem and self-efficacy is recommended. We highlight the need for an individual, holistic approach to adolescent pain.
IoT Big Data provenance scheme using blockchain on Hadoop ecosystem
Authors: Honar Pajooh Houshyar , Rashid Mohammed A. , Alam Fakhrul , Demidenko Serge
Published: August 2021

The diversity and sheer increase in the number of connected Internet of Things (IoT) devices have brought significant concerns associated with storing and protecting a large volume of IoT data. Storage volume requirements and computational costs are continuously rising in the conventional cloud-centric IoT structures. Besides, dependencies of the centralized server solution impose significant trust issues and make it vulnerable to security risks. In this paper, a layer-based distributed data storage design and implementation of a blockchain-enabled large-scale IoT system are proposed. It has been developed to mitigate the above-mentioned challenges by using the Hyperledger Fabric (HLF) platform for distributed ledger solutions. The need for a centralized server and a third-party auditor was eliminated by leveraging HLF peers performing transaction verifications and records audits in a big data system with the help of blockchain technology. The HLF blockchain facilitates storing the lightweight verification tags on the blockchain ledger. In contrast, the actual metadata are stored in the off-chain big data system to reduce the communication overheads and enhance data integrity. Additionally, a prototype has been implemented on embedded hardware showing the feasibility of deploying the proposed solution in IoT edge computing and big data ecosystems. Finally, experiments have been conducted to evaluate the performance of the proposed scheme in terms of its throughput, latency, communication, and computation costs. The obtained results have indicated the feasibility of the proposed solution to retrieve and store the provenance of large-scale IoT data within the Big Data ecosystem using the HLF blockchain. The experimental results show the throughput of about 600 transactions, 500 ms average response time, about 2–3% of the CPU consumption at the peer process and approximately 10–20% at the client node. The minimum latency remained below 1 s however, there is an increase in the maximum latency when the sending rate reached around 200 transactions per second (TPS).
Enhancement of co-production of lutein and protein in Chlorella sorokiniana FZU60 using different bioprocess operation strategies
Authors: Ma Ruijuan , Zhang Zhen , Tang Zhuzhen , Ho Shih-Hsin , Shi Xinguo , Liu Lemian , Xie Youping , Chen Jianfeng
Published: August 2021

Co-production of multiple compounds is an efficient approach to enhance the economic feasibility of microalgae-based metabolites production. In this study, Chlorella sorokiniana FZU60 was cultivated under different bioprocess strategies to enhance the co-production of lutein and protein. Results showed that both lutein and protein content (7.72 and 538.06 mg/g, respectively) were highest at the onset of nitrogen deficiency under batch cultivation. Semi-batch III strategy, with 75% microalgal culture replacement by fresh medium, obtained similar content, productivity, and yield of lutein and protein as batch cultivation, demonstrating that it can be used for stable and continuous production. Fed-batch II strategy, feeding with 1/3 modified BG11 medium, achieved super-high lutein and protein yield (28.81 and 1592.77 mg/L, respectively), thus can be used for high-output production. Besides, two-stage strategy, combining light intensity shift and semi-batch cultivation, gained extremely high lutein and protein productivity (15.31 and 1080.41 mg/L/day, respectively), thereby is a good option for high-efficiency production. Moreover, the fed-batch II and two-stage strategy achieved high-quality lutein and protein, thus are promising for the co-production of lutein and protein in C. sorokiniana FZU60 for commercial application.
The effects of the molecular weights of hyaluronic acid on the immune responses
Authors: Lee Bo Mi , Park Sang Jun , Noh Insup , Kim Chun-Ho
Published: August 2021

Background

The molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages.

Methods

The structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by
1
 H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (10 µg/mL) or high (100 µg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR.

Results

Molecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241 ± 161, 96,531 ± 1,167, 512,657 ± 8,545, and 1,249,500 ± 37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 µg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45 %. Using NanoString technology, we also found that the immune-related genes TNF-α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 µg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages.

Conclusions

High molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.
Tissue-specific systemic responses of the wild tobacco Nicotiana attenuata against stem-boring herbivore attack
Authors: Lee Gisuk , Joo Youngsung , Baldwin Ian T. , Kim Sang-Gyu
Published: August 2021

Background

Plants are able to optimize defense responses induced by various herbivores, which have different feeding strategies. Local and systemic responses within a plant after herbivory are essential to modulate herbivore-specific plant responses. For instance, leaf-chewing herbivores elicit jasmonic acid signaling, which result in the inductions of toxic chemicals in the attacked leaf (tissue-specific responses) and also in the other unattacked parts of the plant (systemic responses). Root herbivory induces toxic metabolites in the attacked root and alters the levels of transcripts and metabolites in the unattacked shoot. However, we have little knowledge of the local and systemic responses against stem-boring herbivores. In this study, we examined the systemic changes in metabolites in the wild tobacco Nicotiana attenuata, when the stem-boring herbivore Trichobaris mucorea attacks.

Results

To investigate the systemic responses of T. mucorea attacks, we measured the levels of jasmonic acid (JA), JA-dependent secondary metabolites, soluble sugars, and free amino acids in 7 distinct tissues of N. attenuata: leaf lamina with epidermis (LLE), leaf midrib (LM), stem epidermis (SE), stem pith (SP), stem vascular bundle (SV), root cortex with epidermis (RCE), and root vascular bundle (RV). The levels of JA were increased in all root tissues and in LM by T. mucorea attacks. The levels of chlorogenic acids (CGAs) and nicotine were increased in all stem tissues by T. mucorea. However, CGA was systematically induced in LM, and nicotine was systematically induced in LM and RCE. We further tested the resource allocation by measuring soluble sugars and free amino acids in plant tissues. T. mucorea attacks increased the level of free amino acids in all tissues except in LLE. The levels of soluble sugars were significantly decreased in SE and SP, but increased in RV.

Conclusions

The results reveal that plants have local- and systemic-specific responses in response to attack from a stem-boring herbivore. Interestingly, the level of induced secondary metabolites was not consistent with the systemic inductions of JA. Spatiotemporal resolution of plant defense responses against stem herbivory will be required to understand how a plant copes with attack from herbivores from different feeding guilds.
A volumetric magnetic resonance imaging study in migraine
Authors: Naguib Laila Elmously , Abdel Azim Ghada Saed , Abdellatif Mohammed Abdelrazek
Published: August 2021

Background

Although migraine phenotype has been widely described, the explanation of migraine pathophysiology still has a gap that might be partly bridged by neuroimaging investigations. The aim of the study is to assess volumetric brain changes in migraineurs compared with controls, and in episodic migraine in comparison to chronic type. Structural brain changes in migraineurs (with and without aura) were assessed by an automated segmentation method (Free Surfer). T1-weighted MRIs of 25 migraineurs (14 diagnosed as episodic type and 11 diagnosed as chronic migraine) and 25 headache-free controls were evaluated and processed.

Results

Migraine patients had significant reduction of the volume of total brain, grey matter, brain stem, cerebellum, basal ganglia, thalamus, hippocampus and amygdala in comparison to control subjects. Patients with chronic migraine had significant reduction in volume of total brain, grey matter, cerebellum and frontal lobe thickness in comparison to those with episodic migraine.

Conclusion

Migraineurs showed volumetric brain changes mainly in areas related to central processing of pain and in areas specific for migraine (such as brain stem) when compared to healthy controls. Chronic migraineurs showed significant reduction in grey matter, in areas involved in processing of pain, cognition and multisensory integration versus patients with episodic migraine, which adds insight into the pathophysiology of migraine as a progressive disorder that may have long-term impacts on the brain as regards structure and function.
Species and genetic variability of sweet potato viruses in China
Authors: Wang Yongjiang , Qin Yanhong , Wang Shuang , Zhang Desheng , Tian Yuting , Zhao Fumei , Wang Yingzhi , Lv Hui , Qiao Qi , Zhang Zhenchen
Published: August 2021

China is the world’s largest producer of sweet potato (Ipomoea batatas (L.) Lam.). Considering that there are numerous sweet potato-producing regions in China and sweet potato is a vegetatively propagated crop, the genetic diversity of sweet potato viruses could be high in the country. However, studies on species and genetic variabilities of sweet potato viruses in China are limited, making it difficult to prevent and control viral diseases in this crop. During 2014–2019, sweet potato samples with viral disease-like symptoms were randomly collected from sweet potato fields in 25 provinces in China. Twenty-one virus species, including 12 DNA and 9 RNA viruses, were identified in the samples using next-generation sequencing, polymerase chain reaction and rolling-circle amplification methods. One novel sweepovirus species, Sweet potato leaf curl Hubei virus (SPLCHbV), was identified. Two species, Sweet potato collusive virus and Tobacco mosaic virus, were identified for the first time in sweet potato in China. Full-length or nearly full-length genomic sequences of 111 isolates belonging to 18 viral species were obtained. Genome sequence comparisons of potyvirus isolates obtained in this study indicate that the genome of sweet potato virus 2 is highly conserved, whereas the other four potyviruses, sweet potato feathery mottle virus, sweet potato virus G, sweet potato latent virus and sweet potato virus C, exhibited a high genetic variability. The similarities among the 40 sweepovirus genomic sequences obtained from eight sweepovirus species are 67.0–99.8%. The eight sweepoviruses include 14 strains, of which 4 novel strains were identified from SPLCHbV and 1 from sweet potato leaf curl Guangxi virus. Five sweet potato chlorotic stunt virus (SPCSV) isolates obtained belong to the WA strain, and the genome sequences of SPCSV are highly conserved. Together, this study for the first time comprehensively reports the variability of sweet potato viruses in China.
First record of stable isotopes (δ13C, δ18O) and element ratios (Mg/Ca, Sr/Ca) of Middle to Late Jurassic belemnites from the Indian Himalayas and their potential for palaeoenvironmental reconstructions
Authors: Alberti Matthias , Fürsich Franz T. , Pandey Dhirendra K. , Andersen Nils , Garbe-Schönberg Dieter , Bhosale Suraj , Chaskar Ketan , Habermann Jörg M.
Published: August 2021

Middle to Late Jurassic belemnites from the Spiti and Zanskar valleys in the Indian Himalayas were used for stable isotope (δ13C, δ18O) and element (Mg/Ca, Sr/Ca) analyses. Although the Himalayan orogeny deformed and altered a large portion of the collected fossils, cathodoluminescence and scanning electron microscopy in combination with analyses of iron and manganese contents allowed the identification of belemnites believed to still retain their original chemical composition. Results indicate a long-term temperature decrease from the Middle Callovian–Oxfordian to the Tithonian, which is proposed to have been caused by a concomitant drift of eastern Gondwana into higher palaeolatitudes. Reconstructed absolute temperatures depend on the used equation and assumed δ18O value of seawater, but most likely varied between 17.6 °C to 27.6 °C in the Kimmeridgian and Tithonian with average values between 22 °C to 24 °C. This way, temperatures were similar to slightly warmer than today at comparable latitudes. The reconstruction of absolute temperatures for the Middle Callovian–Oxfordian was hindered by a larger number of poorly preserved belemnites representing this time interval.
Minimally invasive mitral valve repair for degenerative etiology: a comparative study
Authors: Fouly Mohamed Abdel Hafez , Mousa Tarek K.
Published: August 2021

Background

There is a paucity of data comparing the minimally invasive mitral valve repair (MiMVr) to the conventional approach in patients with degenerative disease. Our objective was to compare the outcomes of MiMVr to the traditional mitral valve repair through median sternotomy in patients with degenerative mitral valve disease. We conducted a retrospective study on 215 patients classified into two groups. Group 1 (n = 80) included those who had mitral valve repair through a right anterolateral video-assisted mini-thoracotomy, and group 2 (n = 135) was approached through a conventional median sternotomy. We compared the preoperative, operative, and postoperative data between groups. Both groups had echocardiographic follow-ups after 6 and 12 months.

Results

There was no difference in gender distribution between both groups, and patients who had median sternotomy were significantly older (median 37 (Q1-Q3, 29-44) vs. 54 (48-60) years; P < 0.001). Cardiopulmonary bypass (134.5 (130-138.5) vs. 99 (97-104) min; P < 0.001) and ischemic times (99 (95-105.5) vs. 78 (75-81) min; P < 0.001) were significantly shorter in patients who had median sternotomy. Patients with MiMVr had significantly lower blood loss (370 (315-390) vs. 550 (490-600) ml; P < 0.001) and ICU stay (5 (4.5-6) vs. 7 (7-8) days; P < 0.001). There was no difference between both groups regarding re-exploration for bleeding, postoperative stroke, wound infection, renal failure, and mortality. As regards postoperative echocardiography follow-up at 6 and 12 months after the operation, there were no significant changes in the mean mitral valve gradient within each group; however, the mean gradient was lower in the MiMVr group (3 (3-3.5) vs. 4 (3-5) mmHg; P < 0.001). There was no significant difference between both groups regarding mitral regurgitation severity during 6 and 12 months follow-up.

Conclusion

Minimally invasive mitral valve repair in patients with degenerative pathology could be an alternative to conventional mitral valve surgery with comparable short-term and long-term outcomes.
Stakeholder perspectives to inform adaptation of a hypertension treatment program in primary healthcare centers in the Federal Capital Territory, Nigeria: a qualitative study
Authors: Okoli Rosemary C. B. , Shedul Gabriel , Hirschhorn Lisa R. , Orji Ikechukwu A. , Ojo Tunde M. , Egenti Nonye , Omitiran Kasarachi , Akor Blessing , Baldridge Abigail S. , Huffman Mark D. , Ojji Dike , Kandula Namratha R.
Published: August 2021

Background

Implementing an evidence-based hypertension program in primary healthcare centers (PHCs) in the Federal Capital Territory, Nigeria is an opportunity to improve hypertension diagnosis, treatment, and control and reduce deaths from cardiovascular diseases. This qualitative research study was conducted in Nigerian PHCs with patients, non-physician health workers, administrators and primary care physicians to inform contextual adaptations of Kaiser Permanente Northern California's hypertension model and the World Health Organization’s HEARTS technical package for the system-level, Hypertension Treatment in Nigeria (HTN) Program.

Methods

Purposive sampling in 8 PHCs identified patients (n = 8), non-physician health workers (n = 12), administrators (n = 3), and primary care physicians (n = 6) for focus group discussions and interviews. The Primary Health Care Performance Initiative (PHCPI) conceptual framework and Consolidated Framework for Implementation Research (CFIR) domains were used to develop semi-structured interviews (Appendix 1, Supplemental Materials) and coding guides. Content analysis identified multilevel factors that would influence program implementation.

Results

Participants perceived the need to strengthen four major health system inputs across CFIR domains for successful adaptation of the HTN Program components: (1) reliable drug supply and blood pressure measurement equipment, (2) enable and empower community healthcare workers to participate in team-based care through training and education, (3) information systems to track patients and medication supply chain, and (4) a primary healthcare system that could offer a broader package of health services to meet patient needs. Specific features of the PHCPI framework considered important included: accessible and person-centered care, provider availability and competence, coordination of care, and proactive community outreach. Participants also identified patient-level factors, such as knowledge and beliefs about hypertension, and financial and transportation barriers that could be addressed with better communication, home visits, and drug financing. Participants recommended using existing community structures, such as village health committees and popular opinion leaders, to improve knowledge and demand for the HTN Program.

Conclusions

These results provide information on specific primary care and community contextual factors that can support or hinder implementation and sustainability of an evidence-based, system-level hypertension program in the Federal Capital Territory, Nigeria, with the ultimate aim of scaling it to other parts of the country.
Addressing the importance of microplastic particles as vectors for long-range transport of chemical contaminants: perspective in relation to prioritizing research and regulatory actions
Authors: Gouin Todd
Published: August 2021

Over the last several years there has been increasing concern regarding the environmental fate and potential global transport of plastic debris, particularly in the form of microplastic particles (MPs). The global transport of MPs has also triggered concerns regarding the potential role that its mobility may represent towards influencing the long-range environmental transport (LRET) of particle-bound chemicals, particularly the large number of chemicals known to be added to plastic. This perspective considers the various lines-of-evidence that might be used towards understanding the LRET of persistent organic pollutants (POPs). For instance, it has been proposed that the LRET of POPs is facilitated by global fractionation processes that facilitate the mobility of chemicals from source regions towards remote locations, such as the polar regions, where they have the potential to accumulate. These processes are influenced by the physicochemical properties of POPs and can result in various transport mechanisms influencing environmental fate and transport. Here I suggest that there are similarities that can be drawn, whereby knowledge of how differences in the physicochemical properties of MPs relative to different emission scenarios, can influence the relative importance of sequestration processes that may result in global fractionation of MPs. Several challenges are identified throughout the perspective, with an urgent need towards the development and application of standard sampling and analytical methods being identified as critical for enabling datasets to be reliably compared for use in better understanding potential source-receptor relationships, as well as advancing the characterization and quantification of various environmental fate processes. In many instances, it is suggested that advances in our understanding can be facilitated based on knowledge obtained in other areas of research, such as in relation to studies developing tools to evaluate the mobility of particulate organic matter in aqueous environments or from studies investigating the fate and mobility of atmospheric particulates. Recognizing that not all MPs are equal, with respect to environmental fate and toxicological effects, knowledge regarding which types of MPs are likely to be subject to LRET can only strengthen our ability to evaluate their role as vectors of transport for plastic associated chemicals and the associated risks that their LRET may represent. Nevertheless, several outstanding issues remain that would benefit from constructive discussions between all stakeholders. It is anticipated that this perspective can play a role in initiating those discussions.
Cryptanalysis of quantum secure direct communication protocol with mutual authentication based on single photons and Bell states
Authors: Das Nayana , Paul Goutam
Published: August 2021

Recently, Yan et al. proposed a quantum secure direct communication (QSDC) protocol with authentication using single photons and Einstein-Podolsky-Rosen (EPR) pairs (Yan L. et al., Comput. Mater. Contin., 63 (2020) 1297). In this work, we show that the above QSDC protocol is secure neither against intercept-and-resend attack, nor against impersonation attack. With any of these two types of attacks, an eavesdropper can recover the full secret message. We also propose a suitable modification of this protocol, which not only defeats the above attacks, but also resists all other common attacks. Thus, our modified protocol provides an improvement over the existing one in terms of security.
Non-adiabatic superconductivity in the electron-doped graphene
Authors: Szczeşńiak Dominik , Drzazga-Szczeşńiak Ewa A.
Published: August 2021

In the present study, we investigate the impact of the non-adiabatic effects on the superconducting state in the electron-doped graphene. In particular, by using the Eliashberg formalism we analyze the case scenario of the nitrogen-doped graphene, showing that the non-adiabatic effects complement electron-electron interaction and notably reduce (up to∼40%) pivotal thermodynamic properties, such as: the critical temperature, the superconducting gap and their characteristic ratio. Interestingly, the influence of the non-adiabatic effects is found to rise together with the increase of the depairing Coulomb interaction. These observations are elucidated based on the structure of the vertex corrections to the electron-phonon interaction. As a result, we draw a direction for the future research in the field of the two-dimensional non-adiabatic superconductivity.