bluuebunny/crossref_metadata_2025 huggingface dataset:
NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice
Authors: Song Ao-Qi , Gao Bo , Fan Jun-Juan , Zhu Ya-Jing , Zhou Jun , Wang Yu-Ling , Xu Li-Zhong , Wu Wen-Ning
Published: June 2020

Background

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression.

Methods

Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion.

Results

Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus.

Conclusions

NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.
Habit formation in support of antiretroviral medication adherence in clinic-enrolled HIV-infected adults: a qualitative assessment using free-listing and unstructured interviewing in Kampala, Uganda
Authors: Jennings Mayo-Wilson Larissa , Devoto Bianca , Coleman Jessica , Mukasa Barbara , Shelton Angela , MacCarthy Sarah , Saya Uzaib , Chemusto Harriet , Linnemayr Sebastian
Published: June 2020

Background

Despite initial high motivation, individuals receiving antiretroviral therapy (ART) for several years may experience incomplete adherence over time, increasing their risk of HIV-related morbidity and mortality. Habits, defined as automatic and regular practices, do not rely on conscious effort, and may therefore support high long-term ART adherence.

Methods

This qualitative study contributes to the evidence on how clients with adherence problems remember and form habits to take ART medications. Free-listing and unstructured interviewing were used among 42 clinic-enrolled adults in Kampala, Uganda who were receiving ART and participating in a randomized clinical trial for treatment adherence (clinicaltrials.gov: NCT03494777). Data were coded and analyzed using inductive content analysis.

Results

Findings indicated that clients’ most routine habits (eating, bathing, sleeping) did not always occur at the same time or place, making it difficult to reliably link to pill-taking times. Efforts to improve ART habits included having a relative to ask about pill-taking, re-packaging medications, leaving medications in view, using alarms, carrying water, or linking pill-taking to radio/prayer schedules. Reported challenges were adhering to ART schedules during changing employment hours, social activities, and travel.

Conclusion

While habit-forming interventions have the potential to improve ART adherence, targeting treatment-mature clients’ existing routines may be crucial in this population.
Analysis of trace metal distribution in plants with lab-based microscopic X-ray fluorescence imaging
Authors: Mijovilovich Ana , Morina Filis , Bokhari Syed Nadeem , Wolff Timo , Küpper Hendrik
Published: June 2020

Background

Many metals are essential for plants and humans. Knowledge of metal distribution in plant tissues in vivo contributes to the understanding of physiological mechanisms of metal uptake, accumulation and sequestration. For those studies, X-rays are a non-destructive tool, especially suited to study metals in plants.

Results

We present microfluorescence imaging of trace elements in living plants using a customized benchtop X-ray fluorescence machine. The system was optimized by additional detector shielding to minimize stray counts, and by a custom-made measuring chamber to ensure sample integrity. Protocols of data recording and analysis were optimised to minimise artefacts. We show that Zn distribution maps of whole leaves in high resolution are easily attainable in the hyperaccumulator Noccaea caerulescens. The sensitivity of the method was further shown by analysis of micro- (Cu, Ni, Fe, Zn) and macronutrients (Ca, K) in non-hyperaccumulating crop plants (soybean roots and pepper leaves), which could be obtained in high resolution for scan areas of several millimetres. This allows to study trace metal distribution in shoots and roots with a wide overview of the object, and thus avoids making conclusions based on singular features of tiny spots. The custom-made measuring chamber with continuous humidity and air supply coupled to devices for imaging chlorophyll fluorescence kinetic measurements enabled direct correlation of element distribution with photosynthesis. Leaf samples remained vital even after 20 h of X-ray measurements. Subtle changes in some of photosynthetic parameters in response to the X-ray radiation are discussed.

Conclusions

We show that using an optimized benchtop machine, with protocols for measurement and quantification tailored for plant analyses, trace metal distribution can be investigated in a reliable manner in intact, living plant leaves and roots. Zinc distribution maps showed higher accumulation in the tips and the veins of young leaves compared to the mesophyll tissue, while in the older leaves the distribution was more homogeneous.
Implementation science in times of Covid-19
Authors: Wensing Michel , Sales Anne , Armstrong Rebecca , Wilson Paul
Published: June 2020

The emergence of SARS-CoV-2/Covid-19 affects all of us and is associated with rapid and massive changes in healthcare and societies. As a response, a range of interventions for patients and populations have been implemented in health and preventive settings, or need to be implemented in the short and long term. Implementation science offers a multidisciplinary perspective and systematic approach for the design, evaluation and analysis of programmes and policies to enhance implementation. The emergence of Covid-19 provides an urgent need to develop new perspectives and approaches in implementation science, such as the addition of innovative and rigorous approaches to the collection, use and analysis of ‘real-world’ data. Above all, we hope that implementation scientists will focus on what they can contribute to manage Covid-19 and its consequences for people, healthcare and society.
Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis
Authors: Trone Jane-Chloe , Vallard Alexis , Sotton Sandrine , Ben Mrad Majed , Jmour Omar , Magné Nicolas , Pommier Benjamin , Laporte Silvy , Ollier Edouard
Published: June 2020

Background

Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line.

Materials/Methods

We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors.

Results

2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose.

Conclusions

Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved.
Cx3cr1CreERT2-driven Atg7 deletion in adult mice induces intestinal adhesion
Authors: Lee Younghwan , Lee Ji-Won , Nam Hyeri , Yu Seong-Woon
Published: June 2020

Microglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a Gαi-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1CreERT2 mice express Cre recombinase in a tamoxifen-inducible manner and have been widely used to delete target genes in microglia, since microglia are long-lived cells and outlive peripheral macrophages, which continuously turn over and lose their gene modification over time. ATG7 is an E1-like enzyme that plays an essential role in two ubiquitin-like reactions, ATG12-ATG5 conjugation and LC3-lipidation in autophagy. To study the role of ATG7 in adult microglia, we generated Cx3cr1CreERT2:Atg7fl/fl mice and deleted Atg7 at the age of 8 weeks, and found induction of intestinal adhesion. Since intestinal adhesion is caused by excessive inflammation, these results suggest that deletion of Atg7 in intestinal macrophages even for a short time results in inflammation that cannot be rescued by replenishment with wild-type intestinal macrophages. Our finding suggests that, depending on the roles of the gene, Cx3cr1-Cre-mediated gene deletion may yield unanticipated physiological outcomes outside the central nervous system, and careful necropsy is necessary to assure the microglia-specific roles of the target gene.
VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3β signaling
Authors: Sun Jinbo , Tang Qisheng , Gao Yongheng , Zhang Wei , Zhao Zhining , Yang Fan , Hu Xiangnan , Zhang Dan , Wang Yong , Zhang Huizhong , Song Bin , Zhang Bo , Wang He
Published: June 2020

Background

Although ongoing development of therapeutic strategies contributes to the improvements in clinical management, clear cell renal cell carcinoma (ccRCC) deaths originate mainly from radiochemoresistant and metastatic disease. Transcription factor SALL4 has been implicated in tumorigenesis and metastasis of multiple cancers. However, it is not known whether SALL4 is involved in the pathogenesis of ccRCC.

Methods

Analyses of clinical specimen and publicly available datasets were performed to determine the expression level and clinical significance of SALL4 in ccRCC. The influence of SALL4 expression on ccRCC tumor growth, metastasis and vascularity was evaluated through a series of in vitro and in vivo experiments. Western blotting, immunofluorescence staining and integrative database analysis were carried out to investigate the underlying mechanism for SALL4-mediated oncogenic activities in ccRCC.

Results

SALL4 expression was increased in ccRCC and positively correlated with tumor progression and poor prognosis. SALL4 could promote ccRCC cell proliferation, colony formation, cell cycle progression, migration, invasion and tumorigenicity and inhibit cell senescence. Further investigation revealed a widespread association of SALL4 with individual gene transcription and the involvement of SALL4 in endothelium development and vasculogenesis. In the context of ccRCC, SALL4 promoted tumor vascularization by recruiting endothelial cells. In addition, we found that SALL4 could exert its tumor-promoting effect via modulating Akt/GSK-3β axis and VEGFA expression. VHL mutation and DNA hypomethylation may be involved in the upregulation of SALL4 in ccRCC.

Conclusions

Overall, our results provide evidence that upregulated SALL4 can function as a crucial regulator of tumor pathogenesis and progression in ccRCC, thus offering potential therapeutic strategies for future treatment.
Expect delays: poor connections between rural and urban health systems challenge multidisciplinary care for rural Americans with diabetic foot ulcers
Authors: Sutherland Bryn L. , Pecanac Kristen , Bartels Christie M. , Brennan Meghan B.
Published: June 2020

Background

Rural Americans with diabetic foot ulcers (DFUs) face a 50% increased risk of major amputation compared to their urban counterparts. We sought to identify health system barriers contributing to this disparity.

Methods

We interviewed 44 participants involved in the care of rural patients with DFUs: 6 rural primary care providers (PCPs), 12 rural specialists, 12 urban specialists, 9 support staff, and 5 patients/caregivers. Directed content analysis was performed guided by a conceptual model describing how PCPs and specialists collaborate to care for shared patients.

Results

Rural PCPs reported lack of training in wound care and quickly referred patients with DFUs to local podiatrists or wound care providers. Timely referrals to, and subsequent collaborations with, rural specialists were facilitated by professional connections. However, these connections often were lacking between rural providers and urban specialists, whose skills were needed to optimally treat patients with high acuity ulcers. Urban referrals, particularly to vascular surgery or infectious disease, were stymied by 1) time‐consuming processes, 2) negative provider interactions, and 3) multiple, disconnected electronic health record systems. Such barriers ultimately detracted from rural PCPs' ability to focus on medical management, as well as urban specialists' ability to appropriately triage referrals due to lacking information. Subsequent collaboration between providers also suffered as a result.

Conclusions

Poor connections across rural and urban healthcare systems was described as the primary health system barrier driving the rural disparity in major amputations. Future interventions focusing on mitigating this barrier could reduce the rural disparity in major amputations.
First metatarsophalangeal joint range of motion is associated with lower limb kinematics in individuals with first metatarsophalangeal joint osteoarthritis
Authors: Allan Jamie J. , McClelland Jodie A. , Munteanu Shannon E. , Buldt Andrew K. , Landorf Karl B. , Roddy Edward , Auhl Maria , Menz Hylton B.
Published: June 2020

Background

Osteoarthritis of the first metatarsophalangeal joint (1st MTP joint OA) is a common and disabling condition that results in pain and limited joint range of motion. There is inconsistent evidence regarding the relationship between clinical measurement of 1st MTP joint maximum dorsiflexion and dynamic function of the joint during level walking. Therefore, the aim of this study was to examine the association between passive non‐weightbearing (NWB) 1st MTP joint maximum dorsiflexion and sagittal plane kinematics in individuals with radiographically confirmed 1st MTP joint OA.

Methods

Forty‐eight individuals with radiographically confirmed 1st MTP joint OA (24 males and 24 females; mean age 57.8 years, standard deviation 10.5) underwent clinical measurement of passive NWB 1st MTP joint maximum dorsiflexion and gait analysis during level walking using a 10‐camera infrared Vicon motion analysis system. Sagittal plane kinematics of the 1st MTP, ankle, knee, and hip joints were calculated. Associations between passive NWB 1st MTP joint maximum dorsiflexion and kinematic variables were explored using Pearson's r correlation coefficients.

Results

Passive NWB 1st MTP joint maximum dorsiflexion was significantly associated with maximum 1st MTPJ dorsiflexion (r = 0.486, p < 0.001), ankle joint maximum plantarflexion (r = 0.383, p = 0.007), and ankle joint excursion (r = 0.399, p = 0.005) during gait. There were no significant associations between passive NWB 1st MTP joint maximum dorsiflexion and sagittal plane kinematics of the knee or hip joints.

Conclusions

These findings suggest that clinical measurement of 1st MTP joint maximum dorsiflexion provides useful insights into the dynamic function of the foot and ankle during the propulsive phase of gait in this population.
Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping
Authors: Zhao Quanyi , Dacre Michael , Nguyen Trieu , Pjanic Milos , Liu Boxiang , Iyer Dharini , Cheng Paul , Wirka Robert , Kim Juyong Brian , Fraser Hunter B. , Quertermous Thomas
Published: June 2020

Background

To investigate the epigenetic and transcriptional mechanisms of coronary artery disease (CAD) risk, as well as the functional regulation of chromatin structure and function, we create a catalog of genetic variants associated with three stages of transcriptional cis-regulation in primary human coronary artery vascular smooth muscle cells (HCASMCs).

Results

We use a pooling approach with HCASMC lines to map regulatory variants that mediate binding of the CAD-associated transcription factor TCF21 with ChIPseq studies (bQTLs), variants that regulate chromatin accessibility with ATACseq studies (caQTLs), and chromosomal looping with Hi-C methods (clQTLs). We examine the overlap of these QTLs and their relationship to smooth muscle-specific genes and transcription factors. Further, we use multiple analyses to show that these QTLs are highly associated with CAD GWAS loci and correlate to lead SNPs where they show allelic effects. By utilizing genome editing, we verify that identified functional variants can regulate both chromatin accessibility and chromosomal looping, providing new insights into functional mechanisms regulating chromatin state and chromosomal structure. Finally, we directly link the disease-associated TGFB1-SMAD3 pathway to the CAD-associated FN1 gene through a response QTL that modulates both chromatin accessibility and chromosomal looping.

Conclusions

Together, these studies represent the most thorough mapping of multiple QTL types in a highly disease-relevant primary cultured cell type and provide novel insights into their functional overlap and mechanisms that underlie these genomic features and their relationship to disease risk.
A microbubble-sparged yeast propagation–fermentation process for bioethanol production
Authors: Raghavendran Vijayendran , Webb Joseph P. , Cartron Michaël L. , Springthorpe Vicki , Larson Tony R. , Hines Michael , Mohammed Hamza , Zimmerman William B. , Poole Robert K. , Green Jeffrey
Published: June 2020

Background

Industrial biotechnology will play an increasing role in creating a more sustainable global economy. For conventional aerobic bioprocesses supplying O2can account for 15% of total production costs. Microbubbles (MBs) are micron-sized bubbles that are widely used in industry and medical imaging. Using a fluidic oscillator to generate energy-efficient MBs has the potential to decrease the costs associated with aeration. However, little is understood about the effect of MBs on microbial physiology. To address this gap, a laboratory-scale MB-basedSaccharomyces cerevisiaeEthanol Red propagation–fermentation bioethanol process was developed and analysed.

Results

Aeration with MBs increased O2transfer to the propagation cultures. Titres and yields of bioethanol in subsequent anaerobic fermentations were comparable for MB-propagated and conventional, regular bubble (RB)-propagated yeast. However, transcript profiling showed significant changes in gene expression in the MB-propagated yeast compared to those propagated using RB. These changes included up-regulation of genes required for ergosterol biosynthesis. Ergosterol contributes to ethanol tolerance, and so the performance of MB-propagated yeast in fed-batch fermentations sparged with 1% O2as either RBs or MBs were tested. The MB-sparged yeast retained higher levels of ergosteryl esters during the fermentation phase, but this did not result in enhanced viability or ethanol production compared to ungassed or RB-sparged fermentations.

Conclusions

The performance of yeast propagated using energy-efficient MB technology in bioethanol fermentations is comparable to that of those propagated conventionally. This should underpin the future development of MB-based commercial yeast propagation.
Update on clinical screening of maturity-onset diabetes of the young (MODY)
Authors: Peixoto-Barbosa Renata , Reis André F. , Giuffrida Fernando M. A.
Published: June 2020

Background

Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes, being characterized by beta-cell disfunction, early onset, and autosomal dominant inheritance. Despite the rapid evolution of molecular diagnosis methods, many MODY cases are misdiagnosed as type 1 or type 2 diabetes. High costs of genetic testing and limited knowledge of MODY as a relevant clinical entity are some of the obstacles that hinder correct MODY diagnosis and treatment. We present a broad review of clinical syndromes related to most common MODY subtypes, emphasizing the role of biomarkers that can help improving the accuracy of clinical selection of candidates for molecular diagnosis.

Main body

To date, MODY-related mutations have been reported in at least 14 different genes. Mutations in glucokinase (GCK), hepatocyte nuclear factor-1 homeobox A (HNF1A), and hepatocyte nuclear factor-4 homeobox A (HNF4A) are the most common causes of MODY. Accurate etiological diagnosis can be challenging. Many biomarkers such as apolipoprotein-M (ApoM), aminoaciduria, complement components, and glycosuria have been tested, but have not translated into helpful diagnostic tools. High-sensitivity C-reactive protein (hs-CRP) levels are lower inHNF1A-MODY and have been tested in some studies to discriminateHNF1A-MODY from other types of diabetes, although more data are needed. Overall, presence of pancreatic residual function and absence of islet autoimmunity seem the most promising clinical instruments to select patients for further investigation.

Conclusions

The selection of diabetic patients for genetic testing is an ongoing challenge. Metabolic profiling, diabetes onset age, pancreatic antibodies, and C-peptide seem to be useful tools to better select patients for genetic testing. Further studies are needed to define cut-off values in different populations.
Genotype distribution of methicillin-susceptible Staphylococcus aureus clinical isolates in Iran: high multiresistant clonal complex 8
Authors: Tayebi Zahra , Goudarzi Hossein , Dadashi Masoud , Goudarzi Mehdi
Published: June 2020

Objective

Compared to methicillin-resistant Staphylococcus aureus (MRSA), there have been few studies focused on the molecular characterization of methicillin-susceptible Staphylococcus aureus (MSSA). In this cross-sectional study, 85 MSSA isolates were characterized by antimicrobial susceptibility testing, virulence genes analysis, accessory gene regulator (agr) typing, and S. aureus protein A locus (spa) typing.

Results

In present study, 9 different clonal complexes namely CC8-MSSA-t037 (22.4%), CC8-MSSA-t008 (11.8%), CC7-MSSA-t091 and CC30-MSSA-t021 (each 9.4%), CC8-MSSA-t037 (8.3%), CC398-MSSA-t034 (7.1%), CC22-MSSA-t005 (5.9%), CC5-MSSA-t002 and CC15-MSSA-t084 (each 4.7%), CC22-MSSA-t790 and CC59-MSSA-t437 (each 3.5%), CC22-MSSA-t1869, CC5-MSSA-t045, and CC45-MSSA-t015 (each 2.3%), CC30-MSSA-t318 and CC15-MSSA-t491 (each 1.2%) were found. agr types detected in tested strains were mainly type I (76.5%), II (12.9%), and III (10.6%). Of 85 MSSA examined isolates, 48 (56.5%) isolates were toxinogenic with 27 producing pvl (31.8%) and 21 tst (24.7%). The findings of the study show a high genetic diversity in MSSA strains warranting continued surveillance to provide critical insights into control and treatment of MSSA infections.
Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion
Authors: Gudbrandsen Maria , Bletsch Anke , Mann Caroline , Daly Eileen , Murphy Clodagh M. , Stoencheva Vladimira , Blackmore Charlotte E. , Rogdaki Maria , Kushan Leila , Bearden Carrie E. , Murphy Declan G. M. , Craig Michael C. , Ecker Christine
Published: June 2020

Background

A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 deletion syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same—or distinct—neural systems that mediate these symptoms in non-deletion carriers.

Methods

We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n = 25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e., idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e., multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers.

Results

The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS (p < 0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers.

Limitations

We employed a multicenter design to overcome single-site recruitment limitations; however, FreeSurfer-derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field strengths. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e., 6–25 years).

Conclusions

Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.
Convolutional neural networks for brain tumour segmentation
Authors: Bhandari Abhishta , Koppen Jarrad , Agzarian Marc
Published: June 2020

The introduction of quantitative image analysis has given rise to fields such as radiomics which have been used to predict clinical sequelae. One growing area of interest for analysis is brain tumours, in particular glioblastoma multiforme (GBM). Tumour segmentation is an important step in the pipeline in the analysis of this pathology. Manual segmentation is often inconsistent as it varies between observers. Automated segmentation has been proposed to combat this issue. Methodologies such as convolutional neural networks (CNNs) which are machine learning pipelines modelled on the biological process of neurons (called nodes) and synapses (connections) have been of interest in the literature. We investigate the role of CNNs to segment brain tumours by firstly taking an educational look at CNNs and perform a literature search to determine an example pipeline for segmentation. We then investigate the future use of CNNs by exploring a novel field—radiomics. This examines quantitative features of brain tumours such as shape, texture, and signal intensity to predict clinical outcomes such as survival and response to therapy.
Antibacterial mechanism of rhodomyrtone involves the disruption of nucleoid segregation checkpoint in Streptococcus suis
Authors: Traithan Apichaya , Tongtawe Pongsri , Thanongsaksrikul Jeeraphong , Voravuthikunchai Supayang , Srimanote Potjanee
Published: June 2020

Rhodomyrtone has been recently demonstrated to possess a novel antibiotic mechanism of action against Gram-positive bacteria which involved the multiple targets, resulting in the interference of several bacterial biological processes including the cell division. The present study aims to closely look at the downstream effect of rhodomyrtone treatment on nucleoid segregation in Streptococcus suis, an important zoonotic pathogen. The minimum inhibition concentration (MIC) and the minimum bactericidal concentration (MBC) values of rhodomyrtone against the recombinant S. suis ParB-GFP, a nucleoid segregation reporter strain, were 0.5 and 1 µg/ml, respectively, which were equivalent to the potency of vancomycin. Using the fluorescence live-cell imaging, we demonstrated that rhodomyrtone at 2× MIC caused incomplete nucleoid segregation and septum misplacement, leading to the generation of anucleated cells. FtsZ immune-staining of rhodomyrtone-treated S. suis for 30 min revealed that the large amount of FtsZ was trapped in the region of high fluidity membrane and appeared to be able to polymerize to form a complete Z-ring. However, the Z-ring was shifted away from the midcell. Transmission electron microscopy further confirmed the disruption of nucleoid segregation and septum misplacement at 120 min following the rhodomyrtone treatment. Asymmetric septum formation resulted in either generation of minicells without nucleoid, septum formed over incomplete segregated nucleoid (guillotine effect), or formation of multi-constriction of Z-ring within a single cell. This finding spotlights on antibacterial mechanism of rhodomyrtone involves the early stage in bacterial cell division process.
Green communication for MIMO SWIPT-powered 5G Internet of Things with full-duplex relay base on secure transmission and energy collection constraints
Authors: Zhang Meng , Zheng Jianhong , Huang Qian , Kadoch Michel
Published: June 2020

The green communication for 5th generation Internet of Things base on the energy collecting and security issues is studied in this paper. The transceiver and power splitting factor are optimized aiming at minimizing the transmitting power at the source node subject to the security performance and energy collection. Since the optimization problem is a nonconvex function, an iteration optimization algorithm is proposed to divide the objective optimization function into two subproblems, namely, a joint transmitter and PS factor optimization subproblem and a minimum mean-square error-based receiving filter optimization subproblem. Furthermore, since the transmitter and PS combining optimization subproblem is still a nonconvex function, the semidefinite relaxation technique is used to transform it into a convex function. The feasibility of the optimization problem and the convergency of the iteration algorithm are proved in theory, and the simulation results show the availability of the proposed scheme.
Predictive models of diabetes complications: protocol for a scoping review
Authors: Ndjaboue Ruth , Farhat Imen , Ferlatte Carol-Ann , Ngueta Gérard , Guay Daniel , Delorme Sasha , Ivers Noah , Shah Baiju R. , Straus Sharon , Yu Catherine , Witteman Holly O.
Published: June 2020

Background

Diabetes is a highly prevalent chronic disease that places a large burden on individuals and health care systems. Models predicting the risk (also called predictive models) of other conditions often compare people with and without diabetes, which is of little to no relevance for people already living with diabetes (called patients). This review aims to identify and synthesize findings from existing predictive models of physical and mental health diabetes-related conditions.

Methods

We will use the scoping review frameworks developed by the Joanna Briggs Institute and Levac and colleagues. We will perform a comprehensive search for studies from Ovid MEDLINE and Embase databases. Studies involving patients with prediabetes and all types of diabetes will be considered, regardless of age and gender. We will limit the search to studies published between 2000 and 2018. There will be no restriction of studies based on country or publication language. Abstracts, full-text screening, and data extraction will be done independently by two individuals. Data abstraction will be conducted using a standard methodology. We will undertake a narrative synthesis of findings while considering the quality of the selected models according to validated and well-recognized tools and reporting standards.

Discussion

Predictive models are increasingly being recommended for risk assessment in treatment decision-making and clinical guidelines. This scoping review will provide an overview of existing predictive models of diabetes complications and how to apply them. By presenting people at higher risk of specific complications, this overview may help to enhance shared decision-making and preventive strategies concerning diabetes complications. Our anticipated limitation is potentially missing models because we will not search grey literature.
The prevalence and risk factors of work-related musculoskeletal disorders among adults in Ethiopia: a study protocol for extending a systematic review with meta-analysis of observational studies
Authors: Gebreyesus Tsiwaye , Nigussie Kalkidan , Gashaw Moges , Janakiraman Balamurugan
Published: June 2020

Background

Work-related musculoskeletal disorders impose a significant and most often underappreciated burden to the individual, nation, healthcare system, and society as a whole. To the best of our knowledge, there is a lack of reliable estimates on the prevalence of work-related musculoskeletal disorders in Ethiopia. The objective of this study will be to assess the existing literature on the prevalence rates and determinant factors of work-related musculoskeletal disorders in Ethiopia.

Method

We will search PubMed/MEDLINE, Embase, SCOPUS, PsycINFO, PEDro, and Ebsco (from January 2000 onwards). Gray literature will be identified through searching Google Scholar and dissertation databases. Observational studies reporting on the prevalence of work-related musculoskeletal disorders among adult Ethiopians will be included. The primary outcome will be the prevalence of work-related musculoskeletal disorders. Secondary outcomes will be the prevalence of any risk factors in association with work-related musculoskeletal disorders. Two reviewers will independently screen all citations, full-text articles, and abstract data. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct random effects meta-analysis of observational data. Subgroup analyses will be conducted to explore the potential sources of heterogeneity (e.g., gender, sample size, type of occupation). Publication bias and heterogeneity between the included studies will also be assessed and reported.

Discussion

This systematic review will provide a synthesis of the literature on the prevalence of work-related musculoskeletal disorders and their risk factors in Ethiopia. The results of this review could help the policymakers in occupational health and healthcare sectors in identifying priority areas for interventions in work-related musculoskeletal disorders and will also serve as a baseline for the decision-making processes of musculoskeletal health promotion, work exposure implementations, and prevention programs in workplaces.

Systematic review registration

PROSPERO, CRD42020164240
Blow-up phenomena for a viscoelastic wave equation with strong damping and logarithmic nonlinearity
Authors: Ha Tae Gab , Park Sun-Hye
Published: June 2020

In this paper we consider the initial boundary value problem for a viscoelastic wave equation with strong damping and logarithmic nonlinearity of the form $$ u_{tt}(x,t) - \Delta u (x,t) + \int ^{t}_{0} g(t-s) \Delta u(x,s)\,ds - \Delta u_{t} (x,t) = \bigl\vert u(x,t) \bigr\vert ^{p-2} u(x,t) \ln \bigl\vert u(x,t) \bigr\vert $$utt(x,t)−Δu(x,t)+∫0tg(t−s)Δu(x,s)ds−Δut(x,t)=|u(x,t)|p−2u(x,t)ln|u(x,t)| in a bounded domain $\varOmega \subset {\mathbb{R}}^{n} $Ω⊂Rn, where g is a nonincreasing positive function. Firstly, we prove the existence and uniqueness of local weak solutions by using Faedo–Galerkin’s method and contraction mapping principle. Then we establish a finite time blow-up result for the solution with positive initial energy as well as nonpositive initial energy.
Impact of hand hygiene intervention: a comparative study in health care facilities in Dodoma region, Tanzania using WHO methodology
Authors: Wiedenmayer Karin , Msamba Vicky-Sidney , Chilunda Fiona , Kiologwe James Charles , Seni Jeremiah
Published: June 2020

Background

Compliance with guidelines on hand hygiene (HH) is pivotal to prevent and control health-care associated infections and contributes to mitigating antimicrobial resistance. A baseline assessment in Dodoma region, Tanzania in March 2018 showed inadequate HH levels across health care facilities. We evaluated the impact of training in HH as part of a water, sanitation and hygiene (WASH) interventions of “Maji kwa Afya ya Jamii” (MKAJI) project.

Methods

A comparative HH assessment was conducted in June 2019 involving health care facilities under MKAJI project (n = 87 from which 98 units were assessed) vs non-MKAJI facilities (n = 85 from which 99 units were assessed). Irrespective of MKAJI interventional status, baseline assessment in March 2018 were compared to re-assessment in June 2019 in all health care facility units (unpaired comparison: 261 vs 236 units, respectively), and in facilities assessed in both surveys (paired comparison: 191 versus 191 units, respectively). The ‘WHO HH Self-Assessment Framework Tool, 2010’ with five indicators each counting 100 points was used. The cumulative scores stratified each health facility’s unit into inadequate (0–125), basic (126–250), intermediate (251–375) or advanced (376–500) HH level (score). The HH compliance rates were also assessed and compared.

Results

The overall post-intervention median HH score [interquartile range (IQR)] was 187.5 (112.5–260). MKAJI health facilities had significantly higher median HH scores (IQR) [190 (120–262.5)] compared with non-MKAJI facilities [165 (95–230); p = 0.038]. Similarly, the HH compliance rate of ≥51% was significantly higher in MKAJI than non-MKAJI facilities [56.1% versus 30.3%; chi2 = 13.39, p < 0.001]. However, the recommended WHO compliance rate of ≥81% was only reached by 6.1 and 3.0% units of MKAJI and non-MKAJI facilities, respectively. Both paired and unpaired comparisons during baseline and re-assessment surveys showed increase in HH level from inadequate to basic level.

Conclusion

The overall HH level after the combined WASH and training intervention was at basic level. Higher median HH scores (IQR) and HH compliance rates were evident in health facilities of the MKAJI project, underscoring the impact of the intervention and the potential value of a national roll-out.
Interleukin-6-knockdown of chimeric antigen receptor-modified T cells significantly reduces IL-6 release from monocytes
Authors: Kang Liqing , Tang Xiaowen , Zhang Jian , Li Minghao , Xu Nan , Qi Wei , Tan Jingwen , Lou Xiaoyan , Yu Zhou , Sun Juanjuan , Wang Zhenkun , Dai Haiping , Chen Jia , Lin Guoqing , Wu Depei , Yu Lei
Published: June 2020

Background

T cells expressing a chimeric antigen receptor (CAR) engineered to target CD19 can treat leukemia effectively but also increase the risk of complications such as cytokine release syndrome (CRS) and CAR T cell related encephalopathy (CRES) driven by interleukin-6 (IL-6). Here, we investigated whether IL-6 knockdown in CART-19 cells can reduce IL-6 secretion from monocytes, which may reduce the risk of adverse events.

Methods

Supernatants from cocultures of regular CART-19 cells and B lymphoma cells were added to monocytes in vitro, and the IL-6 levels in monocyte supernatants were measured 24 h later. IL-6 expression was knocked down in regular CART-19 cells by adding a short hairpin RNA (shRNA) (termed ssCART-19) expression cassette specific for IL-6 to the conventional CAR vector. Transduction efficiency and cell proliferation were measured by flow cytometry, and cytotoxicity was measured by evaluating the release of lactate dehydrogenase into the medium. Gene expression was assessed by qRT-PCR and RNA sequencing. A xenograft leukemia mouse model was established by injecting NOD/SCID/γc-/- mice with luciferase-expressing B lymphoma cells, and then the animals were treated with regular CART-19 cells or ssCART-19. Tumor growth was assessed by bioluminescence imaging.

Results

Both recombinant IL-6 and CART-19 derived IL-6 significantly triggered IL-6 release by monocytes. IL-6 knockdown in ssCART-19 cells dramatically reduced IL-6 release from monocytes in vitro stduy. In vivo study further demonstrated that the mice bearing Raji cells treated with ssCART-19 cells showed significant lower IL-6 levels in serum than those treated with regular CART-19 cells, but comparable anti-tumor efficacy between the animal groups.

Conclusion

CAR T-derived IL-6 is one of the most important initiators to amplify release of IL-6 from monocytes that further drive sCRS development. IL-6 knockdown in ssCART-19 cells by shRNA technology provide a promising strategy to improve the safety of CAR T cell therapy.
The occurrence of cancer in vertebrates: a mini review
Authors: Kitsoulis Christos V. , Baxevanis Athanasios D. , Abatzopoulos Theodore J.
Published: June 2020

Neoplasia is a multilevel condition caused by irregularities over the genome, which can lead to a fatal result. To fully understand this phenomenon, an evolutionary challenge has risen during the last decades, away from human limits, driving the scientific quest into the wild life. The study of wild vertebrate populations in their natural habitats has shown that cancer is rather prominent. Thus, the diversity of vertebrates reported with some form of neoplasia is quite scattered through a variety of habitats. However, some species constitute exceptions by exhibiting cancer-protective features, driven by certain loci in their DNA. It is obvious that from an evolutionary standpoint, the incidence of cancer in different taxa is nowadays studied by seeking for patterns and their roots. The main purpose of the evolutionary approach is no other than to answer a fundamental question: Could cancer be ultimately regarded as another evolutionary force conducive to the formation or shaping-up of species?
Proliferative diabetic retinopathy without preoperative pan-retinal photocoagulation is associated with higher levels of intravitreal IL-6 and postoperative inflammation
Authors: Suzuki Yukihiko , Adachi Kobu , Maeda Natsuki , Tanabu Reiko , Kudo Takashi , Nakazawa Mitsuru
Published: June 2020

Purpose

Intravitreal cytokine levels and differences in the severity of postoperative inflammation in patients with proliferative diabetic retinopathy (PDR) were compared between subjects treated with pan-retinal photocoagulation (PRP) prior to undergoing vitreous surgery and those treated similarly during the surgery.

Subjects and methods

We examined 130 eyes of PDR patients who underwent an initial surgical procedure at Hirosaki University Hospital. A total of 67 out of the 130 eyes were treated with PRP prior to surgery (preoperative group), while 63 underwent similar treatment during surgery (intraoperative group). Vitreous fluid was collected at the start of the vitreous surgical procedure. Following vitrectomy, intraoperative PRP was completed during the surgery in the intraoperative group. This procedure was added to the peripheral part as needed in the preoperative group. The results for the levels of 27 cytokines, including vascular endothelial growth factor (VEGF), were measured using multiplex assays and compared between the groups. For determining postoperative inflammation, eyes in which fibrin was observed for 3 days or longer in the anterior chamber or vitreous cavity were considered to have fibrin deposition. The rate of fibrin deposition was compared between these groups.

Results

Among the vitreous cytokines examined, there was no significant difference in the VEGF levels between the groups (p = 0.70). In contrast, the IL-6 level was significantly higher in the intraoperative group (2813.2 ± 6022.2 vs. 1248.5 ± 1442.2 pg/ml, p = 0.048). Furthermore, the fibrin deposition rate was significantly higher in the intraoperative (44.4%) versus the preoperative group (14.9%) (p = 0.0002).

Conclusion

Severe postoperative inflammation was frequently seen in patients who did not undergo preoperative PRP, which may have been due to the performance of the procedure during the surgery. Moreover, these results may also be associated with a higher level of intravitreal IL-6.
A digital assistant for shading paper sketches
Authors: Parakkat Amal Dev , Gowtham Hari Hara , Joshi Sarang , Muthuganapathy Ramanathan
Published: June 2020

We present a mixed reality-based assistive system for shading paper sketches. Given a paper sketch made by an artist, our interface helps inexperienced users to shade it appropriately. Initially, using a simple Delaunay-triangulation based inflation algorithm, an approximate depth map is computed. The system then highlights areas (to assist shading) based on a rendering of the 2.5-dimensional inflated model of the input contour. With the help of a mixed reality system, we project the highlighted areas back to aid users. The hints given by the system are used for shading and are smudged appropriately to apply an artistic shading to the sketch. The user is given flexibility at various levels to simulate conditions such as height and light position. Experiments show that the proposed system aids novice users in creating sketches with impressive shading.