bluuebunny/crossref_metadata_2025 huggingface dataset:
PPARα and PPARβ/δ are negatively correlated with proinflammatory markers in leukocytes of an obese pediatric population
Authors: Vargas-Sánchez Karina , Vargas Laura , Urrutia Yenny , Beltrán Iván , Rossi Ana Beatriz , Lozano Hernán Yupanqui , Guarín Jorge , Losada-Barragán Monica
Published: October 2020

Background

Obesity configures a pathophysiological profile that predisposes the development of metabolic and cardiovascular diseases, critically impacting public health. The chronic dysregulation of immuno-metabolic components triggered by pediatric obesity is a common but scarcely understood aspect of the disease. Peroxisome proliferator-activated receptors (PPARs) are a group of transcription factors essential for energy and immune homeostasis of different tissues. Besides, the glucagon-like peptide-1 receptor (GLP-1R) activation influences insulin secretion, but also regulates the cytokine profile possibly mediated through a PPAR isotype. However, the role of PPARs and GLP-1R in leukocytes from obese pediatric patients remains unclear. Therefore, we examined the expression of PPARs isotypes and GLP-1R in leukocytes, and its correlation with metabolic, hormonal, inflammatory, and anthropometric markers in an obese pediatric population.

Results

Obese children and adolescents presented a significant increase in anthropometric and body composition parameters, TG, VLDL, TG/HDL, android fat (%)/gynoid fat (%) (A/G%) index, and HOMA score when compared with the control group. Obese participants exhibited a pro-inflammatory profile with an augment of IL-8 (p = 0,0081), IL-6 (p = 0,0005), TNF-α (p = 0,0004), IFN-γ (p = 0,0110), MCP-1 (p = 0,0452), and adipsin (p = 0,0397), whereas displayed a reduction of adiponectin (p = 0,0452). The expression of PPARα and GLP-1R was lower in the leukocytes from obese participants than in lean subjects. Furthermore, PPARα correlates negatively with TNF-α (p = 0,0383), while GLP-1R did not show correlation with any inflammatory variable. However, both receptors correlate negatively with the abdominal skinfold. Although PPARβ/δ expression was similar between groups, it was negatively associated with IL-8 levels (p = 0,0085).

Conclusions

PPARα and PPARβ/δ expression are negatively correlated with the proinflammatory markers TNF-α and IL-8, respectively, suggesting participation in the regulation of inflammation which was observed to be altered in pediatric obesity. Furthermore, PPARα and GLP-1R are downregulated in leukocytes from obese participants. The low expression of both receptors is correlated with an increase in abdominal skinfold, suggesting a role in fat distribution that could indirectly affect cytokine secretion from different immune and adipose cells, likely triggering an inflammatory profile as a consequence of obesity. Altogether, these findings may impact the understanding and implementation of PPARα or GLP-1R agonists in the clinic.
A qualitative study of diphenhydramine injection in Kyrgyz prisons and implications for harm reduction
Authors: Meyer Jaimie P. , Culbert Gabriel J. , Azbel Lyuba , Bachireddy Chethan , Kurmanalieva Ainura , Rhodes Tim , Altice Frederick L.
Published: October 2020

Background

To reduce opioid dependence and HIV transmission, Kyrgyzstan has introduced methadone maintenance therapy and needle/syringe programs into prisons. Illicit injection of diphenhydramine, an antihistamine branded as Dimedrol®, has been anecdotally reported as a potential challenge to harm reduction efforts in prisons but has not been studied systematically.

Methods

We conducted qualitative interviews in Kyrgyz or Russian with prisoners (n = 49), former prisoners (n = 19), and stakeholders (n = 18), including prison administrators and prisoner advocates near Bishkek, Kyrgyzstan from October 2016 to September 2018. Interviews explored social–contextual factors influencing methadone utilization in prisons. Transcripts were coded by five researchers using content analysis. Dimedrol injection emerged as an important topic, prompting a dedicated analysis.

Results

After drinking methadone, some people in prison inject crushed Dimedrol tablets, a non-prescription antihistamine that is banned but obtainable in prison, to achieve a state of euphoria. From the perspectives of the study participants, Dimedrol injection was associated with devastating physical and mental health consequences, including psychosis and skin infections. Moreover, the visible wounds of Dimedrol injecting contributed to the perception of methadone as a harmful drug and supporting preference for heroin over methadone.

Conclusion

Dimedrol injecting is a potentially serious threat to harm reduction and HIV prevention efforts in Kyrgyzstan and elsewhere in the Eastern European and Central Asian region and requires further investigation.
The COVID-19 pandemic presents an opportunity to develop more sustainable health workforces
Authors: Bourgeault Ivy Lynn , Maier Claudia B. , Dieleman Marjolein , Ball Jane , MacKenzie Adrian , Nancarrow Susan , Nigenda Gustavo , Sidat Mohsin
Published: October 2020

This commentary addresses the critically important role of health workers in their countries’ more immediate responses to COVID-19 outbreaks and provides policy recommendations for more sustainable health workforces. Paradoxically, pandemic response plans in country after country, often fail to explicitly address health workforce requirements and considerations. We recommend that policy and decision-makers at the facility, regional and country-levels need to: integrate explicit health workforce requirements in pandemic response plans, appropriate to its differentiated levels of care, for the short, medium and longer term; ensure safe working conditions with personal protective equipment (PPE) for all deployed health workers including sufficient training to ensure high hygienic and safety standards; recognise the importance of protecting and promoting the psychological health and safety of all health professionals, with a special focus on workers at the point of care; take an explicit gender and social equity lens, when addressing physical and psychological health and safety, recognising that the health workforce is largely made up of women, and that limited resources lead to priority setting and unequitable access to protection; take a whole of the health workforce approach—using the full skill sets of all health workers—across public health and clinical care roles—including those along the training and retirement pipeline—and ensure adequate supervisory structures and operating procedures are in place to ensure inclusive care of high quality; react with solidarity to support regions and countries requiring more surge capacity, especially those with weak health systems and more severe HRH shortages; and acknowledge the need for transparent, flexible and situational leadership styles building on a different set of management skills.
Lessons learned from descriptions and evaluations of knowledge translation platforms supporting evidence-informed policy-making in low- and middle-income countries: a systematic review
Authors: Partridge Arun C. R. , Mansilla Cristián , Randhawa Harkanwal , Lavis John N. , El-Jardali Fadi , Sewankambo Nelson K.
Published: October 2020

Background

Knowledge translation (KT) platforms are organisations, initiatives and networks that focus on supporting evidence-informed policy-making at least in part about the health-system arrangements that determine whether the right programmes, services and products get to those who need them. Many descriptions and evaluations of KT platforms in low- and middle-income countries have been produced but, to date, they have not been systematically reviewed.

Methods

We identified potentially relevant studies through a search of five electronic databases and a variety of approaches to identify grey literature. We used four criteria to select eligible empirical studies. We extracted data about seven characteristics of included studies and about key findings. We used explicit criteria to assess study quality. In synthesising the findings, we gave greater attention to themes that emerged from multiple studies, higher-quality studies and different contexts.

Results

Country was the most common jurisdictional focus of KT platforms, EVIPNet the most common name and high turnover among staff a common infrastructural feature. Evidence briefs and deliberative dialogues were the activities/outputs that were the most extensively studied and viewed as helpful, while rapid evidence services were the next most studied but only in a single jurisdiction. None of the summative evaluations used a pre–post design or a control group and, with the exception of the evaluations of the influence of briefs and dialogues on intentions to act, none of the evaluations achieved a high quality score.

Conclusions

A large and growing volume of research evidence suggests that KT platforms offer promise in supporting evidence-informed policy-making in low- and middle-income countries. KT platforms should consider as next steps expanding their current, relatively limited portfolio of activities and outputs, building bridges to complementary groups, and planning for evaluations that examine ‘what works’ for ‘what types of issues’ in ‘what types of contexts’.
‘Recoupling’ the attentional and motor control of preparatory postural adjustments to overcome freezing of gait in Parkinson’s
Authors: Maslivec Amy , Fielding Anna , Wilson Mark , Norris Meriel , Young William
Published: October 2020

Objectives

This study examined if people with Parkinson’s and freezing of gait pathology (FoG) could be trained to increase preparatory weight-shift amplitude, and facilitate step initiation during FoG.

Methods

Thirty-five people with Parkinson’s and FoG attempted to initiate forward walking from a stationary position caused by a freeze (n = 17, FoG-F) or voluntarily stop (n = 18, FoG-NF) in a Baseline condition and two conditions where an increased weight-shift amplitude was trained via: (i) explicit verbal instruction, and (ii) implicit movement analogies.

Results

At Baseline, weight-shift amplitudes were smaller during: (i) unsuccessful, compared to successful step initiations (FoG-F group), and (ii) successful step initiations in the FoG-F group compared to FoG-NF. Both Verbal and Analogy training resulted in significant increases in weight-shift amplitude in both groups, and a corresponding pronounced reduction in unsuccessful attempts to initiate stepping (FoG-F group).

Conclusions

Hypometric preparatory weight-shifting is associated with failure to initiate forward stepping in people with Parkinson’s and FoG. However, impaired weight-shift characteristics are modifiable through conscious strategies. This current study provides a novel and critical evaluation of preparatory weight-shift amplitudes during FoG events. The intervention described represents an attractive ‘rescue’ strategy and should be further scrutinised regarding limitations posed by physical and cognitive deficits.
Virtual reality and non-invasive brain stimulation for rehabilitation applications: a systematic review
Authors: Cassani Raymundo , Novak Guilherme S. , Falk Tiago H. , Oliveira Alcyr A.
Published: October 2020

The present article reports the results of a systematic review on the potential benefits of the combined use of virtual reality (VR) and non-invasive brain stimulation (NIBS) as a novel approach for rehabilitation. VR and NIBS are two rehabilitation techniques that have been consistently explored by health professionals, and in recent years there is strong evidence of the therapeutic benefits of their combined use. In this work, we reviewed research articles that report the combined use of VR and two common NIBS techniques, namely transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). Relevant queries to six major bibliographic databases were performed to retrieve original research articles that reported the use of the combination VR-NIBS for rehabilitation applications. A total of 16 articles were identified and reviewed. The reviewed studies have significant differences in the goals, materials, methods, and outcomes. These differences are likely caused by the lack of guidelines and best practices on how to combine VR and NIBS techniques. Five therapeutic applications were identified: stroke, neuropathic pain, cerebral palsy, phobia and post-traumatic stress disorder, and multiple sclerosis rehabilitation. The majority of the reviewed studies reported positive effects of the use of VR-NIBS. However, further research is still needed to validate existing results on larger sample sizes and across different clinical conditions. For these reasons, in this review recommendations for future studies exploring the combined use of VR and NIBS are presented to facilitate the comparison among works.
Koalas vaccinated against Koala retrovirus respond by producing increased levels of interferon-gamma
Authors: Olagoke Olusola , Quigley Bonnie L. , Timms Peter
Published: October 2020

Koala retrovirus (KoRV) is believed to be in an active state of endogenization into the koala genome. KoRV is present as both an endogenous and exogenous infection in all koalas in northern Australia. KoRV has been linked to koala pathologies including neoplasia and increased susceptibility to Chlamydia. A KoRV vaccine recently trialled in 10 northern koalas improved antibody response and reduced viral load. This communication reports the expression of key immune genes underlining the innate and adaptive immune response to vaccination in these northern koalas. The results showed that prior to vaccination, IL-8 was expressed at the highest levels, with at least 200-fold greater expression compared to other cytokines, while CD8 mRNA expression was significantly higher than CD4 mRNA expression level. Interferon-γ was up-regulated at both 4- and 8-weeks post-vaccination while IL-8 was down-regulated at 8-weeks post-vaccination.
Therapeutic options for patients with rare rheumatic diseases: a systematic review and meta-analysis
Authors: Bender Tim T. A. , Leyens Judith , Sellin Julia , Kravchenko Dmitrij , Conrad Rupert , Mücke Martin , Seidel Matthias F.
Published: October 2020

Background

Rare diseases (RDs) in rheumatology as a group have a high prevalence, but randomized controlled trials are hampered by their heterogeneity and low individual prevalence. To survey the current evidence of pharmacotherapies for rare rheumatic diseases, we conducted a systematic review and meta-analysis. Randomized controlled trials (RCTs) of RDs in rheumatology for different pharmaco-interventions were included into this meta-analysis if there were two or more trials investigating the same RD and using the same assessment tools or outcome parameters. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PUBMED were searched up to April 2nd 2020. The overall objective of this study was to identify RCTs of RDs in rheumatology, evaluate the overall quality of these studies, outline the evidence of pharmacotherapy, and summarize recommended therapeutic regimens.

Results

We screened 187 publications, and 50 RCTs met our inclusion criteria. In total, we analyzed data of 13 different RDs. We identified several sources of potential bias, such as a lack of description of blinding methods and allocation concealment, as well as small size of the study population. Meta-analysis was possible for 26 studies covering six RDs: Hunter disease, Behçet’s disease, giant cell arteritis, ANCA-associated vasculitis, reactive arthritis, and systemic sclerosis. The pharmacotherapies tested in these studies consisted of immunosuppressants, such as corticosteroids, methotrexate and azathioprine, or biologicals. We found solid evidence for idursulfase as a treatment for Hunter syndrome. In Behçet’s disease, apremilast and IF-α showed promising results with regard to total and partial remission, and Tocilizumab with regard to relapse-free remission in giant cell arteritis. Rituximab, cyclophosphamide, and azathioprine were equally effective in ANCA-associated vasculitis, while mepolizumab improved the efficacy of glucocorticoids. The combination of rifampicin and azithromycin showed promising results in reactive arthritis, while there was no convincing evidence for the efficacy of pharmacotherapy in systemic sclerosis.

Conclusion

For some diseases such as systemic sclerosis, ANCA-associated vasculitis, or Behcet's disease, higher quality trials were available. These RCTs showed satisfactory efficacies for immunosuppressants or biological drugs, except for systemic sclerosis. More high quality RCTs are urgently warranted for a wide spectrum of RDs in rheumatology.
Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women
Authors: Cairat Manon , Al Rahmoun Marie , Gunter Marc J. , Severi Gianluca , Dossus Laure , Fournier Agnès
Published: October 2020

Background

Although anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent.

Methods

We investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on lifestyle and medical history has been collected biennially by questionnaires and matched with data from a drug reimbursement database covering the period 2004–2014. Women who self-reported current NSAID use in the 2000 or 2002 questionnaires or with at least two reimbursements in any previous 3-month period were defined as exposed to NSAIDs. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with BC risk.

Results

In the current analysis, 62,512 postmenopausal women were followed between 2004 and 2014 (9 years on average, starting at a mean age of 63 years; 2864 incident BC). In multivariable models, there was no statistically significant association between NSAID use and BC risk [HR = 1.00 (0.92–1.08), compared with non-exposed women]. The NSAID-BC associations did not differ by NSAID types, BC subtypes, risk factors, and comorbidities, nor by duration and dose of use. However, a statistically significant interaction was observed by proton pump inhibitor (PPI) drug use (Pinteraction = 0.01) whereby a decreased risk of BC with NSAID use was only observed among women who also used PPI before.

Conclusion

Only women who used NSAIDs after having used PPI had a lower risk of BC. This result is novel and requires replication in other studies.
α-Secretase nonsense mutation (ADAM10 Tyr167*) in familial Alzheimer’s disease
Authors: Agüero Pablo , Sainz María José , García-Ayllón María-Salud , Sáez-Valero Javier , Téllez Raquel , Guerrero-López Rosa , Pérez-Pérez Julián , Jiménez-Escrig Adriano , Gómez-Tortosa Estrella
Published: October 2020

Background

The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of APP. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset AD, though clear clinical-genetic correlates remain elusive.

Methods

Clinical-genetic and biomarker study of a first family with early- and late-onset AD associated with a nonsense ADAM10 mutation (p.Tyr167*). CSF analysis included AD core biomarkers, as well as Western blot of ADAM10 species and sAPPα and sAPPβ peptides. We evaluate variant’s pathogenicity, pattern of segregation, and further screened for the p.Tyr167* mutation in 197 familial AD cases from the same cohort, 200 controls from the same background, and 274 AD cases from an independent Spanish cohort.

Results

The mutation was absent from public databases and segregated with the disease. CSF Aβ42, total tau, and phosphorylated tau of affected siblings were consistent with AD. The predicted haploinsufficiency effect of the nonsense mutation was supported by (a) ADAM10 isoforms in CSF decreased around 50% and (b) 70% reduction of CSF sAPPα peptide, both compared to controls, while sAPPβ levels remained unchanged. Interestingly, sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPPα and sAPPβ levels resembled those of controls. Therefore, a decreased sAPPα/sAPPβ ratio was an exclusive feature of mutant ADAM10 siblings. The p.Tyr167* mutation was not found in any of the other AD cases or controls screened.

Conclusions

This family illustrates the role of ADAM10 in the amyloidogenic process and the clinical development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model for sporadic late-onset AD due to age-related downregulation of α-secretase. This report encourages future research on ADAM10 enhancers.
Construction of in situ degradation bacteria of corn straw and analysis of its degradation efficiency
Authors: Gong Xiujie , Zou Hongtao , Qian Chunrong , Yu Yang , Hao Yubo , Li Liang , Wang Qiuju , Jiang Yubo , Ma Juntao
Published: October 2020

Purpose

The highly efficient degradation bacteria were selected from the humus from the very cold straw in China for many years to construct the in situ degradation bacteria, and the degradation efficiency of corn straw was determined by process optimization.

Methods

According to the main components of corn straw, through morphological, physiological, and biochemical screening, three highly efficient complementary degradation strains were selected to construct the compound flora, and the degradation efficiency was analyzed by Fourier transform infrared spectrometer, field emission scanning electron microscope, and X-ray diffractometer.

Result

The corn straw selected in this paper is mainly composed of cellulose (31.99%), hemicellulose (25.33%), and lignin (14.67%). Through the determination of enzyme activity, strain Streptomyces sp. G1T has high decomposition ability to cellulose and hemicellulose but weak utilization ability to lignin; strain Streptomyces sp. G2T has the strongest decomposition ability to cellulose and hemicellulose among the three strains. The decomposition ability of strain Streptomyces sp. G3T to lignin was the strongest among the three strains. Therefore, by compounding the three strains, the decomposition ability has been greatly improved. The optimal process conditions obtained by single factor and response surface method are as follows: pH is 7, temperature is 30 °C, inoculation amount is 5%, rotational speed is 210 rpm, and the weight loss rate of straw is 60.55% after decomposing for 7 days. A large amount of degradation of corn straw can be seen by Fourier transform infrared spectrometer, field emission scanning electron microscope, and X-ray diffractometer.

Conclusion

Streptomyces sp. G1T, Streptomyces sp. G2T, and Streptomyces sp. G3T screened from straw humus in very cold areas were used to construct in situ degradation bacteria, which had good straw degradation activity and had the potential to be used for straw treatment in cold areas after harvest. This characteristic makes the complex bacteria become a strong competitive candidate for industrial production, and it is also an effective biotechnology in line with the current recycling of resources.
The combination of trehalose and glycerol: an effective and non-toxic recipe for cryopreservation of human adipose-derived stem cells
Authors: Zhang Tian-Yu , Tan Poh-Ching , Xie Yun , Zhang Xiao-Jie , Zhang Pei-Qi , Gao Yi-Ming , Zhou Shuang-Bai , Li Qing-Feng
Published: October 2020

Background

Adipose-derived stem cells (ADSCs) promote tissue regeneration and repair. Cryoprotective agents (CPAs) protect cells from cryodamage during cryopreservation. Safe and efficient cryopreservation of ADSCs is critical for cell-based therapy in clinical applications. However, most CPAs are used at toxic concentrations, limiting their clinical application.

Objective

The aim of this study is to develop a non-toxic xeno-free novel CPA aiming at achieving high-efficiency and low-risk ADSC cryopreservation.

Methods

We explored different concentrations of trehalose (0.3 M, 0.6 M, 1.0 M, and 1.25 M) and glycerol (10%, 20%, and 30% v/v) for optimization and evaluated and compared the outcomes of ADSCs cryopreservation between a combination of trehalose and glycerol and the commonly used CPA DMSO (10%) + FBS (90%). All samples were slowly frozen and stored in liquid nitrogen for 30 days. The effectiveness was evaluated by the viability, proliferation, migration, and multi-potential differentiation of the ADSCs after thawing.

Results

Compared with the groups treated with individual reagents, the 1.0 M trehalose (Tre) + 20% glycerol (Gly) group showed significantly higher efficiency in preserving ADSC activities after thawing, with better outcomes in both cell viability and proliferation capacity. Compared with the 10% DMSO + 90% FBS treatment, the ADSCs preserved in 1.0 M Tre + 20% Gly showed similar cell viability, surface markers, and multi-potential differentiation but a significantly higher migration capability. The results indicated that cell function preservation can be improved by 1.0 M Tre + 20% Gly.

Conclusions

The 1.0 M Tre + 20% Gly treatment preserved ADSCs with a higher migration capability than 10% DMSO + 90% FBS and with viability higher than that with trehalose or glycerol alone but similar to that with 10% DMSO + 90% FBS and fresh cells. Moreover, the new CPA achieves stemness and multi-potential differentiation similar to those in fresh cells. Our results demonstrate that 1.0 M Tre + 20% Gly can more efficiently cryopreserve ADSCs and is a non-toxic CPA that may be suitable for clinical applications.
Effect of Broussonetia papyrifera silage on the serum indicators, hindgut parameters and fecal bacterial community of Holstein heifers
Authors: Tian Hanchen , Chen Yiye , Zhu Ni , Guo Yongqing , Deng Ming , Liu Guangbin , Li Yaokun , Liu Dewu , Sun Baoli
Published: October 2020

This study investigated the effects of substitution of whole corn silage (WCS) with Broussonetia papyrifera silage (BPS) in different ratios on the serum indicators, hindgut fermentation parameters (pH, ammoniacal nitrogen, and volatile fatty acids), and fecal bacterial community of Holstein heifers. Sixteen heifers (8-month-old, 220 ± 30 kg) were randomly divided into four treatments according to different BPS substitution ratios of feed basis (0%, 25%, 50%, and 75%). The experiment consisted of a 7-day preliminary feeding period and a 30-day experimental period. On the last day of the trial, the blood samples were collected from caudal vein, and the feces samples were collected from rectum. With the increasing of BPS content, the concentration of malondialdehyde (MDA) and interleukin-1β (IL-1β) in serum decreased (P < 0.05), and the immunoglobulin A (IgA) and IL-4 content of serum increased (P < 0.05); and the hindgut pH value increased (P < 0.05). 16S rRNA sequencing found that the dominant phyla were Firmicutes, Bacteroidetes, and Verrucomicrobia; and the dominant genera were Ruminococcaceae_UCG-005, Ruminococcaceae_UCG-010, and Rikenellaceae_RC9_gut_group. Linear Discriminant Analysis Effect Size (LEfSe) analysis found 12 differential operational taxonomic units (OTUs) which have strong correlation with some serum and hindgut indicators, and have the potential to be used as biomarkers. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) found that BPS have impacts on the pathways, such as carbohydrate transport and metabolism, and promotes amino acid transport and metabolism. To sum up, inclusion of BPS in heifer diets can affect serum anti-oxidant and immune indicators, fecal parameters, composition and function of fecal microorganisms in Holstein heifers.
The key technology of computer network vulnerability assessment based on neural network
Authors: Wang Shaoqiang
Published: October 2020

With the wide application of computer network, network security has attracted more and more attention. The main reason why all kinds of attacks on the network can pose a great threat to the network security is the vulnerability of the computer network system itself. Introducing neural network technology into computer network vulnerability assessment can give full play to the advantages of neural network in network vulnerability assessment. The purpose of this article is by organizing feature map neural network, and the combination of multilayer feedforward neural network, the training samples using SOM neural network clustering, the result of clustering are added to the original training samples and set a certain weight, based on the weighted iterative update ceaselessly, in order to improve the convergence speed of BP neural network. On the BP neural network, algorithm for LM algorithm was improved, the large matrix inversion in the LM algorithm using the parallel algorithm method is improved for solving system of linear equations, and use of computer network vulnerability assessment as the computer simulation and analysis on the actual example designs a set of computer network vulnerability assessment scheme, finally the vulnerability is lower than 0.75, which is beneficial to research on related theory and application to provide the reference and help.
Extraction new results of common fixed point theorems for $({T}, {\alpha }_{{s}}, {F})$-contraction of six mappings in a tripled b-metric space with an application of integral equations
Authors: Ranjbar Ghorban Khalilzadeh , Samei Mohammad Esmael
Published: October 2020

The aim of this work is to usher in tripled b-metric spaces, triple weakly $\alpha _{s}$

α
s

-admissible, triangular partially triple weakly $\alpha _{s}$

α
s

-admissible and their properties for the first time. Also, we prove some theorems about coincidence and common fixed point for six self-mappings. On the other hand, we present a new model, talk over an application of our results to establish the existence of common solution of the system of Volterra-type integral equations in a triple b-metric space. Also, we give some example to illustrate our theorems in the section of main results. Finally, we show an application of primary results.
A note on maximal singular integrals with rough kernels
Authors: Zhang Xiao , Liu Feng
Published: October 2020

In this note we study the maximal singular integral operators associated with a homogeneous mapping with rough kernels as well as the corresponding maximal operators. The boundedness and continuity on the Lebesgue spaces, Triebel–Lizorkin spaces, and Besov spaces are established for the above operators with rough kernels in $H^{1}({\mathrm{S}}^{n-1})$

H
1

(

S

n
−
1

)
, which complement some recent developments related to rough maximal singular integrals.
A discussion on the existence of positive solutions of the boundary value problems via ψ-Hilfer fractional derivative on b-metric spaces
Authors: Afshari Hojjat , Karapınar Erdal
Published: October 2020

In this paper, we investigate the existence of positive solutions for the new class of boundary value problems via ψ-Hilfer fractional differential equations. For our purpose, we use the $\alpha -\psi $
α
−
ψ
Geraghty-type contraction in the framework of the b-metric space. We give an example illustrating the validity of the proved results.
Addressing opioid use disorder among rural pregnant and postpartum women: a study protocol
Authors: Bryan M. Aryana , Smid Marcela C. , Cheng Melissa , Fortenberry Katherine T. , Kenney Amy , Muniyappa Bhanu , Pendergrass Danielle , Gordon Adam J. , Cochran Gerald
Published: October 2020

Background

Opioid use disorder (OUD) among women delivering at a hospital has increased 400% from 1999–2014 in the United States. From the years 2007 to 2016, opioid-related mortality during pregnancy increased over 200%, and drug-overdose deaths made up nearly 10% of all pregnancy-associated mortality in 2016 in the US. Disproportionately higher rates of neonatal opioid withdrawal syndrome (NOWS) have been reported in rural areas of the country, suggesting that perinatal OUD is a pressing issue among these communities. There is an urgent need for comprehensive, evidence-based treatment services for pregnant women experiencing OUD. The purpose of this article is to describe a study protocol aimed at developing and evaluating a perinatal OUD curriculum, enhancing evidence-based perinatal OUD treatment in a rural setting, and evaluating the implementation of such collaborative care for perinatal OUD.

Methods

This two-year study employed a one group, repeated measures, hybrid type-1 effectiveness-implementation design. This study delivered interventions at 2 levels, both targeting improvement of care for pregnant women with OUD. The first area of focus was at thecommunity healthcare provider-level, which aimed to evaluate the acceptability and feasibility of perinatal OUD education across time and to improve provider education by increasing knowledge specific to: MOUD provision; screening, brief intervention, and referral to treatment (SBIRT) utilization; and NOWS treatment. The second area of intervention focus was at thepatient-level, which assessed the preliminary effect of perinatal OUD provider education in promoting illicit opioid abstinence and treatment engagement among pregnant women with OUD. We adopted constructs from the Consolidated Framework for Implementation Research (CFIR) to assess contextual factors that may influence implementation, and the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model to comprehensively evaluate implementation outcomes.

Discussion

This article presents the protocol of an implementation study that is employing the CFIR and RE-AIM frameworks to implement and evaluate a perinatal OUD education and service coordination program in two rural counties. This protocol could serve as a model for clinicians and researchers seeking to implement improvements in perinatal care for women with OUD in other rural communities.

Trial registrationNCT04448015 clinicaltrials.gov.
Transdiagnostic treatment of emotional disorders in people with multiple sclerosis: randomized controlled trial
Authors: Nazari Nabi , Sadeghi Masood , Ghadampour Ezatolah , Mirzaeefar Davod
Published: October 2020

Background

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system. MS is significantly associated with a high rate of psychological, behavioral, and emotional consequences. Despite the frequent mental disorders, high rate of psychological comorbidities, and emotional problems in people with MS (PwMS), these conditions are often underdiagnosed and undertreated. This study aimed to examine the efficacy of a group format of the unified protocol for the transdiagnostic treatment of emotional disorders in adult PwMS associated with an emotional disorder.

Methods

Seventy adult PwMS were randomized using an internet-based computer system to either the unified protocol (n = 35) or treatment as usual condition. The assessment protocol included semi-structured clinical interviews and self-reports evaluating diagnostic criteria, depression, anxiety and worry symptoms, emotional dysregulation, and affectivity.

Results

The parametric test of analysis of covariance, followed the intent to treat analyses, revealed the unified protocol significantly changed depression symptoms (Cohen’s d = 1.9), anxiety symptoms (Cohen’s d = 2.16), worry symptoms (Cohen’s d = 1.27), emotion dysregulation (Cohen’s d = 0.44), positive affect (Cohen’s d = 1.51), and negative affect (Cohen’s d = 1.89) compared with the control group. The unified protocol also significantly improved outcome scores at the end of treatment relative to baseline (p < .001).

Conclusion

The findings support that the unified protocol could be an additional efficient psychological treatment for PwMS.

Trial registration IRCT, number: IRCT20190711044173N1. Registered 31october 2019, https://en.irct.ir/user/trial/40779/view.
Non-catecholamine vasopressors in the treatment of adult patients with septic shock—evidence from meta-analysis and trial sequential analysis of randomized clinical trials
Authors: Zhong Lei , Ji Xiao-Wei , Wang Hai-Li , Zhao Guang-Ming , Zhou Qing , Xie Bo
Published: October 2020

Background

Norepinephrine (NE) has currently been the first-choice vasopressor in treating septic shock despite generally insufficient for patients with refractory septic shock. The aim of this update meta-analysis was to assess the safety and efficacy of a combination of non-catecholamine vasopressors (vasopressin/pituitrin/terlipressin/selepressin/angiotensin II) and NE versus NE in managing adult septic shock patients.

Methods

We conducted this study of literatures published from the inception to April 30, 2020, using PubMed, Embase, and the Cochrane Library databases without language restriction. Randomized controlled trials comparing NE with non-catecholamine vasopressors among adult septic shock patients were included in this meta-analysis. Pooled effects of relative risk (RR) or standard mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated using a random-effects model.

Results

Twenty-three studies covering 4380 participants were finally enrolled. The combined analysis of non-catecholamine vasopressors resulted in a nonsignificant reduction in 90-day/ICU/hospital mortality except for a decreased in 28-day mortality (n = 4217; RR, 0.92; 95% CI 0.86–0.99; P = 0.02). This favorable result was subsequently verified by the subgroup analyses of low risk of bias studies (RR = 0.91, 95% CI = 0.84 to 0.98; P = 0.02) and catecholamine-resistant refractory shock patients group (RR, 0.84; 95% CI = 0.70–1.00; P = 0.048). The pooled analysis of non-catecholamine vasopressors showed a 14% higher success rate of shock reversal at 6 h, a 29% decreased risk of continuous renal replacement therapy, but a 51% increased risk of hyponatremia and a 2.43 times higher risk of digital ischemia. Besides, the pooled data showed that non-catecholamine vasopressors decreased heart rate (HR) (SMD, − 0.43; 95% CI − 0.66 – − 0.19; P < 0.001), serum creatinine (− 0.15; 95% CI − 0.29 – − 0.01; P = 0.04), and the length of mechanical ventilation (MV) (− 0.19; 95% CI − 0.31 – − 0.07; P < 0.01, but there was no significant difference in other parameters.

Conclusions

Current pooled results suggest that the addition of NE to non-catecholamine vasopressors was associated with a marginally significant reduction in 28-day mortality. Moreover, they were able to shorten the length of MV, improved renal function, decreased HR, and increased the 6-h shock reversal success rate at the expense of increased the risk of hyponatremia and digital ischemia.
First simulations of day-to-day variability of mid-latitude sporadic E layer structures
Authors: Andoh Satoshi , Saito Akinori , Shinagawa Hiroyuki , Ejiri Mitsumu K.
Published: October 2020

We present the first simulations that successfully reproduce the day-to-day variability of the mid-latitude sporadic E ($$E_s$$Es) layers.$$E_s$$Eslayers appearing in the lower ionosphere have been extensively investigated to monitor and forecast their effects on long-distance communication by radio waves. Although it is widely accepted that the atmospheric tides are important in generating the$$E_s$$Eslayers, no simulations to date have reproduced the$$E_s$$Eslayers observed on a certain day. This is due to the lack of the combination of realistic information on the atmospheric tides in the lower ionosphere and a three-dimensional numerical ionospheric model that can simulate the precise transport of metallic ions. We developed a numerical ionospheric model coupled with the neutral winds from the GAIA (Ground-to-topside model of Atmosphere and Ionosphere for Aeronomy). The fundamental structures and the day-to-day variations of the$$E_s$$Eslayers observed by a$$\hbox {Ca}^+$$Ca+lidar are well-reproduced in the simulations.
Rectal cancer: a methodological approach to matching PET/MRI to histopathology
Authors: Rutegård Miriam K. , Båtsman Malin , Blomqvist Lennart , Rutegård Martin , Axelsson Jan , Ljuslinder Ingrid , Rutegård Jörgen , Palmqvist Richard , Brännström Fredrik , Brynolfsson Patrik , Riklund Katrine
Published: October 2020

Purpose

To enable the evaluation of locoregional disease in the on-going RECTOPET (REctal Cancer Trial on PET/MRI/CT) study; a methodology to match mesorectal imaging findings to histopathology is presented, along with initial observations.

Methods

FDG-PET/MRI examinations were performed in twenty-four consecutively included patients with rectal adenocarcinoma. In nine patients, of whom five received neoadjuvant treatment, a postoperative MRI of the surgical specimen was performed. The pathological cut-out was performed according to clinical routine with the addition of photo documentation of each slice of the surgical specimen, meticulously marking the location, size, and type of pathology of each mesorectal finding. This allowed matching individual nodal structures from preoperative MRI, via the specimen MRI, to histopathology.

Results

Preoperative MRI identified 197 mesorectal nodal structures, of which 92 (47%) could be anatomically matched to histopathology. Of the matched nodal structures identified in both MRI and histopathology, 25% were found to be malignant. These malignant structures consisted of lymph nodes (43%), tumour deposits (48%), and extramural venous invasion (9%). One hundred eleven nodal structures (55%) could not be matched anatomically. Of these, 97 (87%) were benign lymph nodes, and 14 (13%) were malignant nodal structures. Five were malignant lymph nodes, and nine were tumour deposits, all of which had a short axis diameter < 5 mm.

Conclusions

We designed a method able to anatomically match and study the characteristics of individual mesorectal nodal structures, enabling further research on the impact of each imaging modality. Initial observations suggest that small malignant nodal structures assessed as lymph nodes in MRI often comprise other forms of mesorectal tumour spread.

Trial registration

Clinical Trials Identifier:NCT03846882.
Localization of epileptic seizure focus by computerized analysis of fMRI recordings
Authors: Hekmati Rasoul , Azencott Robert , Zhang Wei , Chu Zili D. , Paldino Michael J.
Published: October 2020

By computerized analysis of cortical activity recorded via fMRI for pediatric epilepsy patients, we implement algorithmic localization of epileptic seizure focus within one of eight cortical lobes. Our innovative machine learning techniques involve intensive analysis of large matrices of mutual information coefficients between pairs of anatomically identified cortical regions. Drastic selection of pairs of regions with biologically significant inter-connectivity provides efficient inputs for our multi-layer perceptron (MLP) classifier. By imposing rigorous parameter parsimony to avoid overfitting, we construct a small-size MLP with very good percentages of successful classification.
Heparinized chitosan/hydroxyapatite scaffolds stimulate angiogenesis
Authors: Nájera-Romero Griselda V. , Yar Muhammad , Rehman Ihtesham Ur
Published: October 2020

Formation of blood vessels during bone regeneration represents a major challenge for tissue engineered constructs. Poor revascularization can lead to scaffold failure and consequently, leads to non-healing fracture. Heparin is known to bind with angiogenic growth factors influencing the process of new blood vessels formation. There are several problems associated with the use of growth factors in clinic such as low stability, uncontrolled delivery to the site, and high price. The aim of the present study was to explore the potential of heparin to produce pro-angiogenic bone regeneration materials. Chitosan/hydroxyapatite freeze-gelled scaffolds were prepared and loaded with heparin. Different concentrations of heparin were successfully loaded onto the scaffolds, its release from the scaffold was analysed by toluidine blue assay and their angiogenic effect was evaluated by chorioallantoic membrane (CAM) assay to determine the optimal concentration of heparin to induce a proangiogenic effect. It was noted that low heparin concentrations exhibited a positive effect, with approximately 28 μg per scaffold indicating a significant increment in blood vessels. The synthesized materials showed no cytotoxic effects when evaluated by using U2OS cell line.
Does mouse mammary tumor-like virus cause human breast cancer? Applying Bradford Hill criteria postulates
Authors: Hameed Yasir , Usman Muhammad , Ahmad Mukhtiar
Published: October 2020

Background

The role of mouse mammary tumor-like virus (MMTV-like virus) in human breast cancer (BC) has already been widely investigated worldwide with conflicting results. Although the researchers tried to establish the link between MMTV-like virus and BC through the statistical meta-analysis of the previous studies associating MMTV-like virus with BC, they failed to establish a more reliable link due to the shortcomings of the statistical meta-analysis. In the present study, we identified population-wide studies relating MMTV-like virus with BC through the PubMed search engine. Then, we examined the available data of MMTV-like virus prevalence in BC, normal/benign samples, and applied the postulates of Bradford Hill criteria on the available evidence to investigate the association between MMTV-like virus and BC. In addition, to further enhance the reliability of our outcomes, we have also evaluated the methodologies of the previous studies to address the possibility of false-negative and false-positive results.

Results

After a careful evaluation of the extracted data against the postulates of Bradford Hill criteria, it was observed that none of the studies fulfill all the major postulates of Bradford Hill criteria for causation including temporality, consistency, biological gradient, experiment, coherence, specificity, and analogy. Hence, no causal relationship has been suggested between MMTV-like virus and BC patients of the any included population.

Conclusion

The results failed to prove the causal relationship between MMTV-like virus and BC rather suggested it as a co-participant in the pathogenesis of BC.
Clinical trials: from problem child to the driving force of medical advancement
Authors: Delanerolle Gayathri , Thayanandan Tony , Riga Jenny , Griffiths James , Lawson Jennifer , Au-Yeung Sheena , Haque Nyla , Sandle Natasha , Raymont Vanessa
Published: October 2020

Clinical trials are conducted to find better ways to prevent, screen for, diagnose or treat human disease. The development of clinical trials throughout history has built the foundation for ethically and scientifically robust research. As our healthcare needs have evolved, so have clinical trials and the standards by which they are run. Vanessa Raymont and colleagues explore the past, present and future of the clinical trial.
Recent Studies Highlight the Burden of Comorbidities in Multiple Sclerosis
Authors: Greener Mark
Published: October 2020

People with multiple sclerosis can experience numerous physical and psychological comorbidities, which can delay diagnosis and the start of disease-modifying treatment. Recent studies add to a growing literature that demonstrates that health professionals should investigate, treat and monitor comorbidities from early in the disease's natural history. Mark Greener explains.
Home-Based Exercise And People With Parkinson's Disease: A Systematic Review
Authors: Hare Marianne , Hill James , Clegg Andrew
Published: October 2020

Background

Exercise is seen as an effective intervention to combat the reduction in postural stability and increased chance of falls in Parkinson's patients. However, there is some debate as to where this exercise should take place. This article critically appraises and evaluates a systematic review looking at home-based exercise versus centre-based exercise for improving balance and functional outcomes.