bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot cluster randomised trial of the Medicinesand Alcohol Consultation (MAC): an intervention to discuss alcohol use in community pharmacy medicine review services
Authors: Stewart Duncan , van Dongen Anne , Watson Michelle , Mandefield Laura , Atkin Karl , Dhital Ranjita , Foster Brent , Gough Brendan , Hewitt Catherine , Madden Mary , Morris Stephanie , O’Carroll Ronan , Ogden Margaret , Parrott Steve , Watson Judith , White Sue , Whittlesea Cate , McCambridge Jim
Published: October 2020

Background

Alcohol interventions are important to the developing public health role of community pharmacies. The Medicines and Alcohol Consultation (MAC) is a new intervention, co-produced with community pharmacists (CPs) and patients, which involves a CP practice development programme designed to integrate discussion of alcohol within existing NHS medicine review services. We conducted a pilot trial of the MAC and its delivery to investigate all study procedures to inform progression to a definitive trial.

Methods

This cluster pilot RCT was conducted in 10 community pharmacies in Yorkshire, UK, with a CP from each who regularly conducted Medicine Use Review (MUR) and New Medicine Service (NMS) consultations. Randomisation was conducted using a secure remote randomisation service. Intervention CPs (n = 5) were trained to deliver the MAC in MUR/NMS consultations. Control CPs (n = 5) provided these services as usual. Consecutive MUR/NMS patients were asked by CPs to participate, screened for eligibility (consumption of alcohol at least twice per week), and baseline data collected for those eligible. A two-month follow-up telephone interview was conducted. Blinding of CPs was not possible, but patients were blinded to the alcohol focus of the trial. Primary outcomes were total weekly UK units (8 g of ethanol per unit) of alcohol consumption in the week prior to follow-up, and confidence in medications management. Trial procedures were assessed by recruitment, attrition, and follow-up rates.

Results

260 patients were approached by CPs to take part in the trial, 68% (n = 178) were assessed for eligibility and 30% (n = 54) of these patients were eligible. Almost all eligible patients (n = 51; 94%) consented to participate, of whom 92% (n = 47) were followed-up at 2 months; alcohol consumption was lower in the intervention arm and confidence in medication management reduced slightly for both groups. Exploration of recall issues at follow-up showed a high level of agreement between a two-item quantity/frequency measure and 7-day guided recall of alcohol consumption.

Conclusions

The pilot trial demonstrates the feasibility of implementing the MAC in community pharmacy and trial recruitment and data collection procedures. However, decommissioning of MURs means that it is not possible to conduct a definitive trial of the intervention in this service.

Trial registration

ISRCTN57447996
On the validity of the centrality hypothesis in cross-sectional between-subject networks of psychopathology
Authors: Spiller Tobias R. , Levi Ofir , Neria Yuval , Suarez-Jimenez Benjamin , Bar-Haim Yair , Lazarov Amit
Published: October 2020

Background

In the network approach to psychopathology, psychiatric disorders are considered networks of causally active symptoms (nodes), with node centrality hypothesized to reflect symptoms’ causal influence within a network. Accordingly, centrality measures have been used in numerous network-based cross-sectional studies to identify specific treatment targets, based on the assumption that deactivating highly central nodes would proliferate to other nodes in the network, thereby collapsing the network structure and alleviating the overall psychopathology (i.e., the centrality hypothesis).

Methods

Here, we summarize three types of evidence pertaining to the centrality hypothesis in psychopathology. First, we discuss the validity of the theoretical assumptions underlying the centrality hypothesis in psychopathology. We then summarize the methodological aspects of extant studies using centrality measures as predictors of symptom change following treatment, while delineating their main findings and several of their limitations. Finally, using a specific dataset of 710 treatment-seeking patients with posttraumatic stress disorder (PTSD) as an example, we empirically examine node centrality as a predictor of therapeutic change, replicating the approach taken by previous studies, while addressing some of their limitations. Specifically, we investigated whether three pre-treatment centrality indices (strength, predictability, and expected influence) were significantly correlated with the strength of the association between a symptom’s change and the change in the severity of all other symptoms in the network from pre- to post-treatment (Δnode-Δnetwork association). Using similar analyses, we also examine the predictive validity of two simple non-causal node properties (mean symptom severity and infrequency of symptom endorsement).

Results

Of the three centrality measures, only expected influence successfully predicted how strongly changes in nodes/symptoms were associated with change in the remainder of the nodes/symptoms. Importantly, when excluding the amnesia node, a well-documented outlier in the phenomenology of PTSD, none of the tested centrality measures predicted symptom change. Conversely, both mean symptom severity and infrequency of symptom endorsement, two standard non-network-derived indices, were found to be more predictive than expected influence and remained significantly predictive also after excluding amnesia from the network analyses.

Conclusions

The centrality hypothesis in its current form is ill-defined, showing no consistent supporting evidence in the context of cross-sectional, between-subject networks.
Risk factors for the incursion, spread and persistence of the foot and mouth disease virus in Eastern Rwanda
Authors: Udahemuka Jean Claude , Aboge Gabriel Oluga , Obiero George Ogello , Lebea Phiyani Justice , Onono Joshua Orungo , Paone Massimo
Published: October 2020

Background

Identification of risk factors is crucial in Foot-and-mouth disease (FMD) control especially in endemic countries. In Rwanda, almost all outbreaks of Foot-and-Mouth Disease Virus (FMDV) have started in Eastern Rwanda. Identifying the risk factors in this area will support government control efforts. This study was carried out to identify and map different risk factors for the incursion, spread and persistence of FMDV in Eastern Rwanda. Questionnaires were administered during farm visits to establish risk factors for FMD outbreaks. Descriptive statistical measures were determined and odds ratios were calculated to determine the effects of risk factors on the occurrence of FMD. Quantum Geographic Information System (QGIS) was used to produce thematic maps on the proportion of putative risk factors for FMD per village.

Results

Based on farmers’ perceptions, 85.31% (with p < 0.01) experienced more outbreaks during the major dry season, a finding consistent with other reports in other parts of the world. Univariate analysis revealed that mixed farming (OR = 1.501, p = 0.163, CI = 95%), and natural breeding method (OR = 1.626; p = 0.21, CI = 95%) were associated with the occurrence of FMD indicating that the two risk factors could be responsible for FMD outbreaks in the farms. The occurrence of FMD in the farms was found to be significantly associated with lack of vaccination of calves younger than 12 months in herds (OR = 0.707; p = 0.046, CI = 95%).

Conclusions

This is the first study to describe risk factors for persistence of FMDV in livestock systems in Rwanda. However, further studies are required to understand the role of transboundary animal movements and genotypic profiles of circulating FMDV in farming systems in Rwanda.
Long noncoding RNA LBX2-AS1-modulated miR-4766-5p regulates gastric cancer development through targeting CXCL5
Authors: Peng LiPan , Chen ZeZhong , Wang GuangChuan , Tian ShuBo , Kong Shuai , Xu Tao , An XiaoHua , Chen YueZhi
Published: October 2020

Background

Long noncoding RNAs (LncRNAs) have been reported to critically regulate gastric cancer (GC). Recently, it was reported that LBX2 antisense RNA 1 (LBX2-AS1) is abnormally expressed in GC. However, the role of LBX2-AS1 in the malignancy of GC is worth further discussion.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the LBX2-AS1, miR-4766-5p and C-X-C motif chemokine (CXCL5) expression in GC tissues and cells. Dual-luciferase reporter assay was applied to examine the target relationship between LBX2-AS1 and miR-4766-5p or miR-4766-5p and CXCL5. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect cell proliferation, migration and invasion rates. The protein expression of CXCL5 was confirmed using western blot. The RNA pull down experiment was used to verify the specificity of LBX2-AS1 and miR-4766-5p on BGC-823 and SGC-7901 cells.

Results

LBX2-AS1 was up-regulated in GC tissues and cells, and its knockdown suppressed proliferation, migration and invasion of GC cells. While, overexpression of LBX2-AS1 increased proliferation and increased CXCL5 mRNA level. CXCL5 improved cell proliferation, migration and invasion of GC cells. LBX2-AS1 could bind to miR-4766-5p to regulate CXCL5 expression. Overexpression of CXCL5 overturned those effects of miR-4766-5p in GC cells. RNA Pull down shown that BGC-823 and SGC-7901 cells, miR-4766-5p specifically binds to LBX2-AS1.

Conclusions

In short, this study demonstrated that LBX2-AS1 promoted proliferation, migration and invasion through up-regulation CXCL5 mediated by miR-4766-5p in GC. The LBX2-AS1/miR-4766-5p/CXCL5 regulatory axis provides a theoretical basis for the research on lncRNA-directed therapeutics in GC.
The emerging roles of non-coding competing endogenous RNA in hepatocellular carcinoma
Authors: Xu Gang , Xu Wei-Yu , Xiao Yao , Jin Bao , Du Shun-Da , Mao Yi-lei , Zhang Zhong-Tao
Published: October 2020

Accumulating evidence has emerged revealing that noncoding RNAs (ncRNAs) play essential roles in the occurrence and development of hepatocellular carcinoma (HCC). However, the complicated regulatory interactions among various ncRNAs in the development of HCC are not entirely understood. The newly discovered mechanism of competing endogenous RNAs (ceRNAs) uncovered regulatory interactions among different varieties of RNAs. In recent years, a growing number of studies have suggested that ncRNAs, including long ncRNAs, circular RNAs and pseudogenes, play major roles in the biological functions of the ceRNA network in HCC. These ncRNAs can share microRNA response elements to affect microRNA affinity with target RNAs, thus regulating gene expression at the transcriptional level and both physiological and pathological processes. The ncRNAs that function as ceRNAs are involved in diverse biological processes in HCC cells, such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. Based on these findings, ncRNAs that act as ceRNAs may be promising candidates for clinical diagnosis and treatments. In this review, we discuss the mechanisms and research methods of ceRNA networks. We also reviewed the recent advances in studying the roles of ncRNAs as ceRNAs in HCC and highlight possible directions and possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. Finally, the limitations, gaps in knowledge and opportunities for future research are also discussed.
Novel sequential treatment with palbociclib enhances the effect of cisplatin in RB-proficient triple-negative breast cancer
Authors: Huang Yajing , Wu Hao , Li Xingrui
Published: October 2020

Background

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that lacks sensitivity to chemotherapy, endocrine therapy or targeted therapy. CDK4/6 inhibitors, combined with endocrine therapy, have been shown to be effective in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Therefore, we investigated whether the CDK4/6 inhibitor palbociclib (PD) could enhance the effects of cisplatin (CDDP) on TNBC.

Methods

The effects of different drug regimens consisting of PD and CDDP on MDA-MB-231 and RB-knockdown MDA-MB-231 (sh-MDA-MB-231) cells were assessed in vitro and in vivo. MDA-MB-468 and RB-overexpressing MDA-MB-468 cells were used to assess the effect of the PD-CDDP regimens in vitro. Immunoblotting illustrated the role of the cyclin D1/RB/E2F axis signalling pathway.

Results

PD induced G1 phase cell cycle arrest in the MDA-MB-231 cell line. However, synchronous treatment with PD and CDDP for 24 h, treatment with PD for 24 h followed by CDDP and treatment with CDDP for 24 h followed by PD had no influence on MDA-MB-231 cell apoptosis. We further investigated the effect of PD or CDDP withdrawal on the effects of sequential treatment and found that PD treatment for 48 h followed by withdrawal for 48 h and subsequent CDDP treatment (PD-CDDP) significantly increased apoptosis and inhibited the cell viability and colony formation of MDA-MB-231 cells, while with other regimens, PD and CDDP had an additive or antagonistic response. The preferential use of PD increased DNA damage induced by CDDP, as measured through γH2AX immunofluorescence. These findings were not observed in sh-MDA-MB-231 cells, and experiments to assess cell function in MDA-MB-468 and RB-overexpressing MDA-MB-468 cells yielded similar results, which indicated that PD enhanced the sensitivity of TNBC cells to CDDP in an RB-dependent manner. In vivo, compared with single drug treatment, combination treatment inhibited tumour growth and Ki-67 expression in MDA-MB-231 xenograft models. Western blot analysis revealed that PD enhanced sensitivity to CDDP through the CDK4/6-cyclin D1-RB-E2F pathway.

Conclusions

Pre-treatment with PD synchronized the tumour cell cycle through the CDK4/6-cyclin D1-RB-E2F pathway, which increased the antitumour effect of CDDP. Thus, PD-CDDP might be an effective treatment for RB-proficient TNBC patients.
Correction to: Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence
Authors: Bi Junming , Liu Hongwei , Dong Wei , Xie Weibin , He Qingqing , Cai Zijian , Huang Jian , Lin Tianxin
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
An exploratory non-randomized study of a 3-month electronic nicotine delivery system (ENDS) intervention with people accessing a homeless supported temporary accommodation service (STA) in Ireland
Authors: Scheibein Florian , McGirr Kevin , Morrison Andy , Roche Warren , Wells John Stephen Gary
Published: October 2020

Background

Smoking is endemic amongst people accessing homeless services, and they are disproportionately affected by smoking-related diseases. This paper reports on the results of a 3-month small scale intervention which explored the efficacy, challenges and opportunities of using electronic nicotine delivery systems (ENDS) to support cessation of tobacco smoking with people accessing an Irish supported temporary accommodation (STA) homeless service. It considers the results of this intervention with reference to the balance of harms between the use of vaping to support smoking cessation and continued smoking.

Methods

Twenty-three participants were recruited. Demographic data, carbon monoxide (CO) measurements, homelessness status and smoking history were recorded. Participants were given an ENDS device and two 10-ml bottles containing e-liquid available in several flavours and at several strengths. Participants could pick up new bottles on a weekly basis. At weeks 1, 4, 8 and 12, the Fagerström Test and Mood and Physical Symptoms Scale (MPSS) were administered.

Results

Over 75% of the residents in the participating hostel were recruited (23/30). However, there was a substantial loss to follow-up (n = 14) as a result of data protection issues, the transient nature of the population of interest and non-compliance with the intervention.

Self-reported reductions in cigarette consumption were found to be statistically significant (p < 0.001). However, reductions in carbon monoxide measurements were not statistically significant. Decreases in Fagerström Nicotine Dependence Test were statistically significant (p = 0.001), but decreases in MPSS “urge to smoke” and “strength of urges” composite scores were not.

Reported side effects included coughing, runny nose, bleeding nose, slight sweating, dizziness, increased phlegm and a burning sensation at the back of the throat. Barriers to engagement were peer norms, vaping restrictions in accommodation and adverse life events.

Positive effects reported included increased energy, less coughing, better breathing and financial benefits. An improvement in the domain “poor concentration” was also found to be statistically significant (p = 0.040).

Conclusion

ENDS-based interventions may be effective with this population. Future research should aim to improve follow-up, consider including behavioural components and monitor health effects in relation to ongoing concerns around risks and the balance of harms.

Trial registration

Registered retrospectively ISRCTN14767579
Hostility, compassion and role reversal in West Virginia’s long opioid overdose emergency
Authors: Ondocsin Jeff , Mars Sarah G. , Howe Mary , Ciccarone Daniel
Published: October 2020

Background

West Virginia is a largely rural state with strong ties of kinship, mutual systems of support and charitable giving. At the same time, wealth inequalities are extreme and the state’s drug overdose fatality rate stands above all others in the USA at 51.5/100,000 in 2018, largely opioid-related. In recent years, harm reduction services have been active in the state but in 2018 Charleston’s needle and syringe program was forced to close. This paper considers the risk environment in which the state’s drug-related loss of life, and those attempting to prevent it, exist.

Methods

This rapid ethnographic study involved semi-structured interviews (n = 21), observation and video recordings of injection sequences (n = 5), initially recruiting people who inject heroin/fentanyl (PWIH) at the Charleston needle and syringe program. Snowball sampling led the research team to surrounding towns in southern West Virginia. Telephone interviews (n = 2) with individuals involved in service provision were also carried out.

Results

PWIH in southern West Virginia described an often unsupportive, at times hostile risk environment that may increase the risk of overdose fatalities. Negative experiences, including from some emergency responders, and fears of punitive legal consequences from calling these services may deter PWIH from seeking essential help. Compassion fatigue and burnout may play a part in this, along with resentment regarding high demands placed by the overdose crisis on impoverished state resources. We also found low levels of knowledge about safe injection practices among PWIH.

Conclusions

Hostility faced by PWIH may increase their risk of overdose fatalities, injection-related injury and the risk of HIV and hepatitis C transmission by deterring help-seeking and limiting the range of harm reduction services provided locally. Greater provision of overdose prevention education and naloxone for peer distribution could help PWIH to reverse overdoses while alleviating the burden on emergency services. Although essential for reducing mortality, measures that address drug use alone are not enough to safeguard longer-term public health. The new wave of psychostimulant-related deaths underline the urgency of addressing the deeper causes that feed high-risk patterns of drug use beyond drugs and drug use.
Association of academic performance, general health with health-related quality of life in primary and high school students in China
Authors: Qi Shengxiang , Qin Zhenzhen , Wang Na , Tse Lap Ah , Qiao Huifen , Xu Fei
Published: October 2020

Purpose

To explore the association of academic performance and general health status with health-related quality of life (HRQoL) in school-aged children and adolescents in China.

Methods

In this cross-sectional study conducted in 2018, students (grade 4–12) were randomly chosen from primary and high schools in Nanjing, China. HRQoL, the outcome measure, was recorded using the Child Health Utility 9D, while self-rated academic performance and general health were the independent variables. Mixed-effects regression models were applied to compute mean difference (MD) and 95% confidence interval (CI) of HRQoL utility score between students with different levels of academic performance and general health.

Results

Totally, 4388 participants completed the study, with a response rate of 97.6%. The mean HRQoL utility score was 0.78 (SD: 0.17). After adjustment for socio-demographic attributes, physical activity, sedentary behavior, dietary patterns, body weight status and class-level clustering effects, students with fair (MD = 0.048, 95% CI 0.019, 0.078) and good (MD = 0.082, 95% CI 0.053, 0.112) self-rated academic performance reported higher HRQoL utility scores than those with poor academic performance, respectively. Meanwhile, students with fair (MD = 0.119, 95% CI 0.083, 0.154) and good (MD = 0.183, 95% CI 0.148, 0.218) self-assessed general health also recorded higher HRQoL utility scores than those with poor health, separately. Consistent findings were observed for participants by gender, school type and residential location.

Conclusions

Both self-rated academic performance and general health status were positively associated with HRQoL among Chinese students, and such relationships were independent of lifestyle-related behaviors and body weight status.
Correction to: Self-care and remote care during pregnancy: a new paradigm?
Authors: Gülmezoglu A. Metin , Ammerdorffer Anne , Narasimhan Manjulaa , Wilson Alyce N. , Vogel Joshua P. , Say Lale , Tunçalp Özge
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Endometrial cancer: mapping the global landscape of research
Authors: Brüggmann Dörthe , Ouassou Katja , Klingelhöfer Doris , Bohlmann Michael K. , Jaque Jenny , Groneberg David A.
Published: October 2020

Background

From a global viewpoint, endometrial cancer belongs to the most common female cancers. Despite the heavy burden of diseases and numerous unanswered questions, no detailed pictures of the global structure of endometrial cancer research are available so far. Therefore, this malignancy was reviewed using the New Quality and Quantity Indices in Science (NewQIS) protocol.

Methods

Using NewQIS, we identified endometrial carcinoma related research published in the Web of Science from 1900–2015 (P1) and from 2016–2020 (P2). Item analysis was performed with regard to research activity. Also, semi-qualitative aspects and socio-economic benchmarks were visualized using density equalizing mapping.

Results

In total, 9,141 from 1900–2015 and 4,593 from 2016–2020 endometrial cancer related studies were identified with the USA having the largest numbers of publications, citations, institutions, as well as the highest country-specific h-Index concerning endometrial cancer research in both periods. In contrast to other fields of cancer research, the two East Asian countries Japan and China followed concerning total research activities until 2015. From 2016 until 2020, China was found in short distance to the USA and was ranked second. In the socio-economic analysis, European countries were in prominent positions. Greece published 579.83 endometrial carcinoma-related articles per billion US-$ GDP, Finland (527.29), Sweden (494.65), Israel (493.75), and Norway (367.85) followed in the ranking. Density equalizing mapping visualized that large parts of Africa, Asia and South America with a high burden of disease played almost no visible role in the endometrial cancer research activities.

Conclusions

Endometrial cancer research activity is continuously increasing from a global viewpoint. However, the majority of original articles is published by authors based in high-income countries. Together with the finding that the research field of public health does only play a minimal role, our study points to the necessity that global health aspects should be introduced to endometrial cancer research.
The spectrum of pediatric amplified musculoskeletal pain syndrome
Authors: Sherry David D. , Sonagra Maitry , Gmuca Sabrina
Published: October 2020

Background

Children presenting with musculoskeletal pain to pediatric rheumatology clinics are very heterogeneous and on a continuum from those with localized pain to total body pain. Many report intermittent, rather than constant, pain. We examined clinical and psychological characteristics of these children at presentation and specifically those who fulfilled the criteria for fibromyalgia.

Methods

We performed a retrospective, cross-sectional cohort study of children under ≤18 years old presenting to the pediatric rheumatology pain clinic between January 2015 and July 2019 and enrolled in a patient registry. We included children diagnosed with amplified pain, excluding those fulfilling criteria for complex regional pain syndrome. Abstracted data included clinical characteristics, pain symptoms, functional disability inventory (FDI), widespread pain index, and symptom severity scale.

Results

We analyzed 636 subjects, predominantly non-Hispanic Caucasian females. Using median split method, 54% had diffuse pain (≥ 5 body regions involved), but, of these, only 58% met criteria for fibromyalgia. Subjects with diffuse pain, compared to those with localized pain had a longer duration of pain (24 vs 12 months, p < 0.01), reported greater pain intensity (6/10 vs 5/10, p < 0.001), greater mental health burden, and poorer function (FDI 25 vs 19, p < 0.0001). Subjects with limited pain more often reported a history of trigger event (34% vs 24%, p < 0.01) but not autonomic changes (14% vs 14%, p = 0.94). The presence of adverse childhood experiences did not differ among those with limited versus diffuse pain except for parental divorce (16% vs 23%, p = 0.03). Intermittent pain was reported in 117 children (18%) and, compared to subjects with constant pain, they reported less pain (0/10 vs 6/10) and were more functional (FDI 13 vs 25) (both p < 0.0001).

Conclusions

There exists a wide spectrum of pain manifestations among children with amplified pain including limited or diffuse and constant or intermittent pain. Most children who presented to our clinic did not fulfill criteria for fibromyalgia but nonetheless had significant symptoms and disability. Studies focusing on fibromyalgia may miss the full extent of childhood amplified pain. Additionally, research limited to those meeting the fibromyalgia criteria likely underestimate the significant impact of amplified pain among the pediatric population.
Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis
Authors: Ma Qin , Matsunaga Atsuko , Ho Brenda , Oksenberg Jorge R. , Didonna Alessandro
Published: October 2020

Background

MicroRNAs (miRNAs) belong to a class of evolutionary conserved, non-coding small RNAs with regulatory functions on gene expression. They negatively affect the expression of target genes by promoting either RNA degradation or translational inhibition. In recent years, converging studies have identified miRNAs as key regulators of oligodendrocyte (OL) functions. OLs are the cells responsible for the formation and maintenance of myelin in the central nervous system (CNS) and represent a principal target of the autoimmune injury in multiple sclerosis (MS).

Methods

MiRAP is a novel cell-specific miRNA affinity-purification technique which relies on genetically tagging Argonaut 2 (AGO2), an enzyme involved in miRNA processing. Here, we exploited miRAP potentiality to characterize OL-specific miRNA dynamics in the MS model experimental autoimmune encephalomyelitis (EAE).

Results

We show that 20 miRNAs are differentially regulated in OLs upon transition from pre-symptomatic EAE stages to disease peak. Subsequent in vitro differentiation experiments demonstrated that a sub-group of them affects the OL maturation process, mediating either protective or detrimental signals. Lastly, transcriptome profiling highlighted the endocytosis, ferroptosis, and FoxO cascades as the pathways associated with miRNAs mediating or inhibiting OL maturation.

Conclusions

Altogether, our work supports a dual role for miRNAs in autoimmune demyelination. In particular, the enrichment in miRNAs mediating pro-myelinating signals suggests an active involvement of these non-coding RNAs in the homeostatic response toward neuroinflammatory injury.
RETRACTED ARTICLE: Globalization and vulnerable populations in times of a pandemic: A Mayan perspective
Authors: Sotomayor Claudia Ruiz , Barrero Alejandra
Published: October 2020

Global health conditions are marked by inequities due mostly to poverty and lack of access to healthcare services. In a Pandemic setting, Mayan Communities in the Quintana Roo State in Mexico are a good example of how these disparities are exacerbated. First, they may have difficulty in adhering to directives to stay home from work because of the nature of their job, and the necessity to work, their living conditions are marked by crowding and sometimes lack of basic sanitation. Other susceptibilities generally considered are the underlying host factors and medical conditions that may increase the risk of disease or of complications of disease. In general, our native communities experience a high degree of socio-economic marginalization and are at disproportionate risk in public health emergencies, becoming even more vulnerable during this global pandemic, owing to factors such as their lack of access to effective monitoring and early-warning systems, and adequate health and social services.
Spontaneous pneumothorax as unusual presenting symptom of COVID-19 pneumonia: surgical management and pathological findings
Authors: Bellini Roberto , Salandini Maria Chiara , Cuttin Serena , Mauro Stefania , Scarpazza Paolo , Cotsoglou Christian
Published: October 2020

Background

Spontaneous pneumothorax has been reported as a possibile complication of novel coronavirus associated pneumonia (COVID-19). We report two cases of COVID-19 patients who developed spontaeous and recurrent pneumothorax as a presenting symptom, treated with surgical procedure. An insight on pathological finding is given.

Case presentation

Two patients presented to our hospital with spontaneous pneumothorax associated with Sars-Cov2 infection onset. After initial conservative treatment with chest drain, both patients had a recurrence of pneumothorax during COVI-19 disease, contralateral (patient 1) or ipsilateral (patient 2) and therefore underwent lung surgery with thoracoscopy and bullectomy. Intraoperative findings of COVID-19 pneumonia were parenchymal atelectasis and vascular congestion. Lung tissue was very frail and prone to bleeding.

Histological examination showed interstitial infiltration of lymphocytes and plasma cells, as seen in non specific interstitial pneumonia, together with myo-intimal thicknening of vessels with blood extravasation and microthrombi.

Conclusions

Although rarely, COVID-19 may present with spontaneous pneumothorax. Lung surgery for pneumothorax in COVID-19 patients can be safely and effectively performed when necessary.
Trilobatin ameliorates insulin resistance through IRS-AKT-GLUT4 signaling pathway in C2C12 myotubes and ob/ob mice
Authors: Liu Min , Wang Lujing , Li Xigan , Wu Yucui , Yin Fei , Liu Jianhui
Published: October 2020

Background

Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice.

Methods

Male ob/ob mice (8-10 weeks) and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; protein expression and phosphorylation were measured by western blot; glucose uptake was determined a fluorescent test.

Results

Treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of insulin resistance substrate 1 (IRS1) and protein Kinase B, (PKB/AKT), recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice.

Conclusions

IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.
Early start of growth hormone is associated with positive effects on auxology and metabolism in Prader-Willi-syndrome
Authors: Magill Lucy , Laemmer Constanze , Woelfle Joachim , Fimmers Rolf , Gohlke Bettina
Published: October 2020

Background

Prader-Willi-Syndrome (PWS) is characterized by hypothalamic-pituitary dysfunction. Recent research suggests starting growth hormone-treatment (GHT) as soon as possible. The aim of this study is to analyze possible differences in auxological parameters, carbohydrate and lipid metabolism between two groups of children with PWS that started GHT either during or after their first year of life.

Study design

Retrospective longitudinal study of 62 children (31 males) with genetically confirmed PWS. Upon diagnosis all children were offered GHT, some started immediately, others commenced later. Cohort A (n = 21; 11 males) started GHT at 0.3–0.99 yrs. (mean 0.72 yrs) and Cohort B (n = 41; 20 males) commenced GHT at 1.02–2.54 yrs. (mean 1.42 yrs) of age. Fasting morning blood samples and auxological parameters were obtained before the start of therapy and semi-annually thereafter. Differences between the two cohorts were estimated with a linear mixed-effect model.

Results

Mean length/height-SDSPWS differed significantly between the groups [1 yr: A: 0.37 (±0.83) vs B: 0.05 (±0.56); 5 yrs.: A: 0.81 (±0.67) vs B: 0.54 (±0.64); p = 0.012]. No significant differences were found in BMI, lean body mass or body fat.

Low-density cholesterol was significantly lower in A than in B [LDL: 1 yr: A: 79 (±20) mg/dl vs B: 90 (±19) mg/dl; 5 yrs.: A: 91(±18) mg/dl vs 104 (±26) mg/dl; p = 0.024].

We found significant differences in the glucose homeostasis between the groups [fasting insulin: p = 0.012; HOMA-IR: p = 0.006; HbA1c: p < 0.001; blood glucose: p = 0.022].

Conclusions

An early start of GHT during the first year of life seems to have a favorable effect on height-SDS and metabolic parameters.
The urgent need to empower rare disease organizations in China: an interview-based study
Authors: Li Xuefeng , Lu Zijuan , Zhang Jianyong , Zhang Xiangyu , Zhang Shu , Zhou Jincheng , Li Bingzhe , Ou Li
Published: October 2020

Background

Each rare disease only affects a small number of population. However, a total of 7000 rare diseases may affect 10% of the population. Due to the severity and lack of rare disease awareness, rare disease represents a huge challenge for the healthcare system. In Western countries, patient organizations have been playing an integral role in raising awareness, advocating legislation, and supporting drug development. This study aims to assess the unmet needs of rare disease patient organizations in China, and identify their unmet needs, providing essential information for the government and legislators.

Results

A total of 28 individuals representing 28 patient organizations in China were interviewed. Most organizations do not have official registration, employees, written standard operation protocol, or reliable financial resources. Misdiagnosis or delayed diagnosis is common, and treatment is often lacking. Due to the lack of financial resources, no organizations have been able to sponsor academic research, unlike their counterparts in Western countries. As to challenges, 71.4% of interviewees listed lack of rare disease awareness among the general public, while 67.9% selected lack of financial resources. Further, only 7.3% of these organizations received support from the government, and 28.6% received support from the general public. As to recommendations to the government, 82.1% of interviewees selected special insurance programs for rare diseases because rare diseases have been generally excluded from the national medical insurance programs. In addition, 78.6% of interviewees recommended to stimulate rare disease research, 75% recommended to import orphan drugs, and 71.4% recommended legislation of an orphan drug act, highlighting the urgent need of therapies.

Conclusions

Due to lack of support and rare disease awareness, patient organizations in China are still in the early phase. To empower these patient organizations, the interviewees’ recommendations, including legislating orphan drug act and releasing official definition of rare diseases, should be considered by the government and legislators.
Correction to: YPEL3 suppresses epithelial–mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway
Authors: Zhang Jian , Wen Xin , Ren Xian-Yue , Li Ying-Qin , Tang Xin-Ran , Wang Ya-Qin , He Qing-Mei , Yang Xiao-Jing , Sun Ying , Liu Na , Ma Jun
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry
Authors: Baekgaard Josefine S. , Abback Paer-Selim , Boubaya Marouane , Moyer Jean-Denis , Garrigue Delphine , Raux Mathieu , Champigneulle Benoit , Dubreuil Guillaume , Pottecher Julien , Laitselart Philippe , Laloum Fleur , Bloch-Queyrat Coralie , Adnet Frédéric , Paugam-Burtz Catherine ,   Traumabase® Study Group, Pirracchio Romain , Godier Anne , Harrois Anatole , Geeraerts Thomas , Meaudre Eric , Ausset Sylvain , Gauss Tobias , Meyer Alain , Hamada Sophie , Neuschwander Arthur , Cook Fabrice , Vinour Helene , Hanouz Jean Luc , Foucrier Arnaud , Boutonnet Mathieu , Raclot Pascal , Arthur James , Bruneau Nathalie , Cotte Jean , Leone Marc , Audibert Gerard
Published: October 2020

Background

Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality.

Methods

Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock).

Results

A total of 5912 patients were analyzed. The median age was 39 [26–55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50–0.70], p < 0.0001).

Conclusion

In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association.
The aging mouse microbiome has obesogenic characteristics
Authors: Binyamin Dana , Werbner Nir , Nuriel-Ohayon Meital , Uzan Atara , Mor Hadar , Abbas Atallah , Ziv Oren , Teperino Raffaele , Gutman Roee , Koren Omry
Published: October 2020

Background

During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice.

Methods

Fecal and blood samples from adult (n = 42, 100–300 days) and aging (n = 32, 550–750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin.

Results

We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces.

Conclusions

We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.
Quality of life after gastric bypass surgery in patients with type 2 diabetes: patients’ experiences during 2 years of follow-up
Authors: Katsogiannos Petros , Randell Eva , Sundbom Magnus , Rosenblad Andreas , Eriksson Jan W. , Leksell Janeth
Published: October 2020

Background

To examine the effects of gastric bypass surgery on health-related quality of life (HRQoL) in obese patients with type 2 diabetes, and to investigate their experiences of life adjustments using quantitative and qualitative methods.

Methods

Thirteen patients with type 2 diabetes and obesity, (body mass index, BMI > 30 kg/m2), participating in a randomized clinical trial, completed this sub-study. HRQoL was evaluated before, and at 6 months and 2 years after gastric bypass surgery, using the RAND- 36-item health survey. At 2 years, interviews for in-depth analysis of HRQoL changes were performed.

Results

Significant improvement was observed from baseline to 6 months for 2 of the eight health concepts, general health, and emotional well-being. At 2 years, improvements were also seen in physical functioning, energy/fatigue, as well as sustained improvements in general health and emotional well-being. Multiple regression analyses showed mostly non-significant associations between the magnitude of decrease in weight, BMI, and HbA1c during follow-up and improvement in HRQoL. The analyses from qualitative interviews supported a common latent theme “Finding a balance between the experience of the new body weight and self-confidence”.

Conclusions

The improved HRQoL after gastric bypass surgery in obese patients with type 2 diabetes was not explained specifically by the magnitude of weight loss, but rather by the participants achieving a state of union between body and consciousness.

Trial registration ClinicalTrials.gov Identifier NCT02729246. Date of registration 6 April 2016 – Retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02729246?term=bariglykos&draw=2&rank=1
Sexual violence against women by so-called Islamic state of Iraq and Syria (ISIS): protocol for a systematic review
Authors: Shahali Shadab , Shariati Shahrooz , Montazeri Ali
Published: October 2020

Background

Violence against women and girls (VAWG) has been significantly increased by the rise of conflict and insecurity in the territories under controlling so-called Islamic State of Iraq and Syria (ISIS). This review aims to provide an understanding of the consequences of ISIS sexual violence against women.

Methods

Electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, JSTOR, Web of Science, Scopus, Science Direct, ProQuest, and Google Scholar are searched for the articles published from 2014 to 2020. Then, two reviewers will systematically identify the articles which will meet the inclusion criteria. Using a standard checklist, methodological quality of articles is assessed. The findings will be summarized, and a narrative synthesis of data will be reported.

Discussion

This systematic review with a narrative synthesis approach will provide the important information about the gap in knowledge and detailed summary of the existing evidence on consequences of ISIS's systematic sexual violence against women. The evidence is useful for the international health organizations to plan and develop clinical guidelines with interest to reduce the consequences of sexual violence in the armed conflict territories.

Systematic review registration

PROSPERO CRD42019124215
On the Hermite–Hadamard inequalities for interval-valued coordinated convex functions
Authors: Zhao Dafang , Ali Muhammad Aamir , Murtaza Ghulam , Zhang Zhiyue
Published: October 2020

In this work, we introduce the notion of interval-valued coordinated convexity and demonstrate Hermite–Hadamard type inequalities for interval-valued convex functions on the co-ordinates in a rectangle from the plane. Moreover, we prove Hermite–Hadamard inequalities for the product of interval-valued convex functions on coordinates. Our results generalize several other well-known inequalities given in the existing literature on this subject.