bluuebunny/crossref_metadata_2025 huggingface dataset:
Unexpected Increase of Myocardial Extracellular Volume Fraction in Low Cardiovascular Risk HIV Patients
Authors: Borrazzo Cristian , d'Ettorre Gabriella , Ceccarelli Giancarlo , Pacilio Massimiliano , Santinelli Letizia , Cavallari Eugenio Nelson , Spagnolello Ornella , Silvestri Valeria , Vassalini Paolo , Scagnolari Carolina , Francone Marco , Mastroianni Claudio Maria , Carbone Iacopo
Published: September 2020

Background: People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach.Materials and methods: In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV+ individuals (45 males, age 48 (42.5-48) years) on effective cART (CD4+ cell count: 450 cells/μL (IQR: 328-750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5-56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly.Results: The ECV was significantly higher in HIV+ patients than in the control group (ECV: 31% (IQR: 28%-31%) vs 27.4% (IQR: 25%-28%), p<0.001). The duration of cART (standardized β=0.56 (0.33-0.95), p=0.014) and the years of exposure to HIV infection (standardized β=0.53 (0.4-0.92), p<0.001), were positively and strongly associated with ECV values. Differences in ECV (p<0.001) were also observed regarding the duration of cART exposure (<5 years, 5-10 years and >10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33-0.89), p=0.084).Conclusions: HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH.
Incidence and Time-Varying Predictors of HIV and Sexually Transmitted Infections Among Male Sex Workers in Mexico City
Authors: Ganley Karla , Wilson-Barthes Marta , Zullo Andrew R. , Sosa-Rubí Sandra G. , Conde-Glez Carlos J. , García-Cisneros Santa , Lurie Mark N. , Marshall Brandon D.L. , Operario Don , Mayer Kenneth H. , Galarraga Omar
Published: September 2020

Introduction: Male sex workers (MSWs) are at high-risk for HIV/STI acquisition. We quantified HIV/STI incidence rates and identified their time-varying predictors among MSWs in Mexico City. Methods: MSWs recruited from the largest HIV clinic and community sites in Mexico City were tested for chlamydia, gonorrhea, syphilis, hepatitis, and HIV at baseline, 6-months, and 12-months. Incidence rates with 95% bootstrapped confidence limits were calculated. We examined potential time-varying predictors using generalized estimating equations for a population averaged model. Results and Discussion: Among 227 MSWs, median age was 24 and baseline HIV prevalence was 32%. Incidence rates (per 100 person-years) were as follows: HIV (5.28; 95%CIs 2.52, 11.07), chlamydia (4.63; 95% 2.41, 8.90), gonorrhea (3.92; 95% 1.96, 7.84), syphilis (12.44; 95% 8.11, 19.08), hepatitis B (2.09; 95% 0.79, 5.58), hepatitis C (0.96; 95% 0.24, 3.85), any STI except HIV (17.61; 95% 12.51, 22.72), and any STI including HIV (19.93; 95%CI 14.78, 26.89). In the multivariable-adjusted model, incident STIs (excluding HIV) were lower among those who reported consistently using condoms during anal and vaginal intercourse (odds ratio (OR) = 0.03, 95% 0.00, 0.68) compared to those who reported inconsistently using condoms during anal and vaginal intercourse. Conclusions: HIV/STI incidence is high among MSWs in Mexico City. Consistent condom use is an important protective factor for HIV/STIs, and should be an important component of interventions to prevent incident infections.
The Prevalence of COVID-19 Symptoms in Syria: A Cross-Sectional Study
Authors: Alhaffar MHD Bahaa Aldin , Abbas Ghadir , Nassar Jihad Abou
Published: September 2020

Introduction: The corona virus disease 2019 is a disease caused by the newly discovered human infecting SARS-Co V-2 virus. The COVID-19 virus is highly transmittable, by August 14, 2020, more than 20 million people were confirmed to have COVID-19 worldwide, with more than 750,000 death. Syria was declared to have one of most vulnerable health systems in the world, with poor surveillance systems, unstable conditions, no standardized method for reporting infections, lack of sufficient public awareness, and a continued deterioration of humanitarian and socio-economic conditions across Syria.Objectives: to investigate the prevalence of COVID-19 symptoms among the Syrian population.Methods: this is a cross sectional study in Damascus – Syria, data were collected during August, 2020 using an online questionnaire that contained 3 section (demographic variables, awareness of COVID-19, symptoms of COVID-19) and analyzed using SPSS v.22.Results: 5212 people were included in the study, 59% females and 41% males, 9.6% had chronic medical conditions. 63.4% reported experiencing COVID-19 symptoms during the past 6 months, symptoms lasted 6.9 days on average, the most prevalent symptoms were as anosmia and dysgeusia (42.2%), headache (67.1%), fatigue (70%). Symptoms were significantly more prevalent in the past 14 days (P=0.000).Conclusion: Within the limits of this study, high prevalence of covid-19 symptoms was noticed in the Syrian population. Significant correlation was made between the severity and duration of the symptoms. Measures to slow down spread of COVID-19 need to be taken immediately.
Customer satisfaction with clinical laboratory services provided by the Ethiopian health facilities: a systematic review and meta-analysis
Authors: Deress Teshiwal , Million Yihenew , Belachew Teshome , Girma Mekonnen
Published: September 2020

Background

Medical laboratory helps health professionals and patients with disease diagnosis and treatment monitoring. While providing services, maintaining customer satisfaction is an essential determinant of the success and long-term survival of the facility. So far, several studies conducted in Ethiopia on the evaluation of laboratory customer satisfaction; however, the level of satisfaction was significantly differed from study to study. Therefore, this study aimed to provide an estimated pooled satisfaction level of clinical laboratory customers with laboratory services in Ethiopia.
Methods

Online electronic databases, including Science Direct, Medline, HINARI, TRIP database, and African Journals Online, were searched. The pooled estimate of laboratory service satisfaction was determined using the random-effects model due to the presence of considerable heterogeneity among studies. The possible sources of heterogeneity were analyzed using subgroup analysis, sensitivity analysis, and meta-regression.
Results

The analysis of 18 Full text articles showed that the level of clinical laboratory service satisfaction among Ethiopian laboratories ranged from 48–91%. The pooled estimate was 66% (95% CI: 59–73). Among the moderator variables, sample size (p = 0.34) and year of publication (p ≤ 0.01) of the included studies showed statistically significant associations with the level of service satisfaction. The sensitivity analysis declares no influence on the overall effect estimate while removing a single study from the analysis at a time. The statistical tests declare the absence of publication bias.
Conclusions

In Ethiopia, the pooled level clinical laboratory service satisfaction was low. The year of publication and sample size showed a statistically significant relationship with service satisfaction. Strengthening the scope of existing diagnostic services, implementing immediate corrective actions for the unsatisfied customers, and having a mechanism of continuous monitoring of laboratory activities should be implemented to assure adequate service quality. Generally, the study can provide a current estimate that could be valuable for policymakers.
Relating the past with the present:
Information integration and segregation during ongoing narrative processing
Authors: Chang Claire , Lazaridi Christina , Yeshurun Yaara , Norman Kenneth , Hasson Uri
Published: September 2020

This study examined how the brain dynamically updates event representations by integrating new information over multiple minutes while segregating irrelevant input. A professional writer custom-designed a narrative with two independent storylines, interleaving across minute-long segments (ABAB). In the last (C) part, characters from the two storylines meet and their shared history is revealed. Part C is designed to induce the spontaneous recall of past events, upon the recurrence of narrative motifs from A/B, and to shed new light on them. Our fMRI results showed storyline-specific neural patterns, which were reinstated (i.e. became more active) during storyline transition. This effect increased along the processing timescale hierarchy, peaking in the default mode network. Similarly, the neural reinstatement of motifs was found during part C. Furthermore, participants showing stronger motif reinstatement performed better in integrating A/B and C events, demonstrating the role of memory reactivation in information integration over intervening irrelevant events.
Photoelectrical properties investigated on individual Si nanowires and their size dependence
Authors: Hu Xiaofeng , Li Shujie , Jiang Zuimin , Yang Xinju
Published: September 2020

Periodically ordered arrays of vertically aligned Si nanowires (Si NWs) are successfully fabricated with controllable diameters and lengths. Their photoconductive properties are investigated by photoconductive atomic force microscopy (PCAFM) on individual nanowires. The results show that the photocurrent of Si NWs increases significantly with the laser intensity, indicating that Si NWs have good photoconductance and photoresponse capability. This photo-enhanced conductance can be attributed to the photo-induced Schottky barrier change, confirmed by I-V curve analyses. On the other hand, electrostatic force microscopy (EFM) results indicate that a large number of photo-generated charges are trapped in Si NWs under laser irradiation, leading to the lowering of barrier height. Moreover, the size dependence of photoconductive properties is studied on Si NWs with different diameters and lengths. It is found that the increasing magnitude of photocurrent with laser intensity is greatly relevant to the nanowires’ diameter and length. Si NWs with smaller diameters and shorter lengths display better photoconductive properties, which agrees well with the size-dependent barrier height variation induced by photo-generated charges. With optimized diameter and length, great photoelectrical properties are achieved on Si NWs. Overall, in this study the photoelectrical properties of individual Si NWs are systematically investigated by PCAFM and EFM, providing important information for the optimization of nanostructures for practical applications.
Adenovirus Viremia Predicts Adenovirus Pneumonia Severity in Immunocompetent Children
Authors: Zhang Ruimu , Wang Hongmei , Tian Shufeng , Deng Jikui
Published: September 2020

Background: Previous studies have demonstrated an association between adenovirus viremia and disease severity in immunocompromised children. However, few studies focused on the use of this approach in immunocompetent children. This study explored the association between adenovirus viremia and adenovirus pneumonia severity in immunocompetent children. Methods: We did a retrospective, observational study of immunocompetent children with adenovirus pneumonia admitted in Shenzhen Children’s hospital in Shenzhen, China. Pneumonia was classified as severe or mild, based on the Chinese guideline of pneumonia severity classification. The serum of all the children in the study was tested for adenovirus DNA with quantitative polymerase chain reaction (PCR). Clinical manifestations, laboratory examinations, and disease severity were compared between these two groups. Results: A total of 111 immunocompetent children with adenovirus pneumonia (60 severe, 51 mild) were included. The median age was 40 months and 64 patients were male. Five patients were admitted to intensive care unit and two were endotracheal intubated. All the patients were discharged with recovery or improvement. Univariate analysis and binary logistic regression analysis showed leukocytosis (OR = 1.1; 95% CI: 1.0 to 1.2; P = 0.033), co-infection of mycoplasma pneumoniae (OR = 5.0; 95% CI: 2.1 to 12.3; P < 0.001), and high blood viral load (OR = 1.5; 95% CI: 1.2 to 2.0; P = 0.001) were risk factors for severe adenovirus pneumonia. Conclusions: Leukocytosis, co-infection of mycoplasma pneumoniae, and high blood viral load are risk factors for severe adenovirus pneumonia in immunocompetent children. Blood viral load predicts pneumonia severity.
Microbial Signature of Ocean-Going Syndrome
Authors: Sun Zheng , Zhang Meng , Li Min , Zhao Jinshan , Ji Youran , Cui Hongbing , Zhang Heping , Sun Zhihong
Published: September 2020

Background and aims: During ocean-going voyages, crew members are subject to complex pressures from their living and working environment, which leads to a sub-optimal health status. Although abnormal defecation was observed during voyages, the associations between the gut microbiome and the symptoms are still unclear. Methods: Associations between the gut microbiome and the health status of 77 crew members during a 135 day-long ocean-going voyage were evaluated using shotgun metagenomics of stool samples and health questionnaires (with 24 physical and psychological indicators) taken before and after the voyage.Results: The co-appearance of symptoms e.g. abnormal defecation frequency, insomnia, shallow sleep, nausea and over-eating best described the sub-optimal health status of the majority of crew members, and we named this as ‘Ocean-Going Syndrome (OGS)’. The OGS, instead of any single symptom, has a significant effect on the gut microbiome, and it was proved to be a key factor for individual perturbation in the gut microbiome during the voyage. Co-occurrence network analysis revealed a different microbial dynamic between the OGS and non-OGS crews, and the variation of 19 bacterial species and 31 gene families were identified as microbial signature for the OGS. Moreover, using a Random Forest model, the OGS can be predicted with a high accuracy (AUC=0.91) based on 27 biomarkers from pre-voyage samples. Conclusions: Understanding associations between the gut microbiome and health status under extreme environments could help us discover potential predictors or even therapeutic targets for dysbacteriosis related diseases.
Life weariness, suicidal thoughts and mortality: A seventeen-year longitudinal study among men and women older than 60 years
Authors: Tuvesson Hanna , Fagerström Cecilia , Welmer Anna-Karin , Elmståhl Sölve
Published: September 2020

Background
Suicide in old age is a significant contributor to premature mortality. However, the extent to which life weariness and suicidal thoughts impact on mortality in a long-term perspective is still unknown. The aim of this study was to investigate the effect of life weariness and suicidal thoughts on long-term survival (17 years) in an older Swedish population (60 + years), controlling for demographic and social network factors and depression. A further aim was to investigate differences in sex and age interactions in relation to mortality among individuals with and without life weariness and suicidal thoughts.
Methods
A longitudinal cohort study on a national, representative sample of people 60 + years was conducted through the Swedish National Study of Aging and Care study and included n = 7,213 individuals, who provided information about life weariness and suicidal thoughts, through an item derived from the Montgomery-Åsberg Depression Rating Scale. Data were analysed with multivariate Cox proportional hazards models, adjusted for potential confounders.
Results
At baseline, 12.5% of the participants (14.6% of females and 9.5% of males) reported life weariness and suicidal thoughts. During the 17-year follow-up, survival time was 11.5 years, SD 5.6, and 3,804 individuals died (59.5% females and 40.5% males). Individuals with life weariness and suicidal thoughts had half the survival rate compared with those without such thoughts (24.5% vs. 50.6%), with a survival time of 8.4 years (Standard deviation, SD, 5.7) versus 12.0 years (SD 5.4). The multi-adjusted hazard ratio of mortality for reporting life weariness and suicidal thoughts was 1.44 (95% confidence interval, 1.30–1.59), the population attributable risk was 11.1%. In the models, being male or female 80 + years (ref. female 60–69 years) showed the highest multi-adjusted hazard ratio of long-term mortality.
Conclusions
Findings suggest that life weariness and suicidal thoughts are risk factors for long-term mortality, when controlling for sex and age interactions that were found to strongly predict long-term mortality. The findings have practical implications in prevention of premature mortality, emphasising preventive actions of screening, identifying, and intercepting older men and women with signs of life weariness and suicidal thoughts.
Seizure Detection and Tracking Through Portable Technologies: Study Protocol of a Systematic Review
Authors: Beauchamp-Chalifour Elisabeth , Gagnon Marie-Pierre , Fortin Tamara Herrera , Assi Elie Bou , Nguyen Dang Khoa
Published: September 2020

BackgroundEpilepsy is a chronic neurological disease characterized by recurrent seizures due to excessive neuronal discharges and abnormal neuronal discharges. 30-40% of them are pharmaco-resistant, which is associated with cognitive impairement. seizure-related injuries and a higher risk of sudden unexpected death in epilepsy (SUDEP). The only way to minimize the risk of SUDEP is having a control of seizures. However, epileptics living or get a seizure alone can’t report the exact information to their physicians. Then, the level of gravity of their disease is inexact. Currently, the only way to identify a seizure is by electroencephalography (EEG), used by healthcare resources. It requires medical staff for its installation and interpretation. Nonetheless, a lot of new technologies developed for recording seizures at home have been developed. These one hasn’t optimally included epileptics and only a few went to a clinical trial; thus, scientific evidence is limited regarding their effectiveness. MethodsThe methodological approach is based in the Cochrane handbook for conducting systematic review. All studies in any languages about the technologies detecting seizures will be compared for any type of epilepsy and for any outcome measured. Two reviewers will independently screen the results for MEDLINE [PubMed, 1951-June 2019], EMBASE [OVID, 1947-June 2019], the Cochrane Register of Controlled Trails (CENTRAL) [up to June 2019] and grey literature [up to June 2019]. Extracted data will be recorded, categorized and summarized. DiscussionThe expected results would be the too short time of the trials and many positive false to get a conclusion of the effectiveness of the technologies studied. This systematic review is needed in order to improve knowledge of the effectiveness of technologies for detecting seizures and use this information for the development of a personalized tool for detecting seizures on the basis of the best available scientific evidence.Systematic review registrationPROSPERO CRD42020129787.
Technology-based Health Solutions for Cancer Caregivers to Better Shoulder the Impact of COVID-19: A Systematic Review Protocol
Authors: Su Zhaohui , McDonnell Dean , Liang Bin , Kue Jennifer , Li Xiaoshan , Šegalo Sabina , Advani Shailesh , Flores Bertha E , Wang Jing
Published: September 2020

Background Cancer patients are particularly vulnerable to COVID-19, partially owing to their compromised immune systems and curbed or cut cancer healthcare services caused by the pandemic. As a result, cancer caregivers may have to shoulder triple crises: the COVID-19 pandemic, pronounced healthcare needs from the patient, and elevated need for care from within. While technology-based health interventions have the potential to address unique challenges cancer caregivers face amid COVID-19, limited insights are available. Thus, to bridge this gap, we aim to identify technology-based interventions designed for cancer caregivers and report the characteristics and effects of these interventions concerning the distinctive challenges cancer caregivers face amid COVID-19. Additionally, this paper will present practical insights into the diverse intervention approaches that can assist in the delivery of digital health solutions for cancer caregivers amid and beyond COVID-19.Methods A systematic review of the literature will be conducted in PubMed, PsycINFO, CINAHL, and Scopus in September, 2020. Articles that center on technology-based interventions for cancer caregivers will be included in the review. The search strategy was developed in consultation with an academic librarian who is experienced in systematic review studies. Titles, abstracts, and full-text articles will be screened against eligibility criteria developed a priori. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedures will be followed for the reporting process.Results NA—This is a protocol study.Conclusions COVID-19 has uprooted cancer care as we know it. Due to barriers introduced by the COVID-19 pandemic, such as medical resources rationing, cancer caregivers often have to step up to address patients' healthcare needs and wants. This, in turn, will exert substantial stress on informal caregivers, above and beyond COVID-19-related burdens the general public shoulders on a daily basis. Findings of this study can shed light on evidence-based and practical solutions cancer caregivers can utilize to mitigate the unique challenges they face amid COVID-19. Furthermore, results of this study will also offer valuable insights for researchers who aim to develop interventions for cancer caregivers in the context of COVID-19. In addition, we also expect to be able to identify areas for improvement that need to be addressed in order for health experts to more adequately help cancer caregivers weather the storm of global health crises like COVID-19 and beyond.Study Protocol Registration: PROSPERO CRD42020196301
MiR-144-3p-mediated dysregulation of EIF4G2 contributes to the development of Hepatocellular Carcinoma through ERK pathway
Authors: Li Shuangshuang , Shao Jiajia , Lou Guohua , Wu Chao , Liu Yanning , ZHENG MIN
Published: September 2020

Background
Hepatocellular carcinoma (HCC) is one of the most common cancers with high incidence and mortality. But the underlying mechanisms of HCC still remain unclear. Eukaryotic translation initiation factors (eIFs), showing a large effect on tumor development. In this study, we were aimed to investigate the role of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) in HCC.
Methods
Western blot (WB) in 30 paired HCC tissues and tissue microarrays (TMAs) by immunohistochemistry (IHC) in 89 paired HCC samples were performed to assess EIF4G2 expression. Clone formation, Real-Time Cell Analysis (RTCA), wounding-healing and transwell assays were adopted to evaluate the role of EIF4G2 on HCC cell proliferation, migration and invasion ability. The function of EIF4G2 on HCC tumor growth was conducted by xenograft nude mouse model in vivo. The regulation of miR-144-3p on EIF4G2 was performed by luciferase reporter assay and WB.
Results
EIF4G2 was obviously upregulated in HCC tissues, and high-expression of EIF4G2 was closely related to HCC prognosis. EIF4G2 silencing could inhibit HCC cells growth and metastasis in vitro, and suppress tumorigenesis in vivo by repressing ERK signaling pathway. The results of luciferase reporter assay, WB and IHC staining verified that EIF4G2 was negatively regulated by miR-144. And re-expression of EIF4G2 could partially reverse the inhibiting effect of miR-144 in HCC.
Conclusion
In summary, our study revealed the role of EIF4G2 in HCC development by activating ERK pathway. We also found that EIF4G2 could be negatively regulated by tumor suppressor miR-144. Our investigations indicated that EIF4G2 might be a promising therapeutic target in HCC.
Prognostic Nomogram for Sorafenib Benefit in Hepatitis B Virus related Hepatocellular Carcinoma after Partial Hepatectomy
Authors: Dong Wei , Yan Kai , Yu Hua , Huo Lei , Xian Zhihong , Zhao Yanqing , Li Jutang , Zhang Yuchan , Cao Zhenying , Fu Yong , Cong Wenming , Dong Hui
Published: September 2020

Background The prediction regarding the long-term prognosis of individuals subjected to sorafenib treatment following partial hepatectomy due to hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is rather difficult.The objective behind this work is to create an effective prognostic nomogram of sorafenib for personalized therapy of HBV-relatedHCC. Methods 234 HBV-related HCC patients subjected or not subjected to sorafenibtreatment following partial hepatectomy at the Eastern Hepatobiliary Surgery Hospital from 2008 to 2013 were compared to investigate the association between index levels and sorafenib benefit. The optimal cut-off point of the overall survival (OS) factor level was determined by x-tile.The selection of indicators is based on clinical findings. The Cox regression model with an interaction term was employed for evaluating the predictive value. Using a multivariate Cox proportional hazards model a Nomogram was subsequently formulated to analyze 113 patients treated with sorafenib. Determination of nomogram’s discriminative ability and predictive accuracy was done using the concordance index (C-index), calibration, and ROC curve. Results Subgroup analysis revealed that Low GPC3,pERK, pAKT, serum AFP levels, without MVI, under 50 years old, male, TNM stage I/II and BCLC stage 0/A wereassociated significantly with a better OS in patients subjected to sorafenib treatment compared to those not treated with sorafenib after surgery. The independent factors for OS were found be GPC3, pERK, pAKT, serum AST and BCLC stage, following multivariate analysis of the sorafenib cohort, which was all included in the nomogram. The survival probability based on the calibration curve shows that the prediction of the nomogram was in good agreement with the actual observation. Survival was predicted to be 0.73(95% CI, 0.67 to 0.78) based on the C-index of the nomogram. The area under the ROC curve (AUC) for the nomogram to predict the survival for 1, 3, and 5-year was 0.726, 0.816, and 0.823, respectively. Conclusion This proposed nomogram has the potential to make quite a precise prediction regarding the prognosis of HBV-related HCC patients,who underwent sorafenib therapy following partial hepatectomy.
A novel humanized Frizzled-7-targeting antibody enhances antitumor effects of Bevacizumab against triple-negative breast cancer via blocking Wnt/β-catenin signaling pathway
Authors: Xie Wei , Zhao Huijie , Wang Fengxian , Wang Yiyun , He Yuan , Wang Tong , Zhang Kunchi , Yang Hao , Zhou Zhaoli , Shi Haibin , Wang Jin , Huang Gang
Published: September 2020

Background
Anti-angiogenic therapy has been widely applied to the clinical treatment of malignant tumors. However, the efficacy of such treatments has been called into question, especially in triple-negative breast cancer (TNBC). Bevacizumab, the first anti-angiogenic agent approved by FDA, actually increases invasive and metastatic properties of TNBC cells, resulting from the activation of Wnt/β-catenin signaling in response to hypoxia. As a critical receptor of Wnt/β-catenin signaling, Frizzled-7 (Fzd7) is aberrantly expressed in TNBC, indicating Fzd7 a potential target for developing drugs to be combined with anti-angiogenic agents.
Methods
Hybridoma technique and antibody humanization technique were utilized to generate a Fzd7-targeting antibody (SHH002-hu1). Biolayer interferometry (BLI) assay and near infrared (NIR) imaging were conducted to detect the affinity and targeting ability of SHH002-hu1. Next, whether SHH002-hu1 could suppress the invasion and migration of TNBC cells induced by Bevacizumab were validated, and the underlying molecular mechanisms were elucidated by luciferase reporter and western blot assays. The nude-mice transplanted TNBC models were established to assess the anti-TNBC activities of SHH002-hu1 when combined with Bevacizumab. Then, the effects on putative TNBC stem-like cells and Wnt/β-catenin signaling were evaluated by immunofluorescence (IF). Further, the tumor-initiating and self-renew capacity of TNBC cells were studied by secondary nude mouse xenograft model and sphere formation assay. In addition, the effects of SHH002-hu1 on the adaptation of TNBC cells to hypoxia were evaluated by the detection of vasculogenic mimicry (VM) and hypoxia-inducible factor-1α (HIF-1α) transcriptional activity.
Results
The novel humanized antibody targeting Fzd7 (SHH002-hu1) exhibited extremely high affinity with Fzd7, and specifically targeted to Fzd7+ cells and tumor tissues. SHH002-hu1 repressed invasion, migration and epithelial-mesenchymal cell transformation (EMT) of TNBC cells induced by Bevacizumab through abating Wnt/β-catenin signaling. SHH002-hu1 significantly enhanced the capacity of Bevacizumab to inhibit the growth of TNBC via reducing the subpopulation of putative TNBC stem-like cells, further attenuating Bevacizumab-enhanced tumor-initiating and self-renew capacity of TNBC cells. Moreover, SHH002-hu1 effectively restrained the adaptation of TNBC cells to hypoxia via disrupting Wnt/β-catenin signaling.
Conclusion
SHH002-hu1 significantly enhances the anti-TNBC capacity of Bevacizumab, and shows the potential of preventing TNBC recurrence, suggesting SHH002-hu1 a good candidate for the synergistic therapy together with Bevacizumab.
Exosomal ANGPTL1 Attenuates CRC Liver Metastasis by Regulating Kupffer Cell Secretion Pattern and Impeding MMP9 induced vascular leakiness.
Authors: Jiang Kai , Chen Haiyan , Fang Yimin , Chen Liubo , Zhong Chenhan , Bu Tongtong , Dai Siqi , Pan Xiang , Fu Dongliang , Qian Yucheng , Wei Jingsun , Ding Kefeng
Published: September 2020

Background: Angiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown. This study was designed to explore the role of exosomal ANGPTL1 on liver metastasis in colorectal cancer (CRC).Methods: Exosomes were isolated by ultracentrifugation. The ANGPTL1 level was detected in exosomes derived from human CRC tissues. The effects of exosomal ANGPTL1 on CRC liver metastasis were explored by the intrasplenic injection mouse model. The liver PMN was examined by vascular permeability assays. Exosomal ANGPTL1 localization was validated by exosome labeling. The regulatory mechanisms of exosomal ANGPTL1 on Kupffer cells were determined by RNA sequencing. qRT-PCR, Western Blot, and ELISA analysis were conducted to examine gene expressions at mRNA and protein levels.Results: ANGPTL1 protein level was significantly downregulated in the exosomes derived from CRC tumors compared with paired normal tissues. Besides, exosomal ANGPTL1 attenuated liver metastasis and impeded vascular leakiness in the liver PMN. Moreover, exosomal ANGPTL1 were mainly taken up by KCs and regulated the KCs secretion pattern, especially decreasing the MMP9 expression, which finally prevented the liver vascular leakiness. In mechanism, exosomal ANGPTL1 downregulated MMP9 level in KCs by inhibiting the JAK2-STAT3 signaling pathway.Conclusions: Taken together, exosomal ANGPTL1 attenuated CRC liver metastasis and impeded vascular leakiness in the liver PMN by reprogramming the Kupffer cell and decreasing the MMP9 expression. This study suggests a suppression role of exosomal ANGPTL1 on CRC liver metastasis and expands the approach of ANGPTL1 functioning.
Associations Between Muscle Mass, Muscle Morphology and Bone Health in Older Men With Sarcopenia: A Cross-sectional Study
Authors: Mastaviciute Asta , Kilaite Justina , Petroska Donatas , Laurinavičius Arvydas , Tamulaitiene Marija , Alekna Vidmantas
Published: September 2020

Background: The aim of this study was to explore the association between muscle mass, morphology, bone mineral density, and physical function in community-dwelling older men with sarcopenia.Methods: A total of 151 men, 60 years or older were included in this study. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Low bone mineral density was diagnosed if T-score was equal to or below -1.0 SD of mean young men reference range. Sarcopenia was diagnosed according to European Working Group on Sarcopenia in Older People (EWGSOP) criteria: low muscle mass and low muscle strength or low physical performance. Physical performance was evaluated by short physical performance battery. Microbiopsy of musculus vastus lateralis was performed with disposable muscle microbiopsy system. The perimeter and cross-section area of muscle fibers were calculated using image analysis software in whole slide images; type of fiber and their distribution were evaluated as well. Relationship between variables were examined using Spearman’s and Pearson’s correlations. The level of significance (p-value) of < 0.05 was considered as statistically significant.Results: Mean age of the subjects was 72.9 ± 8.02 years. Sarcopenia was diagnosed in 45 (29.8%) men. In the sarcopenia group, 25 muscle biopsies were examined. The average muscle fiber length was 217.47 ± 25.22 microm and average fiber cross-sectional area was 2446 ± 608.87 microm2. In 9 sarcopenic men with T-scores equal or below -2.5, the muscle fiber area had a significant correlation with balance test (r = 0.73, p = 0.025). Multiple significant correlations were found between bone mineral density, lean mass, appendicular lean mass, arm and leg lean mass, gait speed, balance test and handgrip strength.Conclusions: In men with sarcopenia, low lean muscle mass was associated with low femoral neck and hip BMD, and lower muscle strength. In sarcopenic men with osteoporosis, lower muscle fiber area was associated with lower scores of balance test.Trial registration: study protocol has been approved by Lithuanian regional biomedical research ethics committee (No. 158200-03-208-75).
Impact of autologous platelet rich plasma use on postoperative acute kidney injury in type A acute aortic dissection repair: A retrospective cohort analysis
Authors: Tong Jiaqi , Cao Liang , Liu Liwei , Jin Mu
Published: September 2020

Backround: Perioperative coagulopathy and blood transfusion are common in patients undergoing Stanford type A acute aortic dissection (AAD) repair. The autologous platelet-rich plasmapheresis (aPRP) technique is a blood conservation approach to reduce blood transfusions and morbidity in patients at high risk of bleeding. The purpose of this study was to analyze the effect of aPRP on outcomes, especially in postoperative acute kidney injury (post-AKI), in patients undergoing AAD surgery.Methods: Six hundred sixty patients were divided into aPRP and non-aPRP groups according to aPRP use. The primary endpoint was the difference in the incidence of post-AKI between two groups. The secondary endpoints were risk factors for post-AKI and to assess clinical outcomes. The risk factors associated with post-AKI were calculated, and all outcomes were adjusted by propensity-score matching analysis.Results: A total of 272 patients (41.2%) received aPRP, whereas 388 were in the non-aPRP group. Compared to non-aPRP group, the occurrence of post-AKI increased by 14.1% (p=0.002) and 11.1% (p=0.010) with and without propensity adjustment in the aPRP group, respectively. The aPRP group required fewer intraoperative transfusions (p<0.05) and shortened the duration of mechanical ventilation (p<0.05) than those in the non-aPRP group. Multiple regression analyses showed that aPRP (odds ratio: 1.729, 95% confidence interval: 1.225–2.440; p<0.001) was one of the independent risk factors for post-AKI.Conclusions: The use of aPRP significantly reduced intraoperative blood transfusions and decreased postoperative mortality-adjusted mechanical ventilation. However, aPRP use was independently associated with an increased hazard of post-AKI after adjusting for confounding factors.
Development a Set of Scales to Assess Job Satisfaction Among Physicians in Peru: Validity and Reliability Assessment
Authors: Villarreal-Zegarra David , Torres-Puente Roberto , Castillo-Blanco Ronald , Cabieses Baltica , Bellido-Boza Luciana , Mezones-Holguín Edward
Published: September 2020

Background: To assess the evidences of validity and reliability of a set of scales on different areas of job satisfaction (general professional activity, health services management, and working conditions) in Peruvian physicians based on data from the National Survey of Satisfaction of Users in Health (ENSUSALUD).Method: We carried out a psychometric study based on secondary data analysis. Participants were selected from a two-stage probabilistic national representative sampling stratified by political region. Validity was assessed by exploratory and confirmatory factor analysis and measurement invariance analysis. Reliability was assessed by internal consistency coefficients (alpha and omega). The set of scales was composed of items related to three different areas of job satisfaction: 1) satisfaction with general professional activity, 2) satisfaction with the health services management, and 3) satisfaction with the working conditions of the health center.Results: We included 2,137 participants in the analysis. General professional activity scale with 6 items (CFI=0.946; RMSEA=0.071; SRMR=0.035) and the health services management scale with 8 items (CFI=0.972; RMSEA=0.081; SRMR=0.028) showed good measurement properties for the one-dimensional model. The scale of working conditions presented adequate measurement properties with a two-dimensional model (CFI=0.914; RMSEA=0.080; SRMR=0.055): individual conditions (8 items) and infrastructural conditions (3 items). The invariance analysis presented that comparisons can be made between sex, age, civil status, medical specialty, working in other institutions, work-related illness, chronic disease, and time working in health care center. All scales had adequate internal consistency (ω and α between 0.70 and 0.90).Conclusions: The set of scales solid factorial structure and measurement invariance, which makes it possible for group comparison. They also achieved stability in their scores as they showed adequate internal consistency coefficients. Based on our findings, these instruments are suitable for measuring job satisfaction among outpatient physicians throughout Peru, as our data is representative at the country level.
Abnormal Electrophysiological Phenotypes and Sleep Deficits in a Mouse Model of Angelman Syndrome
Authors: Copping Nycole A , Silverman Jill L
Published: September 2020

Background: Angelman Syndrome (AS) is a rare genetic disorder characterized by impaired communication, motor and balance deficits, intellectual disabilities, recurring seizures and abnormal sleep patterns. The genetic cause of AS is neuronal specific loss of expression of UBE3A (ubiquitin-protein ligase E6-AP), an imprinted gene. Seizure and sleep disorders are highly prevalent (>80%) in the AS population. The present experiments were designed to identify translational, neurophysiological outcome measures in a model of AS.Methods: We used the exon-2 deletion mouse (Ube3a-del) on a C57BL/6J background to assess seizure, sleep and electrophysiological phenotypes. Seizure susceptibility has been reported in Ube3a-del mice with a variety of seizure induction methods. Here, we provoked seizures by a single high-dose injection of 80 mg/kg pentylenetetrazole. Novel experiments included the utilization of wireless telemetry devices to acquire global electroencephalogram (EEG) and neurophysiological data on electrographic seizures, power spectra, light/dark cycles, sleep stages and sleep spindles in Ube3a-del and WT mice.Results: Ube3a-del mice exhibited reduced seizure threshold compared to WT. EEG illustrated that Ube3a-del mice had increased epileptiform spiking activity and delta power, which corroborates findings from other laboratories and recapitulates clinical reports in AS. This is the first report to use a cortical surface-based recording by a wireless telemetry device over tethered/fixed head-mount depth recordings. Less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages, and total less sleep time in Ube3a-del mice were observed compared to WT. For the first time, we detected fewer sleep spindles in the AS mouse model.Limitations: This study was limited to the exon 2 deletion mouse model, future work will investigate the rat model of AS, containing a complete Ube3a deletion and pair EEG with behavior.Conclusions: Our data enhance rigor and translatability as our study provides important corroboration of previous reports on epileptiform and elevated delta power. For the first-time we report neurophysiological phenotypes collected via translational methodology. Furthermore, this is the first report of reduced sleep spindles, a critical marker of memory consolidation during sleep, in an AS model. Our results are useful outcomes for therapeutic testing.
Just Like Fireworks in My Brain – An Interview Study on Experiences of Emotions in Patients with Eating Disorders
Authors: Petersson Suzanne , Gullbing Lydia , Perseius Kent-Inge
Published: September 2020

Background: Patients with eating disorders have reported poorer emotional awareness, more emotional suppression, less use of adaptive emotional regulation strategies, and more use of maladaptive emotional regulation strategies compared to people in healthy control groups. Aim: To explore experiences of emotions by a sample of patients with eating disorders. Method: Nine patients with eating disorder diagnoses at an eating disorder outpatient clinic in Sweden were interviewed for their thoughts on emotions. The interviews were analyzed with Thematic Analysis. Result: Four themes were constructed: "Not knowing what one feels", "Switch off, run away, or hide behind a mask", "Emotions in a lifelong perspective", and "Using eating behaviors to regulate emotions". The patients described uncertainty regarding whether they experienced emotions correctly. They described how they tried to avoid difficult emotions through suppressive strategies and eating disorder behavior. All described strategies were inefficient and all emotions were experienced as problematic, even joy. Since joy was used as a mask, the real experience of happiness was lost and mourned.Conclusion: All kinds of emotions were considered problematic to experience, but shame, fear, and sadness were considered worst. It is difficult to know if the emotional difficulties preceded an eating disorder, but at least those problems seem to have increased by the eating disorder.
Artificial Intelligence Framework for Efficient Detection and Classification of Pneumonia Using Chest Radiography Images
Authors: Alqudah Ali Mohammad , Qazan Shoroq , Masad Ihssan S.
Published: September 2020

BackgroundChest diseases are serious health problems that threaten the lives of people. The early and accurate diagnosis of such diseases is very crucial in the success of their treatment and cure. Pneumonia is one of the most widely occurred chest diseases responsible for a high percentage of deaths especially among children. So, detection and classification of pneumonia using the non-invasive chest x-ray imaging would have a great advantage of reducing the mortality rates.ResultsThe results showed that the best input image size in this framework was 64 64 based on comparison between different sizes. Using CNN as a deep features extractor and utilizing the 10-fold methodology the propose artificial intelligence framework achieved an accuracy of 94% for SVM and 93.9% for KNN, a sensitivity of 93.33% for SVM and 93.19% for KNN and a specificity of 96.68% for SVM and 96.60% for KNN.ConclusionsIn this study, an artificial intelligence framework has been proposed for the detection and classification of pneumonia based on chest x-ray imaging with different sizes of input images. The proposed methodology used CNN for features extraction that were fed to two different types of classifiers, namely, SVM and KNN; in addition to the SoftMax classifier which is the default CNN classifier. The proposed CNN has been trained, validated, and tested using a large dataset of chest x-ray images contains in total 5852 images.
Factors Associated with the Use of Insecticide-Treated Nets: Analysis of the 2018 Burkina Faso Malaria Indicator Survey
Authors: Tassembedo Mahamadi , Coulibaly Soumaila , Ouedraogo Boukary
Published: September 2020

Sleep under an ITN reduce contact with mosquitoes through the combination of a physical barrier and an insecticidal effect, which reduces the incidence of malaria. The 2016–2020 Burkina Faso National Malaria Strategic Plan aims to have at least 90% of the population, 100% of children under age 5, and 100% of pregnant women sleep under an ITN. To help achieve this goal, this analysis examines the factors that are associated with the use of ITN nets by using data from the 2017-18 Burkina Faso Malaria Indicator Survey (MIS). The analysis examines individual, household, and community-level factors associated with ITN usage. According to the 2017-18 Burkina Faso MIS, 58% of individuals in households that own at least one ITN reported that they slept under an ITN on the night before the survey. The use of ITNs was significantly associated with individual, household, and community-level variables that included age, gender, age of household head, number of sleeping rooms, wealth, malaria prevalence, residence, and region. The results highlight areas of intervention at the individual, household, and community levels that can increase ITN use.