bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune checkpoint inhibitor does not increase risks of poor outcomes in cancer patients with COVID-19 infection: A systematic review and meta-analysis
Authors: Lazarus Gilbert , Budiman Refael Alfa , Rinaldi Ikhwan
Published: October 2020

Background The association between prior exposure to immune checkpoint inhibitor (ICI) and outcomes of cancer patients with coronavirus disease 2019 (COVID-19) infection has yet to be systematically evaluated. As the current evidence remains equivocal, this meta-analysis aims to investigate the effects of ICI treatment on COVID-19 prognosis, including mortality, severity, and hospitalization.Methods Eligible studies published up to 14 September 2020 were included and assessed for risk of bias using the Quality in Prognosis Studies tool. A random-effects meta-analysis was conducted to estimate the pooled effect size along with 95% confidence intervals (CIs). The quality of body evidence was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Results Six studies involving a total of 1647 COVID-19-infected cancer patients were included in the systematic review. We discovered that prior ICI exposure was not associated with COVID-19 mortality (odds ratio [OR] 0.93 [95% CI: 0.37-2.36]; I2=30%), severity (OR 1.15 [95% CI: 0.40-3.28]; I2=0%), and hospitalization (OR 1.35 [95% CI: 0.64-2.87]; I2=51%). However, we discovered that prior exposure to chemoimmunotherapy predicted COVID-19 severity (OR 8.19 [95% CI: 2.67-25.08]; I2=0%), albeit with small sample size. GRADE assessments resulted in moderate-quality evidence for mortality, while the other outcomes yielded very low-to-low-quality evidenceConclusion Our findings indicated that ICI treatment should not be adjourned nor terminated during the current pandemic. Rather, COVID-19 vigilance should be increased, especially in patients receiving chemoimmunotherapy. Further studies with larger ICI cohorts are required to confirm our findingsTrial registration number: This project has been prospectively registered at PROSPERO (registration ID: CRD42020202142) on 4 August 2020.
WITHDRAWN: Comparative genome analyses highlight transposon-mediated genome expansion shapes the evolutionary architecture of 3D genomic folding in cotton
Authors: Wang Maojun , Li Jianying , Wang Pengcheng , Liu Zhenping , Liu Fang , Zhao Guannan , Xu Zhongping , Wang Kunbo , Zhang Xianlong
Published: October 2020

Transposable element (TE) amplification has been recognized as a driving force mediating genome size expansion and evolution, but the effect on shaping of 3D genomic architecture remains largely unknown in plants. Here, we report three reference-grade cotton genome assemblies of Gossypium rotundifolium (K2), G. arboreum (A2) and G. raimondii (D5) using Oxford Nanopore sequencing technology. Comparative genome analyses document the details of lineage-specific TE amplification contributing to three-fold change of genome size (K2, 2.44 Gb; A2, 1.62 Gb; D5, 750.19 Mb), and indicate a relatively conserved gene content and synteny relationship among genomes. We found that approximately 17% of syntenic genes exhibit chromatin status switching of A/B compartment, and active TE amplification increases the proportion of A compartment in gene regions in K2 and A2 relative to D5. We also found that only 42% of topologically associating domain (TAD) boundaries were conserved by comparing three genomes, and abundant TE amplification was linked to the organization of lineage-specific TADs. This study sheds light on the regulatory role of transposon-mediated genome expansion in the evolution of higher-order chromatin structure in plants.
SARS-CoV-2 direct cardiac damage through spike-mediated cardiomyocyte fusion
Authors: Schneider Jay , Pease David , Navaratnarajah Chanakha , Halfmann Peter , Clemens Daniel , Ye Dan , Kim Changsung , Barkhymer Alison , Cohle Stephen , Banks Aron , Mehta Arpit , Rantus Joseph , Emmerzaal Tim , Kozicz Tamas , Howell Kyle , Charlesworth Jon , Christensen Trace , Kawaoka Yoshihiro , Cooper Leslie , Ackerman Michael , Cattaneo Roberto
Published: October 2020

Viruses spread between hosts through particles, but within hosts, viral genomes can spread from cell to cell through fusion, evading antiviral defenses and obviating costly infectious virion production1-3. Billions of electromechanically coupled cardiomyocytes (CMs) make myocardium inherently vulnerable to pathological electromechanical short circuits caused by intercellular viral spread 4-6. Beyond respiratory illness, COVID-19 affects the heart7 and cardiac injury and arrhythmias are serious public health concerns8-12. By studying myocardium of a young woman who died suddenly, diagnosed postmortem with COVID-19, we discovered highly focal myocardial SARS-CoV-2 infection spreading from one CM to another through intercellular junctions identified by highly concentrated sarcolemmal t-tubule viral spike glycoprotein. SARS-CoV-2 permissively infected beating human induced pluripotent stem cell (hiPSC)-CMs building multinucleated cardiomyotubes (CMTs) through cell type-specific fusion driven by proteolytically-activated spike glycoprotein. Recombinant spike glycoprotein, co-localizing to sarcolemma and sarcoplasmic reticulum, produced multinucleated CMTs with pathological structure, electrophysiology and Ca2+ excitation-contraction coupling. Blocking cleavage, a peptide-based protease inhibitor neutralized SARS-CoV-2 spike glycoprotein pathogenicity. We conclude that SARS-CoV-2 spike glycoprotein, efficiently primed, activated and strategically poised during biosynthesis, can exploit the CM’s inherent membranous connectivities to drive heart damage directly, uncoupling clinically common myocardial injury from lymphocytic myocarditis, often suspected but rarely confirmed in COVID-19.
An Investigation on the Public's Acceptance of Prevention and Control Measures for COVID-19 in China
Authors: Zhang Ao , Wu Xiang , Gao Jingqi , Zhang Yongbao
Published: October 2020

Background: China has basically succeeded in controlling the COVID-19 epidemic, which is due to the cooperation and acceptance of epidemic prevention measures by the public. However, few studies have examined the measures China has taken to combat COVID-19 in order to reflect on its success in curbing the the spread of epidemic.Methods: In this study, the public acceptance questionnaire was designed based on the epidemic prevention measures adopted in China, to investigate the difference of public acceptance of epidemic prevention measures. The survey data was collected from 2,062 samples with different demographic characteristics from March 8, 2020 to April 9, 2020. And SPSS was used to analyze the data collected in the questionnaire, such as one-way variance, so as to draw conclusions.Results: The results show that age and educational level have a significant influence on public acceptance. In contrast gender and occupation field has no significant impact on it. The acceptance of the emergency prevention and control measures taken by the government during the epidemic period is generally high. With the development of the epidemic, the acceptability is increasing. And the public acceptance of traffic measures was highest. Conclusions: Rapid deployment of epidemic prevention measures and appropriate methods in transportation, economy and education are the key to China's effective containment of the epidemic. Measures such as shutting down cities and encouraging the wearing of masks deserve to be copied by other countries.This study summed up China's scientific experience in the fight against COVID-19 and differences in public acceptance. It can provide a positive reference for the development of epidemic prevention measures in other countries.
Bicelin (B-cell lymphoma 2 inhibitor) a Highly Safe DNA-based Anti-cancer Drug Showed No in vivo Cytopenia, Nephrotoxicity and/or Hepatotoxicity
Authors: Sheikhnejad Reza , Ashrafi Farzaneh , Talebi Ardeshir , Mazaheri Bahar , Moslemi Fatemeh , Nematbakhsh Mehdi
Published: October 2020

Background: Non-Hodgkin's lymphoma is the seventh most common cancer in clinic. Lymphoma could be treated with newly developed anti-apoptotic small molecule inhibitors of bcl-2 such as ABT-199 or venetoclax. However most small molecules present numerous side effects and cancer becomes resistance to them rapidly. PNT100 is a DNA-based bcl-2 inhibitor that has shown great efficacy and safety in treating non-Hodgkin's lymphoma tumors. However, liposomal carrier(smarticles) that was used to deliver PNT100 eventually failed to produce robust efficacy in the latest clinical trial conducted by ProNai Therapeutics (now called Sierra Technology). The high cost of liposomal carriers, makes this targeted drug less affordable. In addition, the liposomal components may also present some minor side effects as reported in pilot phase II trial [17-22]. In this study, we eliminated liposome and used a specific Epigenic modification to deliver this 24bp oligonucleotides (PNT100) without using additional chemicals and named it Bicelin. Methods: In this study, the safety of Bicelin was determined by evaluating the cytopenia, nephrotoxicity and hepatotoxicity effects of this drug in healthy animal model (Rats). The rats in experimental group were received Bicelin (20 mg/kg/day) for 5 days a week. The treatment was continued for 3 consecutive weeks. The blood and urine samples were collected for evaluation and the rats were then sacrificed. The kidneys and liver tissues were fixed in formalin 10% to perform histological investigation using H&E staining. Results: The in vitro and in vivo results clearly demonstrate that Bicelin is target specific and highly safe. We observed no cytopenia when blood tests were performed after 15 consecutive injection of Bicelin; Urine analysis revealed no significant differences between experimental and control group and there was no nephrotoxicity or hepatotoxicity when kidney and liver tissues were examined. Conclusion: based on our in vitro and in vivo safety studies, our bcl2 inhibitor, Bicelin is much safer and about 10-fold more effective than its liposomal form (PNT2258). Considering preclinical, phase I and II studies of PNT2258, Bicelin is expected to be very safe and effective in clinic.
Pacific Biosciences Single-molecule Real-time (SMRT) Sequencing Reveals High Diversity of Basal Fungal Lineages and Stochastic Processes Controlled Fungal Community Assembly in Mangrove Sediments
Authors: Zhang Zhi-Feng , Pan Yue-Ping , Liu Yue , Li Meng
Published: October 2020

Background: Mangrove wetlands are unique ecosystems with specific environmental characteristics, and are a hotspot of biodiversity. Although they probably harbor a variety of mangrove-specific fungi, the compositions of mangrove fungal community has been rarely investigated in detail, except for few published culture-based studies. In addition, the fungal community assembly and interaction patterns that impact the community composition in mangroves have not been explored to date. Results: We used the Pacific Biosciences single-molecule real-time sequencing approach targeting the entire internal transcribed spacer region, to systematically investigate the composition, biogeographical patterns, assembly processes, co-occurrence patterns and shaping factors of the fungal communities in sediments of seven representative mangroves across the Southeast China. We recovered 15 phyla, including some early diverging fungal lineages not previously reported in mangroves. Phylogenetic analysis revealed an incredibly high proportion of Rozellomycota and Chytridiomycota, as accounting for up to one-third of all fungal abundance. Although the neutral community model described a moderate portion of community variation, the similarity of fungal communities exhibited strong distance-decay patterns. Furthermore, the mean values and most beta nearest-taxon index fell between -2 to 2, with Bray–Curtis-based Raup–Crick value generally greater than 0.95, suggesting that stochastic processes strongly shape the fungal community composition. Consistently, nonmetric multidimensional scaling and permutational multivariate analysis of variance confirmed the geographical location as a crucial factor driving the distribution of both, the dominant and rare taxa of mangrove fungi. The db-RDA analyses indicated a minor role of environmental selections in shaping the fungal community. Network analyses revealed that the deep sediments harbor more complex fungal networks with highly connected taxa than surface sediments, and that rare fungal taxa might play important roles in microbial interactions and ecological functions in mangrove sediments.Conclusions: The investigation revealed high fungal diversity in mangrove sediments, with incredibly high numbers of basal fungal lineages, stochastic processes driving the assembly of fungal community, and geographic location strongly shaping fungal community composition in mangroves. These discoveries therefore spur further studies of the utilization and protection of fungal resources and communities in mangrove sediments.
Genome Wide Identification and Characterization of Light-Harvesting Chloro a/b Binding Genes Reveals their Potential Role in Enhancing Drought Tolerance in Gossypium hirsutum
Authors: Gereziher Teame , Xu Yanchao , Magwanga Richard Odongo , Kirungu Joy Nyangasi , Cai Xiaoyan , Hou Yuqing , Wang Yuhong , Wang Kunbo , Zhou Zhongli , Liu Fang
Published: October 2020

BackgroundCotton is an important commercial crop for its valuable source of natural fiber. Its production has undergone a sharp failure because of abiotic stress influences, of significance is drought. Moreover, plants have evolved self-defense mechanisms against the effects of several ways of abiotic factors like drought, salt, cold among others. The evolution of stress responsive transcription factors such as the trihelix, a nodule-inception-like protein (NLP), the late embryogenesis abundant (LEA) proteins among others have shown positive response in improving resistance to several forms of abiotic stress features.ResultsGenome wide identification and characterization of the effects of Light-Harvesting Chloro a/b binding (LHC) genes was carried out in cotton under drought stress conditions. A hundred and nine proteins encoded by the LHC genes were found in the cotton genome, with 55, 27, and 27 genes found to be distributed in Gossypium hirsutum, G. arboreum, and G. raimondii, respectively. The proteins encoded by the genes were unevenly distributed in various chromosomes. The Ka/Ks values were less than one, and an indication of negative selection of the gene family. differential expression arrangement of genes was showed with the majority of the genes being highly upregulated in the root tissues in relative to leave and stem tissues. Moreover, more genes were induced in M85 a relative drought tolerant germplasm.Conclusion:The results provide proof of the possible role of the LHC genes in improving drought stress tolerance, and can be explored by cotton breeders in releasing a more drought tolerant cotton germplasms.
Infectious Complications and Mortality after Noncardiac Surgery Associated with CHA2DS2-VASc Score: A Retrospective Cohort Study Based on a Real-world Database
Authors: Sung Li-Chin , Liu Chih-Chung , Lin Chao-Shun , Yeh Chun-Chieh , Cherng Yih-Giun , Chen Ta-Liang , Liao Chien-Chang
Published: October 2020

Background: Little was know about the association between the CHA2DS2-VASc score and postoperative outcomes. Our purpose is to evaluate the effects of CHA2DS2-VASc score on the perioperative outcomes in patients with atrial fibrillation (AF).Methods: We identified 47,402 patients with AF over the age of 20 years who underwent noncardiac surgeries between 2008 and 2013 from claims data of the National Health Insurance in Taiwan. The CHA2DS2-VASc score was used to evaluate postoperative complications, mortality and the consumption of medical resources by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Results: Compared with patients with a CHA2DS2-VASc score of 0, patients with scores ≥ 5 had an increased risk of postoperative pneumonia (OR 1.81, 95% CI 1.30-2.51), septicemia (OR3.24, 95% CI 2.36-4.43), urinary tract infection (OR 1.64, 95% CI 1.20-2.25), intensive care (OR 2.94, 95% CI 2.46-3.51), and mortality (OR 2.07, 95% CI 1.17-3.64). There was a significant positive correlation between risk of postoperative complication and the CHA2DS2-VASc score (P<0.0001).Conclusion: The CHA2DS2-VASc score was highly associated with postoperative infection and 30-day mortality among AF patients. Cardiologists and surgical care teams may consider using the CHA2DS2-VASc score to evaluate perioperative outcome risks in patients with AF.
Vitamin D, Chronic Migraine and Extracranial Pain: Is there a Link? Data from an Observational Study.
Authors: Rebecchi Valentina , Gallo Daniela , Cariddi Lucia Princiotta , Piantanida Eliana , Damavandi Payam Tabaee , Carimati Federico , Gallazzi Marco , Clemenzi Alessandro , Banfi Paola , Candeloro Elisa , Tanda Maria Laura , Mauri Marco , Versino Maurizio
Published: October 2020

Background: Several studies focused on the possible role of vitamin D (vitD) in pain chronicization.. The aim of this study was to assess the potential implications of VitD deficit on headache characteristics and extracranial pain extension.Methods: Eighty consecutive patients with primary headache underwent neurological examination, laboratory exams including serum calcifediol 25(OH)D and headache features assessment along with three questionnaires investigating depression, anxiety and allodynia. Results: The 82.6% of the population had migraine (48% episodic and 52% chronic form). The 45% of patients had extracranial pain and 47% suffered from allodynia. In the 45% of patients had a VitD deficit since the serum 25(OH)D levels fell below the cut-off level of 20 ng/ml. The occurrence of VitD deficit was significantly higher (p=0.009) in patients suffering from chronic migraine (CM)- medication overuse migraine (MOH) (64.7%) than in episodic migraine (EM) or tension type headache (TTH). The occurrence of subjects with extracranial pain and allodynia was higher, as expected, in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vit-D deficiency (Fischer’s exact test p=0.11 and p=0.32 respectively).Conclusions: Our findings show that 25(OH)D deficit is related to chronic pain suggesting that vitD probably has anti-inflammatory and tolerogenic properties, rather than a direct antinociceptive effect, and reinforce the idea of a neuroinflammatory mechanisms underpinning migraine chronicization.
Delirium Screening in the Emergency Department: A Systematic Review and Meta-analysis
Authors: Zhang Qian , Chen Meixi , Hou Liangying , Guo Ziqi , Zhang Qing , Di Baoshan , Ge Long
Published: October 2020

Background: Delirium is a complex syndrome characterized by a disturbance in attention and awareness, with a prevalence of 10-20% in patients admitted to the Emergency Department (ED). Screening tools have been developed to identify delirium in the ED, but their accuracy of screening remains unclear. To address this challenge, we conducted a comprehensive meta-analysis to systematically review the accuracy of delirium screening tools currently being used to assess ED patients.Methods: PubMed, PsycINFO, EMBASE, and the Cochrane Library were searched. Studies involving ED inpatients which compared diagnostic tools with the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria as a reference standard were included. Two reviewers independently screened the studies, extracted data, and assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 scale. We conducted a conventional meta-analysis for each screening tool. Then we used network meta-analysis method to calculate the relative sensitivity and specificity among the diagnostic tests. The diagnostic accuracies were then ranked through the superiority index.Results: Thirteen studies included six screening tools. The pooled sensitivity and specificity for the Confusion Assessment Method (CAM) were 0.71 and 0.98, and for 4AT (Arousal, Attention, Abbreviated Mental Test 4, Acute change) were 0.83 and 0.93, respectively. The other four tools used were only reported in one or two studies. Their sensitivity ranged from 0.70 to 1.00, and their specificity ranged from 0.64 to 0.99. Moreover, network meta-analysis indicated that the CAM and 4AT had a greater superiority index and a higher diagnostic accuracy.Conclusions: The available data suggested that both the CAM and 4AT can be used as efficient screening tools for the ED patients.
Modelling Bluetongue Risk in Kazakhstan
Authors: Abdrakhmanov Sarsenbay , Kanatzhan Beisembayev , Sultanov Akmetzhan , Mukhanbetkaliyev Yersyn , Kadyrov Ablaikhan , Ussenbayev Altay , Zhakenova Аigerim , Torgerson Paul
Published: October 2020

Background: Bluetongue is a serious disease of ruminants transmitted by biting midges (Culicoides spp). Serological evidence from livestock and the presence of at least one vector competent spp of Culicoides suggests that transmission of bluetongue is possible and may have occurred in Kazakhstan. Methods: We estimated the relative risk of transmission using a mathematical model of the reproduction number R0 for bluetongue. This model depends on livestock density and climatic factors which affect vector density. Data on climate and livestock numbers from the 2466 local communities were used. This together with previously published model parameters was used to estimate R0 for each month of the year, which was rescaled to give a relative risk of transmission. These relative risks were mapped using kernal density estimates using R statistical software and mapping tools.Results: The results suggest that transmission of bluetongue in Kazakhstan is not possible in the winter from November to March. Assuming there are vector competent species of Culicoides endemic in Kazakhstan, then low levels of risk first appear in the south of Kazakhstan in April before spreading north and intensifying reaching maximum levels in northern Kazakhstan in August. The risk decline in September with only a low risk of transmission in October.Conclusion: These results should aid in surveillance efforts for the detection and control of bluetongue in Kazakhstan by indicating where and when outbreaks of bluetongue are most likely to occur.
P2X7R-mediated autophagic impairment contributes to central sensitization in a chronic migraine model with recurrent nitroglycerin stimulation in mice
Authors: Jiang Li , Zhang Yixin , Jing Feng , Long Ting , Qin Guangcheng , Zhang Dunke , chen Lixue , Zhou Jiying
Published: October 2020

Background: Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.Methods: The CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated.Results: The expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by up-regulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos. Conclusions: Our results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.
Rapid Evidence Review of Harm Reduction Interventions and Messaging for People Who Inject Drugs During Pandemic Events: Implications for the On-Going COVID-19 Response
Authors: Wilkinson Rebecca , Hines Lindsey , Holland Adam , Mandal Sema , Phipps Emily
Published: October 2020

Background People who inject drugs (PWID) are at increased health risk in a pandemic due to their greater susceptibility to severe disease and as a consequence of the restrictions put in place to halt the spread of infection. Harm reduction (HR) services, which aim to reduce the negative effects of drug use on health, are likely to be diminished in a pandemic. However, innovative HR interventions and messaging may also develop in response to such a crisis. It is vital to understand the most effective ways to deliver HR in pandemic situations so that guidance can be provided for current and future disruptions to service provision. Methods A rapid evidence review was conducted with the aim of exploring what HR interventions and messaging are most effective during a pandemic type situation. Ten health databases were systematically searched using terms relevant to the research aim. A search was also made of grey literature, including a targeted search of HR messaging from key national and service provider websites. Results In the initial search, 121 pieces of evidence were identified which, after screening and de-duplication, resulted in 60 for inclusion. The included evidence consists mainly of non-peer reviewed, pre-publication or expert opinion pieces. The rapid findings suggest that HR services should be deemed essential during a pandemic, with staff supported to work safely and social distancing adaptations implemented. Services should be encouraged to operate more flexibly; for instance, in deciding the amounts of take-home supplies of injecting equipment and medications. The evidence on HR communication was very limited but key messages on infection control, uncertain drug supply and accessing services were identified.Conclusions This rapid evidence review identifies implications for national policy makers, commissioners and HR service providers. A person-centred rather than disease-centred approach to HR delivered by collaborating partners, as well as prioritizing tailored HR messaging, is recommended. Further research evaluating the delivery of HR services and messaging, particularly focusing on health inequalities, is urgently needed.
Drug Use, Homelessness and Health: Responding to The Opioid Overdose Crisis with Housing First Models
Authors: Milaney Katrina , Passi Jenna , Zaretsky Lisa , Liu Tong , O'Gorman Claire M , Hill Leslie , Dutton Daniel
Published: October 2020

Background: Canada is in the midst of an opioid overdose crisis and Alberta has one of the highest opioid use rates across the country. Populations made vulnerable through structural inequities who also use opioids, such as those who are unstably housed, are at an increased risk of experiencing harms associated with opioid use. The main purpose of this study was to explore if there was an association between unstable housing and hospital use for people who use opioids. Methods: Analysis utilized self-reported data from the Alberta Health and Drug Use Survey which surveyed 813 Albertans in three cities. Hospital use was modeled using a logistic regression with our primary variable of interest being housing unstable status. Chi square tests were conducted between hospital use and variables associated with demographics, characteristics of drug use, health characteristics, and experiences of receiving services to establish model inclusion. Results: Results revealed a significant association between housing instability and hospital use, with unstably housed individuals twice as likely to become hospital users. Conclusions: Results highlight the importance of concurrently addressing housing instability alongside the provision of harm reduction services such as Housing First programs and supervised consumption sites. These findings have significant implications for policy and policymakers during the opioid overdose epidemic, and provide a foundation for future areas of research.
Prevalence of Genital Chlamydia Trachomatis among Pregnant Women in a Northwestern Teaching Hospital, Nigeria
Authors: Muhammad Rabi'at Aliyu , Adesiyun Adebiyi Gbadebo , Sada Shafaatu Ismail , Aliyu Shamsudin , Olorukooba Abdulhakeem Abayomi
Published: October 2020

Background: Chlamydia trachomatis (Ct) is now being considered as an “obstetric pathogen” due to its potential in causing adverse pregnancy and perinatal outcomes. Consequent to being the commonest bacterial sexually transmitted infection, screening is recommended at the initial visit of antenatal care, but few countries have routine pregnancy screening and treatment programs. Prevalence assessment is a core component of the World Health Organisation sexually transmitted infection -surveillance programming which enables a country to monitor trends of this infection, for appropriate implementation of preventive measures. Aim: To determine the prevalence of Ct infection among pregnant women, and to describe sociodemographic characteristics and reproductive profile of seropositive pregnant women attending the antenatal clinic of Ahmadu Bello University Teaching Hospital, Zaria. Methods: Socio-demographic characteristics and risk factors were sought from 90 pregnant women using a proforma. Their sera were assayed for the presence of Ct immunoglobulin G (IgG) using ELISA. Data were analysed using SPSS version 21. Categorical variables were represented using frequency and percentages while associations between categorical variables were determined using Fisher’s exact test with p < 0.05 considered significant. Results: Prevalence of Ct infection was found to be 3.3% (3/90). The mean age of infected women was 34.3 ± 4.6 years. All seropositive women were gainfully employed and had tertiary education. Mean parity was 3, the majority (2/3,66.7%) had no previous miscarriage and none had a history of prior stillbirth.Conclusion: The prevalence of Ct in this study is low compared to the pooled prevalence for the West African sub-region. A broader community-based study using a nucleic acid amplification technique is suggested.
PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
Authors: Zhu Li , Zhang Yan-Jun , Wang Bin , Yang Li , Zheng Yi-Qiong , Sun Lin-De , Tian Lin , Wang Jian-Dong , Chen Tao
Published: October 2020

Breast cancer is one of the most common life-threatening cancers, mainly due to its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK /NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggested that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.
Anlotinib Inhibits the Growth of Breast Cancer Cells by Promoting Autophagy and Apoptosis via the Akt/GSK-3α Signalling Pathway
Authors: chen shuyi , Zhu Ping , Wang Xue , Jin Youping , Zhi Xiuling , Yang Huanjun , Zhou Ping
Published: October 2020

Background: Anlotinib, a multi-target tyrosine kinase inhibitor, has already been indicated to have significant anticancer effects on lung cancer, colon cancer and ovarian cancer in a phase II clinical trial, but its effect on breast cancer (BC) has not been adequately investigated. Methods: The proliferation activity of BC cell lines MCF-7 and MDA-MB-231 with the treatment of anlotinib was tested by Cell Counting Kit-8 (CCK-8) assay and immunocytochemistry (ICC) staining. We investigated the alteration of cell cycle and apoptosis and autophagy level and the underlying mechanism in the cell lines by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), Western blots, ICC and TUNEL staining and flow cytometry. Further, AT-3 cells were subcutaneously injected into C57BL/6 mice, followed by anlotinib intragastrically. The extracted tumours were assessed by qRT-PCR, Western blots and immunohistochemistry.Results: We found that anlotinib suppressed the cell viability and proliferation of MCF-7 and MDA-MB-231 cell lines and tumour growth in BC xenografts in mice, likely due to abnormal cell cycle arrest and induction of autophagy and apoptosis. Then, we further examined the underlying mechanism of anlotinib, and the results indicated that anlotinib induced apoptosis by promoting autophagy in MCF-7 and MDA-MB-231 cells by regulating the Akt/GSK-3α pathway. The analysis of data from patients with BC collected in TCGA revealed that increased VEGFA expression was related to BC.Conclusions: Our study demonstrated that anlotinib inhibited the growth of BC cells via promoting apoptosis through autophagy mediated by Akt/GSK-3α signalling and may be an effective new drug for BC treatment.
Quarantine Due to the COVID-19 Pandemic From the Perspective of Adolescents: The Crucial Role of Technology
Authors: Salzano Giuseppina , Passanisi Stefano , Pira Francesco , Sorrenti Lacrima , Monica Giuseppa La , Pajno Giovanni B , Pecoraro Maria , Lombardo Fortunato
Published: October 2020

Background. The year 2020 will be remembered as the “year of the COVID-19 pandemic”. The world population had to familiarize themselves with words as swabs, personal protective equipment, pandemic. To curb the wave of the pandemic, almost all the countries imposed self-isolation and social distancing. We conducted a web-based survey to investigate the behavioural responses during the quarantine due to the COVID-19 pandemic. Methods. Participants were 1860 youth aged 12-18 years attending lower secondary schools and upper secondary schools. Data were collected on demographic characteristics, lifestyle changes during the quarantine period, and the psychological impact of the lock-down on adolescents’ life.Results. Most adolescents experienced feelings of fear, discouragement, and anxiety which strongly affected the approach to their daily lifestyles. Most of the surveyed subjects reported having used this period to acquire new skills and to practice physical activities at home. The use of technology was predominant both for recreational activities and educational purposes.Conclusions. Despite the strong psychological impact of the quarantine, adolescents showed good levels of resilience. Technology played a crucial role during the quarantine for young subjects who have increased the daily use of technological devices to stay connected with the rest of the world.
The Use of Neck Circumference as Marker of Overweight and Obesity Among Adolescents Aged 12-19 Years. A Case of Southwestern Uganda Secondary School Adolescents
Authors: Katamba Godfrey , Agaba David Collins , Muzaale Francis , Namaganda Agnes , Namayanja Rosemary , Musasizi Abdul , Kinene Mivule Abdul , Migisha Richard
Published: October 2020

Background: Overweight and obesity have become more common among adolescents. Various indicators have been used to assess this burden across populations. Recent findings elsewhere have found neck circumference to be useful in defining overweight and obesity. However, the use of neck circumference as marker of overweight and obesity needs to be further explored among adolescents in Uganda. Objective: To assess the usefulness of neck circumference as a marker of overweight and obesity. Methods: A cross sectional study was conducted among secondary adolescents aged 12-19 years from May to August in 2018, Height was measured using a wall mount height board and weight using a standard weighing scale. Neck circumference was measured using an inelastic measuring tape. Pearson correlation coefficient was used to determine the correlation between neck circumference, height, weight and body mass index. Receiver operating characteristic (ROC) curve analysis was used to determine the suitable cutoff of neck circumference for overweight and obesity. Results: We enrolled 616 adolescents aged 12-19 years, with mean age of 15.6±2.0 years. Most (65.6%) were female. Neck circumference was significantly correlated with height (p<0.01), weight (p<0.01) and body mass index (p<0.01). The best cutoff of neck circumference to identify participants with obesity were ≥31.0 cm with AUC of 0.83[0.73-0.94] and ≥32.0cm with an AUC of 0.59[0.11-1.00] among the females and males respectively. Conclusion: Neck circumference was useful in defining and hence classifying for overweight or obesity among the female adolescents in our study population. It could useful for screening for overweight and obesity among the female adolescents.
Time-Sequential Change in Immune-Related Gene Expression After Irradiation in Glioblastoma: Next-Generation Sequencing Analysis
Authors: Kim Yi-Jun , Kim Kwangsoo , Seo Soo Yeon , Yu Juyeon , Kim Il Han , Kim Hak Jae , Park Chul-Kee , Lee Kye Hwa , Choi Junjeong , Song Myung Seon , Kim Jin Ho
Published: October 2020

The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 hours post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon-γ signals began to increase significantly at 24 hours and were upregulated until 48 hours after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon-γ signaling in cancer cells. In conclusions, In the glioblastoma cell line, immune-related signals were significantly upregulated at 24 hours after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.
Surgery and Financial Toxicity are Risk Factors for Distress in Cancer Survivors: A Cross-sectional Study
Authors: Yu Huihui , Zuo Tingting , Bi Xue , Li Hui , Xing Haiyang , Cao Li , Cai Lijuan , Sun Jianmin , Liu Yunyong
Published: October 2020

Background: Patients with cancer often face some level of distress, regardless of disease stage. Distress in cancer survivors has a negative impact on their quality of life. The goal of this study was to identify risk factors for distress, under­stand how treatment associated with distress and reveal the relationship between the psychological and financial distress. Methods: This was a multi-center cross-sectional study of patients with cancer requiring surgery or chemotherapy. Patients completed questionnaires regarding their demographics, disease characteristics, psychological distress, and financial toxicity. A multivariable logistic regression model was used to examine factors associated with distress in surgical versus chemotherapy treatment groups.Results: A total of 409 patients participated in the study. Patients treated with surgery (n = 172) were more likely to be female, unemployed, early stage compared with patients undergoing chemotherapy (n = 237). Multivariable analysis revealed that surgical patients tended to have a higher risk of distress compared with patients receiving chemotherapy (OR, 95% CI: 3.086, 1.854–5.137) due to higher rates of nervousness, pain, and difficulty with bathing/dressing, and patients with high financial toxicity had a higher risk of distress compared with those with low financial toxicity (OR, 95% CI: 2.000, 1.278–3.130). The relationship between financial toxicity and psychological distress was stronger in the chemotherapy group, with the correction coefficient -0.294 and slope -1.196. Conclusion: Patients who underwent surgery and reported higher financial toxicity were more likely to experience distress. Multidimensional distress screening and psychosocial interventions should be provided pre- and post-operatively for patients.
High Prevalence of Asymptomatic Malaria in Bandafassi, South-east of Senegal: Challenge for Malaria Elimination
Authors: Sadikh Badiane Aida , NDIAYE Tolla , Birane Thiaw Alphonse , Binta Deme Awa , Alpha Diallo Mamadou , Cheikh Seck Mame , Khadim Diongue , Garba Mamane Nassirou , Mouhamadou Ndiaye , Daouda Ndiaye
Published: October 2020

Background: Malaria control and elimination strategies are based on levels of transmission that are usually determined by data collected from health facilities. In endemic areas, asymptomatic malaria is thought to represent the majority of infections and is therefore not diagnosed nor treated. As a consequence, they are missed when analyzing data due to the lack of visiting the health facilities unless they are sick. Therefore, there might be an underestimation of the malaria prevalence resulting in inadequate control strategies. In addition, these untreated asymptomatic cases maintain transmission making it difficult or impossible to reach malaria elimination goals. Thus, the aim of this study was to determine the prevalence of asymptomatic malaria in southeastern Senegal. Methods: A cross sectional study was conducted among asymptomatic individuals (N = 122) living in the village of Andiel located in Bandafassi, Kedougou which consisting of about 200 inhabitants during the malaria transmission season in late October 2019. For each individual without malaria symptoms and who consented to participate in the study, a rapid diagnosis test (RDT) was performed in the field. Results were confirmed in the laboratory with nested PCR and photo-induced electron transfer (PET-PCR). Results: Malaria prevalence was 70.25% with PET-PCR, 41.80% with RDT and 41.32% based on the nested PCR. The majority of the study population; 92.94% was infected with a single species (mono-infection) and 7.06% had two or three species of Plasmodium. P. falciparum was predominant and represented 90.22% of the infections, while 6.52% were due to P. ovale and 3.26% to P. malariae. RDT detected more malaria cases than nested PCR among children and in individuals aged fifteen years and older; PET-PCR detected more cases (64.70%) than nested PCR (62%) and RDT (52.94%) in this age group.Conclusion: Asymptomatic infection is a threat to malaria elimination. In southeastern Senegal, where the transmission is the highest in the country, malaria control strategies should address asymptomatic cases at the community level. This high prevalence of asymptomatic malaria observed suggests that this area is eligible for mass drug administration. Moreover, non-falciparum species could be more common and its prevalence should be determined countrywide.
Diversity, Distribution, and Drivers of Polychromophilus Infection in Malagasy Bats
Authors: Rasoanoro Mercia , Goodman Steven M. , Randrianarivelojosia Milijaona , Rakotondratsimba Mbola , Dellagi Koussay , Tortosa Pablo , Ramasindrazana Beza
Published: October 2020

Background: Numerous studies have been undertaken to improve knowledge on apicomplexan parasites infecting vertebrates, including humans. Of these parasites, the genus Plasmodium has been most extensively studied because of its socio-economic and public health impacts. In non-human vertebrates, studies on malaria or malaria-like groups have been conducted but information is far from complete. On Madagascar, recent studies on bat blood parasites indicate that three families, namely Miniopteridae, Rhinonycteridae, and Vespertilionidae, are infected by the genus Polychromophilus with pronounced host specificity: Miniopterus spp. harbor P. melanipherus, while Myotis goudoti is infected by P. murinus. However, most of the individuals analyzed in these previous studies were sampled on the western and central portions of the island. The aims of this study are 1) to add new information on bat blood parasites in eastern Madagascar and 2) highlight biotic and abiotic variables driving prevalence across the island. Results: In total, 222 individuals belonging to 17 bat species were analyzed. Polychromophilus infections were identified in two families: Miniopteridae and Vespertilionidae. Molecular data showed that Polychromophilus spp. parasitizing Malagasy bats form a monophyletic group composed of three distinct clades displaying marked host specificity. In addition to P. melanipherus and P. murinus, hosted by Miniopterus spp. and Myotis goudoti, respectively, we report a novel Polychromophilus lineage detected from a single individual of S. robustus. Based on the present study and the literature, different biotic and abiotic factors are shown to influence Polychromophilus infection in bats, which is correlated based on MaxEnt modeling. Conclusion: The present study improves our knowledge on Polychromophilus infecting Malagasy bats and highlights the existence of a novel Polychromophilus lineage. Additional studies are needed to get additional representatives of this novel lineage to resolve its taxonomic relationship with known members of the genus. Further, the transmission mode of Polychromophilus in bats as well as its potential effect on bat populations should be investigated to complement the results provided by our modeling and eventually provide a comprehensive picture of the biology of these host-parasite interactions.