bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between social capital and mental health among older people living with HIV: The Sichuan Older HIV-Infected Cohort Study (SOHICS)
Authors: Han Jiayu , Jia Peng , Huang Yuling , Gao Bo , Yu Bin , Yang Shifan , Yu Jun , Xiong Jun , Liu Chang , Xie Tian , Dong Peijie , Yang Chao , Wang Zixin , Yang Shujuan
Published: March 2020

Background: Mental health problems are common among older people living with HIV and associated with poorer health outcomes. Social capital is an important determinant of mental health problems but under-studied in this population. This study investigated the association between social capital and mental health problems among older people living with HIV in China. Methods: The study was based on the baseline data of a cohort study investigating mental health among older people living with HIV in Sichuan, China during November 2018 to February 2019. Participants were people living with HIV aged ≥50 years living in Sichuan province. Stratified multi-stage cluster sampling was used to recruit participants from 30 communities/towns; 529 out of 556 participants being approached completed the face-to-face interview. Social capital was measured by two validated health-related social capital scales: the Individual and Family scale and the Community and Society scale. Presence of probable depression (CES-D-10 score ≥10) and probable anxiety (GAD-7 score ≥5) were used as dependent variables. Two-level logistic regression models were applied to examine the association between social capital and probable depression/anxiety. Results: The prevalence of probable depression and probable anxiety was 25.9% (137/529) and 36.3% (192/529) , respectively. After adjusting for significant covariates, the individual/family level of social capital was inversely associated with both probable depression (Adjusted odds ratios (AOR): 0.89, 95%CI: 0.84-0.93, p <0.001) and probable anxiety (AOR: 0.90, 95%CI: 0.86-0.95, p <0.001). The community/society level social capital was associated with probable depression (AOR: 0.91, 95%CI: 0.84-0.99, p <0.001) but not probable anxiety ( p >0.05). Conclusions: Interventions building up social capital should be considered to improve mental health of older PLWH. Some useful strategies include cognitive processing therapy, improving community networking and engagement, and promoting social bonding with neighborhood.
Multichannel ECG Recording from Waist using Textile Sensors
Authors: Meghrazi Milad Alizadeh , Tian Yupeng , Mahnam Amin , Bhattachan Presish , Eskandarian Ladan , Kakhki Sara Taghizadeh , Popovic Milos , Lankarany Milad
Published: March 2020

Background: The development of wearable health monitoring systems is garnering substantial interest in research and technology due to their unique capabilities in continuous, real-time, and non-invasive tracking of the physiological states of the human body. Wearable devices provide insights into the performance and health of individuals. Despite recent advances in biosensors, most of the currently available wearable devices rely solely on a single sensor attached to the body, limiting the ability to obtain reliable bio-information. However, in engineering systems, sensor fusion, which is the optimal integration and processing of data from multiple sensors, has been a common theme. In recent years due to an increase in the availability and variety of different types of sensors, the possibility of achieving sensor fusion in wearable systems has become more attainable. Sensor fusion in multi-sensing systems results in a significant enhancement of information inference compared to that from systems with a sole sensor. One step towards the development of sensor fusion for wearable health monitoring systems is the accessibility to multiple reliable electrophysiological signals, which can be recorded continuously.Results: In this paper, we develop a textile-based multi-channel ECG band that has the ability to measure from multiple locations on the waist. As a proof of concept, we show that ECG signals can be reliably obtained from different locations on the waist where the shape of the QRS complex is comparable with that recorded from the chest using traditional gel electrodes. As well, we develop a probabilistic approach to detect R-Peaks from noisy textile data in different sitting, standing, and jogging statuses. We show that the performance of the proposed algorithm is significantly better than that based on Pan-Tompkins and optimal-threshold methods. Conclusion: This band can be easily integrated into garments such as underwear, bras or pants. We predict that the textile-based multi-channel ECG band can be considered as an effective wearable system which enables the development of sensor fusion methodology for pervasive and non-invasive health monitoring through continuous tracking of heart rate variability (HRV) from the waist.
Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia
Authors: Peiffer-Smadja Nathan , BOUADMA Lila , MATHY Vincent , ALLOUCHE Kahina , PATRIER Juliette , REBOUL Martin , MONTRAVERS Philippe , TIMSIT Jean-François , ARMAND-LEFEVRE Laurence
Published: March 2020

Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 hours. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods: In this prospective study we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheters (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital; the medical and infectious diseases ICU, the surgical ICU and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotics changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 hours (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95%CI, 73-88%) and specificity of 99% (95%CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p=0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.
The Influence of Self-construal on Entrepreneurial Orientation and Growth of Micro-enterprises
Authors: Oni Francis Adedara , Khaola Peter , Rambe Patient
Published: March 2020

Literature acknowledges the critical role of self-construal in shaping entrepreneurial orientation and behaviour. While explanations for societal differences in entrepreneurial behaviours vary at organisational level, limited attention has been devoted to explaining the influence of self-construal on entrepreneurial orientation (EO) and growth of micro-enterprises. This study examined the influence of self-construal of micro-enterprise owners on their EO (risk-taking and innovativeness) and growth of their firms. Data collected using structured interviews administered on 80 micro-enterprise owners from Roma, Maseru, and Teya-Teyaneng in Lesotho were analysed using descriptive correlations, hierarchical regression analyses and partial least squares structural equation modeling (PLS-SEM). Findings show that the independent self-construal had positive and significant influence on the EO of micro-enterprises but the inter-dependent self-construal construct did not have a positive and significant effect on the EO. While independent self-construal negatively and significantly influenced enterprise growth, the interdependent self-construal did not have any influence on growth of micro-enterprises. the study recommends that universities and government departments such as Ministry of Small Business Development, Cooperatives and Marketing must provide entrepreneurial training to micro-enterprise owners on how to improve enterprise-oriented cultures and self-confidence in independent decision-making for the growth and survival of their enterprises.
Fruitflow attenuates human platelet granule secretion through down-regulating Src/PLCγ2/PKC signaling pathway
Authors: Fan Die , Ma Xilin , Ya Fuli , Tian Zezhong , Shi Yilin , Gao Xiaoli , Wang Sijia , Ling Wenhua , Song Fenglin , Yang Yan
Published: March 2020

Background : Platelet can release lots of active molecules from granules in active state, which contributes to the progress of atherosclerosis and thrombosis. Fruitflow is a water-soluble tomato extract that has been reported to exert protective cardiovascular effects. The present study aims to investigate whether Fruitflow acts on human platelet granule secretion in vitro and further explore its underlying mechanisms. Methods: Recruit healthy volunteers to collect their peripheral blood and isolate gel-filtered platelets for in vitro experiments. Agonist-induced platelet granule secretion was detected by flow cytometry or ELISA kit. To elucidate the molecular mechanisms, the signaling pathway was tested by western blotting. Results: Fruitflow inhibited platelet surface expression of CD62P, CD40L, and CD63. Moreover, agonist-induced release of platelet factor 4 (PF4), β-thromboglobulin (β-TG), Regulated on Activation Normal T cell Expressed and Secreted (RANTES), transforming growth factor-β1 (TGF-β1), ATP, Ca 2+ , and serotonin were also significantly attenuated by Fruitflow. Furthermore, Fruitflow down-regulated expression of Lyn and phosphorylation of Src, LAT, Syk, PLCγ2 and PKC. However, PKC inhibitor GF109203X did not show additive effects on platelet granule secretion when combined with Fruitflow. Conclusion: Fruitflow effectively inhibited platelet granule secretion via down-regulating platelet Src/PLC-γ2/PKC signaling pathway in vitro , which may provide a novel evidence for the cardioprotective benefits of tomato.
Men and loneliness in the ‘west’: A critical interpretive synthesis
Authors: Ratcliffe John Martyn , Galdas Paul , Kanaan Mona
Published: March 2020

BackgroundLoneliness has received considerable attention in recent years, but has seldom been investigated through a gendered lens. This review aims to critically summarise research substantively related to men and loneliness.MethodA critical interpretive synthesis, incorporating a pre-defined search strategy, was employed to analyse a broad variety of data. The searches were conducted in July 2019, across seven databases: MEDLINE; PsycINFO; Scopus, ASSIA, SSCI; Sociological Abstracts; and Social Policy and Practice. Included studies were written in English, conducted in high income nations in Western Europe, North America, and Australasia, with no date limitations. Qualitative studies required a substantive focus on sex/men or gender/masculinities and loneliness, and quantitative studies either an explicit focus on sex differences in loneliness, or data substantially relevant to loneliness and men. Seventy-nine studies met the inclusion criteria.ResultsSeven ‘synthetic constructs’ were built: i) men’s loneliness appears more associated with their social network; ii) men may be less emotionally forthright, thus both less inclined to discuss loneliness and less likely to form meaningful relationships; iii) romantic relationships may be more important for preventing loneliness in men; iv) different measurements of loneliness do not show the same sex differences in the prevalence of loneliness; v) lonely men may be more likely to engage in risky/unhealthy behaviour; vi) feeling/being ‘insufficiently masculine’ can result in loneliness; and vii) intersections of identity facilitate different gendered results.ConclusionThese constructs offer a framework that can help inform interventions aimed at preventing/alleviating loneliness in men, and a foundation for future research. Overcoming men’s emotional reticence, and facilitating better quality social networks, appeared critical goals for interventions. Men’s emotional reticence may constitute both a barrier to discussing loneliness, and to forming loneliness preventing relationships. It also appeared to be characterised either by the construction of a masculine persona, or a fear of the repercussions for initiating intimate conversation. When attempting to ascertain whether a man is lonely, acknowledging gendered variation in survey responses is required. However, it is unclear how generalisable these ‘synthetic constructs’ are, and their potential inter-relatedness requires further research.
Bone mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury
Authors: zhou song , Qiao Yu-ming , Liu Yong-guang , Liu Ding , Hu Jian-min , Liao Jun , Li Min , Guo Ying , Fan Li-pei , Li Liu-Yang , Zhao Ming
Published: March 2020

Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI).The main drawbacks of MSC therapy including the lack of specific homing following systemic infusion and early death of the cells in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning promotes the therapeutic effect of the MSCs, although the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO on bone marrow mesenchymal stem cells (BMSCs) for the treatment of AKI.Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in the BMSCs, which was decreased following EPO pretreatment indicating that EPO protected the cells from apoptosis. Further, we found that EPO upregulated SIRT1 and Bcl-2 expression, and downregulated p53 expression. The EPO-mediated anti-apoptotic mechanism in pretreated BMSCs may be mediated though the SIRT1 pathway. In a rat AKI model, our data showed that 24 h following intravenous infusion, GFP-BMSCs were predominantly in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs, and increased the distribution of the BMSCs to the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-a and significantly higher level of IL-10 compared to rats infused with BMSCs. The administration of EPO-BMSCs after reperfusion was more effective in reducing serum creatinine, blood urea nitrogen, and pathological scores in the I/R-AKI rats than BMSCs.Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs in improving renal function and pathological presentation in I/R-AKI rats.
Association between suicide risk severity and sarcopenia in non-elderly Chinese inpatients with major depressive disorder
Authors: Fan Xinxin , Yuan Jing , Wei Yujun , Zhou Fang , Xu Li , Zhang Yan , Meng Junyu , Jin Xiaolong , Yang Jianzhong
Published: March 2020

Background: Sarcopenia is a skeletal muscle disorder. Recent studies showed high rates of suicide in non-elderly adults and the association between muscle health and suicide. But there have been no previous studies on the relationship between suicide risk severity and sarcopenia in major depressive disorder (MDD). This study aimed to explore the association between suicide risk severity and sarcopenia in non-elderly Chinese inpatients with MDD. Methods: The first-episode drug-naïve MDD inpatients aged 20-59 years with the 24-item Hamilton Rating Scale for Depression (HAMD-24) scores of ＞20 were included, who were then classified into low, intermediate, high and very high suicide risk groups according to the Nurses' Global Assessment of Suicide Risk (NGASR). The HAMD-24, the Hamilton Rating Scale for Anxiety (HAMA) and the SARC-F questionnaire were used to assess depression severity, anxiety severity and sarcopenia, respectively. The plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were measured. Results: A total of 192 MDD inpatients (122 females, 70 males; aged 39.3 ± 11.7 years) were included, with 12.5% of sarcopenia. There were significant differences in gender, HAMD score and prevalence of sarcopenia among the suicide risk groups. Adjusted ordinal regression analysis showed that sarcopenia was significantly associated with severer suicide risk (OR=2.39, 95%CI 1.02-5.58, p=.044). Conclusions: This study revealed that sarcopenia was significantly associated with higher suicide risk in non-elderly Chinese MDD inpatients after adjustment for depression severity. Intervention of sarcopenia might be effective to reduce the risk of suicide in non-elderly MDD patients.
Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman
Authors: Alawi Intisar Al , Molinari Elisa , Salmi Issa Al , Rahbi Fatma Al , Mawali Adhra Al , Sayer John A.
Published: March 2020

Background There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients.Methods We studied patients with a clinical diagnosis of ARPKD ( n =40) and their relatives [parents ( n =24) and unaffected siblings ( n =10)] from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 was performed through next generation sequencing (NGS) and Sanger sequencing.Results A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. 24 patients had documented chronic kidney disease. 24 out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was confirmed in 38 patients from 30 different families, giving a detection rate of 94%. Two unrelated patients remained genetically unsolved. In all of the solved cases, only four different PKHD1 missense pathogenic variants were identified: c.107C>T, p.(Thr36Met); c.406A>G, p.(Thr136Ala); c.4870C>T, p.(Arg1624Trp) and c.9370C>T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A>G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C>T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C>T; (Thr36Met), which was seen in 24 families.Conclusion Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The four PKHD1 missense variants identified suggest there may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.
Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: Evaluation of outcomes after liver transplantation
Authors: Shimura Masaru , Kuranobu Naomi , Ogawa-Tominaga Minako , Akiyama Nana , Sugiyama Yohei , Ebihara Tomohiro , Fushimi Takuya , Ichimoto Keiko , Matsunaga Ayako , Tsuruoka Tomoko , Kishita Yoshihito , Umetsu Shuichiro , Inui Ayano , Fujisawa Tomoo , Tanikawa Ken , Ito Reiko , Fukuda Akinari , Kasahara Mureo , Murakami Jun , Kaji Shunsaku , Shiraki Kazuo , Ohtake Akira , Okazaki Yasushi , Murayama Kei
Published: March 2020

BackgroundHepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate outcomes LT in MTDPS patients in Japan.ResultsWe retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 20 of 23 patients: MPV17 (n=13), DGUOK (n=4), POLG (n=1), MICOS13 (n=1), and TWNK (n=1). Eight MPV17-deficient patients harbored c.451dupC and all four DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n=13, 56.5%). The most frequent liver symptom was cholestasis (n=21, 91.3%). LT was performed on 11 patients, including eight MPV17-deficient and two DGUOK-deficient patients. Four patients, including one with mild intellectual disability, survived; seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G>A or c.293C>T.ConclusionsMPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, but patients who had MPV17 mutations associated with mild phenotypes such as c.149G>A or c.293C>T and no marked neurologic manifestations before LT, had moderately better outcomes.
Hierarchical porous ceramics with multiple open pores from boehmite gel emulsions
Authors: Zheng Yu , Luo Xudong , You Jiegang , Li Ting , Hou Qingdong
Published: March 2020

Ceramic foams with highly porous microstructure play significant roles in increasing area, especially those with open channels and superior specific surface area. A simple and versatile route to prepare ceramic foams with open pores has been put forward in this research, via gelation of boehmite nanoparticles-assembled emulsions. Notably, hierarchical porous microstructure with open channels and uniform pore structure was prepared. High specific surface area up to 389.4 m2/g is attainable, making them excellent adsorption material, when combining the merit of hierarchical pore structure. Furthermore, lattice-shaped ceramics are prepared via direct ink printing gelled emulsion, displaying the potential of forming lightweight material with complex shape and designable macro-structure. The 3D printed foams exhibit multiple open pores, which cover the length scale from mm-scale, to μm-scale and nm-scale, making them promising materials in several fields, including adsorption, catalysts supports, and filtrations, etc.
Cost-effectiveness of ceritinib in previously untreated anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in Hong Kong
Authors: Loong Herbert , Wong Carlos K H , Leung Linda K S , Chan Catherine P K , Chang Andrea , Zhou Zheng-yi , Xie Jipan , Gibbs Meaghan
Published: March 2020

Background: Lower-dose ceritinib (450mg) once-daily with food was approved in 2018 in Hong Kong (HK) for first-line treatment of patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC). This study examined the cost-effectiveness of ceritinib vs. crizotinib in the first-line treatment of ALK+ NSCLC from a HK healthcare service provider's or government's perspective.Methods: Costs and effectiveness of first-line ceritinib vs. crizotinib over a 20-year time horizon was evaluated using a partitioned survival model with three health states (stable disease, progressed disease, and death). The efficacy data for ceritinib were obtained from ASCEND-4 and extrapolated using parametric survival models. Long-term survival associated with crizotinib were estimated using hazard ratio of crizotinib vs. ceritinib obtained from matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014 trials. Drug acquisition, administration, adverse events costs, and medical costs associated with each health state were obtained from public sources and converted to 2018 US Dollars. Incremental costs per quality-adjusted-life-year (QALY) and life-year (LY) gained were estimated for ceritinib vs. crizotinib.Results: The base case results showed that ceritinib was associated with 3.22 QALYs, 4.51 LYs, and total costs of $157,581 over 20 years. Patients receiving crizotinib had 2.68 QALYs, 3.85 LYs, and $150,424 total costs over the same time horizon. The incremental cost per QALY gained for ceritinib vs crizotinib was $13,343. Results were robust to deterministic sensitivity analyses in most scenarios.Conclusion: Ceritinib offers a cost-effective option compared to crizotinib for previously untreated ALK+ advanced NSCLC in HK.New knowledge added by this study• In order to optimize patient outcomes and effectively allocate healthcare resources, rigorous economic evaluations are needed to inform reimbursement decision-making regarding the cost-effectiveness of available therapies.• With ceritinib's recent introduction as a first-line targeted therapy, these results provide important insight for decision-makers considering treatments for ALK+ advanced NSCLC in Hong Kong.Implication for clinical practice or policy• Ceritinib offers a cost-effective option compared to crizotinib for previously untreated ALK+ advanced NCSLC in HK with an incremental cost per QALY of $13,343 USD, which is significantly lower than the willingness to pay threshold in Hong Kong.• In previously untreated adult patients with ALK+ advanced NCSLC, ceritinib is predicted to offer marked benefits in PFS, LYs, and QALYs compared to crizotinib.• Ceritinib offers a valuable treatment option for front-line treatment of patients with ALK+ advanced NCSLC in HK.
miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6
Authors: An Yunhe , Zhang Jun , Tian Yanjie , Li Baoming , Cheng Xiaoyan , Zhang Xiaoli , Zhao Fangqi
Published: March 2020

Background: It has been reported that hypoxia is closely related to the tumor malignancy and recurrence and regulates multiple hub genes in ovarian cancer. MicroRNA-454 (miR-454) has been confirmed to be involved in tumorigenesis and tumor development. However, the functional role of miR-454 in ovarian cancer remains unclear.Methods: The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry assay. The relative expression of related proteins was examined using western blot analysis.Results: miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal serum, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and was correlated with the clinicopathological stage of ovarian cancer patients. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454. Bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, immunohistochemical analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression.Conclusion: Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer by targeting E2F6, indicating that the hypoxia/miR-454/E2F6 pathway may be a novel therapeutic approach for ovarian cancer.
Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole
Authors: Martin Frida , Dube Faruk , Lindsjö Oskar Karlsson , Eydal Matthías , Höglund Johan , Bergström Tomas F. , Tydén Eva
Published: March 2020

Background: Parascaris univalens is a pathogenic parasite of foals and yearlings worldwide. In recent years Parascaris spp. worms have developed resistance to several of the commonly used anthelmintics, though currently the mechanisms behind this development is unknown. The aim of this study was to investigate the transcriptional responses in adult P. univalens worms after in vitro exposure to different concentrations of three anthelmintic drugs, focusing on drug targets and drug metabolising pathways. Methods: Adult worms were collected from the intestines of two foals at slaughter. The foals were naturally infected and had never been treated with anthelmintics. Worms were incubated in cell culture media containing different concentrations of either ivermectin (10-9 M, 10-11 M, 10-13 M), pyrantel citrate (10-6 M, 10-8 M, 10-10 M), thiabendazole (10-5 M, 10-7 M, 10-9 M) or without anthelmintics (control) at 37 °C for 24 h. After incubation the viability of the worms was assessed and RNA extracted from the anterior end of 36 worms and sequenced on an Illumina NovaSeq 6000 system. Results: All worms were alive at the end of the incubation but showed varying degrees of viability depending on the drug and concentration used. Differential expression (p < 0.05 and fold change ≥ 2) analysis showed similarities and differences in the transcriptional response after exposure to the different drug classes. Candidate genes up- or downregulated in drug exposed worms include members of the phase I metabolic pathway short-chain dehydrogenase/reductase superfamily (SDR), flavin containing monooxygenase superfamily (FMO) and cytochrome P450-family (CYP) as well as members of the membrane transporters major facilitator superfamily (MFS) and solute carrier superfamily (SLC). Generally, different targets of the anthelmintics used were found to be up- and downregulated in an unspecific pattern after drug exposure, apart from the GABA receptor subunit lgc-37, which was upregulated only in worms exposed to 10-9 M of ivermectin. Conclusions: This is the first time the expression of these genes has been described in P. univalens and future work should be focused on characterising these candidate genes further to explore their potential involvement in drug metabolism and anthelmintic resistance.
Brassicaceous roots as an unexpected diversity hot-spot of helotialean endophytes
Authors: Macia-Vicente Jose G , Piepenbring Meike , Koukol Ondřej
Published: March 2020

A high number of fungal strains were isolated from roots of Brassicaceae species all over Europe, resulting in an unexpectedly rich collection of Cadophora species. These isolates enable us to present a new and comprehensive view of the ecological, morphological, and phylogenetic traits of root-inhabiting members of this helotialean genus. We provide phylogenetic placement of all of our isolates based on a four-gene dataset, analyze their phenotypic traits in relation to their phylogenetic relationships, and infer the potential distribution ranges of the species by sequence comparisons with available databases. We consider seven well supported phylogenetic lineages as species new to science. Six further lineages probably also represent new species but remain undescribed due to the lack of diagnostic morphological characters. Our results show that Cadophora, as currently circumscribed, is paraphyletic and encompasses a broad spectrum of morphologies and lifestyles. Among the new species, only two (C. ferruginea and C. constrictospora) form phialides and conidia typical of Cadophora, three species (C. echinata, C. gamsii and C. variabilis) produce chains of swollen hyphal segments that may function as holoblastic conidia, and one species (C. fascicularis) produces chains of holoblastic ramoconidia and conidia. Ancestral state reconstruction analysis suggests that phialidic conidiogenesis evolved several times in Cadophora sensu lato from a putatively holoblastic common ancestor. Most Cadophora lineages are rare as estimated from the availability of sequence data, in spite of having relatively wide distribution ranges, whereas five lineages may represent endemic relationships given their restricted distributions. Our dataset, probably the most comprehensive available for Cadophora, nevertheless shows knowledge gaps concerning the phylogenetic relationships within this genus and highlights a need for further investigation.
Age-stratified anti-tuberculosis drug resistance profiles in South Korea: a multicenter retrospective study
Authors: Lee Eung Gu , Min Jinsoo , Kang Ji Young , Kim Sung Kyoung , Kim Jin Woo , Kim Yong Hyun , Yoon Hyoung Kyu , Lee Sang Haak , Kim Hyung Woo , Kim Ju Sang
Published: March 2020

Background: The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea.Methods: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15–34 years), middle (35–59 years), and older (≥60 years) to compare drug-resistance patterns.Results: Among the 4,417 cases investigated, 179 (4.1%), 53 (1.2%), and 316 (7.2%) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were similar among the three groups (11.2%, 12.2%, and 10.4% in the younger, middle, and older groups, respectively). MDR/RR-TB case numbers decreased significantly as age increased (8.6%, 6.3%, 3.3%, respectively). Proportions of MDR/RR-TB among retreated patients in the younger generation decreased from 50.0% to 18.2%, but remained higher than that in the older generation. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups.Conclusions: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.
Autologous bone marrow-derived mononuclear cell therapy in three patients with severe asthma​
Authors: Aguiar Fabio S. , Melo André S. , Araújo Ana Maria Silva , Cardoso Alexandre Pinto , de Souza Sergio A. Lopes , Lopes-Pacheco Miquéias , Cruz Fernanda F. , Xisto Debora G. , Asensi Karina D. , Faccioli Lanuza , Salgado Anna Beatriz S. , Landesmann Maria Carolina P. P. , Goldenberg Regina C. dos S. , Gutfilen Bianca , Morales Marcelo M. , Rocco Patricia Rieken Macêdo , Silva Jose Roberto Lapa e
Published: March 2020

Background: Despite recent advances in understanding its pathophysiology and development of novel therapies, asthma remains a serious public health issue worldwide. Combination therapy with inhaled corticosteroids and long-acting β2-adrenoceptor agonists results in disease control for many patients, but those who exhibit severe asthma are often unresponsive to conventional treatment, experiencing worse quality of life, frequent exacerbations, and increasing healthcare costs. Bone marrow-derived mononuclear cell (BMMC) transplantation has been shown to reduce airway inflammation and remodeling and improve lung function in experimental models of allergic asthma. However, to date, no study has evaluated the therapeutic effects of BMMCs in patients with severe asthma. Methods: This is a case series of three patients who presented with severe asthma unresponsive to conventional therapy and omalizumab. All received a single intravenous dose of autologous BMMCs (2×107) and were periodically evaluated for 1 year after the procedure. Endpoint assessments included physical examination; quality of life questionnaires; imaging (computed tomography, single-photon emission computed tomography, and ventilation/perfusion scan); lung function tests; and a 6-min walk test.Results: All patients completed the follow-up protocol. No serious adverse events attributable to BMMC transplantation were observed during or after the procedure. Lung function remained stable throughout. A slight increase in ventilation of the right lung was observed on day 120 after BMMC transplantation in one patient. All three patients reported improvement in quality of life in the early post-procedure course. Conclusions: This paper is the first to describe the effects of BMMC therapy in patients with severe asthma, providing a basis for subsequent trials to assess efficacy.
Eravacycline susceptibility was impacted by genetic mutation of 30S ribosome subunits, and branched-chain amino acid transport system II carrier protein, Na/Pi cotransporter family protein in Staphylococcus aureus
Authors: Wang Zhanwen , Lin Zhiwei , Bai Bing , Xu Guangjian , Li Peiyu , Yu Zhijian , Deng Qiwen , Shang Yongpeng , Zheng Jinxin
Published: March 2020

Objectives: Our previous research indicated the excellent in vitro antibacterial activity of Eravacycline (Erava) and its heteroresistance frequency against clinical Staphylococcus aureus isolates. In this study, we further aimed to investigate the Erava resistance and heteroresistance in S. aureus.Methods: Eight parental S. aureus isolates were induced under Erava pressure in vitro and the Erava-resistant isolates were selected and identified. Then, the genetic mutations of 30S ribosomal subunits were analyzed by PCR and sequence alignment. RT-qPCR analysis were performed to compare the relative expression of eight candidate genes impacting the susceptibility of tetracycline (Tet) between the resistant or heteroresistant and parental isolates. Furthermore, the in vitro overexpression vectors of three selected candidate genes were constructed to test their impact on the heteroresistance and resistance of Erava in S. aureus.Results: The MICs elevation in Erava-induced resistant S. aureus isolates were identified and the increasing MICs values of another two Tet class antibiotics, including both omadacycline (Omada) and tigecycline (Tige) were also tested. Genetic mutations in 30S ribosomal protein S10 were found frequently in Erava-derived resistant isolates. RT-qPCR analysis and the in vitro overexpression experiments indicated that USA300HOU_RS00550 (an Na/Pi cotransporter family protein) and USA300HOU_RS01625 (a branched-chain amino acid transport system II carrier protein) contributed to Erava heteroresistance in S. aureus.Conclusion: Genetic mutation of 30S ribosome subunits contributed to Erava resistance, and the transcriptional overexpression of USA300HOU_RS01625 and USA300HOU_RS00550 also participated in the occurrence of Erava heteroresistance in S. aureus.
Curcumin ameliorates protein expression changes involved in mitochondrial fatty acids metabolism in heart of mice fed a high-fructose diet
Authors: Meléndez-Salcido Cecilia Gabriela , Vargas-Ortiz Katya , Silva-Gaona Oscar Gerardo , León-García María Cristina , Ortega-Hernández Luz Arcelia , Macías-Cervantes Maciste Habacuc , Ramírez-Emiliano Joel , Perez-Vazquez Victoriano
Published: March 2020

Background: It has been proposed that curcumin modulates the gene expression of different signaling pathways, improve the fatty acids metabolism and exerts a potential beneficial effect on cardiometabolic disease, but this has not been thoroughly demonstrated. In the present study, we evaluated the effect of curcumin upon the expression of PPARα, CPT1, MCAD, VLCAD and ACAA2 in heart of mice fed a high-fructose diet (HFD). Methods: Twenty-four mice C57BL/6 were divided into four groups (n=6) and treated for 15 weeks. Control group (C) received standard diet (SD), Curcumin group (C+Cur), Fructose group (F) and Fructose with Curcumin group (F+Cur). The groups were treated with 0.75% w/w curcumin mixed in the SD and 30% w/v fructose in water, respectively. Heart proteins expression were analyzed by Western Blot. Results: Curcumin supplementation increased PPARα and ACAA2 expression and decreased CPT1 and MCAD expression in heart of mice fed a HFD. However, it did not modify the VLCAD expression. Conclusions: Curcumin regulated PPARα, CPT1 and MCAD expression and increased ACAA2 expression; suggesting a therapeutic potential in the prevention of alterations in mitochondrial fatty acids metabolism in heart of mice fed a HFD.
Feasibility of ultra-low dose CT for bronchoscopy of peripheral lung lesions
Authors: Eom Jung Seop , Lee Geewon , Kim Insu , Seol Hee Yun , Roh Jiyeon , Jeong Yeon Joo
Published: March 2020

Background Thin-section CT is essential for identification of small bronchi during bronchoscopy using radial endobronchial ultrasound. Some patients should receive an additional CT for a thin-section image. We performed a retrospective study with a prospectively collected database to identify the optimal radiation dose for thin-section CT during peripheral bronchoscopy. Methods In total, 91 patients with peripheral lung lesions underwent thin-section CT (both standard CT as a reference and ultra-low dose CT [LDCT]). The patients were randomly assigned to one of four groups according to the ultra-LDCT parameters: group 1 = 120 kVp, 25 mAs; group 2 = 100 kVp, 15 mAs; group 3 = 120 kVp, 5 mAs; and group 4 = 100 kVp, 5 mAs. Two radiologists and two physicians analyzed both the standard CT and ultra-LDCT. Results The effective doses (EDs) of ultra-LDCT significantly differed among the four groups (median EDs were 0.88, 0.34, 0.19, and 0.12 mSv for groups 1–4, respectively; P < 0.001). Median differences in peripheral airway wall thickness were higher in group 4 than in other groups (differences in median wall thickness measured by two radiologists were 0.4–0.5 mm and 0.8–0.9 mm for groups 1–3 and group 4, respectively). Bronchus signs on ultra-LDCT in groups 1 and 2 were well correlated with those of the standard dose CT (accuracies of two radiologists and two pulmonary physicians were 95–100%). Conclusions Our results indicate that ultra-LDCT with ED of > 0.34 mSv (ED of group 2) is feasible for peripheral bronchoscopy.
Preoperative anxiety in Ethiopia: a systematic review and meta-analysis
Authors: Yohanes Yeneabat Birhanu , Yazew Kassahun Gebeyehu
Published: March 2020

Background: Anxiety is a vague and uneasy feeling of the individual. It is one of the commonest events that can happen to surgical patients. The prevalence is higher in low-income countries. In Ethiopia, the prevalence of preoperative anxiety reported is variable. This meta-analysis aimed to find the pooled prevalence of preoperative anxiety. Methods: The databases for the search were PubMed, Web of Science, and Google Scholar by the date 02/03/2020. To assess publication bias Egger's test regression analysis was applied. Results: This meta-analysis included a total of 6 studies with 1832 study subjects. The pooled prevalence of preoperative anxiety was 55.54 %( 95% CI, 46.30 to 64.78%). Based on the subgroup analysis, the Oromia region ranked first (63.27%). Conclusions: The national prevalence of preoperative anxiety was high. Oromia region ranked first followed by Amhara, SNNP, and Addis Ababa. Patients need to assess often for anxiety during the preoperative visit.
Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection
Authors: Totura Allison , Livingston Virginia , Frick Ondraya , Dyer David , Nichols Donald , Nalca Aysegul
Published: March 2020

Emerging highly pathogenic coronaviruses (CoV) are a global public health threat due to the potential for person-to-person transmission and higher mortality rates than common seasonal respiratory pathogens. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing lethal respiratory disease in approximately 35% of human cases. Primate models of highly pathogenic coronavirus infection are needed to support development of therapeutics or vaccines, but few models exist that recapitulate severe disease signs. For initial development of a MERS-CoV primate model, twelve African green monkeys (AGMs) were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. We observed a dose-dependent increase of respiratory disease signs and viral titers in serum and throat swabs between the 103 PFU and the 105 PFU dose groups, although all AGMs survived for the 28 day duration of the study. This study is the first to describe dose-dependent effects of highly pathogenic coronavirus infection of primates and uses a route of infection (small particle aerosol) with potential relevance to MERS-CoV transmission in humans. Aerosol exposure of AGMs may provide a platform for the development of primate models of novel coronavirus disease, with potential utility in therapeutic development and viral pathogenesis studies.
Temporal expression patterns of fruit-specific α- EXPANSINS during cell expansion in bell pepper (Capsicum annuum L.)
Authors: Nambeesan Savithri , Mayorga-Gómez Andrés
Published: March 2020

BackgroundExpansins (EXP) facilitate non-enzymatic cell wall loosening during several phases of plant growth and development including fruit growth, internode expansion, pollen tube growth, leaf and root development, and during abiotic stress responses. In this study, we characterized the spatial and temporal expression pattern of C. annuum α- EXPANSINS (CaEXPA) genes. Additionally, we correlated fruit-specific CaEXPA expression with the rate of cell expansion during bell pepper fruit development. ResultsSpatial expression patterns revealed that CaEXPA13 was up-regulated in vegetative tissues and flowers, with the most abundant expression in mature leaves. Expression of CaEXPA4 was associated with stems and roots. CaEXPA3 was expressed abundantly in flower at anthesis suggesting a role for CaEXPA3 in flower development. Temporal expression analysis revealed that 9 out of the 21 genes were highly expressed during fruit development. Of these, expression of six genes, CaEXPA5, CaEXPA7, CaEXPA12, CaEXPA14 CaEXPA17 and CaEXPA19 were abundant 7 to 21 days after anthesis (DAA), whereas CaEXP6 was strongly expressed between 14 and 28 DAA. Further, this study revealed that fruit growth and cell expansion occur throughout bell pepper development until ripening, with highest rates of fruit growth and cell expansion occurring between 7 and 14 DAA. The expression of CaEXPA14 and CaEXPA19 positively correlated with the rate of cell expansion, suggesting their role in post-mitotic cell expansion-mediated growth of the bell pepper fruit. In this study, we also identified high transcript abundance of CaEXPA9 during ripening.ConclusionThis is the first genome-wide study of CaEXPA expression during fruit growth and development. We identified a fruit-specific EXPA that may be important in facilitating cell expansion during growth and cell wall loosening during ripening in bell pepper. These EXPA genes could be important targets for future manipulation of fruit size and ripening characteristics.