bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of two POC technologies for CD4 count in Morocco
Authors: Elharti Elmir , Abbadi Halima , Bensghir Rajae , Filali Kamal Marhoum El , Elmrabet Hajar , Oumzil Hicham
Published: June 2020

Background : In the era of “test and treat strategy”, CD4 testing remains an important tool for monitoring HIV-infected individuals. Since conventional methods of CD4 count measurement are costly and cumbersome, POC CD4 counting technique are more affordable and practical for countries with limited resources. Before introducing such methods in Morocco, we decided to assess their reliability. Methods : In this study 92 blood samples from HIV-infected patients, were tested by PIMA and FACSPresto to derive CD4 count. Flow cytometry using FacsCalibur, was used as reference method for CD4 count comparison. Linear regression, Bland-Altman analysis were performed to assess correlation and agreement between these POC methods and the reference method. In addition, sensitivity and specificity, positive predictive value (PPV), negative predictive value (NPV) and misclassification percentage at 350 and 200 CD4 count thresholds; were also determined. Finally, because FACSPresto can also measure hemoglobin (Hb) concentration, 52 samples were used to compare FACSPresto against an automated hematology analyzer. Results : The coefficient of determination R 2 was 0.93 for both methods. Bland-Altman analysis displayed a mean bias of -32.3 and -8.1 cells/µl for PIMA and FACSPresto, respectively. Moreover, with a threshold of 350 CD4 count, PIMA displayed a sensitivity, specificity, PPV, NPV, were 88.57%, 94.12%, 91.18%, 92.31%; respectively. FACSPresto showed 88.23%, 96.23%,93.75% and 92.73%; respectively. Furthermore, the upward misclassification percentage was 8.57 and 5.88%, for PIMA and FACSPresto, respectively; whereas the downward misclassification percentage was 7.84% and 7.54%; respectively. With 200 cells/µl threshold, PIMA had a sensitivity, specificity, PPV and NPV of 83.33%, 98.53%, 93.75% and 95.71%, respectively. Regarding FACSPresto, sensitivity, specificity, PPV and NPV was 82.35%, 98.57%, 88.57% and 95.83%; respectively. Upward misclassification percentage was 5.56% and 5.88%, for PIMA and FACSPresto, respectively; whereas downward misclassification percentage was 4.41% and 4.29%; respectively. Finally, the hemoglobin measurement evaluation displayed an R 2 of 0.80 and a mean bias of-0.12 with a LOA between -1.75 and 1.51. Conclusion : When compared to the reference method, PIMA and FACSPresto have shown good performance, for CD4 counting. The introduction of such POC technology will speed up the uptake of patients in the continuum of HIV care, in our country.
Distinct evolutionary trajectories of V1R clades across mouse species
Authors: Miller Caitlin H , Campbell Polly , Sheehan Michael J
Published: June 2020

Background Many animals rely heavily on olfaction to navigate their environment. Among rodents, olfaction is crucial for a wide range of social behaviors. The vomeronasal olfactory system in particular plays an important role in mediating social communication, including the detection of pheromones and recognition signals. In this study we examine patterns of vomeronasal type-1 receptor (V1R) evolution in the house mouse and related species within the genus Mus . We report the extent of gene repertoire turnover and conservation among species and clades, as well as the prevalence of positive selection on gene sequences across the V1R tree. By exploring the evolution of these receptors, we provide insight into the functional roles of receptor subtypes as well as the dynamics of gene family evolution. Results We generated transcriptomes from the vomeronasal organs of 5 Mus species, and produced high quality V1R repertoires for each species. We find that V1R clades in the house mouse and relatives exhibit distinct evolutionary trajectories. Some clades are highly conserved, while others reveal patterns of rapid evolutionary change. We identify putative species-specific gene expansions, including a large clade D expansion in the house mouse. While gene gains are abundant, we detect very few gene losses. We describe a novel V1R clade and highlight candidate receptors for future study. We find evidence for different clades experiencing distinct evolutionary processes, from large scale turnover to highly conserved repertoires. Patterns of positive selection are similarly variable across clades, some clades reveal abundant positive selection across branches and orthologs while others display high gene sequence conservation. Based on clade-level evolutionary patterns, we identify receptor families that are strong candidates for detecting social signals and predator cues. Our results reveal that clades with receptors detecting female reproductive status are among the most conserved across species, suggesting an important role in V1R chemosensation. Conclusion Analysis of clade-level evolution is critical for understanding species’ chemosensory adaptations. This study provides clear evidence that V1R clades are characterized by distinct evolutionary trajectories. As receptor evolution is shaped by ligand identity, these results provide a framework for examining the functional roles of different receptors.
Malaria in children and women of childbearing age: prevalence and knowledge in the province of Nyanga, Gabon
Authors: IMBOUMY-LIMOUKOU Roméo Karl , MAGHENDJI-NZONDO Sydney , SIR-ONDO-ENGUIER Pater Noster , Niemczura Julie , TEGOMO Nathalie Pernelle TSAFACK , Buekens Julie Julie , OKOUGA Alain Prince , ONDEME Augustin MOUINGA , NOLNA Sylvie KWEDY , LEKANA-DOUKI Jean Bernard
Published: June 2020

Background: There is little information on the social perception of malaria and the use of preventative measures in Gabon, especially in rural areas. Adequate knowledge of malaria prevention and control can help in reducing the burden of malaria among vulnerable groups, particularly pregnant women and children aged under 5 years old living in malaria endemic settings. This study was designed to assess the prevalence of malaria and the knowledge and attitude towards this disease in households in the Nyanga Province. Methods: A cross-sectional study was conducted to assess malaria knowledge, prevention practices and prevalence of the infection in five departments of the Nyanga Province. Malaria infection was confirmed using rapid diagnostic tests. A questionnaire was administered randomly to 535 households during a two weeks period in March 2018. Overall, the respondents’ socio-demographic characteristics, knowledge on malaria, malaria prevention practices and malaria prevalence were evaluated and compared across the five departments. Results: Data was collected on 1,307 participants were included in this study, 631 women of childbearing age (including 61 pregnant women) and 676 children. Practically the entire (97.7%) interviewed population had already heard about malaria and attributed the cause of malaria to a mosquito bite (95.7%). This survey revealed that the bed net coverage rate was 73.3%. The study observed an average malaria parasite prevalence of 13.9%. All departments of Nyanga province had significant level of malaria infection except for the Mayumba department where no plasmodial infection was found. The overall prevalence of the plasmodial infection was significantly higher in children and pregnant women compared to adults in the cities of Tchibanga and Moabi. Conclusion: Malaria is highly prevalent in the province of Nyanga. Our findings show that children under five and pregnant women are more vulnerable to malaria in this area of the country. This study reveals that respondents have a high knowledge of mode of transmission, malaria symptoms and preventive measures. Despite this high level of knowledge of the disease and its preventive measures, the incidence of malaria remains relatively high in this rural community highlighting the need for continuous strategic interventions particularly health awareness and educational programs
Is a Differentiated Care Model needed for Patients with TB? A cohort analysis of risk factors contributing to unfavourable outcomes among TB patients in two states in south India.
Authors: Washington Reynold , Potty RAJARAM Subramanian , Rajesham A , Seenappa T , Singarajipura Anil , Swamickan Reuben , Shah Amar , Prakash KH , Kar Arin , Kumaraswamy Karthikeyan , BS Prarthana , Maryala Bala Krishna , Sushma J , Dasari Ramesh , Shetty Bharath , Panibatla Vikas , Mohan HL , Becker Marissa
Published: June 2020

Background: TB is a preventable and treatable disease. Yet, successful treatment outcomes at desired levels are elusive in many national TB programs, including India. We aim to identify risk factors for unfavourable outcomes to TB treatment, in order to subsequently design a care model that would improve treatment outcomes among these at-risk patients. Methods: We conducted a cohort analysis among TB patients who had been recently initiated on treatment. The study was part of the internal program evaluation of a USAID-THALI project, implemented in select towns/cities of Karnataka and Telangana, south India. Community Health Workers (CHWs) under the project, used a pre-designed tool to assess TB patients for potential risks of an unfavourable outcome. CHWs followed up this cohort of patients until treatment outcomes were declared. We extracted treatment outcomes from patient’s follow-up data and from the Nikshay portal. The specific cohort of patients included in our study were those whose risk was assessed during July and September, 2018, subsequent to conceptualisation, tool finalisation and CHW training. We used bivariate and multivariate logistic regression to assess each of the individual and combined risks against unfavourable outcomes; death alone, or death, lost to follow up and treatment failure, combined as ‘unfavourable outcome’. Results: A significantly higher likelihood of death and experiencing unfavourable outcome was observed for individuals having more than one risk (AOR: 4.19; 95% CI: 2.47-7.11 for death; AOR 2.21; 95% CI: 1.56-3.12 for unfavourable outcome) or only one risk (AOR: 3.28; 95% CI: 2.11-5.10 for death; AOR 1.71; 95% CI: 1.29-2.26 for unfavourable outcome) as compared to TB patients with no identified risk. Male, a lower education status, an initial weight below the national median weight, co-existing HIV, previous history of treatment, drug-resistant TB, and regular alcohol use had significantly higher odds of death and unfavourable outcome, while age >60 was only associated with higher odds of death. Conclusion: A rapid risk assessment at treatment initiation can identify factors that are associated with unfavourable outcomes. TB programs could intensify care and support to these patients, in order to optimise treatment outcomes among TB patients.
Haemato-immunological responses and effectiveness of feed-based bivalent vaccine against Streptococcus iniae and Aeromonas hydrophila infections in hybrid red tilapia (Oreochromis mossambicus × O. niloticus)
Authors: Monir Md. Shirajum , Yusoff Md Sabri bin Mohd , Zulperi Zarirah binti Mohamed , Hassim Hasliza binti Abu , Mohamad Aslah , Sofie Mohd Hafiz Ngoo Muhamad , Ina-Salwany Md Yasin
Published: June 2020

Background Streptococcosis and Motile Aeromonad Septicemia (MAS) are important diseases of tilapia, Oreochromis spp. and causes huge economic losses in aquaculture globally. The feed-based vaccination may be an alternative to minimize major infectious diseases in tilapia. Thus, this study aims to evaluate the haemato-immunological responses and effectiveness of a newly developed feed-based killed bivalent vaccine against Streptococcus iniae and Aeromonas hydrophila in hybrid red tilapia. A total of 495 hybrid red tilapia of 61.23±4.95 g were distributed into 5 groups (each with triplicate). The fish were immunized orally through bivalent (combined S. iniae and A. hydrophila ) spray vaccine (BS group), bivalent formulate vaccine (BF group), monovalent S. iniae vaccine (MS group), monovalent A. hydrophila vaccine (MA group) and unvaccinated as a control group. The vaccine was orally administered on days 0, 14 and 42 applied feed-based bacterin at 5% body weight. The blood and spleen samples were collected from all groups on 7, 21 and 49 days post-vaccination, and also 96 hours post-infection to assess their haemato-immune responses. Results Compared with the unvaccinated group, leukocyte, lymphocytes, monocytes, granulocytes counts in vaccinated groups were significantly ( P < 0.05) increased on 21, 49 days post-vaccination and also 96 hours post-infection, while erythrocytes, haemoglobin and haematocrit in vaccinated groups were significantly ( P < 0.05) enhanced only 96 hours post-infection. Additionally, the lysozyme and phagocytic activity and, serum antibody (IgM) were significantly higher ( P < 0.05) against S. iniae and A. hydrophila in vaccinated groups compared to the unvaccinated group in the pre- and post-infection. Results from the challenge through co-infection with S. iniae and A. hydrophila showed the relative percent survival (RPS) in BF group was 76.37±5.14%, which had the capacity to induce significant protection ( P < 0.05) compared to others groups. Conclusions This study demonstrates the bivalent formulate (BF) group could elicit significant non-specific and specific immunological responses with higher protection in hybrid red tilapia. In addition, this newly developed feed-based bivalent vaccination can be a promising technique for effective and large scale fish immunization in the aquaculture industry.
A high fat diet with a high C18:0/C16:0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice
Authors: Wang Liqiang , Xu Fei , Song Zhenfeng , Han Dan , Zhang jingyi , Chen Linjun , Na Lixin
Published: June 2020

Background: Differential effects of individual saturated fatty acids (SFAs), particularly stearic acid (C18:0) relative to the shorter-chain SFAs have drawn an interest for more accurate nutritional guidelines. But specific biologic and pathologic functions that can be assigned to particular SFAs are very limited. The present study was designed to compare changes in metabolic and transcriptomic profiles in mice caused by high C18:0 diet and high palmitic acid (C16:0) diet.Methods: Male C57BL/6 mice were assigned to a normal fat diet (NFD), a high fat diet with high C18:0 / C16:0 ratio (HSF) or an isocaloric high fat diet with a low C18:0 / C16:0 ratio (LSF) for 10 weeks. Oral glucose tolerance test, 72h-energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an auto-biochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α)，and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay methods. Free fatty acids (FFAs) profiles in blood and liver were determined by using Gas Chromatography-Mass Spectrometry. Microarray analysis was applied to investigate changes in transcriptomic profiles in liver. Pathway analysis and Gene Ontology analysis were applied to describe the roles of differentially expressed mRNAs. Results: Compared with NFD group, body weight, body fat ratio, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, IL-6, serum and liver FFAs including total FFAs, C16:0 and C18:0 were increased in both high fat diet groups, which were much higher in HSF group than those in LSF group. Both HSF and LSF mice exhibited distinguishable lncRNA, microRNA and mRNA expression profiles, compared with NFD mice. And more differentially expressed lncRNAs and mRNAs were observed in HSF group than those in LSF group. Some biological functions and pathways, other than energy metabolism regulation, were identified that differentially expressed mRNAs between HSF group and LSF group probably involved in. Conclusion: The high fat diet with a high C18:0/C16:0 ratio induced much severe glucose and lipid metabolic disorders and inflammation, and affected more lncRNAs and mRNAs expression than an isocaloric low C18:0/C16:0 ratio diet in mice. These results provide new insights into the different biological functions and related mechanisms, other than glucose and lipid metabolism, between C16:0 and C18:0.Take home message: A high fat diet with a high C18:0/C16:0 ratio probably leads to more changes in multiple biological processes or signaling pathways at transcriptional level than an isocaloric low C18:0/C16:0 ratio diet. The ratio of C18:0/C16:0 in diets should be taken into account for accurate nutrition and health in future.
Host DNA released by NETosis in neutrophils exposed to seasonal H1N1 and highly pathogenic H5N1 influenza viruses
Authors: Chan Louisa L.Y. , Nicholls John M. , Peiris J.S. Malik , Lau Yu Lung , Chan Michael C.W. , Chan Renee WY
Published: June 2020

Background: Neutrophil is of the most abundant number in human immune system. During acute influenza virus infection, neutrophils are already active in the early phase of inflammation-a time in which clinical biopsy or autopsy material is not readily available. However, the role of neutrophil in virus infection is not well understood. Here, we studied the role of neutrophil in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease. Methods: Neutrophils were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro. The ability of the naïve neutrophils to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of neutrophils upon influenza virus infection were evaluated. Results: Our results demonstrated that influenza virus infected alveolar epithelium allowed more neutrophils transmigration. Significantly more neutrophils migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Neutrophils were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected neutrophils. H5N1 induced higher cytokine and chemokine gene transcription than H1N1 infected neutrophils, including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was only observed in H1N1 infected neutrophils at 6 hpi while no NET formation was observed upon H5N1 infection.Conclusion: Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection and might contribute to the severity of H5N1 disease.
Discriminative Validity of the Core Outcome Set Functional Independence in a Population of Older Adults
Authors: Dockx Yvonne , Molenaar Esther , Barten Di-Janne , Veenhof Cindy
Published: June 2020

Background: Clinicians are currently challenged to support older adults to maintain a certain level of Functional Independence (FI). FI is defined as “functioning physically safely and independent from another person, within one’s own context”. A Core Outcome Set was developed to measure FI. The purpose of this study was to assess discriminative validity of the Core Outcome Set FI (COSFI) in a population of Dutch older adults (³ 65 years) with different levels of FI. Secondary objective was to assess to what extent the underlying domains ‘coping’, ‘empowerment’ and ‘health literacy’ contribute to the COSFI in addition to the domain ‘physical capacity’. Methods: A population of 200 community-dwelling older adults and older adults living in residential care facilities were evaluated by the COSFI. The COSFI contains measurements on the four domains of FI: physical capacity, coping, empowerment and health literacy. In line with the COSMIN Study Design checklist for Patient-reported outcome measurement instruments, predefined hypotheses regarding prediction accuracy and differences between three subgroups of FI were tested. Testing included ordinal logistic regression analysis, with main outcome prediction accuracy of the COSFI on a proxy indicator for FI. Results: Overall, the prediction accuracy of the COSFI was 68%. For older adults living at home and depending on help in (i)ADL, prediction accuracy was 58%. 60% of the preset hypotheses were confirmed. Only physical capacity measured with Short Physical Performance Battery was significantly associated with group membership. Adding health literacy with coping or empowerment to a model with physical capacity improved the model significantly (p<0.01). Conclusions: The current composition of the COSFI, did not yet meet the COSMIN criteria for discriminative validity. However, with some adjustments, the COSFI potentially becomes a valuable instrument for clinical practice. Context-related factors, like the presence of a spouse, also may be a determining factor in this population. It is recommended to include context-related factors in further research on determining FI in subgroups of older people.
The human gut archaeome: identification of diverse haloarchaea in Korean subjects
Authors: Kim Joon Yong , Whon Tae Woong , Lim Mi Young , Kim Yeon Bee , Kim Namhee , Kwon Min-Sung , Kim Juseok , Lee Se Hee , Choi Hak-Jong , Nam In-Hyun , Chung Won-Hyung , Kim Jung-Ha , Bae Jin-Woo , Roh Seong Woon , Nam Young-Do
Published: June 2020

Background: Archaea are one of the least-studied members of the gut-dwelling autochthonous microbiota. Few studies have reported the dominance of methanogens in the archaeal microbiome (archaeome) of the human gut, although limited information regarding the diversity and abundance of other archaeal phylotypes is available.Results: We surveyed the archaeome of faecal samples collected from 897 East Asian subjects living in South Korea. In total, 42.47% faecal samples were positive for archaeal colonisation; these were subsequently subjected to archaeal 16S rRNA gene deep sequencing and real-time quantitative polymerase chain reaction-based abundance estimation. The mean archaeal relative abundance was 10.24% ± 4.58% of the total bacterial and archaeal abundance. We observed extensive colonisation of haloarchaea (95.54%) in the archaea-positive faecal samples, with 9.63% mean relative abundance in archaeal communities. Haloarchaea were relatively more abundant than methanogens in some samples. The presence of haloarchaea was also verified by fluorescence in situ hybridisation analysis. Owing to large inter-individual variations, we categorised the human gut archaeome into four archaeal enterotypes.Conclusions: The study demonstrated that the human gut archaeome is indigenous, responsive, and functional, expanding our understanding of the archaeal signature in the gut of human individuals.
International relevance of Two Measures of Awareness of Age-Related Change (AARC)
Authors: sabatini serena , Ukoumunne Obioha C , Ballard Clive , Brothers Allyson , Kaspar Roman , Collins Rachel , Kim Sarang , Corbett Anne , Aarsland Dag , Hampshire Adam , Brooker Helen , Clare Linda
Published: June 2020

Background: A questionnaire assessing awareness of positive and negative age-related changes (AARC gains and losses) was developed in the US and Germany. We validated the short form of the measure (AARC-10 SF) and the cognitive functioning subscale from the 50-item version of the AARC (AARC-50) questionnaire in the UK population aged 50 and over. Methods: Data from 9,410 participants (Mean (SD) age= 65.9 (7.1)) in the PROTECT cohort were used to explore and confirm the psychometric properties of the AARC measures including: validity of the factor structure; reliability; measurement invariance across males and females and across individuals with and without a university degree; and convergent validity with measures of self-perception of aging and mental, physical, and cognitive health. We also explored the relationship between demographic variables and AARC. Results: We confirmed the two-factor structure (gains and losses) of the AARC-10 SF and the AARC-50 cognitive functioning subscale. Both scales showed good reliability. Convergent validity was good for AARC losses, but weaker for AARC gains. The meaning of AARC gains and losses was the same across males and females and across individuals with and without a university degree. Items in the AARC scales had the same meaning across individuals with and without a university degree. Items in the AARC-50 cognitive functioning subscale had the same meaning across males and females. Single items in the AARC-10 SF had different meaning across males and females. Demographic variables predicted AARC gains and losses. Conclusions: The AARC-10 SF and AARC-50 cognitive functioning subscale can help to identify UK individuals who perceive age-related changes in their mental, physical, and cognitive health.
Prevalence of Primary Headache Disorder Among Primary and middle School students in Kuwait.
Authors: Shuaibi Sameera , AlAshqar Abdelrahman , Ahmed Samar Farouk , Alroughani Raed , AlThufairi Hawraa , Owayed Shaikhah , AlHamdan Fajer , Al-Hashel Jasem Yousef
Published: June 2020

Background: Primary headaches are remarkably prevalent worldwide and increasingly reported among children. However, the exact trend in this age group, particularly in the gulf region, remains scarce. Aims and Objectives: To examine the prevalence of primary headache disorders among primary and middle school students in Kuwait.Methods: We conducted a cross-sectional study that included Kuwaiti primary and middle school children and adolescents of both genders in randomly selected schools located in two governorates in Kuwait in 2018/2019 academic year. Prevalence and attributable burden of headache, definite and probable migraine,definite and probable tension-type headache, chronic headache ≥15 days/month and probable medication over use headache were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Results: Of 1485 questionnaires that were distributed, 1089 students completed the questionnaire with a respondent rate of 73.4%. The study population consisted of 420 boys (38.56%) versus 669 girls (61.43%) students with a mean age of 11.5 ± 2.11 years. The lifetime prevalence of any headache was 85.2%. The one-year prevalence of primary headache disorders was 42.71% with more middle schoolers reporting headaches than primary schoolers (50.37% versus 30,48%; p <0.02). The mean age of students with primary headaches was 11.98 ± 2.03 years in both genders. When stratified according to diagnostic criteria, migraine headaches were the most frequently reported (20.75%) followed by tension type headaches (18.8%), chronic headaches (2.75%), and probable medication-overuse headaches (0.46%.). Primary headaches were more frequently reported in middle school compared to primary school It was significantly higher among girls compared to boys in middle-schoolers (66.46% versus 38.49%; p<0.001), however no significant difference in gender among primary school students(33.12% versus 22.33%; p<0.118). Conclusion: Primary headaches are remarkably common in Kuwaiti school students with migraine headache being the most frequently reported type. Age and female gender pay a role in the development of primary headaches. The results attract attention of health services for those group, the need for further epidemiological researches.
Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge
Authors: Yang Ting , Chen Wei-Cong , Shi Pei-Cong , Liu Man-Ru , Jiang Tao , Song Hu , Wang Jia-Qi , Fan Rui-Zhi , Pei Dong-Sheng , Song Jun
Published: June 2020

Background: Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown.Methods: In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 (CCK8), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation (RIP), dual luciferase reporter assay, chromatin immunoprecipitation (CHIP) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model. Results: We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p and cis-regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter. Conclusions: MK5-AS1 cis-regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.
Cetuximab-Conjugated Perfluorohexane/Gold Nanoparticles for Low Intensity Focused Ultrasound Diagnosis Ablation of Thyroid Cancer Treatment
Authors: Ma Yue , Wang Lingling , Li Haixia , Cheng Wen , Zheng Xiulan , Liu Ying
Published: June 2020

Chemotherapeutic efficacy plays a significant role in the development of nanotheranostic systems for drug delivery in tumor cells. In this study, we demonstrate the self-assembly of C225 conjugate, Perfluorohexane/Gold Nanoparticles (Au-PFH-NPs), which results in low-intensity focused ultrasound diagnosis ablation of thyroid cancer treatment. Cetuximab-Conjugated Perfluorohexane/Gold Nanoparticles (C-Au-PFH-NPs) showed excellent stability in water, PBS, and 20% rat serum. Transmission electron microscopy images revealed the effective construction of C-Au-PFH-NPs with commonly spherical assemblies. The incubation of C625 thyroid carcinoma with C-Au-PFH-NPs triggered apoptosis, which was confirmed by flow cytometry analysis. The C-Au-PFH-NPs showed remarkable antitumor efficacy in human thyroid carcinoma xenografts. The histopathological results additionally confirm the achieved outcomes. Furthermore, we successfully examined the efficiency of C-Au-PFH-NPs when using the thyroid carcinoma low-intensity focused ultrasound (LIFUS) diagnostic imaging in vivo. These findings are clear for LIFUS agents with high performing images. It is also identified that different therapeutic purposes will have extensive potential for future biomedical purposes.
Herd-level risk factors for chronic pleurisy in finishing pigs: a case-control study
Authors: Hälli Outi , Haimi-Hakala Minna , Oliviero Claudio , Heinonen Mari
Published: June 2020

Background Chronic pleurisy is a common finding in slaughtered pigs in post-mortem meat inspection. The prevalence of pleurisy has been increasing during the last decade also in Finland. The aim of this prospective case-control study was to search for environmental, infectious and management-related herd-level risk factors for pleurisy in the slaughterhouse. Altogether 46 Finnish pig herds, including 25 control (low pleurisy prevalence in meat inspection) and 21 case (high pleurisy) herds, were enrolled in the study and visited during the tenth week of the rearing period of finishing pigs. Herd personnel were asked about basic herd information, management and environmental factors. Selected pigs were examined clinically, environmental parameters were measured and 15 blood samples per herd were taken during herd visits. Antibodies against Actinobacillus pleuropneumonia serotype 2 (APP2) and ApxIV toxin and swine influenza virus were measured. After the slaughter of study pigs, meat inspection results of the batch were gathered from slaughterhouses. Multivariate logistic regression model was built to identify possible risk factors for a herd to be a case herd (i.e. having high pleurisy values). Results Finishing herd type and herd size were observed to act as risk factors. None of clinical signs of pigs, management-related factors or environmental measurements were associated with herd status. Conclusions As previously known, in endemic and subclinical infections such as APP, herd factors are important, but detailed risk factors seem to be difficult to identify.
Potential risks in sentinel lymph node biopsy for cervical cancer: a single-institution pilot study
Authors: Tu Hua , Wan Ting , Zhang Xinke , Gu Haifeng , Feng Yanling , Huang He , Liu Jihong
Published: June 2020

Background：Sentinel lymph node (SLN) biopsy is an attractive technique that widely performed in many oncological surgeries. However, the potential risks in SLN biopsy for cervical cancer remains largely unclear. Methods：Seventy-five patients with histologically confirmed cervical cancer were enrolled between May 2014 and June 2016. SLN biopsies were performed followed by pelvic lymphadenectomies and all resected nodes were labeled according to their anatomic areas. Only bilateral detections of SLNs were considered as successful. Patients’ clinicopathologic feature, performance of SLN detection, and distributions of lymph node metastases were analyzed. Results: Of the 75 enrolled patients, at least one SLN was detected in 69 (92.0%), including 33 in bilateral and 36 in unilateral. SLNs were most detected in obturator area (52 of 69 patients, 75.4%) and 26 (37.7%) patients presented SLNs in more than one area of hemipelvis. Lymphovascular invasion was found to be the only factor that adversely influenced SLN detection, while the tumor diameter, growth type, histological grade, deep stromal invasion and neoadjuvant chemotherapy showed no significant impacts. Patients with lymphovascular invasion showed significantly higher rate to have unsuccessful detection (90.9% versus 41.5%, P<0.001) and lymph node metastasis (40.9% versus 3.8%, P<0.001) compared with those without. Nodal metastases were confirmed in 11 patients, of whom 9 (81.8%) had lymphovascular invasion and 7 (63.6%) had non-SLN metastasis. The most frequently involved SLNs were obturator nodes (9/11, 81.8%). In addition, the parametrial nodes also has high rate to be positive (4/11, 36.4%), although they were relatively less identified as SLNs. Besides, 3 patients showed metastases in the laterals without SLN detected.Conclusions: In cervical cancer, lymphovascular invasion is a significant factor for unsuccessful SLN detection. The risk of having undetected metastasis is high when SLN is positive, therefore further lymphadenectomy may be necessary for these patients.
Distraction by a cognitive task has a higher impact on electrophysiological measures compared with conditioned pain modulation
Authors: Do A. T. Lisa , Enax-Krumova Elena , Özgül Özüm , Eitner Lynn B. , Heba Stefanie , Tegenthoff Martin , Maier Christoph , Höffken Oliver
Published: June 2020

Background
Conditioned pain modulation (CPM) evaluates the effect of a painful conditioning stimulus (CS) on a painful test stimulus (TS). Using painful cutaneous electrical stimulation (PCES) as TS and painful cold water as CS, the pain relief was paralleled by a decrease in evoked potentials (PCES-EPs). We now aimed to compare the effect of CPM with cognitive distraction on PCES-induced pain and PCES-EP amplitudes.
Methods
PCES was performed in 38 healthy subjects using surface electrodes inducing a painful sensation of 60 (NRS 0-100) on one hand. In a crossover design subjects immersed the contralateral hand into painful cold water (10 °C, CS) for CPM evaluation and performed the 1-back task for cognitive distraction. Before and during the CS and 1-back task, respectively, subjects rated the pain intensity of PCES and simultaneously cortical evoked potentials were recorded.
Results
Both CPM and cognitive distraction significantly reduced PCES-EP amplitudes (CPM: from 30.9 ± 9.9 µV to 24.35 ± 8.41 µV, cognitive distraction: from 33.0 ± 8.8 µV to 19.5 ± 6.5 µV, p < 0.05) and PCES-induced pain (CPM: from 58 ± 4 to 39 ± 12, cognitive distraction: from 58 ± 4 to 36 ± 14, p < 0.05), though the changes in pain intensity and PCES-amplitude did not correlate. The changes of the PCES-EP amplitudes during cognitive distraction were significantly more pronounced than during CPM.
Conclusions
The amount of pain relief induced by CPM and cognitive distraction seems to be similar. However, the even more pronounced decrease of PCES-EP amplitudes after distraction by a cognitive task implies that both conditions do not represent the general pain modulatory capacity of individuals, but may underlie different neuronal mechanisms with the final common pathway of perceived pain reduction.
Prediction of biological age and all-cause mortality by 12-lead electrocardiogram in patients without structural heart disease
Authors: Hirota Naomi , Suzuki Shinya , Arita Takuto , Yagi Naoharu , Otsuka Takayuki , Kishi Mikio , Semba Hiroaki , Kano Hiroto , Matsuno Shunsuke , Kato Yuko , Uejima Tokuhisa , Oikawa Yuji , Matsuhama Minoru , Inoue Tatsuya , Yajima Junji , Yamashita Takeshi
Published: June 2020

Background:
The 12-lead electrocardiogram (ECG) is affected by not only the cardiovascular but also the non-cardiovascular status. Whether ECG can be the determinant of biological age (BA) and the gap between chronological age (CA) and ECG-predicted BA reflect differences in prognosis are unclear.
Methods:
In the Shinken Database 2010 – 2017 (n = 19170), 12-lead ECG was analyzed in 13005 patients excluding those with structural heart disease or having pacing beats, atrial or ventricular tachyarrhythmia, and indeterminate axis (R axis > 180˚) on index ECG. The prediction model of BA was developed by principal component analysis with 438 ECG parameters. The gap between ECG-predicted BA and CA was calculated (AgeDiff = ECG-predicted BA − CA).
Results:
The ECG-predicted BA was significantly correlated with CA (r = 0.967). Patients with a positively wide AgeDiff had a higher incidence of all-cause mortality compared to those with a narrow AgeDiff or those with negative AgeDiff. The risk of AgeDiff > 0 for all-cause mortality compared with AgeDiff ≤ 0 was 1.78 (95%CI: 1.00 − 3.16), which increased according to the aging and became the highest in patients with CA of 71 − 80 years.
Conclusion:
Our data suggested that 12-lead ECG can be a tool to estimate BA. The gap between ECG-predicted BA and CA allowed estimation of increased risk of all-cause mortality in patients without structural heart disease.
Very Low Risk of Lymph Node Metastasis in Epstein-Barr Virus-associated Early Gastric Carcinoma With Lymphoid Stroma
Authors: Cheng Yuqing , Zhou Xiaoli , Xu Kequn , Huang Jin , Huang Qin
Published: June 2020

Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma (EBV-GCLS) is a rare variant of early gastric carcinomas. Clinicopathological features of this variant remain obscure, especially in Chinese patients. By a retrospective review of 595 consecutive radical gastrectomies for early gastric carcinoma from 2006 to 2018, we identified 8 (1.3%, 8/595) EBV-GCLS cases. Clinicopathologic characteristics were compared between EBV-GCLSs and 109 conventional early gastric carcinomas, which were divided into 3 subgroups, according to the invasion depth. All 8 EBV-GCLSs occurred in male patients and invaded deep submucosa (SM2) without lymph node metastasis (LNM), four (50%) of which had synchronous non-gastric malignant tumors (3 gastric gastrointestinal stromal tumors and 1 primary clear cell renal cell carcinoma), and four (50%) arose in the proximal stomach. Compared to conventional early gastric carcinomas, EBV-GCLS was more frequent with SM2 invasion, poor differentiation, and synchronous non-gastric carcinoma tumor, but not in age, gender, macroscopic type, location, size, perineural invasion, lymphovascular invasion, and pathologic stage. In invasion-depth stratified comparisons with the SM2 subgroup, the frequency of LNM in EBV-GCLS was significantly lower than that of conventional early gastric carcinomas ( p < 0.05) and the 5-year survival rate of patients with EBV-GCLS was better than that of conventional early gastric carcinomas in 3 subgroups (100% vs 91.5%, 85.7%, 83.9%, respectively), although the differences did not reach a statistically significant level due to the small sample size. In conclusion, Even with poor differentiation and SM2 invasion, EBV-GCLS showed very low risk of LNM and may be a candidate for endoscopic therapy.
Effectiveness of extracorporeal blood purification (hemoadsorption) in patients with severe coronavirus disease 2019 (COVID-19)
Authors: Asgharpour Masoumeh , Mehdinezhad Hamed , Bayani Masoumeh , Zavareh Mahmoud Sadeghi Haddad , Hamidi Seyed Hossein , Akbari Roghayyeh , Ghadimi Reza , Bijani Ali , Mouodi Simin
Published: June 2020

Background
Extracorporeal blood purification has been proposed as one of the therapeutic approaches in patients with coronavirus infection, because of its beneficial impact on elimination of inflammatory cytokines.
Methods
This controlled trial has been conducted on critically ill COVID-19 patients admitted in the state hospital affiliated to Babol University of Medical Sciences, Iran who received different antiviral and antibacterial drugs, and different modalities of respiratory treatments and did not have positive clinical improvement. No randomization and blindness was considered. All of the participants underwent three sessions of resin-directed hemoperfusion using continuous renal replacement therapy with a mode of continuous venovenous hemofiltration (CVVH).
Results
Five men and five women with a mean age of 57.30 ± 18.07 years have been enrolled in the study; and six of them have improved after the intervention. Peripheral capillary oxygen saturation (SpO2) changed after each session. Mean SpO2 before the three sessions of hemoperfusion was 89.60%±3.94% and increased to 92.13%±3.28% after them (p < 0.001). Serum IL-6 showed a reduction from 139.70 ± 105.62 to 72.06 ± 65.87 pg/mL (p = 0.073); and c-reactive protein increased from 136.25 ± 84.39 to 78.25 ± 38.67 mg/L (P = 0.016).
Conclusions
Extracorporeal hemoadsorption could improve the general condition in most of recruited patients with severe coronavirus disease; however, large prospective multicenter trials in carefully selected patients are needed to definitely evaluate the efficacy of hemoperfusion in COVID-19 patients.
Locking Intramedullary Nails Versus Locking Plates in the Treatment of 2-part and 3-part Proximal Humeral Surgical Neck Fractures in Elderly Patients: A Prospective Cohort Study
Authors: Geng Rui , Wu Hao , Ren Ke , Chang Qing , Yusufu Yalikun , Xu Jihao , Lu Jun
Published: June 2020

The authors have withdrawn this preprint due to erroneous posting.
Dysphagia and Masticatory Performance as a Mediator of the Xerostomia to Quality of Life Relation in the Older Population: A Structural Equation Model Approach
Authors: Lu Ting-Yu , Chen Jen-Hao , Du Je-Kan , Lin Ying-Chun , Ho Pei-Shan , Lee Chien-Hung , Hu Chih-yang , Huang Hsiao-Ling
Published: June 2020

Background: The adverse impact of poor oral conditions in older adults on their quality of life is a public health problem. This study assessed the mediating effects of dental status, occlusal condition, dysphagia and masticatory performance on the association between xerostomia and oral health-related quality of life (OHRQoL) in the older population. Methods: A total of 1100 representative community-dwelling adults aged 65 years and older were recruited from a large-scale survey conducted in Kaohsiung, Taiwan. Dental status and occlusal condition were performed by dentists. Information on demographics, physical function, xerostomia, and dysphagia was collected using face-to-face interview. Masticatory performance was evaluated using color-changeable chewing gum. OHRQoL was measured using Geriatric Oral Health Assessment Index. Results: Comparing with non-xerostomia, participants with xerostomia had a 0.20 decrease in the level of OHRQoL (p< .001), and the direct effect was accounted for 83.3% of the total effect. The dysphagia and the masticatory performance were found to have a significant mediating effect on the association between xerostomia and OHRQoL (βs = 0.20 and −0.13, respectively; βs = 0.05 and −0.08, respectively) and 10.8% of the effect was attributed to dysphagia mediation. Furthermore, the functional teeth and occlusal condition had a significant mediating effect on the association between xerostomia and masticatory performance , and the functional teeth was accounted for 43.6% of the effect. Conclusions: Xerostomia had the greatest effect on OHRQoL. The mediating role of dysphagia and masticatory performance on the association between xerostomia and OHRQoL was significant and deserves further attention. Older adults could improve their OHRQoL through a community-based oral function intervention. Our results further suggest that early screening for swallowing and masticatory function is essential to prevent or delay the onset of complications.
WITHDRAWN: First Study of Molecular detection of Ovine Herpesvirus 2 DNA using heminested PCR in Pakistan
Authors: Riaz Aayesha , Dry Inga , Dalziel Robert G. , Rehman Saif Ur , Shah Muhammad Ali Abdullah , Akhtar Naeem , Yousaf Arfan , Baig Ruqia Mehmood
Published: June 2020

Background
Malignant catarrhal fever (MCF) is a highly fatal lymphoproliferative disease of cattle, deer, bison, water buffalo and pigs caused by the gamma herpesviruses; alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2 (OvHV-2). AlHV-1 is known to cause wildebeest-associated MCF whereas OvHV-2 is known to cause sheep-associated MCF. AlHV-1 and OvHV-2 cause inapparent infection in their reservoir hosts (wildebeest for AlHV-1 and sheep for OvHV-2) but fatal lymphoproliferative disease in susceptible species.
Methods
This study was aimed to find prevalence of OvHV-2 in sheep, goat, cattle and buffalo in Rawalpindi and Islamabad cities of Pakistan, using molecular and phylogenetic methods. Blood samples were collected consisting of sheep (n = 54), goat (n = 50), cattle (n = 46) and buffaloes (n = 50) from slaughter houses and farms. The samples were subjected to hemi-nested PCR, sequencing, and phylogenetic analysis of OvHV-2 POL gene and OvHV-2 tegument protein gene.
Results
The highest percentage of positive samples was found to be in sheep (13%) whereas positive samples from goat, cattle and buffaloes had percentage of 11%, 9% and 6.5% respectively. Four positive PCR products from sheep samples were also sequenced. The sequences obtained were submitted to NCBI GenBank database under the accession numbers of MK852173 for POL gene, and MK840962, MK852171 and MK852172 for ORF75 tegument protein gene. Phylogenetic analysis revealed close identities with some sequences of this virus from worldwide including neighbouring countries including China, India and Iran.
Conclusion
This study is the first study in Pakistan on the prevalence of OvHV-2 in carrier and susceptible species. This report provides important data about the presence of OvHV-2 in apparently healthy cattle and buffaloes, which might transmitted to them from OvHV-2 positive sheep or goats. It is concluded that a countrywide, large scale OvHV-2 prevalence study should be conducted to avoid economic losses due to any outbreak of MCF.