bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and correlates of non-daily and daily cannabis use among persons 15 years and older in South Africa: Results of a national survey in 2017
Authors: Ramlagan Shandir , Peltzer Karl , Pengpid Supa
Published: December 2020

BackgroundThe study aimed to assess the prevalence and correlates of non-daily and daily cannabis use among persons 15 years and older in South Africa.MethodIn a national cross-sectional 2017 survey, 39,207 persons 15 years and older (Median = 34 years) responded to a questionnaire on substance use and health variables. Multinominal logistic regression was used to assess the determinants of nondaily and daily cannabis use and logistic regression for the determinants of daily cannabis use among active cannabis users.ResultsResults indicate that 5.0% of the participants engaged in non-daily and 2.8% in daily cannabis use in the past 3 months. In adjusted multinomial logistic regression analysis, male sex, having Grade 8–11 education, Coloureds, alcohol use disorder, living with husband or wife, not living with a partner, and other drug use were positively and students were negatively associated with daily cannabis use. Male sex, younger age, living alone or single, living with a partner, alcohol use disorder, and other drug use were positively and multimorbidity was negatively associated with nondaily cannabis use. Compared to nondaily cannabis users, male sex had higher odds and students and other drug use had lower odds of daily cannabis use.ConclusionAbout one in ten participants engaged past 3-month cannabis use, and several sociodemographic and health indicators were identified associated with non-daily and daily cannabis use.
Health Risks in a Street Population Using Illegal Drugs in Norway 2010 to 2012, with a Long-Term Follow-up Regarding Mortality and Morbidity, As Well As Local and National Harm Reduction Measures
Authors: Amundsen Ellen Johanna , Løchen Maja-Lisa , Melsom Anne-Karine M. , Eriksen Bjørn O.
Published: December 2020

Background Mapping the heterogeneity of high-risk drug users is necessary to target harm reduction measures and drug policy. The aim of this study was to find if and how risk factors of adverse health outcomes varied for subgroups among illicit drug users from 2010 to 2012 and explore whether harm reduction measures, low-threshold services and treatment met such health risks from 2010 to 2019. Methods We interviewed 413 drug users at low-threshold facilities in three Norwegian cities from 2010 to 2012, and 351 respondents had a full dataset. The inclusion criterion was use of amphetamines, cocaine, heroin or opioids during the previous 12 months. Latent profile analysis was applied to establish subgroups with different health risk profiles. City-specific as well as national drug-induced deaths (2010-18) and injecting-related infectious diseases (2010-2019) were applied as outcomes. Harm reduction measures, low-threshold services and treatment in Norway from 2010 to 2019 are described. Results Reporting amphetamines (68%), heroin (60%) and opioids (65%) last 30 days were frequent, while reporting of cocaine was not (14%). Frequent use, injecting and co-use of amphetamines, heroin, and other opioids (prescribed or illicit) was high. The latent profile analysis separated users into five subgroups. Time since debut of use of amphetamines, cocaine, heroin or opioids varied between groups, as did types of psychoactive substances used and dependence. Injecting practices varied from 51% to 97% in the subgroups. Harm reduction measures in Norway since 2010 have been targeted to reduce the high level of injecting practices and their health consequences. However, drug-induced deaths at the national level and in the cities of the interviewees did not decline up to 2018. HIV among people who inject drugs at the national level declined from 2010 to 2019, while Hepatitis B did not, and the result for Hepatitis C was inconclusive. Conclusions Even though harm reduction measures for high-risk drug users in Norway have been targeted to reduce the high level of injecting practices and other health risks found in five subgroups in our sample from 2010 to 2012, further measures to reduce such risks and their health consequences must be tailored.
A generative network model of neurodevelopment
Authors: Akarca Danyal , Vertes Petra , Bullmore Edward , team The CALM , Astle Duncan
Published: December 2020

The emergence of large-scale brain networks, and their continual refinement, represent crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. But how does this organization arise, and what mechanisms govern the diversity of these developmental processes? There are many existing descriptive theories, but to date none are computationally formalized. We provide a mathematical framework that specifies the growth of a brain network over developmental time. Within this framework macroscopic brain organization, complete with spatial embedding of its organization, is an emergent property of a generative wiring equation that optimizes its connectivity by renegotiating its biological costs and topological values continuously over development. The rules that govern these iterative wiring properties are controlled by a set of tightly framed parameters, with subtle differences in these parameters steering network growth towards different neurodiverse outcomes. Regional expression of genes associated with the developmental simulations converge on biological processes and cellular components predominantly involved in synaptic signaling, neuronal projection, catabolic intracellular processes and protein transport. Together, this provides a unifying computational framework for conceptualizing the mechanisms and diversity of childhood brain development, capable of integrating different levels of analysis – from genes to cognition.
Hierarchical Hidden Community Detection for Protein Complex Prediction
Authors: Li Chao , He Kun , Liu Guang shuai , Hopcroft John E.
Published: December 2020

BackgroundDiscovering functional modules in protein-protein interaction networks through optimization remains a longstanding challenge in Biology. Traditional algorithms simply consider strong protein complexes found in the original network by optimizing some metric, which may cause obstacles for discovering weak and hidden complexes that are overshadowed by strong complexes. Additionally, protein complexes have not only different densities but also various ranges of scales, making them extremely difficult to be detected. We address these issues and propose a hierarchical hidden community detection approach to predict protein complexes of various strengths and scales accurately. ResultsWe propose a meta-method called HirHide (Hierarchical Hidden Community Detection). It is the first combination of hierarchical structure with hidden structure, which provides a new perspective for finding protein complexes of various strengths and scales. We compare the performance of several standard community detection methods with their HirHide versions. Experimental results show that the HirHide versions achieve better performance and sometimes even significantly outperform the baselines. ConclusionsHirHide can adopt any standard community detection method as the base algorithm and enable it to discover hidden hierarchical communities as well as boosting the detection of strong hierarchical communities. Some biological networks are too complex for standard community detection algorithms to produce a positive performance. Most of the time, a better choice is to choose a corresponding algorithm based on the characteristics of a specific biological network. Under these circumstances, HirHide has clear advantages because of its flexibility. At the same time, according to the natural hierarchy of cells, organelle, intracellular compound etc., hierarchical structure with hidden structure is in line with the characteristics of the data itself, thus helping researchers to study biological interactions more deeply.
Seroprevalence and Knowledge of Viral Hepatitis and HIV Among People Who Use Drugs Attending Methadone Therapy Clinic in Tanzania: A Cross-sectional Study.
Authors: Kilonzo Semvua , Gunda Daniel W. , Majinge David C. , Jaka Hyasinta , Manyiri Paulina M. , Kalokola Fredrick , Mtui Grahame , Shao Elichilia R. , Bakshi Fatma A. , Stephano Alex
Published: December 2020

Background: Methadone therapy clinics have been recently introduced in Tanzania, aiming at reducing risk behaviors and infection rates of viral hepatitis and HIV among people who use drugs. The objective of this study was to estimate the prevalence, associated factors and knowledge level of these conditions among people who use drugs attending a methadone clinic in Tanzania.Methods: We enrolled 253 People who using drugs receiving Methadone therapy. Clinical data was retrospectively collected from the medical records and face-to face interviews were conducted to determine the behavioral risk factors and respondents’ knowledge on viral hepatitis and HIV.Results: An overall seroprevalence of viral hepatitis (either hepatitis B surface antigen or anti-hepatitis C virus) was 6.3%, while that of hepatitis B virus mono infection was 3.5% and anti-hepatitis C virus mono infection was 3.5%. Seroprevalence of HIV was 12.6%. Viral hepatitis was strongly predicted by advanced age (>35 years) (p=0.02) and staying at Kirumba area (p=0.004), and HIV infection was predicted by increased age (>37 years) (p=0.04) and female sex (p<0.001). Regarding the knowledge of viral hepatitis, majority of the respondents were unaware of the transmission methods and availability of hepatitis B virus vaccines and only 17% were classified as well informed (provided ≥ 4 correct answers out of 7 questions). Good knowledge was highly predicted by higher education level of the individual (p=0.001).Conclusions: Despite the efforts to curb viral hepatitis and HIV infections through Methadone clinics, infection rates among people who use drugs are still high and the general knowledge on preventive measures is inadequate.
Lateral Decubitus Position to Facilitate Pelvic Examination of the Patient with Severe Obesity
Authors: Breitkopf Daniel M.
Published: December 2020

Background: Patients with elevated BMI pose a number of challenges for the gynecologist. Pelvic examination may be more difficult due to adiposity in the perineum and labia, increasing the distance between the vulva and cervix. The objective of the current work was to describe use of the lateral decubitus position to improve visualization of the cervix in women with severe obesity. Methods: From 7/1/2010 until 1/31/2020, all records of patients with obesity and unsuccessful cervical visualization during pelvic exam in the dorsal lithotomy position in the author’s clinical practice were reviewed after obtaining Mayo Clinic Institutional Review Board approval. For the lateral decubitus position, the patient was asked to lie on her side on the exam table, facing away from the examiner with knees bent. An assistant elevated the upper bent leg 45 degrees from horizontal, exposing the perineum. A vaginal speculum was then placed in the vagina with the posterior blade toward the anus. The speculum was opened gently as would be done with examination in dorsal lithotomy position until the cervix was visualized.Results: Eleven patients with severe obesity in the gynecologic practice of the author with prior unsuccessful cervical visualization in dorsal lithotomy position were examined in the lateral decubitus position. In all but one case the cervix was successfully visualized in the lateral decubitus position and all intended intrauterine procedures were successfully performed. Conclusions: The use of the lateral decubitus position appears to improve visualization of the cervix in the outpatient setting among women with severe obesity. Consideration should be given to use of the lateral decubitus position when the cervix cannot be visualized in the dorsal lithotomy position.Trial registration: not applicable
Is More Better? An Analysis of Toxicity and Response Outcomes From Dose-Finding Clinical Trials in Cancer
Authors: Brock Kristian , Homer Victoria , Soul Gurjinder , Potter Claire , Chiuzan Cody , Lee Shing
Published: December 2020

BackgroundThe overwhelming majority of dose-escalation clinical trials use methods that seek a maximum tolerable dose, including rule-based methods like the 3+3, and model-based methods like CRM and EWOC. These methods assume that the incidences of efficacy and toxicity always increase as dose is increased. This assumption is widely accepted with cytotoxic therapies. In recent decades, however, the search for novel cancer treatments has broadened, increasingly focusing on inhibitors and antibodies. The rationale that higher doses are always associated with superior efficacy is less clear for these types of therapies. MethodsWe extracted dose-level efficacy and toxicity outcomes from 115 manuscripts reporting dose-finding clinical trials in cancer between 2008 and 2014. We analysed the outcomes from each manuscript using flexible non-linear regression models to investigate the evidence supporting the monotonic efficacy and toxicity assumptions. ResultsWe found that the monotonic toxicity assumption was well-supported across most treatment classes and disease areas. In contrast, we found very little evidence supporting the monotonic efficacy assumption. ConclusionsOur conclusion is that dose-escalation trials routinely use methods whose assumptions are violated by the outcomes observed. As a consequence, dose-finding trials risk recommending unjustifiably high doses that may be harmful to patients. We recommend that trialists consider experimental designs that allow toxicity and efficacy outcomes to jointly determine the doses given to patients and recommended for further study.
Unique Circulating microRNA Profiles in Epidemic Kaposi’s Sarcoma
Authors: Muwonge Haruna , Kasujja Hassan , Atugonza Carolyne , Kasolo Josephine , Lugaajju Allan , Nfambi Joshua , Fred Sembajwe Larry , Damani Ali Moses , Kimuli Ivan , Nakazzi Faith , Nakanjako Damalie , Kateete David Patrick , Bwanga Freddie
Published: December 2020

BackgroundThe Human herpesvirus 8 (HHV-8), causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS, and is the most common HIV-related malignancy worldwide. Lack of a diagnostic assay to detect latent and early stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled the unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based non-invasive biomarker assay for Epidemic KS. MethodsThis was a comparative cross-sectional study involving 27 patients with epidemic KS, and 27 HIV-positive adults with no prior diagnosis, or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants respectively. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA was performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyze the sequencing data. Results Fifteen out of the 27 epidemic KS positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV positive, KS negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs down regulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. ConclusionsThis study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.
Atypical Respiratory Distress Suspect of COVID-19 in Eastern Democratic Republic of the Congo prior to the Pandemic. A Case Report
Authors: Mateso Guy-Quesney , BAGUMA Marius , Mwene-Batu Pacifique , Balemba Ghislain Maheshe , Nzabara Fabrice , Makali Samuel , Bedha Aline , Furaha Bonheur , Minani Jimmy , Muhindo Christian Tshongo , Malembaka Espoir Bwenge , Masimango Mannix Imani , Shindano Tony Akilimali , Cikomola Justin Cirhuza , Mubagwa Kanigula
Published: December 2020

Background: Predictions have been made that Africa would be the most vulnerable continent to the novel Coronavirus disease 2019 (COVID-19). Interestingly, the spread of the disease in Africa seems to have been delayed and initially slower than in many parts of the world. Here we report on two cases which make us suspect that COVID-19 might have been present in our region before the official declaration of the disease in December 2019. Case presentation: These two cases (one 55-year-old man and one 25-year-old woman) of acute respiratory distress secondary to atypical pneumonia were seen in Bukavu, in Eastern Democratic Republic of the Congo (DRC), between September and December 2019. One patient had returned from China and the other had close contacts with travellers from China in the 2 weeks prior to the onset of symptoms. In either case, the aetiology could not be accurately determined. However, the two cases presented a clinical picture (progressive dyspnoea, preceded by dry cough and fever) and laboratory changes (procalcitonin within the normal range, slight inflammation, and lymphopenia) compatible with a viral infection. The chest X-Rays series of the first patient showed lesions (reticulations, ground glass, and nodules ≤ 6 mm) similar to those found in COVID-19. In addition, unlike the 25-year-old female patient who had no comorbidity, the 55-year-old male patient who had hypertension as comorbidity, developed a more severe acute respiratory distress which progressed to death.Conclusion: These cases bring to the attention a number of facts which make us suspect that COVID-19 may have already been present in the region months before the official beginning of the pandemic. This is important, as prior presence of the disease or infections with related virus may account for the delayed and less extensive development of the epidemic in the region.
Entry Point of Sports Network Course Resource Development and its Management Performance Evaluation
Authors: Qin Weifeng , Shi Qian , Shao Wei
Published: December 2020

With the rapid development and popularization of network technology, the application of the network in the field of education has become more and more extensive. Currently, network technology is affecting all aspects of sports with unprecedented influence. At present, there are many researches on the development of sports network curriculum resources, but there are relatively few researches on the entry point of the development of sports network curriculum resources and which management mode to implement. In order to study the resource development entry point and management performance evaluation of sports network courses, This article uses the method of literature data to consult and refer to various domestic and foreign literature related to this article to study the management performance evaluation of sports network courses. The final results show that the development of physical education network curriculum resources should be based on the design concept of physical education network teaching, starting from physical education teaching materials, and combining the needs of students and schools to excavate and collect curriculum resources. In the experimental research on the performance evaluation of online course resource management, we found that the humanistic management mode and technical management mode of online course resources have a great influence on the performance evaluation of online course resource management. In the management model before the improvement, students choose courses based on their own interests and hobbies. The newly added course resources are more attractive to students, and the number of students who choose them accounts for about 50% of the total number; in the management model after the improvement , The effective management model is more attractive to students, and the number of students who choose the improved old curriculum resources has increased by 5%. Therefore, to manage the online course resources with a scientific and reasonable management mode is the focus of the development of sports online course resources.
Eco-geographic Study of Mahaleb (Prunus Mahaleb. L) in the Middle and Northern Parts of the Eastern Mediterranean
Authors: Husein Hussam Hag , Tawaklna Mahasen , Bäumler Rupert , Pham Quoc Bao
Published: December 2020

Background: Mahaleb still exists in most of the eastern Mediterranean forests associated with Cilician fir (Abies cilicica) and Lebanon cedar (Cedrus libani). However, there is an importance of conservation of its germplasm in hereditary banks due to their degradation in natural habitats, as well as there is growing interest in expanding Mahaleb cultivation due to its low requirements and endurance of harsh environments.Methods: The study used the approaches of the autecology concepts to study Mahaleb in situ. The field surveys have been conducted on an investigated homogeneous area of about 100m2 to 400m2 as a (relevé area).Results: Mahaleb occurs in its habitat in isolated individuals form and fragile structures of populations that were largely believed to have been in clumped or linear populations. The spatial distribution is restricted to small isolated zones in half-open, treeless or rocky outcrops areas of deciduous forests or rugged areas of barren mountains. The root sprouting seems to be the dominant mode of recruitment. However, all sites showed missing age classes that may indicate human infringement or the failure of recruitment in some years. The spatial distribution showed that Mahaleb exists in different environmental and climatic conditions regarding soil, landscape, rainfall, temperature. This can be attributed to its possession of genetic capabilities that enable it to adapt to varying environmental conditions in addition to the presence of different genotypes or higher taxa such as subspecies or even it may reflect the differences of environmental resilience inside some species themselves.Conclusions: this reflecting Mahaleb's high ability to withstand environmental, thermal, and water stresses. Notable, strong, long roots were found at different depths of soils, some within the joints of the rocks, and this strengthens its role in protecting soil conservation. The geo-distribution of Mahaleb suggests different genotypes or higher taxa such as subspecies or even the differences of environmental resilience inside some species themselves.It is also necessary to predict new potential areas for growth Mahaleb in the eastern Mediterranean to increase production either by introducing its cultivation in unconventional areas or by enhancing its productivity in the areas currently cultivated, which appears to be an important issue soon.
Trust in the Bangladeshi Health System During the COVID-19 Pandemic: A Mixed-Methods Exploration
Authors: Joarder Taufique , Khaled Muhammad Nahian Bin , Zaman Shahaduz
Published: December 2020

BackgroundLack of trust in public health institutions hinders care-seeking and limits community support for contact tracing, information and communication uptake, and multi-sectoral or multi-stakeholder engagement. In light of these understandings, our aim was to determine levels of impersonal and interpersonal trust in the context of COVID-19 pandemic response in Bangladesh.MethodsAs this mixed-methods research was conducted during the pandemic, data was gathered via an online survey involving 508 respondents, along with seven online focus group discussions in which 50 purposively selected male and female clinicians and non-clinicians took part. Quantitative data was subjected to descriptive and comparative analysis, whereas content analysis was applied to the qualitative data.ResultsSurvey respondents have less trust in the health system (a mean score of 3.77/10) than in the service providers (4.95/10). In the context of impersonal trust, the lowest level of trust is observed in the Fairness domain (3.12/10), followed by the Confidence domain (3.38/10). In the context of interpersonal trust, the lowest level of trust is observed in the Fairness domain (3.81/10), followed by the Communication domain (4.83/10). While some non-clinical participants blamed doctors for shying away from caregiving during the early days of the pandemic, most praised them for providing care, risking their life due to the shortage of PPE, and even sacrificing their life in the process. Several participants also cited lack of fairness in pandemic management, such as imposing lockdown in periphery areas of the country without arranging transport for those requiring medical help to the centrally located modern health facilities, and visible attempts by the political decision-makers to protect the business interests without consideration for the safety of the poor. However, both clinicians and non-clinicians concurred on the need for the service providers to improve communication related to COVID-19 management.ConclusionsHealth sector stewards in Bangladesh should learn the lessons from other countries, ensure multi-sectoral engagement involving the community and political forces, and empower public health experts to organize and consolidate a concerted health system effort in gaining trust in the short term while striving to build a resilient and responsive health system in the long term.
Gender and Socioeconomic Disparities in Reasons for Not Smoking Cigarettes Among Danish Adolescents
Authors: Kjeld Simone Gad , Lauemøller Stine Glenstrup , Bast Lotus Sofie
Published: December 2020

Objective: To examine gender and socioeconomic differences in adolescents’ reasons for not smoking cigarettes using self-reported data from Danish 14-year-olds (N = 1,559) collected in 2018. χ2-tests were used to assess whether the proportion of students who rated 12 statements as important reasons for not smoking cigarettes differed according to gender and family occupational social class (OSC).Results: More girls than boys stated that thinking the taste of cigarettes is disgusting, not being allowed to smoke by parents, knowing smoking is dangerous, not being allowed to smoke before the age of 18, not wanting to be addicted to smoking, and that smoking makes you smell bad were important reasons for choosing not to smoke cigarettes. More boys than girls reported exercising a lot and having a partner that does not smoke as important reasons for not smoking cigarettes. More students with a high OSC compared with a low OSC stated exercising a lot and that smoking makes you smell bad were important reasons. In conclusion, reasons for not smoking cigarettes differed substantially across gender and less according to socioeconomic position.
Relationship of Anthropometric Indices with Rate Pressure Product, Pulse Pressure and Mean Arterial Pressure Among Secondary Adolescents of 12-17 Years
Authors: Katamba Godfrey , Musasizi Abdul , Kinene Mivule Abdul , Namaganda Agnes , Muzaale Francis
Published: December 2020

Objectives: To determine the correlation between anthropometric indices and the selected hemodynamic parameters among secondary adolescents aged 12-17 years.Results: Our findings showed weak positive correlation between generally body surface area, neck circumference and conicity index with the hemodynamic parameters (systolic blood pressure, diastolic blood pressure, resting pulse rate, mean arterial pressure, rate pressure product and pulse pressure). However, the ponderosity index, body mass index and waist hip ratio showed negative weak correlations with the hemodynamic parameters. There was a significant difference in pulse pressure among the BMI categories. All parameters showed significant (p<0.05) differences across the categories of neck circumference and waist hip ratio. Generally, in multivariate regression analysis, anthropometric indices showed significant prediction of the hemodynamic parameters.
Dysphagia and Its Impact on Quality of Life of Head and Neck Cancer Patients: Institution Based Cross sectional Study
Authors: Yifru Tseganesh Asefa , Kisa Sezer , Dinegde Negalegn Getahun , Atnafu Niguse Tadele
Published: December 2020

Objective: Assessing swallowing function using symptom-specific questionnaires on head and neck cancer (HNC) patients and supporting impaired swallowing to improve quality of life (QoL) of patients is recommended in different studies. However, there is no data that shows the effect of dysphagia on quality of life of Ethiopian patients. Hence, this study assessed the effect of dysphagia on quality of life domains of the MD Anderson Dysphagia inventory (MDADI) among head and neck cancer patients.Results: The study sample consisted of mostly male (53.90%), employed (70.6%), single (57.80 %) and completed some level of formal education (66.60 %) with mean age of 42.58 years (SD ± 14.08 years) and medical expense for about 69.6% of patients was covered by the government. Most of the patients were suffering from advanced stage HNC (59.80%) and squamous cell carcinoma (62.70%) and the most prevalent tumor location was nasal cavity/ nasopharyngeal carcinoma (40.20%). The mean MDADI composite score was 53.29 (SD± 15.85). Being female, low income, suffering from laryngeal/ hypo pharyngeal cancer, suffering from advanced tumor and those undergoing a single modality therapy were key determinants of poor QoL related to swallowing problems in HNC patients.
Presence and Quantification of Microplastic in Urban Tap-Water
Authors: Pratesi Claudia B. , Almeida Maria Aparecida A.L. Santos , Paz Geysa S. Cutrim , Teotonio Marcelo H. Ramos , Cardia Felipe Mendes dos Santos , Gandolfi Lenora , Pratesi Riccardo , Hecht Mariana
Published: December 2020

Background: Plastic pollution is a rapidly growing environmental and human health crisis, with no sign of improvement. Since 2012 the number of studies on plastic pollution has quadrupled, and macro to nano-size plastics have been documented even in the planet's remote biomes. Studies have shown contamination by microplastics (MPs) in various types of food consumed by humans, including seafood, honey, sugar, salt, tap-water and bottled water and beer. The study's objective was to detect the possible contamination by MPs in drinking water samples collected from the two main residential and commercial areas of Brasília.Methods: A total of 32 samples of tap water were collected, 16 samples in the south zone, and 16 samples in the north zone of the city (respectively, South Wing and North Wing). Samples were processed and transferred to the Sedgewick-Rafter counting cell chamber. The presence of MPs particles was analyzed using a Nikon Eclipse fluorescence microscope.Results: MPs were found in 100% of the samples. The mean MPs per 500 ml found in the South Wing area was 97, while the mean number of particles in the North Wing area was 219.Conclusion: The study results reveal a disturbing amount of MP particles in Brasilia's tap-water. This surprising number of particles in tap-water is especially concerning considering that tap-water is not the only source of MPs to which people are exposed. The cumulative and toxicological effect of this chronic exposure is alarming.
The Association of Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio and Lymphocyte-Monocyte Ratio With Post-Thrombolysis Early Neurological Outcomes in Patients With Acute Ischemic Stroke
Authors: Gong Pengyu , Liu Yukai , Gong Yachi , Chen Gang , Zhang Xiaohao , Wang Siyu , Zhou Feng , Duan Rui , Chen Wenxiu , Huang Ting , Wang Meng , Deng Qiwen , Shi Hongchao , Zhou Junshan , Jiang Teng , Zhang Yingdong
Published: December 2020

Background and Purpose: To investigate the association of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS).Methods: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as National Institutes of Health Stroke Scale (NIHSS) score increase of ≥4 within 24 hours after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥4 or complete recovery within 24 hours. Multivariable logistic regression analyses were performed to explore the relationship of NLR, PLR and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI.Results: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with ENI and 398 (37.5%) were diagnosed with END. Multivariable logistic models indicated that NLR (odds ratio [OR], 1.652; 95% confidence interval [CI] 1.510-1.807, P=0.001) and PLR (OR, 1.015; 95% CI 1.012-1.018, P=0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.686; 95% CI 0.631-0.745, P=0.001), PLR (OR, 0.997; 95% CI 0.994-0.999, P=0.006) and LMR (OR, 1.170; 95% CI 1.043-1.313, P=0.008) served as independent factors for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR and LMR to discriminate END were 0.763, 0.703 and 0.551, respectively. AUC of NLR, PLR and LMR to discriminate ENI were 0.695, 0.530 and 0.547, respectively.Conclusions: NLR and PLR were associated with and may predict post-thrombolysis END. NLR, PLR and LMR were related to post-thrombolysis ENI.
Biomarkers-based Personalized Follow-up in Chronic Heart Failure Improves Patient’s Outcomes and Reduces Care Associate Cost
Authors: Justel Antonio Leon , Garcia-Polavieja Jose Ignacio Morgado , Rios Ana Isabel Alvarez , Fernandez Francisco Jose Caro , Merino Pedro Agustin Pajaro , Rios Elena Galvez , Rico Ignacio Vazquez , Fernandez Jose Francisco Diaz
Published: December 2020

BACKGROUNDHeart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF.METHODSThis is a real-world, before-and after-intervention trial, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before and after an intervention. The primary objective was the rate of readmissions, due to a HF event, post-intervention compared to pre-intervention. Secondary outcomes compared the rate of ED visits and the number of patients who had reduced NYHA score pre and post-intervention. A cost- analysis was also performed on these data.RESULTSAdmission rates significantly decreased by 41% after the intervention (total length of stay was reduced by 55%). The rate of ED visits was reduced by 55%. Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was €139,717.65 for the whole group over 1 year.CONCLUSIONSA personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care- associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.
RBM15 Facilitates Laryngeal Squamous Cell Carcinoma Progression by Regulating TMBIM6 Stability Through IGF2BP3 Dependent
Authors: Wang Xin , Tian Linli , Li Yushan , Wang Jingting , Yan Bingrui , Yang Like , Li Qiuying , Zhao Rui , Liu Ming , Wang Peng , Sun Yanan
Published: December 2020

Background: Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the m6A regulatory mechanism underlying the carcinogenesis or progression of LSCC remains poorly understood. Methods: The m6A RNA methylation quantification kit was used to detect tissue methylation levels. m6A microarray analysis, mRNA transcriptomic sequencing (mRNA-seq), and proteomics were used to determine RBM15, TMBIM6, and IGF2BP3. Immunohistochemical (IHC), quantitative real-time PCR (qRT-PCR) and Western blot were used to investigate RBM15, TMBIM6, and IGF2BP3 expression in tissue samples and cell lines. The biological effects of RBM15 were detected both in vitro and in vivo. The combination relationship between RBM15/IGF2BP3 and TMBIM6 was verified by RNA immunoprecipitation (RIP) assay, Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNase Mazf, and luciferase report assay. RNase Mazf was used to determine the methylation site on TMBIM6 mRNA. Hoechst staining assay was used to confirm the apoptotic changes. The actinomycin D verified TMBIM6 stability. Results: The global mRNA m6A methylation level significantly increased in LSCC patients. RBM15, as a “writer” of methyltransferase, was significantly increased in LSCC and was associated with unfavorable prognosis. The knockdown of RBM15 reduced the invasion, migration, and apoptosis of LSCC both in vitro and in vivo. The results were reversed after overexpressing RBM15. Mechanically, TMBIM6 acted as a downstream target of RBM15-mediated m6A modification. Furthermore, RBM15-mediated m6A modification of TMBIM6 mRNA enhanced TMBIM6 stability through IGF2BP3-dependent. Conclusion: Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism.
Liver Cirrhosis Promotes Immune Escape in Hepatocellular Carcinoma via GOLM1-mediated PD-L1 Upregulation 
Authors: Ke Meng-yun , Li Zhi-jin , Ye Yuan-peng , Ren Feng-gang , Lu Shao-ying , Zhang Xu-feng , Wu Rong-qian , Lv Yi , Dong Jian
Published: December 2020

Background:Immune checkpoint blockade is considered a breakthrough in cancer treatment. However, the low response rates and therapeutic resistance of patients with hepatocellular carcinoma (HCC) represent significant challenges in the application of this treatment. Liver cirrhosis is a key driver of tumor immune escape. However, the mechanism underlying this outcome has never been clarified. This study sought to explore the role of liver cirrhosis in regulating tumor-infiltrating lymphocytes (TILs) and inducing tumor immunosuppression. Methods:Ninety-nine fixed HCC tissue samples were used to analyze the association between liver cirrhosis and immune escape by immunohistochemistry. H22 cells with or without GOLM1 knockdown were inoculated subcutaneously into BALB/c and BALB/c-nu/nu mice. We also created hepatocyte-specific GOLM1 transgenic mice (Alb/GOLM1 mice) and induced chemical carcinogenesis. The efficacy of anti-PD-L1 therapy combined with GOLM1 inhibition was estimated in GOLM1 -overexpressing subcutaneous model of HCC.Results:In HCC patients, low FIB-4 values and high CD8+ T cell infiltration were correlated with prolonged survival. Elevated expression of immune checkpoints and attenuated antitumor immunity were observed in CCl4-induced mice liver fibrosis models and human fibrotic livers compared to control group. GOLM1 levels were increased in livers of patients with cirrhosis and mice in response to CCl4-induced liver fibrosis. CD8+ T cell infiltrations were significantly decreased and PD-L1 expression was significantly increased in tumor tissues from Alb/GOLM1 mice compared to their corresponding control WT mice. GOLM1 induced PD-L1 expression via EGFR pathway activation. EGFR inhibitors, especially together with anti-PD-L1 therapy, improved the efficacy of immunotherapy in HCC. Conclusions:These findings illustrate the importance of liver fibrosis-induced immunosuppression as a tumor-promoting mechanism. GOLM1, which is highly upregulated in the fibrotic liver, regulates tumor microenvironmental immune escape via the EGFR/PD-L1 signaling pathway. EGFR blockade may bolster the efficacy.
Radical Hysterectomy Versus Simple Hysterectomy and Brachytherapy for Patients with Stage II Endometrial Cancer
Authors: Wang Ming , Ran Ran , Wu Yu-Mei
Published: December 2020

Purpose To compare the survival outcome between radical hysterectomy and total hysterectomy with radiation therapy in patients with stage II endometrial cancer.MethodsThis is a retrospective cohort study. We identified 1349 patients diagnosed with stage II endometrial cancer from Jan 1, 1988 to Dec 31 2015 in the Surveillance, Epidemiology, and End Results. Patients were divided into two groups based on the primary treatment (total hysterectomy combined with brachytherapy or radical hysterectomy). All patients received external beam radiation therapy after the surgery. The primary outcome was the rate of 5-year-cause-specific survival and 5-year-overall survival.Results A total of 1349 patients were enrolled in the study, 117(7.35%) patients received radical hysterectomy and 460 patients who received total hysterectomy combined with vaginal brachytherapy were selected as control. All patients received external beam radiation therapy after the surgery. Overall, the median follow-up duration was 82.77±1.44months (95%CI: 79.94-85.61months). There was no difference in the baseline information between two groups, including ages, ethnicity, and rates of histologic subtypes. The 5-year overall survival was 62.31% among women who underwent radical hysterectomy which was lower than 78.48% among those who underwent total hysterectomy combined with vaginal brachytherapy (HR, 2.22; 95% CI, 1.52 to 3.24; P <0.001 by the log-rank test). Women who underwent radical hysterectomy also had shorter 5-year cause-specific survival (74.60 vs.85.38%; HR, 1.91; 95% CI, 1.13 to 3.23; P =0.01 by the log-rank test) than those who underwent total hysterectomy combined with vaginal brachytherapy. However, the negative outcomes were further validated in patients with high-risk endometrial cancer, not in patients with grade 1-2 low-risk endometrial cancer both on cause-specific survival and overall survival. In patients with grade 3 low-risk endometrial cancer, the tendency was only found with lower overall survival not cause-specific survival.ConclusionsThis study revealed that in patients’ stage II endometrial cancer, radical hysterectomy was associated with shorter overall survival and cause-specific survival than total hysterectomy combined with vaginal brachytherapy. The choice of different treatment modalities should base on the histology subtype of patients and further study based on molecular classification is needed.
IL-17A Polymorphism (rs2275913) and Levels Are Associated With Preeclampsia Pathogenesis in Chinese Patients  
Authors: Lang Xiao , Liu Wei , Hou Yanyan , Zhao Wenxia , Yang Xingyu , Chen Lan , Yan Qi , Cheng Weiwei
Published: December 2020

BackgroundPreeclampsia (PE) is a pregnancy-related condition that affects both the infant and the mother. Although the role of various inflammatory molecules in PE has been demonstrated, the importance of pro-inflammatory molecules such as IL-17A, IL-23 is not well understood. In the present investigation, a potential association of common genetic variants in the IL-17A and IL-23A genes with PE was investigated. Methods115 PE clinically diagnosed patients who registered to the International Peace Maternity and Child Health Hospital were enrolled in this research. 102 pregnant women and 147 healthy Chinese women were also included. ELISA was used to measure IL-17A and IL-23 serum levels in all enrolled subjects. Common genetic polymorphisms in IL-17A (rs 2275913, rs1974226, and rs1974226), IL-23A (rs11171806), and IL-12B (rs3212227) were genotyped using the PCR-RFLP or TaqMan probe-based method. ResultsElevated serum IL-17A levels were found in PE patients compared to pregnant (P<0.0001) and healthy women (P<0.0001). However, IL-23 levels were comparable across various clinical groups. In addition, heterozygous (GA) and minor allele (A) for IL-17A (rs2275913) and IL-23A (rs11171806) were more prevalent in PE patients compared to pregnant women indicating an important role in the predisposition to PE growth. Interestingly, IL-17A (r 2275913) mutants were associated with elevated IL-17A levels relative to wild type (GG). ConclusionsIL-17A (rs2275913) variants are associated with higher serum levels of cytokine, and predisposed PE development.
In Silico Docking for Inhibition Neuropilin-1 (SARS-CoV-2 receptor) by Some Natural and Approved Drugs
Authors: seadawy mohamed , Shamel Mohamed , Ahmed Aya , Zekri Abdel Rahman N.
Published: December 2020

Background: Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. Beside its role in cancer, NRP-1 is a reported entrance for several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19). Methods: We made Insilco docking between the spike protein and Neuropilin-1 using Cluspro 2.0 software. Therefore, Neuropilin-1 becomes host factor for SARS-CoV-2 infection. Then by using molecular docking, we test nine compounds against Neuropilin-1 for its inhibition. Results: Our result revealed that NRP-1 receptor is considered as Therapeutic target for SARS-CoV2 treatment and screened with natural compounds and drugs (e.g. Carvacrol, Thymol, Amantadine, Daclatasvir, Ravidasvir, Remdesivir, Sofosbuvir, Hesperidine and Thymoquinone) by molecular docking study. Conclusion: These natural products and drugs may emerge as potential Neuropilin-1 inhibitor. However, additional exploration is predictable for the investigation of the essential use of the drugs and herbs containing these natural products and their in-vivo activity.