bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio-economic drivers of Drug-Resistant Tuberculosis in Africa: A Scoping Review
Authors: Cannon Lesley-Ann Lynnath , Oladimeji Kelechi Elizabeth , Goon Daniel Ter
Published: April 2020

Background
Drug-resistant TB (DR-TB) remains a public health concern due to the high morbidity and mortality rates from the disease. The DR-TB is a multifaceted illness with expensive treatment regimens, toxic medications and most often the long duration of treatment constitutes a substantial financial burden on both infected patients and the health system. Despite significant research advances so far in the diagnosis and treatment, there is a paucity of synthesized evidence on how socio-economic factors are associated with DR-TB. This review aims to address this gap by synthesizing available evidence and data on the main socio-economic drivers of DR-TB infection in Africa.
Methods
We conducted a systematic search on PUBMED and Google Scholar databases from January 2011 to March 2020 using Joanna Briggs Institute’s scoping review approach. Our eligibility criteria only included systematic reviews and studies conducted with quantitative research methods (cross-sectional, case-control, cohort and randomized-control trials) in this review. We also considered studies conducted in Africa and focused on socio-economic factors influencing DR-TB burden in African countries. Data was extracted from all the studies that met the eligibility criteria based on the study’s objectives.
Results
Out of the 154 articles that were retrieved for review, 20 abstracts of these articles met all the eligibility criteria and were fully reviewed. Of the 20 articles, one was a mixed-method study, 16 quantitative and 3 reviews. The following themes were identified as major findings: Social and economic drivers associated with DR-TB. Substance abuse of which, stigma and discrimination were the prominent social drivers. Economic drivers included poverty, financial constraints because of job loss, loss of productive time during hospital admission and treatment costs.
Conclusion
Our findings provide insights on the socio-economic drivers of DR-TB burden. This is relevant to assist DR-TB management program and TB stakeholders in different settings to address identified socio-economic gaps and to reduce its negative impact on the programmatic management of DR TB. Therefore, redirecting strategies with more focus on socio-economic empowerment of DR-TB patients could be one of the innovative solutions to reduce the spread and eliminate DR-TB in Africa.
An Investigation Into The Livelihoods Strategies Of Informal Women Traders In Zimbabwe
Authors: Takaza Stella , Chitereka Chipo
Published: April 2020

This article investigated the livelihoods strategies of informal women traders doing business at flea markets in Zimbabwe. The study was conducted in Harare Province at a flea market near the Harare Central Business District. The study was informed by the Sustainable Livelihood Approach proffered by the Swedish International Development Cooperation Agency Division (SIDA, 2001) for Policy and Socio-Economic Analysis. A qualitative design was utilised and data was gathered through interviews, focus group discussions and observations during transect walks. The specific objectives of the study included the following; to discover micro credit schemes used by the informal women traders doing business at this particular flea market, to explore the impact of microcredit schemes as pathways towards poverty eradication amongst informal women traders; to examine the survival and coping challenges experienced by women doing business under socio-economic environment hardships and finally, to determine possible interventions and sustainable strategies that could be used to out-scale and throw a lifeline to the informal women traders. The study revealed that while women informal traders engaged in diverse activities for their sustainable livelihoods strategies that eradicate poverty, vast majority of informal women traders encountered numerous challenges, resulting in them employing unpleasant survival and tough coping techniques. The study concluded that if financing institutions and Non Governmental Organizations could give them small funds for capacity building for local empowerment; this would help them to gain access and control of their sustainable livelihoods resources in a meaningful way. The study is therefore proposing sound policy interventions and sustainable strategies that could be used to empower informal women traders doing business at flea markets for them to gain access and full control over livelihoods resources in Zimbabwe.
Short Wave Enhances Mesenchymal Stem Cell Recruitment through Hypoxia-Inducible Factor-1 Signaling in Fracture Healing
Authors: Ye Dongmei , Chen Chen , Wang Qiwen , Zhang Qi , Li Sha , Liu Hongwei
Published: April 2020

Background: As a type of high-frequency electrotherapy, a short wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms still remain unclear.Purpose: To observe the effect of short wave on mesenchymal stem cell (MSC) homing and its mechanisms associated with fracture healing.Materials and Methods: The effect of short wave on a fracture healing was examined in 40 rats. Stabilized femur fractures were established by intramedullary fixation; radiography was used to analyze the morphology and micro-architecture of the callus. Additionally, fluorescence assays were used to analyze the MSC migration after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast simulated fracture site was first irradiated by the short wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast cultured supernatant was then collected as chemotaxis content of MSC, and the migration of MSC was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by qRT-PCR, ELISA, and Western blot.Results: Our in vivo experiment indicated that short wave could promote MSC migration, increase local and serum HIF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that short waves upregulated HIF-1 expression in osteoblast and increased HIF-1, SDF-1 protein levels in the supernatant, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast and it partially inhibited the migration of MSC.Conclusions: These results suggested that short wave could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.
De Novo Molecular Design of Caspase-6 Inhibitors by GRU-Based Recurrent Neural Network Combined with Transfer Learning Approach
Authors: Huang Shuheng , Mei Hu , Lu Laichun , Shi Tingting , Chen Linxin , Kuang Zuyin , Heng Yu , Xu Lei , Pan Xianchao
Published: April 2020

Due to the potencies in the treatments of neurodegenerative diseases, caspase-6 inhibitors have attracted widespread attentions. Herein, gated recurrent unit (GRU)-based recurrent neural network (RNN) combined with transfer learning was used to build the molecular generative model of caspase-6 inhibitors. The results showed that the GRU-based RNN model can learn accurately the SMILES grammars of about 2.4 million chemical molecules including ionic and isomeric compounds, and can generate potential caspase-6 inhibitors after transfer learning of the known 433 caspase-6 inhibitors. Further exploration of the chemical space and molecular docking showed that the generated potential inhibitors have similar chemical space distributions and binding mechanisms with the known caspase-6 inhibitors. In addition, 3 potential caspase-6 inhibitors with nanomolar-level activities were obtained and proved to be the most promising candidates for the further researches. In general, this paper provides an efficient combinational strategy for de novo molecular design of caspase-6 inhibitors.
TUG1 as ceRNA combined with miR-29a to promotes the expression of IFITM3 in hepatocellular carcinoma
Authors: Liu Weiwei , Feng Qian , Liao Wenjun , Gao Jun , Ai Jiyuan , Zhang Rongguiyi , Li Enliang , Wu Linquan
Published: April 2020

Background: Numerous studies have shown that TUG1 has an important relationship with tumorigenesis. TUG1 is highly expressed in most tumors and can promote tumor development. However, the role of TUG1 in hepatocellular carcinoma (HCC) remains to be studied. miR-29a plays a tumor suppressor role in a variety of tumors, and there is a relationship between TUG1 and miR-29a, but the specific relationship and mechanism of action are still unclear. miR-29a can inhibit the expression of IFITM3. However, the regulatory relationship between these three components requires elucidation. This study aimed to investigate the regulatory relationship between TUG1, miR-29a, and IFITM3 in human hepatocarcinogenesis.Methods: The expression levels of TUG1 and miR-29a in tumor tissues and adjacent non-tumor tissues of 41 HCC patients were detected by real-time quantitative polymerase chain reaction. The migration and invasion of liver cancer cells were studied by a wound healing assay and the Transwell method. The apoptosis rate of hepatocarcinoma cells was detected by flow cytometry, and the proliferation rate of hepatoma cells was detected by the EdU method. Immunofluorescence was selected to detect the expression of TUG1 and IFITM3 in HCC-LM3 and HL-7702. The relationship between TUG1 and miR-29a was detected using a double luciferase report and FISH. Tumors were established in vivo by subcutaneous injection of hepatocellular carcinoma cells into nude mice and injection of these cells into the tail vein. Western blotting was used to quantify the biomarkers. Results: TUG1 expression increased significantly in both tumor tissues and HCC cells. The expression of miR-29a in liver cancer tissues was also significantly lower than that in normal human liver tissues. The expression of TUG1 in HCC tissue samples was negatively correlated with that of miR-29a. Moreover, the expression of TUG1 was positively correlated with the expression of IFITM3. TUG1 can regulate the migration, invasion, apoptosis, and proliferation of HCC lines in vitro and regulate the development of tumors in vivo. Knocking down TUG1 will increase miR-29a expression, and thus, weaken the invasion, migration, and proliferation of HCC cells and enhance their apoptosis. miR-29a can affect the occurrence and progression of liver cancer through IFITM3. It was found that TUG1 regulates IFITM3 in HCC cells via miR-29a, and its expression affects cell invasion, migration, proliferation, and apoptosis.Conclusion: As a CeRNA, TUG1 competitively binds mir-29a to regulate IFITM3 and promote the development of liver cancer. Downregulation of TUG1 can significantly inhibit the migration, invasion, and proliferation of liver cancer cells, and TUG1 is expected to serve as a key gene to improve the prognosis of patients.
Gumbel-softmax-based Optimization: A Simple General Framework for Optimization Problems on Graphs
Authors: Li Yaoxin , Liu Jing , Lin Guozheng , Hou Yueyuan , Mou Muyun , Zhang Jiang
Published: April 2020

In computer science, there exist a large number of optimization problems defined on graphs, that is to find a best node state configuration or a network structure such that the designed objective function is optimized under some constraints. However, these problems are notorious for their hardness to solve because most of them are NP-hard or NP-complete. Although traditional general methods such as simulated annealing (SA), genetic algorithms (GA) and so forth have been devised to these hard problems, their accuracy and time consumption are not satisfying in practice. In this work, we proposed a simple, fast, and general algorithm framework based on advanced automatic differentiation technique empowered by deep learning frameworks. By introducing Gumbel-softmax technique, we can optimize the objective function directly by gradient descent algorithm regardless of the discrete nature of variables. We also introduce evolution strategy to parallel version of our algorithm. We test our algorithm on three representative optimization problems on graph including modularity optimization from network science, Sherrington-Kirkpatrick (SK) model from statistical physics, maximum independent set (MIS) and minimum vertex cover (MVC) problem from combinatorial optimization on graph. High-quality solutions can be obtained with much less time consuming compared to traditional approaches.
A case report of moderate COVID-19 with an extremely long-term viral shedding period in China
Authors: Wang Yonghong , Liu Chaoyuan , Meng Qinghui , Gui Shuang , Wu Yu , Cheng Pengjiang , Wang Peng , Liao Xiuyong
Published: April 2020

Background: An ongoing outbreak of novel coronavirus disease 2019 (COVID-19) from Wuhan, China, is currently recognized as a global public health emergency, which has subsequently spread to the rest of China and other countries. The WHO raised the COVID-19 alert to the highest level. The virus is a new highly contagious via human-to-human transmission. The median duration of viral shedding is 20.0 days. We report that the longest duration of viral shedding was 32.0 days from illness onset in a patient with moderate COVID-19 admitted to QianJiang Central Hospital.Case presentation: A 37-year-old male sought medical advice while suffering from fever, dry cough, fatigue, dizziness, runny nose and diarrhoea. Five days before the visit, he had a history of travel from affected geographic areas. The patient had a positive RT-PCR test, and chest CT images showed multiple nodules and mixed ground-glass opacification with consolidation in both lungs. Laboratory findings showed that his lymphocyte and CD4+ counts were below the normal range. The patient was given antiviral treatment, including arbidol, lopinavir, IFN-α, and traditional Chinese medicine, and other necessary support care. All clinical symptoms and CT imaging manifestation abnormalities resolved during the course of therapy.Conclusion: Although the positive RT-PCR tests were verified in consecutive upper respiratory specimens, the clinical symptoms, CT imaging findings, CD4+ lymphocyte counts, and IgG antibody levels had obviously improved. Positive tests may be detecting pieces of inactive viruses, which would not be transmissible in individual cases.
Clinical Application of Chromosomal Microarray Analysis for Fetuses with Craniofacial Malformations
Authors: Xu Chenyang , Xiang Yanbao , Xu Xueqin , Zhou Lili , Li Huanzheng , Dong Xueqin , Tang Shaohua
Published: April 2020

Background This study aimed to evaluate the applicability of chromosomal microarray analysis (CMA) for prenatal diagnosis of craniofacial malformations (CFMs). We also investigated the potential correlations between chromosomal abnormalities and CFMs. To this end, 118 fetuses with CFMs were enrolled in the study and underwent both G-banded chromosome analysis and CMA. Results Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities or submicroscopic chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic CNVs only (10/118; 8.5%). We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes. Conclusion CMA is a rapid and reliable molecular technique to identify fetal chromosomal aberrations associated with CFMs. Identification of the genetic basis of CFMs contributes to the understanding of their pathogenesis and etiology.
Effects of Short-term Existential Group Therapy for Breast Cancer Patients
Authors: Nakamura Chizu , Kawase Masatoshi
Published: April 2020

Objectives: Cancer patients who suffer from existential difficulties, including fear of death, isolation, or loss of human relationships, try to accept these fears by exploring the meaning of their life. In particular, earlier psychological intervention for patients prevents them from psychosocial maladjustment afterwards. Therefore we have developed the Short-term Existential Group therapy Program (Short-term EGP) for cancer patients focusing on relief of existential or spiritual suffering and/or pain. This study aims to statistically evaluate the effects of this program on breast cancer patients within the first year after cancer diagnosis.Methods: 31 patients completed our research program. A ninety-minute therapeutic group session was held once a week for five weeks. We performed the above assessments three times: just before and after the intervention, as well as a month after the end of intervention. Outcome assessment included measures of spiritual well-being (SELT-M), Mental Adjustment to Cancer (MAC) and Profile of Mood States (POMS).Results: The SELT-M “Overall QOL” scores were significantly increased after intervention, and these scores were maintained a month after intervention, particularly in those with high MAC “Hopelessness” scores. Subscales of the SELT-M scores were significantly increased after intervention, and these scores were maintained up to a month after interventionSignificance of Results: We observed that the Short-term EGP intervention was effective in helping patients relieve their existential distresses. Some of the treatment effects were observed to be maintained a month after end of the intervention. In addition, Short-term EGP is particularly effective for those patients who feel hopelessness after cancer diagnosis.Trial registration The study protocol was approved by the ethics committee of the Department of Psychology of Kyoto Notre Dame University (H22-3,14-008).
Electroacupuncture preconditioning alleviated myocardial injury via regulating mitochondrial function
Authors: Wang Chunai , Liang Xi , Yu Yan , Li Yulan , Wen Xiaohui , Liu Min
Published: April 2020

BackgroundIn clinical research, integrated Chinese and Western medicine has been increasing accepted due to the advantages. Clinical studies related to bupivacaine-induced myocardial injury are considered indispensable. Therefore, the purpose of this study is to verify whether acupuncture preconditioning could alleviate side effect of bupivacaine-induced. MethodsSimulating bupivacaine-induced myocardial injury in clinical surgery, western blot, PCR, transmission electron microscope, Elisa methods were used to evaluate the bupivacaine-induced structure injury and dysfunction of mitochondria, and alleviating effect of lipid emulsion, acupoint injection, and electroacupuncture pre-treatment oxidase stress response. ResultsBupivacaine caused structural damage, degradation, and swelling of mitochondria. Furthermore, it reduced adenosine triphosphate (ATP) synthesis and impaired energy metabolism in mitochondria. Structural and functional impairment of mitochondria were alleviated via lipid emulsion injection, acupoint injection, and electroacupuncture pre-treatment. Electroacupuncture pre-treatment yielded a greater alleviating effect than the other two approaches. Following electroacupuncture pre-treatment, the number of mitochondria increased, apoptosis was reduced, enzymatic activity of cytochrome C oxidase and superoxide dismutases, expression of uncoupling protein 2, Voltage-dependent anion channel 1, and Bcl 2 were upregulated and SLC25A6, MDA level was downregulated. Additionally, our findings indicated that electroacupuncture pre-treatment exerted an effect on mitochondria via the mitochondrial transcription factor A / nuclear respiratory factor 1 / proliferator-activated receptor-gamma coactivator -1 pathway. ConclusionOur study revealed that electroacupuncture pre-treatment could effectively alleviate bupivacaine-induced myocardial mitochondrial damage, thereby providing a theoretical basis for clinical studies and application of this treatment method.
Is limited aortic resection more justified in elderly patients with type A acute aortic dissection?
Authors: Qin Wei , Su Cunhua , Li Liangpeng , Carmichael Michael , Huang Fuahua , Chen Xin
Published: April 2020

Objective
This study compared limited aortic repair (ascending, and /or hemi-arch replacement) versus extended-arch repair (ascending, arch and proximal descending aortic replacement) used for patients aged 65 or older, who had type A acute aortic dissection (AAD), analyzing the influence of the extent of aortic repair on outcomes.
Methods
From January, 2001 to December, 2015, 103 patients aged 65 or older underwent operation due to type A AAD in Nanjing First Hospital. The cohort was divided into two subgroups according to the surgical approaches, including limited aortic replacement (LAR, n = 41) and total arch replacement + stent elephant trunk implantation (TAR + SET, n = 62).
Results
There was no significant difference in gender, age, hypertension, diabetes, smoking, PCI history, atrial fibrillation, pericardial effusion, aortic valve insufficiency (≥ moderate), shock situation before operation, and Euro-score II between the two groups except limb malperfusion and tear location. The cross-clamp time, CPB time, intubation time, ICU stay time and hospital time were all significantly less in the LAR group than in the TAR + SET group. A total of 89 patients were discharged home successfully after operation, with a difference of hospital mortality (P = 0.04). The overall survival rates at 5-year follow-up were 82.5 ± 6.0% in LAR group and 75.2 ± 5.6% in TAR + SET group, but with no difference (p = 0.151). The freedom from adverse aortic events at 5-year was 84.3 ± 6.5% in LAR group versus 97.9 ± 2.1% in TAR + SET group, with a statistical difference (p = 0.03).
Conclusion
These findings support limited aortic resection is acceptable for elderly patients with type A AAD if surgical principles allow.
The role of Nrf2 in acute and chronic muscle injury
Authors: Bronisz-Budzyńska Iwona , Kozakowska Magdalena , Łoboda Agnieszka , Dulak Józef
Published: April 2020

The nuclear factor erythroid 2-related factor (Nrf2) is considered as a master cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory, and detoxifying proteins. The role of Nrf2 in the pathophysiology of skeletal muscles has been evaluated in different experimental models, however, due to inconsistent data, we aimed to investigate how Nrf2 transcriptional deficiency (Nrf2tKO) affects muscle functions both in acute and chronic injury. The acute muscle damage was induced in mice of two genotypes – WT and Nrf2tKO mice by cardiotoxin (CTX) injection. To investigate the role of Nrf2 in chronic muscle pathology, mdx mice that share genetic, biochemical, and histopathological features with Duchenne muscular dystrophy (DMD) were crossed with mice lacking transcriptionally active Nrf2 and double knockouts (mdx/Nrf2tKO) were generated. We have observed slightly increased muscle degeneration and delayed regeneration in Nrf2tKO mice after CTX treatment. Nevertheless, transcriptional ablation of Nrf2 in mdx mice did not significantly aggravate the most deleterious pathological hallmarks of DMD such as degeneration, inflammation, fibrotic scar formation, and decreased angiogenesis, as well as the number and proliferation of satellite cells. In conclusion, our analyses in both acute and chronic injury mouse models have revealed no significant influence of Nrf2 transcriptional deficiency on skeletal muscle regeneration and function.
Safety and tolerability of prescribed usage of Derise® (Darbepoetin Alfa, Hetero) in symptomatic anemia: A Phase IV Post-Authorization Study
Authors: Sinha Shubhadeep , Bandi Vamsi Krishna , Bheemareddy Bala Reddy , Thakur Pankaj , Chary Sreenivasa , Talluri Leela , Kakkunnath Sheejith , Das Priyanka , Sanka Srinivasa
Published: April 2020

Background This phase IV, post–authorisation safety & efficacy study evaluated the safety, immunogenicity and tolerability of prescribed usage of Darbepoetin alfa, (DA-α, manufactured by Hetero Biopharma) for the treatment of symptomatic anemia in Indian patients with chronic renal failure.Methods Adults patients of either gender suffering from anemia associated with chronic renal failure patients were prescribed and treated with DA-α and followed up for 1 year. 503 patients were enrolled into the study, of which 121 patients were evaluated for immunogenicity at the end of treatment phase (up to 24 weeks) and after 1-year (52 weeks after start of treatment) follow up. Safety end points were the incidence of treatment emergent adverse events (TEAEs) and immunogenicity as assessed by anti-drug antibody titers using validated enzyme linked immunosorbent assay (ELISA) methods. Efficacy end point included improvement in the hemoglobin, mean change in Hemoglobin (Hb) levels from baseline to end of treatment (up to 24 weeks). Statistical analyses were performed to explore and analyze details of individual case safety reports of adverse events such as incidence, severity, seriousness, outcome, duration, action taken, and causality relationship of individual adverse event (AE) to the prescribed study drug. Results 87 AEs were reported in this study and most of them were mild to moderate in intensity. No deaths or serious adverse events (SAEs) were reported in this study. Anti-drug antibodies were not detected in any subject at the end of treatment phase and after 12 months long term follow up period. Baseline mean Hemoglobin value was 8.34 (SD 1.24) g/dL and last visit mean Hemoglobin value was 10.42 (SD 1.28) g/dL. The mean difference between baseline and last visit was 2.10 [2.00, 2.20], statistically significant (p-value <.0001). Clinical Trial Registry Number: CTRI/2017/04/008338 [Registered on CTRI http://ctri.nic.in/Clinicaltrials/login.php : 12/04/2017]; Trial Registered Retrospectively
Master of public health practicum: Global trends and current practices.
Authors: Gummeson Hannah , Goel Sonika Raj , Elmusharaf Khalifa
Published: April 2020

Background The field of graduate public health (GPH) education currently lacks clear, universal criteria for the integration of practice-based elements into the curriculum. The concept of the ‘practicum’ is well endorsed and there is a growing recognition that experiential learning is a crucial aspect of career development for the next generation of public health professionals, benefiting not only students, but also the profession and communities it serves. However, many leading academic institutions continue to emphasize research over experiential learning in public health, making practicums much less commonplace in education centers across the globe. Methods The purpose of this research was to review global best practices in graduate public health program design in order to identify commonalities and use the findings to inform practicum development.Data collection for this research was entirely web-based. Practicum guidelines from a globally diverse sample of graduate public health programs were reviewed. Data was compiled from universities’ websites and available online sources and collated into an Excel file. Descriptive statistics were computed for each study variable.Results We screened 108 graduate public health programs and 35 eligible programs were included in the study. Results were reported according to prerequisites & practicum scheduling, practicum contact hours & duration, credit hours & overall credit weighting, competencies, supervision, written agreement, objectives & deliverables, and approach to assessment. This research resulted in 13 recommendations intended to guide graduate public health practicum design. Based on the analysis of current best practice, the recommendations address the following four key domains: practicum design, mentorship & supervision, learning outcomes and evaluation. Conclusions This research demonstrates a global recognition of the benefit of practice experience in graduate public health education. However, the integration of practical components into curricula is inconsistent when viewed through a global lens. There is also significant variation in the structure of existing practical components. We propose that this study be utilized as a tool spark a global dialogue about best practices in graduate public health education through the identification common practices and opportunities for improvement.
Sex-bias in COVID-19: a meta-analysis and review of sex differences in disease and immunity
Authors: Peckham Hannah , Gruijter Nina de , Raine Charles , Radziszewska Anna , Ciurtin Coziana , Wedderburn Lucy R. , Rosser Elizabeth C. , Deakin Claire , Webb Kate
Published: April 2020

A striking anecdotal feature of the Coronavirus disease 2019 (COVID-19) outbreak is the difference in morbidity and mortality between the sexes. Here, we present a meta-analysis of 206, 128 reported cases to demonstrate that whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have more than double the odds of requiring intensive treatment unit admission (OR 2.5) and higher odds of death (OR 1.60) when compared to females. We review data revealing how previous Coronavirus outbreaks have demonstrated a similar pattern. Important differences in the immune response to infection exist between sexes, which are likely to contribute to this observation. In this review, we discuss these differences highlighting that females have a more robust innate antiviral response and a better adaptive immune response to infection. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease.
Unique Immunological Profile In Patients With COVID-19
Authors: Varchetta Stefania , Mele Dalila , Oliviero Barbara , Mantovani Stefania , Ludovisi Serena , Cerino Antonella , Vecchia Marco , Roda Silvia , Sachs Michele , Bruno Raffaele , Mondelli Mario U.
Published: April 2020

The relationship between SARS-CoV-2 and host immunity is unknown. We show here that patients with COVID-19 had an altered immune phenotype, with an expansion of adaptive FceRIgneg NK cells, and inflammatory CD14+CD16+ monocytes. T cells were reduced and overexpressed the Tim-3 exhaustion molecule. Low frequencies of CD8 T cells and NKG2A+ NK cells, and expansion of mature CD57+ NK cells were associated with poor prognosis. These findings unveil a unique immunological profile in COVID-19 patients.
Simulation of Ventilator Allocation Strategies During the COVID-19 Pandemic
Authors: Bhavani Sivasubramanium V. , Miller William D. , Han Xuan , Malec Monica , Ross Lainie F. , Siegler Mark , Parker William F.
Published: April 2020

As the number of SARS-CoV-2 infections mount globally, hospital systems face unprecedented demands on limited resources, including ventilators. Existing ventilator allocation strategies have not undergone rigorous analyses to evaluate their real-world implications. To address this critical gap in knowledge with profound societal implications, we present a simulation model to evaluate the proposed allocation strategies and report the trade-offs between these strategies that merit careful consideration.
Tjelovježba i igranje-igara u četirima konstrukcijama sretnog ljudskog života
Authors: Škerbić Matija Mato
Published: April 2020

Potaknut B. H. Suitsovom konstrukcijom Utopije i ponuđenih rješenja za smislen i sretan život čovjeka, predstavljenom u djelu Skakavac: igre, život i utopija (The Grasshopper: Games, Life and Utopia, 1978.), autor sučeljava, razmatra i kritički vrjednuje ulogu ljudske tjelovježbe i igranja-igara u četirima konstrukcijama sretnog ljudskog življenja iznesena u trima renesansnim filozofskim spisima: O najboljem uređenju države i o novom otoku Utopiji (De optimo reipublicae statu deque nova insula Utopia libelous, 1516.) T. Morea, Sretni grad (La città felice, 1553.) F. Petrića i Grad Sunca. Ideja filozofske države (Civitas Solis. Idea reipublicae philosophicae, 1603.) T. Campanelle, te spomenutom postmodernom spisu B. H. Suitsa. Teza je autora da su u Suitsovu rješenju za sretan i smislen život čovjeka, koji se sastoji u neprestanom igranju-igara ili bavljenju jedino autoteličnim i intrinzično vrijednim aktivnostima, sadržane dokoličarske nakane svih ostalih navedenih konstrukcija. Štoviše, to rješenje ili odgovor, premda konstruirano za suvremena čovjeka, jest rješenje za čovjeka svakog vremena i uvjeta ili okolnosti.
Transboundary water allocation in critical scarcity conditions: a stochastic bankruptcy approach
Authors: Janjua Shahmir , Hassan Ishtiaq
Published: April 2020

A common problem in water resource allocation is to design a stable and feasible mechanism of water sharing in critical scarcity conditions. The task becomes very challenging when the water demand exceeds the available water resources reserves. To address this pervasive allocation problem related to transboundary rivers, the bankruptcy method is used. The bankruptcy method distributes water among riparian states when their total demand exceeds the total available water. This paper describes a new methodology for the allocation of scarce water resources in a complex system using a stochastic game theory which is an extension of bankruptcy theory. The authors have also proposed ‘weighted bankruptcy’ approach that can be used under a stochastic setting. The weighted bankruptcy approach favors agents with ‘high agricultural productivity’. The bankruptcy rules have been applied in the water resource system in four critical scarcity scenarios. The available water is allocated under the simple and weighted bankruptcy rules. The results showed that under all four scenarios, the weighted bankruptcy rules favor the agents which have a high agricultural productivity. The stochastic bankruptcy approach under the simple and the weighted bankruptcy rules can provide important strategic information for better management and sustainable sharing of water resources.
A socio-ecological perspective of the facilitators and barriers to uptake of water, sanitation and hygiene interventions in a slum setting in Kampala, Uganda: a qualitative study
Authors: Ssemugabo Charles , Halage Abdullah Ali , Namata Carol , Musoke David , Ssempebwa John C.
Published: April 2020

We explored the facilitators and barriers to uptake of water, sanitation and hygiene (WASH) interventions among slum dwellers in Kampala, Uganda using a socio-ecological perspective. This qualitative exploration used focus group discussions with community members and key informant interviews with community leaders and technocrats to collect data. Among facilitators to uptake of WASH interventions were susceptibility to WASH-related diseases and low WASH knowledge levels at individual level, peer practices at household level, and promotion of WASH at organizational level. At community and public policy levels, community engagement and empowerment, and formation and enforcement of ordinances and bye-laws, respectively, motivated slums dwellers to adopt WASH interventions. Conversely, individual knowledge, beliefs, language, and financial status inhibited individuals from taking up WASH interventions. Negative peer practices and upbringing at peer level; unsupportive environments, and engagement of communities at organizational level; cultural beliefs and lack of space at community level; and unexamplary leaders and political interference barred slum dwellers in Kampala from embracing the WASH interventions. Uptake of WASH interventions in the slum community is influenced by a cascade of facilitators and barriers across the socio-ecological realm. Hence, a multi-faceted approach targeting all stakeholders is required in planning and implementation of WASH interventions.
Annual precipitation analysis and forecasting – taking Zhengzhou as an example
Authors: Tuo Wei , Zhang Xianqi , Song Chao , Hu Dengkui , Liang Tianyi
Published: April 2020

Precipitation is greatly affected by natural conditions and human activities, and its sequence has the characteristics of periodic variation and non-stationarity. In order to study the periodic characteristics of regional precipitation, reduce the non-stationarity of the water sequence and improve the forecasting accuracy, the Morlet wavelet model and CEEMD − Elman + ARIMA model are introduced, and applied to the precipitation sequence of Zhengzhou. The results show that the annual precipitation in Zhengzhou is mainly affected by periodic fluctuations of 55a, 40a and 15a, and the mean absolute error of the CEEMD − Elman + ARIMA model in 2013–2017 is 14.1%. Based on the analysis of precipitation period and forecast of future precipitation, the characteristics and evolution of precipitation in Zhengzhou are revealed. This provides a theoretical basis for rational utilization of water resources, prevention, industrial and agricultural production in Zhengzhou.
Design characteristics of perforated tray aerator
Authors: Roy Subha M. , Tanveer Mohammad , Mukherjee C. K. , Mal B. C.
Published: April 2020

The performance of the perforated tray aerator (PTA) was evaluated by conducting experiments in a tank of size 4 m × 4 m × 1.5 m. Based on the dimensional analysis, non-dimensional numbers related to geometric variables, viz. numbers of trays (n), ratio of consecutive width of tray to total height of aerator , ratio of perforation diameter to total height of aerator and ratio of the volume of water in the tank to total height of aerator were developed. Experiments were conducted with different numbers of trays (n): 1, 2, 3 and 4, keeping = 0.33, = 2.5 × 10−4, = 2,500 and pump flow rate (Q) = 0.010 m3/s as constants. The optimum number of perforated trays was found to be 3. Response surface methodology (RSM) and central composite rotatable design (CCRD) were used to further optimize the geometric variables with combinations of non-dimensional geometric variables , and . The flow rate (Q) of 0.013 m3/s and number of trays (n) as 3 were kept as constants. The optimum performance of PTA was obtained at = 0.665, = 1.85 × 10−4 and = 312.50 with the maximum non-dimensional standard aeration efficiency (NDSAE) and standard aeration efficiency (SAE) of 35.58 × 10−3 and 1.45 kgO2/kWh.
Movilidad de población y comportamiento reproductivo: El caso de Baja California
Authors: Estrella Valenzuela Gabriel
Published: April 2020

Este trabajo tiene como objetivo central evaluar el impacto indirecto que genera la inmigración hacia Baja California a través del comportamiento reproductivo de la población que, al migrar, ha cambiado su residencia habitual a la entidad. Para lograr ese objetivo, se analiza la información de las Encuestas Demográficas de Baja California de 1986 y 1990 con el modelo de los determinantes próximos de la fecundidad. Los resultados de dicho análisis muestran, por una parte, que los patrones reproductivos de la población migrante y no-migrante son c1aramentediferenciados (tanto en términos de fecundidad ilegítima como de formación de uniones, de sus prácticas anticonceptivas y de lactancia postparto), y que de ello se deriva un diferencial de fecundidad que resulta ser 17.5% superior para la población migrante en 1990. Por otra parte, los resultados también permiten estimar que, por cada tres nuevos inmigrantes que por año recibe la entidad, la inmigración acumulada aporta dos nuevos residentes con los nacimientos generados por las mujeres migrantes. Dada la magnitud que adquieren esos procesos (i.e. 59 mil nuevos habitantes por año ~ total), se concluye sugiriendo líneas generales de acción que permitan) adecuar la política de población a las condiciones específicas de Baja California
Inflammatory Bowel Diseases: The Role of Gut Microbiota
Authors: De Musis Cristiana , Granata Lucia , Dallio Marcello , Miranda Agnese , Gravina Antonietta G. , Romano Marco
Published: April 2020

:

Inflammatory bowel diseases (IBD) are chronic multifactorial diseases characterized by partially unclear
pathogenic mechanisms including changes in intestinal microbiota. Despite the microbiota, alteration is well
established in IBD patients, as reported by 16RNA sequencing analysis, an important goal is to define if it is just
a consequence of the disease progression or a trigger factor of the disease itself. To date, gut microbiota composition
and gut microbiota-related metabolites seem to affect the host healthy state both by modulating metabolic
pathways or acting on the expression of different genes through epigenetic effects. Because of this, it has been
suggested that intestinal microbiota might represent a promising therapeutic target for IBD patients.

:

The aim of this review is to summarize both the most recent acquisitions in the field of gut microbiota and its
involvement in intestinal inflammation together with the available strategies for the modulation of microbiota,
such as prebiotics and/or probiotics administration or fecal microbiota transplantation.
Drug-induced Bile Duct Injury - A Short Review
Authors: Dobreva Inna , Karagyozov Petko
Published: April 2020

:

The liver represents the major site of drug metabolism, i.e. the key organ in the processes of detoxification and elimination of drugs from the organism. It is therefore often affected by toxic metabolites and suffers sometimes fatal consequences. The spectrum of pathologies differs by the cell type primarily damaged and the group of the cholangiopathies includes those conditions affecting the bile duct epithelium or the cholangiocytes. They can range from transient cholestasis to vanishing bile duct syndrome and sclerosing cholangitis, both leading eventually to the development of biliary fibrosis and cirrhosis.

:

In this review article, we focus on the etiology, predisposing factors, clinical manifestations, and histopathological characteristics of bile duct injury as a consequence of drug treatment and discuss separately the different bile duct pathologies.
MicroRNA: Promising Roles in Cancer Therapy
Authors: Hashemi Atieh , Gorji-bahri Gilar
Published: April 2020

MicroRNAs (miRNA) are small non-coding RNAs that act as one of the main regulators of
gene expression. They are involved in maintaining a proper balance of diverse processes, including differentiation,
proliferation, and cell death in normal cells. Cancer biology can also be affected by these
molecules by modulating the expression of oncogenes or tumor suppressor genes. Thus, miRNA based
anticancer therapy is currently being developed either alone or in combination with chemotherapy
agents used in cancer management, aiming at promoting tumor regression and increasing cure rate.
Access to large quantities of RNA agents can facilitate RNA research and development. In addition to
currently used in vitro methods, fermentation-based approaches have recently been developed, which
can cost‐effectively produce biological RNA agents with proper folding needed for the development of
RNA-based therapeutics. Nevertheless, a major challenge in translating preclinical studies to clinical
for miRNA-based cancer therapy is the efficient delivery of these agents to target cells. Targeting
miRNAs/anti-miRNAs using antibodies and/or peptides can minimize cellular and systemic toxicity.
Here, we provide a brief review of miRNA in the following aspects: biogenesis and mechanism of action
of miRNAs, the role of miRNAs in cancer as tumor suppressors or oncogenes, the potential of using
miRNAs as novel and promising therapeutics, miRNA-mediated chemo-sensitization, and currently
utilized methods for the in vitro and in vivo production of RNA agents. Finally, an update on the viral
and non-viral delivery systems is addressed.
Acetate Suppresses Lipopolysaccharide-stimulated Nitric Oxide Production in Primary Rat Microglia but not in BV-2 Microglia Cells
Authors: Moriyama Mitsuaki , Nishimura Yasunori , Kurebayashi Ryosuke , Minamihata Tomoki , Kawabe Kenji , Takano Katsura , Nakamura Yoichi
Published: April 2020

Aims:

To show that acetate attenuates neuroinflammatory responses in activated microglia.

Background:

Dietary acetate supplementation alleviates neuroglial activation in a rat model of
neuroinflammation induced by intraventricular administration of lipopolysaccharide (LPS). However, the
precise mechanism(s) underlying the anti-inflammatory effect of acetate is not fully understood.

Objective:

To determine whether acetate has inhibitory effects on LPS-induced neuroinflammatory
responses in microglia.

Methods:

We examined LPS-stimulated nitric oxide (NO) production in primary rat microglia and BV-2
cells. Protein expression of inducible NO synthase (iNOS) was determined by western blot analysis. The
intracellular generation of reactive oxygen species (ROS) and glutathione (GSH) were also evaluated.

Results:

In primary microglia, acetate decreased LPS-stimulated NO production in a dose-dependent
manner, reaching significance at greater than 10 mM, and cell viability was not affected. Acetate suppressed
LPS-induced expression of iNOS protein concomitantly with the decrease in NO. The LPS-induced
increase in intracellular ROS production was attenuated by acetate. In addition, acetate prevented LPSinduced reduction of GSH. Notably, such suppressive effects of acetate on NO and ROS production were
not observed in BV-2 cells.

Conclusion:

These findings suggest that acetate may alleviate neuroinflammatory responses by attenuating
NO and ROS production in primary microglia but not in BV-2 cells.
Other: All animals received humane care and the animal protocols used in this study were approved by the
Ethics Committees for Animal Experimentation.
Analyzing Phytochemicals as Inhibitors of Diabetes Mellitus 2 Causing Proteins based on Computer-Aided Drug Discovery Protocols
Authors: Chaudry Sobia Nazir , Hussain Waqar , Rasool Nouman
Published: April 2020

Background:

Diabetes Mellitus type 2 is one of the complex diseases, affecting people both in developed
and developing countries. Plant extracted compounds known as phytochemicals are worthy because they
have various medicinal properties.

Objective:

The present study aims at the in silico discovery of novel potent inhibitors against Diabetes
Mellitus type 2.

Methods:

A total of 2750 phytochemicals from various medicinal important plants were collected for this
study. Origin of these plants was Pakistan and India. The ADMET, molecular docking approaches were
used to determine the binding and reactivity of these phytochemicals as Diabetes Mellitus type 2 inhibitors.

Results:

The ADMET analysis and molecular docking resulted in the selection of 42 phytochemicals (3
against Glucokinase receptor, 22 against Fructose 1,6 Bisphosphate protein and 17 for multidrug-resistant
protein) showing high binding affinity as compared to the previously reported inhibitors of Diabetes
Mellitus type 2.

Conclusions:

These 42 phytochemicals can be considered novel inhibitors against Diabetes Mellitus
type 2 and can be selected for additional in vitro and in vivo studies to develop a suitable drug
against diabetes.