bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventing laboratory-associated infections in the COVID-19 era: experience from a tertiary care infectious disease hospital in Southern Vietnam
Authors: Huy Man Dinh Nguyen , My Ngoc Nghiem , Minh Hoang Dang , Hoa Trang Nguyen , Phuong Thao Duong Thi , Ty Hang Vu Thi , Van Tan Le , Quynh Nga Nguyen Thi , Thanh Dung Nguyen , Manh Hung Le , Quang Thai Pham , Vinh Chau Nguyen Van , Thwaites Guy , Choisy Marc , Rahman Motiur
Published: October 2020

Background: Laboratory staff is at higher risk of infection owing to the handling and testing of coronavirus disease 2019 (COVID-19) patient samples. Reviewing the existing risk assessment and improving risk management are essential for preventing laboratory acquired infections (LAIs) related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing during the COVID-19 epidemic. We present herein the steps taken to prevent LAIs related to SARS-CoV-2 testing in a tertiary care hospital in Vietnam. Methods: A SARS-CoV-2-focused risk assessment exercise was conducted for laboratory processes and workflow. Risk management strategies, including engineering, administrative and operations control procedures, were established. Standard operating procedure (SOP), staff training, COVID-19 symptom reporting, enhanced cleaning and decontamination, and inventory monitoring protocols were implemented. Sample reception and results reported from February 1, 2020 to September 17, 2020 were documented. Results: Based on risk assessment, a risk management strategy for SARS-CoV-2 testing was developed. This strategy includes the use of dedicated facility, instrument, and cold chain units for testing; SOPs; training (testing, decontamination and cleaning staff); the introduction of biosafety level (BSL)2+ laboratory practices; enhanced cleaning protocols for testing; and the assigning of additional staff for testing and safety system implementation. In total, 38,377 (daily mean and range: 166; 3 – 2,377) samples were received, including 301 (0.8%) samples that were rejected. The turnaround time (median ± standard deviation (SD)) was 3.54 ± 2.97 days. Altogether, 32 staff members were involved with SARS-CoV-2 testing and biosafety management, and there were no reports of COVID-19 symptoms among them. Conclusion: For epidemics and outbreak diagnostics, risk assessment and risk management strategies are important for the prevention of LAIs. Clear instruction on revised risk management protocols, necessary training, and leadership in risk management strategy implementation are essential.
Explaining the experiences, challenges and adaptation strategies of nurses in caring for patients with COVID-19: A qualitative study in Iran
Authors: Irandoost Seyed Fahim , Lebni Javad Yoosefi , Safari Hossein , Khoram Farhad , Ahmadi Sina , Soofizad Goli , Azar Farbod Ebadi Fard
Published: October 2020

Background: Nurses as the main human resource in coping with COVID-19 face many challenges and problems. Therefore, the present study aimed to explain the experiences, challenges, and adaptation strategies of nurses in taking care of patients with COVID-19 with a qualitative approach.Methods: The present study was conducted with a qualitative conventional content analysis approach among 30 nurses working in wards for COVID-19 patients, in Tehran hospitals. Access to participants and data collection was done through purposive sampling, snowball sampling and semi-structured interviews. Data were analyzed using qualitative content analysis (conventional) and MAXQDA-18 software. Guba and Lincoln criteria were observed to evaluate the quality of research results.Results: From data analysis, 2 main categories and 16 subcategories were obtained, including (1) experiences and challenges (lack of protective equipment, high work pressure, marginalized physical health, problems related to the use of protective equipment, getting excluded, lack of supportive work environment, problems related to patients, psychological problems, fear, marginalized personal and family life and the challenge of communication with patients' families) (2) Strategies for adapting to working conditions (performing religious-spiritual activities, creating an empathetic atmosphere in the workplace, spiritualizing their work , trying to convince the family and gain their support, strengthening sense of self-worth and responsibility).Conclusion: The working conditions for nurses can be improved through providing adequate protective equipment, providing a suitable work environment and more social and financial support, more attention to the physical and mental health of nurses and considering appropriate mechanisms for nurses to communicate with their families and patients' families.
Does Early ART Initiation is Better than Later ART Initiation in TB/HIV Co-infected Patients? A Retrospective Cohort Study
Authors: Atey Tesfay Mehari , Girma Fikermaryam , Tuem Kald Beshir , Gebre Abadi Kahsu , Gidey Hagos , Kahssay Mola , Gebreyesus Hiluf Hindeya , Asgedom Solomon Weldegebreal , Desta Desilu Mahari
Published: October 2020

Background: The co-infection of TB/HIV poses a significant burden in the health care system of developing countries like Ethiopia. There are conflicting results on the preference of the time to initiate antiretroviral therapy (ART) and hence assessing the survival experience and treatment outcomes associated with ART initiation is crucial to settle the controversies. The study compared the treatment outcomes in early versus later ART initiation in TB/HIV co-infected patients. Methods: A retrospective cohort study was conducted in Ayder Comprehensive Specialized Hospital and Mekelle Referral Hospital on 77 and 105 patients that started ART early and lately, respectively. An assumption for proportional hazard was met. Kaplan-Meier and life-table analyses were used to compare survival curves; and an independent samples t-test was used to compare means of the continuous variables between the two cohorts. Moreover, incidence per 100 persons-years was employed to crudely determine new morality rates, and Cox regression analysis was done to find out the effects of independent variables on the outcome variables. Results: The mean survival time was 5.8 months after ART initiation. A 9.9 and 5.5 new incident mortality rates per 10,000 persons–years for the early and late ART initiation were observed, respectively. There was a statistically significant difference in mean CD4+ T cells between early (208.20 ± 11.94 cells/mm3) and late (245.94 ± 11.69 cells/mm3) ART initiators (t180 = -2.213, p < 0.028). Additionally, late initiators had a better survival chance at all levels of time (Log Rank c2=5.56, p<0.018) than early initiators. Having normal body mass index [adjusted hazard ratio [AHR=0.263; 95% confidence interval [CI]: 0.089–0.778] and having a ‘working’ baseline functional status [AHR=0.151; 95% CI: 0.054–0.427] were found to be preventive factors from death. However, patients with < 250 CD4+ T cells/mm3 were more likely to die earlier [AHR=12.023; 95%: 1.588–91.005] than their counterpart groups.Conclusion: TB/HIV co-infected patients who had a CD4 count of below 250 cells/ul started ART regimen within two weeks of TB treatment initiation were found to have better survival outcomes than those who start ART beyond two weeks in the study settings. Moreover, female patients were more likely to die than males and, patients with the functional status of bedridden were more likely to die in contrast to working and ambulatory functional status. Moreover, body mass index, baseline functional status, and CD4 count were found to be independent predictors of mortality.
World Health Organisation Disability Assessment Schedule (WHODAS 2.0): development and validation of the Nigerian Igbo version in patients with chronic low back pain
Authors: Igwesi-Chidobe Chinonso N , Kitchen Sheila , Sorinola Isaac Olubunmi , Godfrey Emma Louise
Published: October 2020

BackgroundGlobally, the leading cause of years lived with disability is low back pain (LBP). Chronic low back pain (CLBP) is responsible for most of the cost and disability associated with LBP. This is more devastating in low income countries, particularly in rural Nigeria with one of the greatest global burdens of LBP. No Igbo back pain specific measure captures remunerative or non-remunerative work outcomes. Disability measurement using these tools may not fully explain work-related disability and community participation, a limitation not evident in the World Health Organisation Disability Assessment Schedule (WHODAS 2.0). This study aimed to cross-culturally adapt the WHODAS 2.0 and validate it in rural and urban Nigerian populations with CLBP.MethodsTranslation, cultural adaptation, test–retest, and cross-sectional psychometric testing was performed. WHODAS 2.0 was forward and back translated by clinical/non-clinical translators. Expert review committee evaluated the translations. Twelve people with CLBP in a rural Nigerian community piloted/pre-tested the questionnaire. Cronbach’s alpha assessing internal consistency; intraclass correlation coefficient and Bland–Altman plots assessing test–retest reliability; and minimal detectable change were investigated in a convenient sample of 50 adults with CLBP in rural and urban Nigeria. Construct validity was examined using Spearman’s correlation analyses with the back-performance scale, Igbo Roland Morris Disability Questionnaire and eleven-point box scale; and exploratory factor analysis in a random sample of 200 adults with CLBP in rural Nigeria. Ceiling and floor effects were investigated in both samples.ResultsPatient instructions were also translated. ‘Waist pain/lower back pain’ was added to ‘illness(es)’ to make the measure relevant for this study whilst allowing for future studies involving other conditions. The Igbo phrase for ‘family and friends’ was used to better represent ‘people close to you’ in item D4.3. The Igbo-WHODAS had good internal consistency (α = 0.75–0.97); intra class correlation coefficients (ICC = 0.81–0.93); standard error of measurements (5.05–11.10) and minimal detectable change (13.99–30.77). Igbo-WHODAS correlated moderately with performance-based disability, self-reported back pain-specific disability and pain intensity, with a seven-factor structure and no floor and ceiling effects.ConclusionsIgbo-WHODAS appears psychometrically sound. Its research and clinical utility require further testing.
Risk factors associated with renal crescentic formation in pediatric Henoch–Schönlein purpura nephritis: a retrospective cohort study
Authors: Song Yong-rui , Guo Wan-liang , Sheng Mao , Lin Qiang , Zhu Xue-ming , Li Xiao-Zhong
Published: October 2020

Background: The long-term prognosis of Henoch-Schönlein purpura (HSP) depends on the severity of renal involvement, and crescent formation is considered an important risk factor for poor prognosis of Henoch-Schönlein purpura nephritis (HSPN). The objective of this study was to evaluate factors affecting crescent formation in children with HSPN.Methods: Demographic factors, clinical characteristics, and laboratory data of children with HSPN with or without crescents were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the risk factors of crescent formation in HSPN.Results: A total of 191 children with HSPN were enrolled in the study. There were 107 (56%) males and 84 (44%) females, with a median age of 7 years (range: 2 years–15 years). International Study of Kidney Disease in Children (ISKDC) grading was used to divide subjects into two groups: those without glomerular crescent formation (ISKDC grades I–II, n = 146 cases) and those with glomerular crescent formation (ISKDC grades III–V, n = 45 cases). Logistic regression analysis showed that higher urinary white blood cell (WBC) count (OR = 3.300; 95% CI, 1.119–9.739; P = 0.0306) and higher urinary microalbumin/creatinine ratio (ACR) (OR = 25.053; 95% CI, 1.354–463.708; P = 0.0305) were independent risk factors for the formation of crescents in HSPN. The area under the receiver operating characteristic curve of urinary WBC and ACR were 0.753 and 0.698 respectively, with the Hosmer and Lemeshow goodness-of-fit test (P = 0.0669, P > 0.05).Conclusion: These results suggest that higher urinary WBC count and ACR should be strictly monitored for children with HSPN. Adequate clinical intervention for these risk factors may limit or prevent renal crescent formation.
Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation
Authors: Gottwald Dorian , Putz Florian , Hohmann Nora , Büttner-Herold Maike , Hecht Markus , Fietkau Rainer , Distel Luitpold
Published: October 2020

Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally.Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival.Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.
Feasibility of circulating tumor cells (CTCs) combined with medical imaging examinations to screen for cancer and improve diagnosis in non-metastatic invasive breast cancer patients: a cohort study
Authors: Shao Xuan , jin xiao yan , chen zhi gang , zhang zhi gang , wang ke , yu xiu yan , chen wu zhen , jiang jing xin , wang zhen , cui ying , fan wan hung , huang jian
Published: October 2020

Background: Previous study has reported that circulating tumor cells (CTCs) could be served as a diagnostic biomarker in breast cancer (BC) screening. However, the differential efficacy of routine examination including ultrasound (US), mammogram (MG), magnetic resonance imaging (MR), and breast-specific gamma imaging (BSGI) and CTCs is unknown. This study aimed to compare CTCs with common used BC screening imaging modalities and to evaluate whether their combination would enhance the diagnostic potency in non-metastatic BC patients.Methods: 102 treatment-naive non-metastatic BC patients, 177 patients with breast benign diseases (BBD) and 64 healthy females, who had CTC detection and at least one of the following medical imaging examinations, US, MG or MR between December 2017 and November 2018, were enrolled in this study.Correlations of CTC enumeration with patients’ clinicopathological characteristics and medical imaging examinations were evaluated. Results: CTC detection rates (average CTC counts) in stage I-III BC patients were 92.9% (2.1), 87.2% (2.4) and 100% (4.2), respectively. CTCs counts were positively associated with cancer stage (p = 0.0084) and tumor size (p = 0.0301). CTC counts were more correlated with US than MR or MG. CTC counts were not associated with molecular subtypes of BC nor breast-specific gamma imaging (BSGI) results, indicating that CTC enumeration cannot be used to predict molecular signatures of BC. CTCs and medical imaging examinations would have the best diagnostic performance for BC when CTC cut-off was set to 2 and imaging Breast Imaging-Reporting and Data System (BI-RADS) was set to 4b. Combination of CTC with US, MG or MR increased the sensitivity for BC diagnosis, especially for MG. Sensitivity of MG increased from 0.694 to 0.917, even more than in conjugation with US (0.901). Conclusion: CTCs counts can be used as a diagnostic aid in BC screening and early diagnosis. CTCs counts were more relevant to US than MR or MG. Conjugation of CTCs counts would improve the diagnostic potency of medical imaging examinations for diagnosing BC, especially for MG in Chinese women.
Restoring a butterfly hot spot by large ungulates refaunation: The case of the Milovice military training range, Czech Republic
Authors: Konvicka Martin , Ričl David , Vodičková Veronika , Beneš Jiří , Jirků Miloslav
Published: October 2020

Background: Refaunation/rewilding by large ungulates represents a cost-efficient approach to managing natural biotopes and may be particularly useful for areas, whose biodiversity depends on disturbance dynamics and is imperilled by successional changes. To study impacts of refaunation on invertebrates, we focused on butterflies inhabiting the former military training range Milovice, Czech Republic, refaunated since 2015 by a combination of Exmoor pony (“wild” horse), Tauros cattle (“aurochs”) and European wisent.Methods: We compared butterfly presence-absence patterns immediately after the military use termination (early 1990s), prior to the refaunation (2009) and after it (2016–19); and quantitative data gained by monitoring butterflies at refaunated and neglected plots. We used the correspondence analysis for the presence-absence comparison and the canonical correspondence analysis for the quantitative data, and related results of both ordination methods to the life history, climatic and conservation-related traits of recorded butterflies. Results: Following the termination of military use, several poorly mobile species inclining towards oceanic climates were lost. Newly gained species are more mobile and prefer warmer continental conditions. The numbers of butterfly species did not differ between refaunated and neglected plots, but the former hosted higher abundances. Butterflies developing on coarse grasses and shrubs inclined towards neglected plots, whereas refaunated plots supported species developing on small forbs. Conclusion: The changes in species composition following the cessation of military use were attributable to successional change, coupled with climate-driven changes in species pool. By blocking succession, large ungulates support butterflies depending on competitively poor plants. Restoring large ungulates populations represents a great hope for conserving specialised insects, provided that settings of the projects, and locally adapted ungulate densities, do not deplete resources for species with often contrasting requirements.
Comparative study on lesions of reproductive disorders of cows and female dromedary camels slaughtered at Addis Ababa, Adama and Akaki abbatoirs with bacterial isolation and characterization
Authors: Mandefro Aynalem , Ayana Tilaye Demissie , Hunderra Gemechu Chala , Gebrezihar Tadesse Gidey , Boru Bulto Giro , Desta Natnael Teshager
Published: October 2020

Background: Reproduction is a basic prerequisite to efficient livestock production. Reproductive performance depends upon the normal structure and function of genital organs. Methods: A cross-sectional study was conducted from November 2016 to May 2017 to identify and compare the frequency of pathological lesions in the reproductive tract and to isolate bacteria associated to uterine lesions in female dromedary camels and cows slaughtered at Akaki camel slaughter house and Addis Ababa and Adama municipal abattoirs. Abattoirs were visited once per week for 28 weeks during which three to seven animals on average were slaughtered per day. A purposive sampling technique was employed to examine reproductive tracts of all slaughtered animals (280; 140 cows and 140 camels). Following gross inspection at abattoirs, tissue samples with lesion were collected for histopathological and bacteriological investigation. Result: Various pathological lesions with different degrees of severity were observed in 48 (34.2%) and 51 (36.4%) of dromedary camels and cows, respectively. Uterine lesions were the most prevalent 21.4% lesions observed in dromedary camels followed by ovarian lesions 7.14%; while in cows, ovarian lesions were the major prevalent 16.4% lesions followed by uterine lesion 14.2%. The result showed that there were 56 bacteria isolated from cows uterine lesion with Staphylococcus species 28.5%, Streptococci species 19.6%, Coynebacterium species 8.9%, Escherichia coli 26.78%, Salmonella species 10.7% and Klebsiella species 5.35% being the prominent isolates; while in camels, there were 45 bacteria isolated with Escherichia coli 35.5%, Staphylococcus species 26.6%, Streptococcus species 13.3%, Pseudomonas species 6.6 %, Proteus species 4.4%, Salmonella species 8.8% and Klebsiella species 4.4% being the most frequently isolated. The result showed that the major isolates were similar with slightly higher in cows. Histopathologically, endometrial glands degeneration, sloughing of epithelium, peri-glandular cuffing and infiltrations of inflammatory cell were some of characteristic changes observed in uterus. Conclusions: Pathological lesions in reproductive organs in female dromedary camels and cows showed great prevalence, with similarity in bacterial isolates between the two species. The role of each reproductive lesions and bacterial isolates incriminated as causes of reproductive failures in this livestock species needs further investigation.
MtNIP5;1, a novel Medicago truncatula boron diffusion facilitator induced under deficiency
Authors: Granado-Rodríguez Sara , Bolaños Luis , Reguera Maria
Published: October 2020

Background: Legumes comprise important crops that offer major agronomic benefits, including the capacity of establishing symbiosis with rhizobia, fixing atmospheric N2. It has been proven that legumes are particularly susceptible to boron (B) stress, which leads to important yield penalties. Boron (B) deficiency or toxicity in plants causes the inhibition of growth and an altered development. Under such conditions, the participation of two distinct protein families (the major intrinsic protein family MIP and the Boron transporter family BOR) is required to minimize detrimental effects caused by B stress. However, in legumes, little is known about the transport mechanisms responsible for B uptake and distribution, especially under deficiency. Results: A Medicago truncatula protein, MtNIP5;1 (Medtr1g097840) (homologous to the Arabidopsis thaliana AtNIP5;1) was identified as a novel legume B transporter involved in B uptake under deficiency. Further analyses revealed that this M. truncatula aquaporin expression was boron-regulated in roots, being induced under deficiency and repressed under toxicity. It localizes at the plasma membrane of root epidermal cells and in nodules, where B plays pivotal roles in symbiosis. Furthermore, the partial complementation of the nip5;1-1 A. thaliana mutant phenotype under B deficiency supports a functional role of MtNIP5;1 as a B transporter in this legume model plant. Conclusions: The results here presented support a functional role of MtNIP5;1 in B uptake under deficiency and provides new insights into B transport mechanisms in legume species.
In situ virtual restoration of artifacts by imaging technology
Authors: Qiao Chengquan , Zhang Wenwen , Gong Decai , Gong Yuxuan
Published: October 2020

The restoration of incomplete artifacts is important for presenting the value of artifacts. Even though the existing methods provide rich solutions for the restoration of artifacts, they may not be the ultimate and perfect methods. The innovation of restoration methods may provide better restoration effects in some aspects or bring people a different visiting experience, which motivates people to explore new restoration methods. In this paper, based on virtual imaging technology, a virtual imaging restoration method for incomplete artifacts were proposed. In order to examine the effects and potential of the virtual imaging restoration, a bronze mirror and a mural were restored through our newly invented virtual imaging restoration device. The effects of the restorations were evaluated through the illumination test and the questionnaire surveys. The results proved that the virtual imaging restoration can visually achieve in-situ restoration, and it is completely reversible. Virtual imaging restoration also performed well in terms of visiting experience, authenticity, discernibility, and economy. Limitations of this restoration method are related to the scope of application, the viewing angle, and the imaging effects. Overall, virtual imaging restoration is worth recommending and the potential of this method and its encouraging results may provide a choice or pretest tool for the restoration of some incomplete artifacts in the near future.
Effectiveness Of Fiberoptic Phototherapy Compared To Conventional Phototherapy In Treating Hyperbilirubinemia Amongst Term Neonates: A Randomized Controlled Trial
Authors: Joel Helvi Ndeshihala , Mchaile Deborah , Philemon Rune , Mbwasi Ronald , Msuya Levina
Published: October 2020

Background: Neonatal jaundice is one of the most common problems in newborns. Effective treatment of jaundice requires therapeutic intervention with phototherapy. Over recent years, several studies reported fiberoptic phototherapy to be less effective than conventional phototherapy in term neonates. Our study aimed to compare the effectiveness of fiberoptic phototherapy with a larger illuminated area and higher irradiance to conventional phototherapy methods.
Methods: This was a randomized controlled trial conducted at Kilimanjaro Christian Medical Centre (KCMC). A total of 41 term neonates, less than 7 days of age with unconjugated hyperbilirubinemia were randomized. Thirteen (13) newborns were allocated to receive fiberoptic phototherapy, 13 to blue light conventional phototherapy and 15 to white light conventional phototherapy. Effectiveness was assessed by comparing the duration of phototherapy, bilirubin reduction rate and side effects of treatment. The data was analyzed with the independent t-test.
Results: The mean overall bilirubin reduction rate was comparable in the fiberoptic phototherapy group (0.74%/h) and the blue light conventional phototherapy group (0.84%/h), with no statistically significant difference ( p -value 0.124). However, white light conventional phototherapy had a significantly lower mean overall bilirubin reduction rate (0.29%/h) as compared to fiberoptic phototherapy ( p -value <0.001). The mean treatment duration of phototherapy was 69 h, 68 h and 90 h in the fiberoptic, blue light conventional and white light conventional phototherapy groups respectively. Side effects such as loose stool and skin rash were noted in some participants who received conventional phototherapy. No side effects of treatment were noted in the fiberoptic phototherapy group.
Conclusion: The effectiveness of fiberoptic PT and blue light conventional PT were comparable in terms of bilirubin reduction rate and treatment duration, whereas fiberoptic phototherapy was more effective than white light conventional PT, with a significantly lower bilirubin reduction rate and treatment duration. Fiberoptic phototherapy may mitigate side effects caused by conventional phototherapy.
Trial registration: The Pan African Clinical Trial Registry, PACTR202004723570110. Registered 22 nd April 2020- Retrospectively registered, http://www.pactr.org/
MAIP: A web service for predicting blood-stage malaria inhibitors
Authors: Bosc Nicolas , Felix Eloy , Arcila Ricardo , Mendez David , Saunders Martin , Green Darren , Ochoada Jason , Shelat Anang , Martin Eric , Iyer Preeti , Engkvist Ola , Verras Andreas , Duffy James , Burrows Jeremy , Gardner Mark , Leach Andrew
Published: October 2020

Malaria is a disease affecting hundreds of millions of people across the world, mainly in developing countries and especially in Sub-Saharan Africa. It is the cause of hundreds of thousands of deaths each year and there is an ever-present need to identify and develop effective new therapies to tackle the disease and overcome increasing drug resistance. Here, we extend a previous study in which a number of partners collaborated to develop a consensus in silico model that can be used to identify novel molecules that may have antimalarial properties. The performance of machine learning methods generally improves with the number of data points available for training. One practical challenge in building large training sets is that the data are often proprietary and cannot be straightforwardly integrated. Here, this was addressed by sharing QSAR models, each built on a private data set. We describe the development of an open-source software platform for creating such models, a comprehensive evaluation of methods to create a single consensus model and a web platform called MAIP available at https://www.ebi.ac.uk/chembl/maip/. MAIP is freely available for the wider community to make large-scale predictions of potential malaria inhibiting compounds. This project also highlights some of the practical challenges in reproducing published computational methods and the opportunities that open-source software can offer to the community.
Perceived social support and coping style as mediators between resilience and health-related Quality of Life in women newly diagnosed with breast cancer: A cross-sectional study
Authors: Zhou Kaina , Li Lulu , Zhao Wenqian , Bai Xue , Zhang Mengyue , Han Dongfang , Li Xiaomei
Published: October 2020

Background: Breast cancer may impair health-related quality of life (HRQoL). We examined the mediating roles of perceived social support (PSS) and coping style (CS) in the relationship between resilience and HRQoL in newly diagnosed breast cancer patients.

Methods: Four-hundred thirty-one patients completed a survey at two hospitals in Shaanxi Province, China, using self-report measures assessing HRQoL, resilience, PSS, and CS. A one-sample t-test analyzed differences between resilience, PSS, and CS in breast cancer patients and the corresponding norm. Multivariate linear regression analyzed the independent predictors of HRQoL. The mediating roles of PSS and CS between resilience and HRQoL were investigated using structural equation modeling (SEM).

Results: Participants had significantly lower scores for resilience and PSS and higher scores for the avoidance and resignation CSs than their corresponding norm. SEM analysis showed resilience had significant direct effects on PSS (B = 0.59, 95% CI [0.49, 0.68], P = 0.003), CS (confrontation: B = 0.53, 95% CI [0.44, 0.62], P = 0.001; resignation: B = -0.66, 95% CI [-0.74, -0.57], P = 0.002), and HRQoL (B range from 0.54–0.58). Resilience had significant indirect effects (B range from 0.09–0.27), and PSS and CS had significant direct effects on HRQoL (P < 0.05).

Conclusions: Newly diagnosed breast cancer patients had lower resilience and PSS and higher negative CSs. PSS and CS appeared to mediate the influence of resilience on HRQoL. Multimodal intervention programs focusing on PSS and CS might increase the influence of resilience on HRQoL in breast cancer patients.
DNA Barcoding Reveals Cryptic Diversity in the Underestimated Genus Triplophysa (Cypriniformes: Cobitidae, Nemacheilinae) from the Northeastern Qinghai-Tibet Plateau
Authors: Wang Tai , Zhang Yanping , Yang Zhuoyu , Liu Zhe , Du Yanyan
Published: October 2020

Background: The northeastern part of the Qinghai-Tibet Plateau (QTP) presents a high number of plateau loach species. As one of the three major groups of fishes distributed on the QTP, plateau loach has high ecological value. However, the taxonomy and systematics of these fish are still controversial, and a large number of new species have been reported. The reason for this phenomenon is that the degree of morphological variation is low, the phylogenetic information provided by morphological and anatomical features used for species identification is relatively poor, and many cryptic species are observed. Based on the high-density sampling points from the biodiversity hotspots surveyed, this study aims to evaluate the biodiversity of plateau loach in the northeastern part of the QTP and reveal the hidden diversity by comparing morphological species with molecular operational taxonomic units (MOTUs).Results: After careful identification and comparison of the morphology and DNA barcoding of 1,630 specimens, 22 species were identified, with 20 considered valid local species and two identified as new species that had not been previously described. Based on the combination of morphological and molecular methods, a total of 24 native species were found, two of which were cryptic species: Triplophysa robusta sp1 and Triplophysa minxianensis sp1. Fourteen of the 24 species form clusters of barcodes that allow them to be reliably identified. The remaining cases involved 10 closely related species, including rapidly differentiated species and species that seemed to have experienced incomplete lineage sorting or showed introgressions.Conclusions: The results highlight the need to combine traditional taxonomies with molecular methods to correctly identify species, especially closely related species, such as the plateau loach. This study provides a basis for protecting the biodiversity of plateau loach.
Protein over-expression in Escherichia coli triggers adaptation analogous to antimicrobial resistance
Authors: James Jack , Yarnall Benjamin , Koranteng Andy , Gibson Jane , Rahman Tahmina , Doyle Declan Anthony
Published: October 2020

Background: The E. coli pET system is the most widely used protein over-expression system worldwide. It relies on the assumption that all cells produce target protein and it is generally believed that integral membrane protein (IMP) over-expression is more toxic than their soluble counterparts. Results: Using GFP-tagged proteins, high level over-expression of either soluble or IMP targets results in > 99.9 % cell loss with survival rate of only < 0.03 %. Selective pressure generates three phenotypes: large green, large white and small colony variants. As a result, in overnight cultures, ~50 % of the overall cell mass produces no protein. Genome sequencing of the phenotypes revealed genomic mutations that causes either the loss of T7 RNAP activity or its transcriptional downregulation. The over-expression process is bactericidal and is observed for both soluble and membrane proteins.Conclusions: We demonstrate that it is the act of high-level over-expression of exogenous proteins in E. coli that sets in motion a chain of events leading to > 99.9 % cell death. These results redefine our understanding of protein over-production and link it to the adaptive survival response seen in the development of antimicrobial resistance.
Quality of life of children with spinal muscular atrophy and their caregivers from the perspective of caregivers : a Chinese cross-sectional study
Authors: Yao Mei , Ma Ying , Qian Ruiying , Xia Yu , Yuan Changzheng , Bai Guannan , Mao Shanshan
Published: October 2020

Background: Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease leading to dysfunction of multiple organs. SMA can impair the quality of life (QoL) of patients and family. We aimed to evaluate the QoL of children with SMA and their caregivers and to identify the factors associated with QoL in a cross-sectional study conducted in China.Methods: We recruited 101 children aged 0-17 years with SMA and their caregivers from a children’s hospital in China. Twenty-six children had type I SMA, 56 type II and 19 type III. Each child’s QoL was measured by the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM), which was completed by the child’s caregivers. The caregiver’s QoL was measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Information on sociodemographic characteristics, disease-specific characteristics, and treatments were collected using the proxy-reported questionnaire. Two-sample t-tests and one-way ANOVA were used to compare differences in average scores of QoL across subgroups.Results: Children with type III SMA had a higher average Total score of PedsQL NMM and higher average scores in domains Neuromuscular disease and Family resources than children with type I or type II SMA (p < 0.001). Caregivers of children with type III SMA reported higher average scores in the domains of Physical, Emotional, Social, and Cognitive functioning of the PedsQL FIM than those of children with types I or II SMA (p < 0.05). In addition, disease-related characteristics (e.g. limited mobility, motor degeneration, skeleton deformity, and digestive system dysfunction) and respiratory support were associated with lower average scores of PedsQL NMM and PedsQL FIM (p < 0.05). Exercise training, multidisciplinary team management and use of the medication Nusinersen were each associated with higher average scores in both PedsQL NMM and FIM (p < 0.05).Conclusion: Our study has demonstrated factors that may impair or improve QoL of children patients with SMA and their parents. Particularly, QoL was relatively poor in children with type I and type II SMA as well as in their caregivers compared to those with type III SMA. We strongly recommend that standard of care in a multidisciplinary team (MDT) be strengthened to improve the QoL of SMA patients. Our study called for increased attention from clinical physicians on measuring QoL in their clinical practices in order to enhance the understanding of impacts of SMA and to make better decisions regarding treatment.
Scar quality examination comparing titanium coated suture material and non-coated suture material on flap donor sites in reconstructive surgery
Authors: Berninghausen Laura Katharina , Osterhoff Georg , Langer Stefan , Kohler Lukas Herbert
Published: October 2020

Background Wound healing and scar quality after trauma are subject to impairment through excessive wound healing, chronic wound or even surgical site infections. Optimizing the process of scar formation and skin healing is crucial in virtually all fields of medicine. In this regard, we tested the possible usage and advantages of titanium coated suture material.METHODS We performed a prospective observational cohort study including 30 patients who underwent soft tissue reconstruction. One half of the donor flap site was sutured with titanium coated suture material, while the other half was closed with non-coated sutures. Scar quality of the donor flap site was assessed by photographs and POSAS scores on days 2-5, 14, 42, 72 and 180 postoperatively. RESULTS No difference between the titanium coated sutures and non-coated sutures was seen in the POSAS assessment, neither for the patient scale at 14, 42, 72 and 180 days, nor for the observer scale on the same dates. Comorbidities like diabetes, chronic renal failure and smoking as well as the BMI of each patient affected the wound healing process to an equal degree on both sides of the suture. CONCLUSIONSNo difference between the titanium coated and non-titanium-coated suture material was seen in the POSAS assessment in regard to scar quality and wound healing. The titanium-coated suture material can be considered to be equally as effective and safe in all qualities as the non-titanium-coated suture material, even in patients with comorbidities. Clinical Trial RegisterThis study is registered at the German Clinical Trials Register (DRKS) under the registration number DRKS00021767. (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021767)
Relationship between blood Lead status and anemia in Ugandan children with malaria infection
Authors: Mukisa Ambrose K , Kasozi Denis M , Aguttu Claire , Vuzi Peter C. , Kyambadde Joseph
Published: October 2020

Background In Uganda, childhood anemia remains a health challenge and is associated with malaria infection as well as iron deficiency. Iron deficiency is intertwined with nutritional status, age and other comorbidities including helminths and Lead toxicity. Environmental Lead levels accounts for one’s blood Lead (BL) levels. Blood Lead competitively blocks iron absorption, inhibits hemoglobin (Hb) biosynthesis and elevates free erythrocyte protoporphyrin (FEP) levels. Lead toxicity’s contribution towards anemia pathogenesis, especially during malaria infection has not been studied. Concomitant exposure to both malaria infection and Lead pollution, exacerbates the anemia status. This study therefore aimed at expounding the anemia status of these Ugandan children aged under 5years who are exposed to both malaria infection and environmental Lead pollution. Methods Briefly, venous blood samples from 198 children were microscopically assayed for malaria parasite density (PD), and hemoglobin (Hb) concentrations using the cyanmethemoglobin method, while BL and FEP levels were determined by the standard atomic absorption spectrophotometric and fluorometric methods respectively. Results One hundred and fifty-one (76.3%) of the children analyzed had moderate anemia (Hb <10>5 g/dL) with Means of BLL=8.6 µg/dL, Hb =7.5 g/dL, FEP/Hb =8.3 µg/g and PD =3.21×103 parasites / µL, while eight (4%) were severely anemic (<5 g/dL). Regression analysis and statistical correlation between PD and Hb (r = -0.231, R2= 0.15 P-value < 0.001) was negative and weak as compared to that between FEP/Hb and Hb (r = -0.6, R2=0.572 P-value=0.001). Conclusion Based on the study’s findings, we conclude that BL significantly contributes to the pathogenesis of anemia and therefore its co-existence with malaria infection in the host exacerbates the anemia status.Trial registration Not applicable
Gut Microbiota: Effect of Pubertal Status
Authors: Yuan Xin , Chen Ruimin , Zhang Ying , Lin Xiangquan , Yang Xiaohong
Published: October 2020

Background: The make-up of gut microbiota at different puberty stages has not been reported. This cross-sectional study analyzed the bio-diversity of gut microbiota at different puberty stages. Result: The subjects (aged 5-15 years) were divided into non-pubertal (n=42, male%: 66.7%) or pubertal groups (n=47, male%:44.68); in both groups, Firmicutes, Bacteroidetes and Proteobacteria were the dominant phylum. There was no difference of alpha- and beta-diversity among disparate puberty stages. Non-pubertal subjects had members of the order Clostridiales, family Clostridiaceae, genus Coprobacillus which were significantly more prevalent than puberty subjects. Also, the pubertal subjects had members of class Betaproteobacteria, order Burkholderiales which were significantly more prevalent than the non-pubertal subjects. Their relative abundance was independent of BMI-Z. In the pubertal subjects, the abundance of genus Adlercreutzia, Ruminococcus, Dorea, Clostridium and Parabacteroides was associated with the level of testosterone.Conclusions: This is the first report of the diversity of gut microbiota at different puberty stages. The various species of gut microbiota changed gradually associated with puberty stages. Differences in gut microflora at different pubertal status may be related to androgen levels.
MiRNA-340-5p mediates the functional and infiltrative promotion of tumor-infiltrating CD8+ T lymphocytes in human diffuse large B cell lymphoma
Authors: Xu Yangyang , Liu Zhenchuan , Lv Lixin , Li Ping , Xiu Bing , Qian Wenbin , Liang Aibin
Published: October 2020

Background: CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions. Methods: Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models. Results: MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation. Conclusions: MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.
Baseline assessment of antibiotics prescribing for acute, non-complicated infections in primary care in Germany in the cluster randomized trial ARena
Authors: Poss-Doering Regina , Weber Dorothea , Kamradt Martina , Andres Edith , Kaufmann-Kolle Petra , Szecsenyi Joachim
Published: October 2020

Background Antimicrobial resistance is fueled by inappropriate prescribing and use of antibiotics. Global and national strategies support rational and adequate use of antibiotics to retain treatment options and fight resistances. In Germany, the ARena project (Sustainable reduction of antibiotic-induced antimicrobial resistance) was intended to promote the rational and appropriate use of antibiotics for acute non-complicated infections by addressing physicians, care teams and patients through multiple interacting interventions. This paper presents patterns of antibiotics prescribing for patients with acute non-complicated infections in participating primary care networks prior to the start of the ARena project, explores variation across subgroups of patients and draws comparisons to reference groups which represent standard care. Methods In mixed logistic regression models, we explored factors associated with the primary outcome defined as the proportion of patients with acute non-complicated infections consulting primary care practices who received an antibiotic prescription. Secondary outcomes concerned the prescription of different types of antibiotics. Descriptive methods were used to summarize the data referring to primary care networks, reference groups, and subgroups. Results Across all observed cases, antibiotic prescription rates were 31.7% in reference groups and 32.0% in primary care networks. Being the largest group of physicians observed, General practitioners prescribed antibiotics more frequently than other medical specialist groups (otolaryngologists vs. General practitioners OR=0.465 CI=[0.302; 0.719], p<0.001, pediatricians vs. General practitioners: OR=0.369 CI=[0.135; 1.011], p=0.053). Quinolone prescription rates were moderate (8.1% in reference groups and 9.9% in primary care networks). Patients with comorbidities had a higher likelihood of receiving an antibiotic and quinolone prescription and were less likely to receive a recommended substance. Younger patients were less likely to receive antibiotics (OR=0.771 CI=[0.636; 0.933], p=0.008). Female gender was associated with higher rates of antibiotic prescriptions compared to males (OR=1.293 CI=[1.201, 1.392], p<0.001).Conclusion Prior to the ARena project, observed antibiotic prescription rates for acute non-complicated infections were moderate, but there was still room for improvement. The use of recommended substances was low which indicates a need for creating stronger awareness of guideline-conform use of antibiotics.