bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of renal function after transcatheter aortic valve replacement and its impact on survival
Authors: Kylies Dominik , Freitag-Wolf Sandra , Fulisch Florian , Seoudy Hatim , Kuhn Christian , Kihm Lars Philipp , Pühler Thomas , Lutter Georg , Dempfle Astrid , Frey Norbert , Feldkamp Thorsten , Frank Derk
Published: November 2020

BackgroundChronic kidney disease as well as acute kidney injury are associated with adverse outcomes after transcatheter aortic valve replacement (TAVR). However, little is known about the prognostic implications of an improvement in renal function after TAVR. Methods Renal improvement (RI) was defined as a decrease in postprocedural creatinine in µmol/l of ≥ 1% compared to its preprocedural baseline value. A propensity score representing the likelihood of RI was calculated to define patient groups which were comparable regarding potential confounders (age, sex, BMI, NYHA classification, STS score, log. EuroSCORE, history of atrial fibrillation/atrial flutter, pulmonary disease, previous stroke, CRP, creatinine, hsTNT and NT-proBNP). The cohort was stratified into 5 quintiles according to this propensity score and the survival time after TAVR was compared within each subgroup. Results Patients in quintile 5 (n=93) had the highest likelihood for RI. They were characterized by higher creatinine, lower eGFR, higher NYHA class, higher NT-proBNP, being mostly female and having shorter overall survival time. Within quintile 5, patients without RI had significantly shorter survival compared to patients with RI (p=0.002, HR=0.32, 95% CI=[0.15-0.69]). There was no survival time difference between patients with and without RI in the whole cohort (p=0.12) and in quintiles 1 to 4 (all p > 0.16). Analyses of specific subgroups showed that among patients with NYHA class IV, those with RI also had a significant survival time benefit (p<0.001, HR = 0.15; 95%-CI= [0.05-0.44]) compared to patients without RI. Conclusions We here describe a propensity score-derived specific subgroup of patients in which RI after TAVR correlated with a significant survival benefit.
Origin of the vast height difference between the African and Pacific LLSVPs
Authors: Yuan Qian , Li Mingming
Published: November 2020

Seismic observations have revealed two Large Low Shear Velocity Provinces (LLSVPs) beneath Africa and the Pacific Ocean in the lowermost mantle1–4. However, the detailed morphology and stability of the LLSVPs and their interaction with the surrounding mantle remain unclear. Here we show that, whereas the maximum height of the Pacific LLSVP is ~500 – 700 km, the African LLSVP reaches a height of ~1,500 – 1,800 km from the core-mantle boundary. With numerical modeling experiments, we find that the height of the Pacific LLSVP can be reconciled by a wide range of the LLSVP density and surrounding mantle viscosity. However, the large height of the African LLSVP indicates that it may be less dense and thus less stable than the Pacific LLSVP.
Factors influencing Adolescent Girls and Young Women's participation in a Combination HIV Prevention Intervention in South Africa
Authors: Appollis Tracy McClinton , Duby Zoe , Jonas Kim , Dietrich Janan , Maruping Kealeboga , Abdullah Fareed , Slingers Nevilene , Mathews Catherine
Published: November 2020

Background: For interventions to reach those they are intended for, an understanding of the factors that influence their participation, as well as the facilitators and barriers of participation are needed. This study explores factors associated with participation in a combination HIV prevention intervention targeting adolescent girls and young women (AGYW) aged 15–24-years-old, as well as the experiences of AGYW, intervention implementers, and facilitators who participated in this intervention.Methods: This study used mixed-methods approach with quantitative household survey data from 4399 AGYW aged 15-24-years-old in six of the ten districts in which the intervention was implemented. In addition, qualitative methods included semi-structured in-depth interviews and focus group discussions in five of the ten intervention districts with 185 AGYW who participated in one or more of the key components of the intervention, and 13 intervention implementers and 13 facilitators. Results: Findings reveal that almost half of AGYW (48.4%) living in the districts where the intervention took place, participated in at least one of the components of the intervention. For both 15-19-year-olds and 20-24-year-olds, factors associated with increased participation in the intervention included being HIV negative, in school, never been pregnant, and having had a boyfriend. Experiencing intimate partner violence (IPV) and/or sexual violence in the past 12 months was associated with increased levels of participation in the intervention for 20-24-year-olds only. In our analysis of the qualitative data, facilitators to participation included motivating participants to join the interventions through explaining the benefits of the programme. Barriers included misguided expectations about financial rewards or job opportunities; competing responsibilities, interests or activities; family responsibilities including childcare; inappropriate incentives; inability to disrupt the school curriculum and difficulties with conducting interventions after school hours due to safety concerns; miscommunication about meetings; as well as struggles to reach out-of-school AGYW.Conclusion: Designers of combination HIV prevention interventions need to address the structural barriers to participation so that AGYW can attend without risking their safety and compromising their family, childcare and schooling responsibilities. Strategies to create demand need to include clear communication about the nature and potential benefits of such interventions, and the inclusion of valued incentives.
Fear of childbirth among pregnant women attending antenatal care in Arba Minch town, southern Ethiopia: A cross-sectional study
Authors: Gelaw Tiruset , Ketema Teklemariam Gultie , Beyene Kassaw , Gurara Mekdes Kondale , Ukke Gebresilasea Gendisha
Published: November 2020

Background: Fear of childbirth is one of the life challenges the women encounter during pregnancy. It is an important source of distress for the women and their families and also increases the odds of obstetric complications during childbirth. The aim of this study was to assess the magnitude of fear of childbirth and associated factors among pregnant women attending antenatal care at public health facilities in Arba Minch town, southern Ethiopia.Methods: Institution-based cross-sectional study was carried out among pregnant women who attended antenatal care at public health facilities in Arba Minch from November 1st –30th 2019. A systematic random sampling technique was employed to include the participants. Data were collected through a face-to-face interview by using a structured and pretested questionnaire. Wijma Delivery Expectancy Questionnaire was used to score fear of childbirth. Epi Data version 3.1 and Statistical Package for the Social Sciences version 25.0 software were used for data management. Descriptive and analytic analyses were done and statistical significance was declared at a p-value <0.05 and 95% confidence level in multivariable analysis. Results: A total of 387 pregnant women have participated in this study. Forty (10.3%) of the pregnant women had a low degree fear, 154(39.8%) had a moderate degree fear, 98(25.3%) had a high degree fear, and 95(24.5%) had severe degree fear of childbirth. Unplanned pregnancy (AOR=2.30, 95% CI: 1.12, 4.74), current pregnancy-related complications (AOR=6.24, 95% CI: 2.72, 14.29), and poor social support (AOR=1.93, 95%CI: 1.01, 3.68) were factors significantly associated with severe degree fear of childbirth. Conclusion: Almost three-fourth of the pregnant women in this study area had moderate to severe degree fear of childbirth. Tailoring counseling during antenatal care visits is needed to address those women who are at a high risk of considerable childbirth fear and its health consequences.
Lasting consequences of psyllid (Bactericera cockerelli L.) infestation on tomato plant gene expression
Authors: Harrison Kyle , Mendoza-Herrera Azucena , Levy Julien Gad , Tamborindeguy Cecilia
Published: November 2020

Background.
The tomato psyllid, Bactericera cockerelli Šulc (Hemiptera: Triozidae), is a pest of solanaceous crops such as tomato (Solanum lycopersicum L.) in the U.S. and vectors the disease-causing pathogen ‘Candidatus Liberibacter solanacearum’. Currently, the only effective strategies for controlling the diseases associated with this pathogen involve regular pesticide applications to manage psyllid population density. However, such practices are unsustainable and will eventually lead to widespread pesticide resistance in psyllids. Therefore, new control strategies must be developed to increase host-plant resistance to insect vectors. For example, expression of constitutive and inducible plant defenses can be improved through selection. Currently, it is still unknown whether psyllid infestation has any lasting consequences on tomato plant defense or tomato plant gene expression in general.
Results.
In order to characterize the genes putatively involved in tomato defense against psyllid infestation, RNA was extracted from psyllid-infested and uninfested tomato leaves (Moneymaker) three weeks post-infestation. Transcriptome analysis identified 362 differentially expressed genes. These differentially expressed genes were primarily associated with defense responses to abiotic/biotic stress, transcription/translation, cellular signaling/transport, and photosynthesis. These gene expression changes suggested that tomato plants underwent a reduction in plant growth/health in exchange for improved defense against stress that was observable three weeks after psyllid infestation. Consistent with these observations, tomato plant growth experiments determined that the plants were shorter three weeks after psyllid infestation. Furthermore, psyllid nymphs had lower survival rates on tomato plants that had been previously psyllid infested.
Conclusion.
These results suggested that psyllid infestation has lasting consequences for tomato gene expression, defense, and growth.
Development of a risk scoring system for prognostication in HIV-related toxoplasma encephalitis
Authors: Li Yao , Zeng Yanming , Liu Min , Lu Yanqiu , Liu Xueyan , Zhang Yulin , Jiang Zhongsheng , Yang Tongtong , Sun Yan , Lan Ke , Chen Yaokai
Published: November 2020

Objective: This study aims to evaluate specific risk factors influencing prognosis of HIV-infected patients with toxoplasma encephalitis (TE) in order to develop a prognostic risk scoring system for them.Methods: This is a six-center retrospective study of hospitalized HIV/TE patients. Data including six-week mortality after diagnosis, baseline characteristics, clinical features, laboratory tests and radiological characteristics of eligible patients were assimilated for risk model establishing.Results: In this study, the six-week mortality among 94 retrospective cases was 11.7% (11/94). Seven specific risk factors, viz. time from symptom onset to presentation, fever, dizziness, CD4+ T-cell counts, memory deficits, patchy brain lesions, and disorders of consciousness were calculated to be statistically associated with mortality. A criterion value of ‘9’ was selected as the optimal cut-off value of the established model. The AUC of the ROC curve of this scoring model was 0.976 (p<0.001). The sensitivity and specificity of the risk scoring model was 100.0% and 86.9%, respectively, which were 81.8% and 94.1% of this scoring model in the verification cohort, respectively. Conclusions: The developed scoring system was established with simple risk factors, which also allows expeditious implementation of accurate prognostication, and appropriate therapeutic interventions in HIV-infected patients with TE.
Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting
Authors: Turner Triniti C. , Arama Charles , Ongoiba Aissata , Doumbo Safiatou , Doumtabé Didier , Kayentao Kassoum , Skinner Jeff , Li Shanping , Traore Boubacar , Crompton Peter D. , Götz Anton
Published: November 2020

Background: Plasmodium falciparum causes the majority of malaria cases world-wide, mostly affecting children in sub-Saharan Africa. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, here we sought to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.Methods: In this cross-sectional study we assessed the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n=27) or asymptomatically infected with P. falciparum (n=8). Additionally, we measured plasma cytokine and chemokine levels in these adults and in Malian children (n=19) with acute symptomatic malaria.Results: With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.Conclusions: Our findings indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to our understanding of asymptomatic P. falciparum infections in malaria-endemic areas.
Sex-based clinical and immunological differences in COVID-19
Authors: Huang Bin , Li Ning , Cai Yun , Li Kening , Wang Zhihua , Li Lu , Wu Lingxiang , Zhu Mengyan , Li Jie , Wang Ziyu , Wu Min , Li Wanlin , Wu Wei , Zhang Lishen , Xia Xinyi , Wang Shukui , Chen Hongshan , Wang Qianghu
Published: November 2020

Background
Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take sex as consideration.
Methods
We performed an unbiased sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and SARS-CoV-2 specific antibody levels of 1,558 males and 1,499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. Total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.
Results
We found that the mortality and ICU admission rates were approximately 2-fold higher in males than that in females (P < 0.005). Survival analysis revealed that sex is an independent prognostic factor for COVID-19 (Hazard ratio = 2.2, P = 0.003). The concentration of inflammatory factors in peripheral blood was significantly higher in males. Besides, the renal and hepatic abnormality induced by COVID-19 was more common in males during the hospitalization. The analysis of lymphocyte subsets revealed that the percentage of CD19 + B cell and CD4 + T cell was significantly higher in females (P < 0.001) during hospitalization, indicating the stronger humoral immunity in females than males. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in females, while gradually increased and reached a peak in the seventh week in males.
Conclusions
The unfavorable prognosis of male COVID-19 patients may result from the weak humoral immunity and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients. Convalescent plasma therapy may help improve the immunity of males to fight against SARS-CoV-2 infection.
Axonal TDP-43 Drives NMJ Disruption through Inhibition of Local Protein Synthesis
Authors: Altman Topaz , Ionescu Ariel , Ibraheem Amjad , Priesmann Dominik , Gradus-Pery Tal , Farberov Luba , Alexandra Gayster , Shelestovich Natalia , Shomron Noam , Dori Amir , Krueger Marcus , Perlson Eran
Published: November 2020

Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons of ~95% of ALS patients, but the contribution of axonal TDP-43 to this fatal neurodegenerative disease is unclear. Here, we find TDP-43 accumulation in the axons of intra-muscular nerves from ALS patients, and in motor neurons and neuromuscular junctions (NMJs) of a mouse model with TDP-43 mislocalization. This leads to the formation of G3BP1- and TDP-43- positive RNA-granules in motor neuron axons, and to inhibition of local protein synthesis in axons and NMJs. Specifically, the axonal and synaptic levels of nuclear-encoded mitochondria proteins are reduced. Clearance of axonal TDP-43 restored local translation of the nuclear-encoded mitochondrial proteins and rescued TDP-43-derived axonal and NMJ toxicity. These findings suggest that targeting TDP-43 axonal gain of function may mediate a therapeutic effect in ALS.
Food price volatility and socio-inequalities in household food insecurity during coronavirus disease-2019 lockdown in Nansana municipality, Wakiso district Uganda
Authors: Buzigi Edward , Onakuse Stephen
Published: November 2020

BackgroundThis study assessed staple food price volatility, food consumption scores (FCS) and prevalence of household food insecurity (HHFI) and its socio-inequalities during enforcing and lifting corona virus disease -2019 (COVID-19) lockdown in Nansana municipality, Uganda.MethodsA repeated households (HHs) based cross-sectional study was conducted in urban Nansana Municipality, Uganda. A total of 405 HHs (205 slum and 200 non-slum) were selected using stratified random sampling. Data on social demographics and FCS in the previous 7 days were collected using questionnaire-based telephone interviews with HH heads. Prices for staple foods was collected by asking food sellers from local markets. Mean staple food price differences between before COVID-19 lockdown and during enforcing or lifting the lockdown was tested by paired t test. A binary outcome of HHFI (FCS of 0-35) and food secure (FCS>35) HHs was created. The association between exposure variables and HHFI was tested using multivariate logistic regression analysis at a probability value of 5%.ResultsMean price of staple food significantly increased between before and during enforcing the COVID-19 lockdown (p <0.0001). Mean FCS during COVID-19 lockdown were at borderline for either slum (22.8) or non-slum (22.9) HHs, and were not significantly different from each other (p=0.06). During partial lifting of the lockdown, FCS among slum HHs were significantly lower at 20.1 (poor) compared to non-slum HHs at 22.7 (borderline) (p=0.01). The mean FCS was significantly higher at borderline (24.5) among HHs that received food aid compared to poor FCS (18.2) among slum HHs that did not receive food aid (p<0.0001). The prevalence of HHFI was high and not significantly different (p>0.05) between slum (94.6%) and non-slum (93.5%) HHs during COVID-19 lockdown. HHFI was higher in slum (98.5%) than non-slum (94%) HHs (p<0.05) on partial lifting of the lockdown. Adjusted odds ratio (AOR) showed that being a wage earner and employed HH head was positively (AOR: 8.3, 95% CI: 1.9-36.2) and negatively (AOR: 0.07, CI: 0.02-0.2) associated with HHFI, respectively. During partial lifting of COVID-19 lockdown, slum HHs (AOR: 11.8, 95% CI: 1.5-91.3), female headed HHs (AOR: 11.9, 95%CI: 1.5-92.7), wage earners (AOR: 10.7, 95% CI: 1.4-82.9) and tenants (AOR: 4.0, 95% CI: 1.1- 14.7) were positively associated with HHFI. Conclusion Staple food prices increased during enforcing COVID-19 lockdown compared before lockdown. Food aid distribution during COVID-19 lockdown improved FCS among slum HHs, however, it did not prevent against slum HHFI.
Inhibitory effect of Fruitflow on platelet function: a randomized placebo-controlled trial in elderly subjects
Authors: Chen Huilian , Zhang Shenghao , Wang Hui , Jiang Yun , Bao Li , Wu Wei , Qi Ruomei
Published: November 2020

Background: The elderly have a high risk of cardiovascular disease, which is often accompanied by platelet hyperactivity. Tomato extracts can inhibit platelet activation and have beneficial health effects. We aimed to investigate the effect of Fruitflow (FF), a water-soluble tomato extract, on platelet function in elderly subjects.Methods: This randomized group study was conducted with people over 50 years old. The participants were randomly divided into four groups: placebo (150 mg/day), FF (150 mg/day), acetylsalicylic acid (ASA; 100 mg/day), and FF (150 mg/day) + ASA (100 mg/day). These groups received the respective supplements after dinner daily for 7 days. Fasting blood was collected from the participants on days 0 and 8 to analyze platelet aggregation and the content of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α, and platelet factor 4 (PF4). Results: One hundred ninety elderly subjects were recruited and completed this clinical trial. The results showed that the FF intervention for 7 days decreased platelet aggregation by 7.7% in adenosine diphosphate-stimulated platelets, which was similar to the effect of ASA, which decreased platelet aggregation by 9.4%. Fruitflow reduced platelet aggregation by 10.2% in collagen-stimulated platelets, and ASA reduced platelet aggregation by 38.3% in collagen-activated platelets. This suggests that ASA exerts a stronger inhibitory effect than FF on collagen-stimulated platelet aggregation. The combination of FF + ASA did not exert a synergistic inhibitory effect on platelet aggregation. Treatment with FF significantly decreased plasma TXB2, 6-keto-PGF1α, and PF4 levels, and its effects were similar to ASA. Conclusion: Fruitflow suppressed platelet aggregation and decreased TXB2, 6-keto-PGF1α, and PF4 levels in elderly subjects. These findings indicate that FF might reduce the risk of thrombosis in cardiovascular diseases.Trial registration code: ChiCTR2000034647 at www.clinicaltrials.gov.
Physician perceived barriers and solutions to DASH diet recommendations for hypertension prevention and management
Authors: Park Ha Eun , Billups Sarah J , Schilling Lisa M
Published: November 2020

BackgroundThe Dietary Approach to Stopping Hypertension (DASH) is proven to lower systolic and diastolic blood pressure up to 7.8 and 3.7 mmHg, respectively and is considered first-line therapy per national guidelines. Yet, implementation into clinical practice remains suboptimal. MethodsWe designed a provider survey to identify and characterize physician-identified barriers to providing DASH diet to eligible primary care patients to reduce blood pressure. The survey assessed four domains: (1) provider beliefs/knowledge of DASH benefits (2) patient characteristics influencing likelihood of recommendation, (3) practice barriers to provision of DASH diet advice/education, and (4) resources necessary to facilitate use. We conducted qualitative interviews with 4 primary care physicians and designed a 7-item Likert scale-based survey.Participants: University of Colorado affiliated primary care clinics and School of medicine faculty providers working in Denver metro.ResultsThe survey was sent electronically to 149 providers, with 49 (33%) responders. Most providers (65%) believed DASH diet is as effective at lowering blood pressure as adding a medication for patients with pre-hypertension and established hypertension. Providers identified perceived low patient motivation (88%) and low ability to implement DASH diet into patient’s lifestyle (88%) as patient factors influencing their decision to provide DASH diet education. The most significant practice barriers were lack of time (71%) and lack of patient-directed educational resources (67%). Resources providers would find useful included resources accessible through the electronic medical record, (88%), a dietician (83%), and printed patient education materials (59%).ConclusionMost physicians believe DASH diet is effective at lowering blood pressure. The most common barriers to providing DASH education are low perceived patient ability or motivation, lack of provider time, and lack of patient-directed educational resources. Providers identified that readily available electronic and printed materials and access to dieticians would help improve DASH counseling in practice.
Giant optical anisotropy in transition metal dichalcogenides for next-generation photonics
Authors: Ermolaev Georgy , Grudinin D. , Stebunov Y. , Voronin K. , Kravets Vasyl , Duan Jiahua , Mazitov A. , Tselikov G. , Bylinkin Andrei , Yakubovsky D. , Novikov S. , Baranov Denis , Nikitin Alexey , Kruglov Ivan , Shegai Timur , Alonso-González Pablo , Grigorenko Alexander , Arsenin Aleksey , Novoselov Kostya , Volkov V.
Published: November 2020

Large optical anisotropy observed in a broad spectral range is of paramount importance for efficient light manipulation in countless devices. Although a giant anisotropy was recently observed in the mid-infrared wavelength range, for visible and near-infrared spectral intervals, the problem remains acute with the highest reported birefringence values of 0.8 in BaTiS3 and h-BN crystals. This inspired an intensive search for giant optical anisotropy among natural and artificial materials. Here, we demonstrate that layered transition metal dichalcogenides (TMDCs) provide an answer to this quest owing to their fundamental differences between intralayer strong covalent bonding and weak interlayer van der Walls interaction. To do this, we carried out a correlative far- and near-field characterization validated by first-principle calculations that reveals an unprecedented birefringence of 1.5 in the infrared and 3 in the visible light for MoS2. Our findings demonstrate that this outstanding anisotropy allows for tackling the diffraction limit enabling an avenue for on-chip next-generation photonics.
Oral health, caries risk profiles, and oral microbiome of pediatric patients with leukemia submitted to chemotherapy
Authors: Wang Yan , Zeng Xinyi , Yang Xue , Que Jiajia , Du Qin , Zhang Qiong , Zou Jing
Published: November 2020

Background: Chemotherapy is the primary treatment modality used for patients with acute lymphoblastic leukemia (ALL), but inevitably causes microbiota-related oral complications. This study aims to investigate the effects of chemotherapy on oral health status, caries risk, and oral microbiome in pediatric patients with ALL. Methods: Thirty-nine children with ALL receiving chemotherapy were enrolled, and a gender-, age-, dentition stage and socioeconomic class matched healthy counterpart (HC) were recruited. Demographic information and overall health condition were obtained through questionnaire or medical records. Oral examination was performed to assess caries and salivary status, plaque index and other oral manifestations. Cariogram was used to assess the overall caries risk. Supragingival samples of thirteen ALL subjects and their counterparts were randomly selected to perform a 16S ribosomal RNA gene 454 pyrosequencing. Raw sequence data were screened, trimmed, and filtered using Seqcln and MOTHUR. Results: The prevalence of dental caries, gingivitis, oral mucositis, xerostomia and candidiasis in ALL group was higher than that of control group (p < 0.05). Children with ALL demonstrated higher caries risk compared with healthy controls based upon Cariogram (p < 0.05). The oral microbial structure of ALL patients receiving chemotherapy is different from that of healthy controls. Oral microbiota of ALL group showed less alpha diversity and significant differences in the composition of the oral microbiome compared to healthy controls. Conclusions: ALL patients receiving chemotherapy demonstrated compromised oral health, high caries risk, alteration of caries related factors and dysbiosis of oral microbiota. These findings may possibly be of clinical importance in developing better strategies for personalized preventive management of oral diseases for pediatric children with ALL.
Cranioplasty with three-dimensional customised mould for polymethylmethacrylate implant: a series of 11 consecutive patients with cost-effectiveness consideration
Authors: Silva Erasmo Barros da , de Aragão Afonso Henrique , Loureiro Marcelo de Paula , Lobo Caetano Silva , Oliveti Ana Flávia , de Oliveira Rafael Martinelli , Ramina Ricardo
Published: November 2020

Background
Different methods of cranioplasty for the reconstruction of bony skull defects exist. In the absence of the autologous bone flap, a customised manufactured implant may be the optimal choice, but this implant has several limitations regarding its technical standardisation and better cost-effectiveness.
Methods
This study presents a series of 11 consecutive patients who had undergone cranioplasty with customised three-dimensional (3D) template moulds for polymethylmethacrylate (PMMA) implants manufactured after 3D modelling on a specific workstation. The virtual images were transformed into a two-piece physical model using a 3D printer for the biomaterials. PMMA implant was produced intraoperatively with the custom mould. Cosmetic results were analysed by comparing pre- and postoperative 3D computed tomography (CT) images and asking if the patient was satisfied with the result.
Results
The average total time for planning and production of customised mould was 10 days. The 11 patients were satisfied with the result, and CT images presented harmonious symmetry when comparing pre- and postoperative scans. Cases of postoperative infection, bleeding, or reoperation in this series were not observed.
Conclusion
Cranioplasty with high-technology customised 3D moulds for PMMA implants can allow for an aesthetic reconstruction with a fast and cost-effective manufacturing process and possibly with low complication rates.
Effects of Coronavirus Disease 2019 (COVID-19) Pandemic on Antimicrobial Prevalence and Prescribing in a Tertiary Hospital in Singapore
Authors: Ng Tat Ming , Tan Sock Hoon , Heng Shi Thong , Tay Hui Lin , Yap Min Yi , Chua Boon Hou , Teng Christine B , Lye David C , Lee Tau Hong
Published: November 2020

Background: The deployment of antimicrobial stewardship (AMS) teams to deal with the COVID-19 pandemic can lead to a loss of developed frameworks, best practices and leadership resulting in adverse impact on antimicrobial prescribing and resistance. We aim to investigate effects of reduction in AMS resources during the COVID-19 pandemic on antimicrobial prescribing and resistance.Methods: One of 5 full-time equivalent AMS pharmacists was deployed to support pandemic work and AMS rounds with infectious disease physicians were reduced from 5 to 2 times a week. A survey in acute inpatients was conducted using the Global Point Prevalence Survey methodology in July 2020 and compared with those in 2015 and 2017-2019.Results: The prevalence of antimicrobial prescribing (55% in 2015 to 49% in 2019 and 47% in 2020, p =0.02) and antibacterials (54% in 2015 to 45% in 2019 and 42% in 2020, p < 0.01) have been reducing despite the pandemic. Antimicrobial prescribing in infectious disease wards with suspected or confirmed COVID-19 cases was 29% in 2020. Overall, antimicrobial prescribing quality indicators continued to improve (e.g. reasons in notes, 91% in 2015 to 94% in 2019 and 97% in 2020, p <0.01) or remained stable (compliance to guideline, 71% in 2015 to 62% in 2019 and 73% in 2020, p =0.08). Conclusion: AMS efforts over the years paid dividends during the COVID-19 pandemic to sustain the control of antimicrobial prevalence and quality of AMU in non-COVID-19 wards and plausibly also in COVID-19 wards.
The Regulation of Macrophage Polarization by Hypoxia-PADI4 Coordination in Rheumatoid Arthritis
Authors: Cheng Yu , Si Yuying , Wang Lan , Ding Menglei , Yu Shanshan , Chen Cuncun , Lu Liu , Guo Yide , Zong Ming , Fan Lieying
Published: November 2020

Background: Hypoxia, a common feature of rheumatoid arthritis (RA), induces the overexpression of peptidyl arginine deiminase 4 (PADI4) in fibroblast-like synoviocytes (FLSs) and macrophages. However, the roles of PADI4 and its inducer hypoxia in the regulation of macrophage polarization remain unclear. This study aimed to investigate the role of hypoxia-PADI4 for macrophage polarization in RA patients.Methods: synovial tissue(ST) and synovial fluid(SF) were collected from 3 OA patients and 6 RA patients. The distribution of M1 and M2 in ST and cytokines in SF were examined by immunohistochemical analysis and BioPlex immunoassays. THP-1 macrophages and BMDM polarization were determined under normoxic (21% oxygen) or hypoxic (3% oxygen) conditions. The effects of PADI4 on macrophages were determined by transfection of adenovirus vector-coated PADI4 (AdPADI4) and the use of PADI4 inhibitor. To mimic the environment of RA joints, THP-1 macrophages polarization was examined after coculturing with RA-FLSs. Finally, the roles of PADI4 in joint synovial lesions on macrophage polarization were investigated in collagen-induced arthritis(CIA) rats.Results: We found increased macrophage polarization of M1 and M2 in the RA ST, compared with OA ST. The ratio of M1/M2 for RA and OA was 1.633 ± 0.1443 and 2.544 ± 0.4429, respectively. The concentration of M1- and M2-type cytokines was higher in RA than that in OA patients. Hypoxia contributed to the increase of the gene and protein expression of M1 and M2 markers. M1- but not M2-type gene expression showed a positive relationship with PADI4 expression while the level of expression of M2-type genes showed no significant difference. RA-FLSs could promote the copolarization of M1 and M2, and PADI4 inhibitor reversed M1 activation. The degree of joint swelling and destruction was effectively alleviated, and the number of macrophages especially M1 decreased in CIA rats after downregulating PADI4 expression.Conclusion: Hypoxia is responsible for the copolarization of M1 and M2. Hypoxia-associated PADI4 is responsible for M1 macrophage activation, implying that inflammatory environment can be eased by decreasing PADI4 expression and improving the hypoxic environment.
Effects of Co-substrates’ Mixing Ratios and Loading Rate Variations on Food and Agricultural Wastes’ Anaerobic co-digestion Performance
Authors: Chaher Nour El houda , Engler Nils , Nassour Abdallah , Nelles Michael
Published: November 2020

Tunisia is one of the developing countries which faces crucial challenges, the most prominent of which are the production of organic waste, the need for an appropriate waste treatment, and the demand for water and energy conservation. To this end, the present research was designed to develop a technical concept on closed cycle ‘biowaste to bioenergy’ treating food waste (FW) through combined biological processes. In this approach, semi-continuous anaerobic co-digestion (ACoD) of FW, wheat straw (WS), and cattle manure (CM) was tested to investigate the relationship between the effect of the feedstock mixtures and C:N ratio on biogas and digestate generation at different organic loading rates (OLRs) ranging from 2 to 3.6 kg VS/m3.d. Results showed that the mono-digested FW was optimal and reached 565.5 LN/kg VSin at an OLR of 2.4 kg VS/m3.d, and then a drop of biogas production was recorded. However, for co-digested substrates, the optimum mixture ratio was FW:CM 75:25, where 62%, 39.89%, 91.26%, 130.9% and 119.97% of the biogas yield improved for OLRs ranging from 2 to 3.6 kg VS/m3. d, respectively. Admittedly, the target of this work was to enhance the ACoD process, but it also examined the exploitation of different AD-effluents. Therefore, special attention was paid to the generated digestates to decide how it can be efficiently upcycled later. Thus, the closed cycle ‘biowaste to bioenergy’ treatment met two of the major Tunisian concerns: efficient organic waste management as well as sustainable bioenergy production.
Potential aggregation hot spots in recombinant human keratinocyte growth factor; a computational study
Authors: Dastjerdeh Mansoureh Shahbazi , Shokrgozar Mohammad Ali , Rahimi Hamzeh , Golkar Majid
Published: November 2020

Background: Recombinant human keratinocyte growth factor is a highly aggregation-prone therapeutic protein. The high aggregation liability of rhKGF is manifested by loss of the monomeric form of the protein and accumulation of the aggregated species even at moderate temperatures. Here, we analyzed rhKGF for its vulnerability towards aggregation by detection of aggregation-prone regions (APRs) using several sequence-based computational tools including TANGO, SolubiS, ZipperDB, AGGRESCAN, Zyggregator, Camsol, PASTA, SALSA, WALTZ, SODA, Amylpred, AMYPDB, and structure-based tools including Aggrescan3D and molecular dynamics-based spatial aggregation propensity (SAP) algorithm. Results: The sequence-based prediction of APRs in rhKGF indicated that they are mainly located at positions 10-30, 40-60, 61-66, 88-120, and 130-140 which are rich in β-branched aliphatic, hydrophobic, aromatic and Glutamine/Aspargine (Q/N) residues. Mapping on the rhKGF tertiary structure revealed that most of these residues including F16-R25, I43, E45, R47-I56, F61, Y62, N66, L88-E91, E108-F110, A112, N114, T131, and H133-T140 are surface-exposed in the natively folded protein which can promote aggregation without major unfolding event or the conformational change may occur in the oligomers composed of natively folded monomers. The other regions are buried in the native state and their contribution to non-native aggregation is mediated by a preceding unfolding event in the monomeric state of the protein. The structure-based prediction of APRs using SAP tool limited the number of identified APRs to the dynamically-exposed hydrophobic residues including V12, A50, V51, L88, I89, L90, I118, L135, and I139 mediating the native-state aggregation. Conclusion: Our analysis of APRs in rhKGF identified the regions determining the intrinsic aggregation propensity in both folded (native) and unfolded state of the protein. These regions are the candidate positions for engineering the rhKGF sequence to reduce its aggregation tendency.
A Negative Feedback Model to Explain Regulation of SARS-CoV-2 Replication and Transcription
Authors: Li Xin , Cheng Zhi , Wang Fang , Xuan Yibo , Zhao Qiang , Zhou Hao , Liu Chang , Ruan Jishou , Duan Guangyou , Gao Shan
Published: November 2020

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription mechanisms of SARS-CoV-2 has recently emerged, their regulation remains unclear.Results: Based on reanalysis of public data, we propose a negative feedback model to explain the regulation of replication and transcription in—but not limited to—CoVs. The key step leading to new discoveries was the identification of the cleavage sites of nsp15—an RNA uridylate-specific endoribonuclease, encoded by CoVs. According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs) and genomic RNAs (gRNAs) by cleaving transcription regulatory sequences in the body. The expression level of nsp15 determines the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nps15 to reach equilibrium between the replication and transcription of CoVs.Conclusions: The replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g. uridine derivatives) against CoVs.
Baicalein Inhibits Heparin-induced Tau Aggregation by Initializing Tau Oligomer Formation 
Authors: Sonawane Shweta K , Uversky Vladimir N , Chinnathambi Subashchandrabose
Published: November 2020

BackgroundAmyloid aggregate deposition is the key feature of Alzheimer’s disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (Aβ) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable of preventing the aggregation of these intrinsically disordered proteins by inhibiting the early stages of their pathological transformations. Polyphenols are known to be neuroprotective agents with the noticeable potential against many neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Prion diseases. MethodsWe analyzed the capability of Baicalein to inhibit aggregation of human Tau protein by a multifactorial analysis that included several biophysical and biochemical techniques. ResultsThe potency of baicalein, a polyphenol from the Scutellaria baicalensis Georgi, against many neurodegenerative diseases has been screened and validated. ThS fluorescence assay revealed the potent inhibitory activity of Baicalein, whereas ANS revealed its mechanism of Tau inhibition viz. by oligomer capture and dissociation. In addition, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action. Tau oligomers formed by Baicalein were non-toxic to neuronal cells, highlighting its role as a potent molecule to be screened against AD. ConclusionIn conclusion, Baicalein inhibits aggregation of hTau40 by enhancing the formation of SDS-stable oligomers and preventing fibril formation. Baicalein-induced oligomers do not affect the viability of the neuroblastoma cells. Therefore, Baicalein can be considered as a lead molecule against Tau pathology in AD.
Numerical Study of Reasonable Cycle Step Length for Longwall Top-coal Drawing in Extra-thick Coal Seams Based on the Particle-block Element Coupling Approach
Authors: Wang Yaochuang , Li Dongyin , Wang Shen , Zhu Shiting , Wang Zuguang
Published: November 2020

The cycle step length (CSL) is a significant parameter for longwall top-coal drawing technology that remarkably affects the top-coal recovery rate and the rock-mixing rate, especially for extra-thick coal seams. In this study, a particle-block element coupling approach is performed to investigate a reasonable CSL for extra-thick coal seams. By comparing this approach to the Bergmark-Roos analytical result, the proposed numerical model is verified, showing good performance in modeling top-coal caving. A 2-D numerical model of hydraulic support considering the mechanical behavior of the legs is established, which can be used for modeling the interaction between the hydraulic support and the top coals during the top-coal drawing process. The top-coal recovery rate, the top-coal drawing body shape, and the evolution characteristics of the coal-rock interface under different CSL conditions are compared. In addition, the mechanism of the lost top coal affected by the CSL is revealed. The results show that the CSL of top-coal drawing has a significant effect on the morphology of the coal-rock interface and the mutual invasion of coal and rock, which is the primary reason for coal loss and further affects the top-coal recovery rate and the rock-mixing rate. It is suggested that the CSL should be 0.8 m when the top-coal thickness is 12 m.
Caveolin-1 Mediated Endocytic Pathway is Involved in Encephalomyocarditis Virus Replication in BHK-21 Cells
Authors: Li Qiongyi , Liu Yang , Xu Shujuan , Zhao Kexue , Ling Ying , Liu Rongxiu , Ali Amjad , Bai Jialin
Published: November 2020

Background: Encephalomyocarditis virus, member of Cardiovirus genus within Picornaviridae family, is an important pathogen that infects different domestic and wild animals. However, the molecular mechanism of its entry remains unclear. In this study, we investigated the mechanism of EMCV infectivity in relation to endocytic pathway using BHK-21 cells. Methods: The function of numerous cellular key factors implicated in the various endocytic mechanisms were systematically explored using chemical inhibitors. Furthermore, RNA interference (RNAi) as well as the overexpression of dominant protein combined to virus infectivity assays, and confocal microscopy was used to examine EMCV infection in details. Results: The results indicated that the EMCV entry into BHK-21 cells depends on caveolin, dynamin, and actin but not clathrin nor macropinocytosis pathways. The effects of overexpression and knockdown of caveolin-1, one components of the caveolae, was examined on EMCV infection. The results showed that EMCV infection was positive correlation with caveolin-1 expression. Confocal microscopy analysis and internalization assay showed that caveolin-1 is required at the early stage of EMCV infection. Conclusions: Caveolin-1, dynamin, and actin-dependent endocytosis pathways are necessary for EMCV infection in vitro.
A Case of Right Shoulder Penetrating Injury Inflicted by a Hollow Metal Fence
Authors: Guo Peng-chao , Zhao Guang-feng , Zhang Mao
Published: November 2020

Background: Right shoulder penetrating injury are rare and challenging diagnoses that should not be missed.Case presentation: The patient, a 30-year-old male, had a clear mind, stable vital signs, a gcs score of 15 points, unbearable pain in his right shoulder and chest wall, and no abnormal breathing. His right radial artery was unclear, and the right ulnar artery was thin and unclear, suggesting comminuted fractures of the right humeral shaft and scapula. After the multi-disciplinary discussion in the emergency department, we planned to perform an emergency operation to take out the foreign body from his right shoulder.Conclusions: Penetrating injury is very important to systematically and comprehensively assess the peripheral vascular nerve and muscle tissue at the site of injury. The foreign body should be carefully removed during the operation to avoid further damage to the patient, and it is necessary to perform fluoroscopy again after the removal of the foreign body. The placement of drainage, secondary debridement and sutures, and fixation can effectively reduce postoperative infection.