bluuebunny/crossref_metadata_2025 huggingface dataset:
The Function Role of Ubiquitin Proteasome Pathway in the ER Stress-induced AECII Apoptosis during Hyperoxia Exposure
Authors: Zhu Yue , Ju Huimin , Lu Hongyan , Tang Wei , Lu Junying , Wang Qiuxia
Published: July 2021

Backgroud: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and morbidity in premature infants, characterized by alveolar dysplasia and pulmonary microvascular remodeling. In the present study, we have investigated the functional roles of ubiquitin proteasome pathway (UPP) in BPD, and its relationship with endoplasmic reticulum stress (ER stress, ERS) mediated AECII apoptosis. Methods: A hyperoxia-induced BPD rat model was constructed and the pathologic changes of lung tissues were evaluated by Hematoxylin-Eosin staining. Cell apoptosis and protein expression were determined by TUNEL assay and Western blotting, respectively. Further reagent kit with specific fluorescent substrate was utilized to measure the activity of 20s proteasome. Meanwhile, AECII were cultured in vitro and exposed to hyperoxia. AECII apoptosis were measured by flow cytometry. In contrast, MG132 treatment was induced to explore ubiquitin proteasome pathway during hyperoxia exposure on AECII apoptosis and ERS sensors expression.Results: A significant increase in apoptosis and total ubiquitinated proteins expression were observed in BPD rats and AECII culture, and the change of UPP was associated with ERS. In order to confirm the role of UPP in AECII apoptosis of BPD, AECII cells were treated by MG132 with the concentration of 10 μmol/L under hyperoxia exposure. We found that the proteins expression of GRP-78, PERK, ATF4, ATF6 and CHOP, as well as AECII apoptosis were increased following MG132 treatment. Furthermore, the relatively up-regulated in the levels of total ubiquitinated proteins expression and 20S proteasome activity were correlated with increased ERS sensors expression. Conclusions: Our findings indicate that UPP may participate in the ERS-induced AECII apoptosis under hyperoxia condition.
Surgically Managed Symptomatic Intraspinal Lumbar Facet Synovial Cyst: Outcome of surgical treatment with resection and instrumented posterolateral fusion, a case series.
Authors: Lalanne Lyonel Beaulieu , Lemos Facundo Alvarez , Carmona Roberto Larrondo , Totera Juan Ignacio Cirillo , Montoya Andre Beaulieu , Wilson Jose Muñoz
Published: July 2021

PURPOSE: There is controversy regarding the treatment of symptomatic synovial cysts (SSC), specifically, the need for a concomitant fusion when surgical resection of the CS is required. We present a retrospective review of a series of patients treated for SSC of the lumbar region during the last 20 years by a single surgeon, analyzing the current available literature. METHODS: Retrospective review. The same surgical technique was applied to all patients. Demographic, clinical, surgical data and synovial cyst recurrence rate were recorded. Postoperative results reported by patients were documented according to the McNab score. RESULTS: 69 subjects, with mean follow-up of 7.4 years. 62% (43) were female, with a mean 57.8 years at the time of surgery. In 91.3% (63), the primary management was conservative for a minimum period of 3 months. All subjects underwent surgery due to the failure of conservative treatment. The segment most operated on was L4-L5 (63.77%). 91.3% (63) of the sample reported excellent and good and 6 subjects (8.6%) fair or poor results. There was no evidence of CS recurrence at the operated level. CONCLUSION: In SSC, it seems that conservative treatment is only effective in a limited number of patients and in the short term. Thus, the recommendation of a surgical indication should proceed as soon as the conservative management fails to result in significant symptom relief. Based on our results, we recommend, together with the resection of the cyst, the instrumentation of the segment to avoid its recurrence and the management of axial pain.
Meteorological Analysis of the Relationship between Climatic Parameters: Understanding the Dynamics of the Troposphere
Authors: Agbo Emmanuel P , Edet Collins
Published: July 2021

Understanding the relationship between the variations of meteorological parameters is vital in tackling the climatic problem. This paper presents methods for analyzing parameters that relate directly and indirectly to each other and accurate methods for interpreting their results. Using obtained data for 14 years and calculated data for other parameters, we adopt the Mann-Kendall (M-K) test for the trend analysis of the annual and seasonal variations, the correlation matrixes, and linear regression pair plots to discern the relationship between all parameters using the python programming software. To crystalize results, partial derivatives relating the equivalent potential temperature (EPT) for a pseudo-adiabatic process with parameters affecting its variation from equations are being obtained. The magnitude of these derivatives' gradients was used to bolster regression results, showing the mixing ratio (MR) of air as the parameter with the most effect on EPT variation. The MK test results show that the atmospheric pressure (AP) and average ambient temperature (AT) were all increasing significantly for all variations (annual, dry and wet seasons). In contrast, others varied between dry and wet seasons after adopting a benchmark significance level of 5% (0.05). The correlation matrixes and linear regression pair plots show a strong relationship between the variations of refractivity, EPT, the temperature at the lifting condensation level (TL), MR, vapor pressure (VP), specific humidity (SH), and the dew point temperature (DPT). The potential temperature (PT), saturated vapor pressure (SVP), saturated mixing ratio (SMR), and the AT relationships showed a robust positive correlation/regression. This correlation offers a connection between the AT and the PT. The processes, including the partial derivatives, pair plots, correlation matrixes, and tests for trends, provide a solution to the meteorological analysis problem. Results and methods can be applied in other regions.
Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
Authors: Singh Dhiraj , Aladyeva Ekaterina , Das Shibali , Singh Bindu , Esaulova Ekaterina , Swain Amanda , Ahmed Mushtaq , Cole Journey , Moodley chivonne , Mehra Smriti , Schlesinger Larry , Artyomov Maxim , Khader Shabaana , Kaushal Deepak
Published: July 2021

The emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. While studies have reported immune profiling using single cell RNA sequencing in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. We performed longitudinal single-cell RNA sequencing of bronchoalveolar lavage (BAL) cell suspensions from adult rhesus macaques infected with SARS-CoV-2 (n=6) to delineate the early dynamics of immune cells changes. The bronchoalveolar compartment exhibited dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi) (peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline). We observed the accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I IFN response was highly induced in the plasmacytoid dendritic cells. The presence of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin converting enzyme 2 (ACE2) expression was also observed. These macrophages were significantly recruited to the lungs of macaques at 3dpi and harbored SARS-CoV-2, while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery. The recruitment of a myeloid cell-mediated Type I IFN response is associated with the rapid clearance of SARS-CoV-2 infection in macaques.
Predicting Harmful Algal Blooms and Impacts on Shellfish Mariculture using Novel Data-Driven Approaches
Authors: Stoner Oliver , Economou Theo , Torres Ricardo , Ashton Ian , Brown Andrew
Published: July 2021

Harmful algal blooms (HABs) intoxicate and asphyxiate marine life, causing devastating environmental and socio-economic impacts costing at least $8bn/yr globally. Accumulation of phycotoxins from HAB phytoplankton in filter-feeding shellfish can poison human consumers, prompting site harvesting closures if concentrations in shellfish exceed safe levels. To better quantify both long- and short-term HAB risks, we developed novel data-driven approaches to predict phycotoxin concentrations in bivalve shellfish associated with HAB forming Dinophysis species. Our spatiotemporal statistical modelling framework assesses long-term HAB risks for different shellfish species in both data-rich and data-poor locations. This can revolutionise mariculture management by more confidently informing optimal siting of new shellfish operations and safe harvesting periods for businesses. Meanwhile, our machine learning framework forecasts phycotoxin concentrations further into the future than previously possible. Across 6 coastal, estuarine and loch sites, we achieve 87% overall accuracy in predicting future harvesting shutdowns 0-8 weeks ahead.
Cremation Based Estimates Suggest Significant Under- and Delayed Reporting of COVID-19 Epidemic Data in Wuhan and China
Authors: He Mai , Li Li , Yan Weisi , Dehner Louis P. , Dunn Lucia F.
Published: July 2021

Objective:China’s COVID-19 statistics fall outside of recognized and accepted medical norms. Here we estimated the incidence, death and starting time of the COVID-19 outbreak in Wuhan and China based on cremation related information. Methods: Data sources included literature on COVID-19 in China, official Chinese government figures, and media reports. A range of estimates is presented by an exponential growth rate model. Results:For the cumulative infections and total deaths, under different assumptions of case fatality rates (from 2.5% to 10%) and doubling time 6.4 days, the estimates projected on February 7, 2020 in Wuhan range from 305,000 to 1,272,000 for infections and from 6,811 to 7,223 for deaths - on the order of at least 10 times the official figures (13,603 and 545). The implied starting time of the outbreak is October 2019. The estimates of cumulative deaths, based on both funeral urns distribution and continuous full capacity operation of cremation services up to March 23, 2020, give results around 36,000, more than 10 times of the official death toll of 2,524. Conclusions:Our study indicates a potential significant under- and delayed reporting in Chinese official data on the COVID-19 epidemic in Wuhan in early February, 2020.
Multi-Objective Optimization of Properties of Sponge Gourd-Bagasse Hybrid Reinforced Polymer Composite Using Fuzzy Logic, PSO, Modified Desirability Function and NSGA II
Authors: Chibueze Ikechukwu , Obele Chizoba , NWOBI-OKOYE CHIDOZIE , Atuanya Clement
Published: July 2021

Development of mathematical models for prediction of properties of materials is often complex and cumbersome. This led to the advent of simpler, and often more accurate, computational models based on artificial intelligence for predicting materials properties. The aim of this study is to predict the mechanical properties of a newly developed hybrid composite material made with sponge gourd, baggase and epoxy resin for golf club application using fuzzy logic (FL) and carry out a multi-objective optimization of the properties with modified desirability function (DF) and NSGA II algorithm. The inputs were %Wt of baggase, %Wt of Sponge gourd and Fiber size (µm) while the response variables were tensile strength, hardness, flexural strength, modulus, elongation and impact strength. The FL model was separately coupled, as fitness function, with the modified DF algorithm and the NSGA II algorithm respectively. The DF was optimized with particle swarm optimization (PSO) algorithm. The results showed that the FL model predicted the mechanical properties accurately and the minimum correlation coefficient (R) between the experimental responses and FL predictions was 0.9529. The modified algorithms took care of certain peculiarities in the desirability properties such as elongation whose desirability is constant over a range. The optimized properties were found to be worse if the optimization algorithms were not modified.
Optimization of Multimode Fibers for Surface Plasmon Resonance based Sensors under Spectral and Single Wavelength Intensity Interrogation
Authors: Sital Shivani , Baliyan Anjli , Sharma Enakshi Khular , Gupta Mridula
Published: July 2021

In an optical fiber based SPR sensor, a segment of metal clad silica fiber is used as the sensing element and resonant coupling occurs to the surface plasmon mode excited at the interface of the metal and ambient which surrounds the sensing element. When polychromatic light is transmitted through the sensing element the spectrum of light detected at the other end shows minima at a resonance wavelength. In wavelength interrogation the shift in the resonance wavelength is a measure of change in the refractive index of the ambient. Alternatively, intensity interrogation can be used in which the change in transmitted power at a given wavelength is a measure of change in refractive index of the ambient. The sensitivity and detection accuracy of the sensor depend on the numerical aperture (NA) of the multimode optical fiber used to fabricate the sensor. We have carried out a study of the dependence of the sensitivity and detection accuracy on numerical aperture to obtain the optimal value for a multimode optical fiber which is used to fabricate the sensing element under both wavelength and intensity interrogation. Experimental results on a sensing element fabricated with gold coating on the core of a plastic clad silica fiber are also reported.
Comprehensive Analysis of DNA Damage Repair Genes and Identification of RAD54L as an Immunological and Prognostic Biomarker in Clear Cell Renal Cell Carcinoma and Other Cancers
Authors: Wang Song , Yang Zitong , Yi Jiahe , Liu Zixiang , Li Jiangfeng , Wang Xiao , Liu Ben , Xie Liping
Published: July 2021

Background: DNA damage repair (DDR) plays a pivotal role in the tumorigenesis and progression of multiple cancers, including clear cell renal cell carcinoma (ccRCC), and immunotherapy is galvanizing research on ccRCC, while the interactions between DDR and tumor microenvironment (TME) in ccRCC still remain elusive. Methods: The expression, mutation and clinical data were downloaded from public datasets in TCGA, GTEx and human protein atlas (HPA) database. Consensus clustering analysis was used to cluster subtypes based upon the expression of DDR genes. Cox regression analysis was adopted to conduct survival analysis, and qRT-PCR method was used to verify the expression of RAD54L in ccRCC samples. GSEA was employed to explore potential enriched KEGG pathways. CIBERSORT, ssGSEA and xCell algorithms were used to evaluate the tumor microenvironment (TME).Results: Two subtypes were identified according to the expression of DDR genes in ccRCC. Subtype1 was correlated with increased proportion of higher-grade tumors, worse prognosis and lower PD-L1 expression compared to subtype2. Distinct TME was also noted between two subtypes. GSEA revealed that the TGF-β signaling pathway was significantly enriched in subtype1. RAD54L was subsequently determined as a potential immune-related DDR gene, which was positively associated with PD-L1 expression and its elevated expression predicted unfavorable prognosis in ccRCC. qRT-PCR also verified the overexpression of RAD54L in ccRCC samples. Additionally, a systematic analysis involving 33 cancer types demonstrated that RAD54L was remarkably upregulated and its overexpression tightly linked to worse prognosis in multiple cancers. Moreover, both xCell and ssGSEA algorithm showed the strong associations between RAD54L expression and immune infiltration in more than 30 cancers. Conclusions: DDR is implicated in regulating TME of ccRCC, and RAD54L is a potential immunological and prognostic biomarker in multiple types of cancer, including ccRCC.
Study On Plasma Exosome Biomarkers Of Pregnant Women With Intrahepatic Cholestasis of Pregnancy
Authors: Feng Fan , Jiang Mei , Liu Wei , Xu Di , Huang Xiao-Mei , Shao Yong
Published: July 2021

Background：Elevated serum total bile acid level is currently the main index for clinical diagnosis of intrahepatic cholestasis of pregnancy, but the use of TBA as a detection index has certain limitations. The early diagnosis of ICP and new treatment options still need to be further strengthened. Methods: Plasma samples were collected, and exosomes were isolated. Key differential proteins were screened by bioinformatics methods. ELISA method was used to detect the concentration of the key differential protein cluster in plasma samples, and the ROC curve was drawn to find out the best critical value. Results: There were 138 differentially expressed proteins between the ICP group and the normal group by quantitative analysis. Cluster protein was screened as a clinical validation index. The cluster protein concentration of plasma exosomes in the ICP group was significantly higher than that in the normal group (P<0.0001). ROC curve analysis showed that the best critical point for diagnosing ICP according to the plasma exosome cluster protein concentration of pregnant women was 255.28 ng/ml. In the ICP group, the best crucial point for predicting ICP with premature delivery is 286.72 ng/ml. Conclusion: the plasma exosome cluster protein concentration of ICP pregnant women is significantly higher than that of normal pregnant women. When the plasma cluster protein concentration of pregnant women is more remarkable than 255.28ng/ml, ICP can be diagnosed. When the plasma cluster protein concentration of pregnant women is higher than 286.72ng/ml, ICP pregnant women are more likely to have a premature birth.
Highly stretchable or extremely soft silicone elastomers? One reaction to make them all - from easily available materials!
Authors: Hu Pengpeng , Madsen Jeppe , Skov Anne Ladegaard
Published: July 2021

An easy curing reaction to prepare silicone elastomers is reported, in which a platinum catalyzed reaction of telechelic/multi-hydrosilane (Si-H) functional polydimethylsiloxane (PDMS) in the presence of oxygen and water leads to slow crosslinking. This curing chemistry allows versatile tailoring of elastomer properties, which exceed their intrinsic limitations. Both highly stretchable silicone elastomers and extremely soft silicone elastomers are prepared by creating highly entangled elastomers and bottle-brush elastomers from commercial precursor polymers, respectively. The highly stretchable elastomers can be uniaxially stretched to a maximum strain of 2800% and their areas can be biaxially extended 180-fold. The extremely soft silicone elastomers exhibit shear moduli of 1.2-7.4 kPa, depending on composition, values that are comparable to hydrogels and human soft tissues. The reported curing chemistry can be used to prepare a range of silicone elastomers with carefully tailored mechanical properties.
Chestnut Polysaccharides Rescue Impaired Spermatogenesis by Adjusting Gut Microbiota
Authors: Sun Zhong-Yi , Yu Shuai , Tian Yu , Han Bao-Quan , Zhao Yong , Li Ya-Qi , Wang Yan , Sun Yu-Jiang , Shen Wei
Published: July 2021

Background: Our previous study confirmed the beneficial effects of chestnut polysaccharides on the spermatogenesis process, but the exact mechanism is not clear. Several studies have demonstrated the importance of a balanced gut microbiota in maintaining normal reproductive function. In this study, we investigated the biological functions of chestnut polysaccharides from the perspective of gut microbiota function, expecting to elaborate the specific mechanism of chestnut polysaccharides beneficial to spermatogenesis.Results: Compared with the Vehicle group, germ cell quantity, intestinal structure and tight junction of intestinal tissue were altered in the Busulfan-treated mice, and the intestinal microbiota was also disturbed at several levels, including phylum and genus. The Firmicutes was predominant bacteria in all group followed by Proteobacteria, Bacteroidetes, Actinobacteria, Tenericutes, Cyanobacteria and unidentified-Bacteria, however, the composition of those gut microbiota changes caused by different treatment. Busulfan disturbed the homeostasis of the intestinal microenvironment. Chestnut polysaccharides could rescue this aberrance and improve spermatogenesis via steroid hormone synthesis process. Conclusions: Chestnut polysaccharides can change gut structure and tight junctions to rescue Busulfan-impaired spermatogenesis by altering the composition of different groups of gut microbes, a rescue process that is most likely related to hormone synthesis processes. It will provide a new insight for treating the male-related infertility.
Retrospective Data Analysis for Enhanced Recovery after Surgery (ERAS) Protocol for Elderly Patients with Long-Level Lumbar Fusion
Authors: WANG PENG , KONG CHAO , TENG ZE , LI ZHONGEN , ZHANG SITAO , SUN WENZHI , Lu Shibao
Published: July 2021

Background: Currently, ERAS for spinal surgery field is still in its beginnings, the major protocol lessons learned from other surgical specialties and lack of ERAS program for elderly patients (>70 years old). Geriatric patients has its own special characteristics resulting in more harmed by surgical stress. The enhanced recovery after surgery (ERAS) are designed to improving recovery after surgery and can result in substantial benefits in both clinical outcomes and cost-effectiveness. In the present study, we aimed to determine whether enhanced recovery after surgery (ERAS) significantly improved satisfaction and outcomes in elderly patients (>70 years old) with long-level lumbar fusion. Methods: A total of 154 patients were included, 72 in the ERAS group and 82 case-matched patients in the non-ERAS group. Data including demographic, comorbidity and surgical information were collected from electronic medical records. ERAS interventions were categorised as preoperative, intraoperative and postoperative. We also evaluated primary outcome, surgical complication and length of stay (LOS).Results: There were no statistically significant intergroup differences in regards to demographics, comorbidities, American Society of Anaesthesiologists (ASA) grade, or the number of fusion levels. There were also no differences between mean surgery time of intraoperative blood loss between the ERAS and non-ERAS groups. In addition, the mean preoperative Visual Analogue Score (VAS) for the back and legs and Oswestry Disability Index (ODI) score were not significantly different between the two groups. Overall, ERAS pathway compliance was 91.5%. There were no significant differences in the readmission and mortality rates at 30-day follow-up between the ERAS and non-ERAS groups. However, we observed a statistically significant decrease in the complications in the ERAS group(8 in the ERAS group versus 23 in the non-ERAS group, p=0.009) and LOS in the ERAS group (17.74±5.56 of ERAS group versus 22.13±12.21 in non-ERAS group, p=0.041). Multivariable linear regression showed that comorbidities (p=0.028) and implementation of ERAS program (p=0.002) were correlated with prolonged LOS. Multivariable logistic regression showed that comorbidities (p=0.029)， implementation of ERAS program (p=0.043) and preoperative VAS Back (p=0.046), were correlated with complications. Conclusions: This report describes the first ERAS protocol used in elderly patients after long-level lumbar fusion surgery. Our ERAS program is safe and could help decreases LOS and complication in elderly patients with long-level lumbar fusion.
Title Determinants of the Quality of Childbirth Care Along the Continuum in Limited Resource Settings: A Structural Equation Modeling Analysis of Cross-sectional Data from Burkina Faso and Côte d’Ivoire
Authors: Millogo Tieba , Kourouma Raïssa Kadidiatou , Méda Bertrand Ivlabéhiré , Agbre-Yace Marie Laurette , Dosso Abdul , Yaméogo Maurice W E , Kouanda Seni
Published: July 2021

Introduction: Despite important increase in in-facility births, perinatal mortality rates have remained high and slow to decrease in many developing countries. This situation is attributed to the poor quality of childbirth care. The reason why women delivering in health facilities do not always receive standards of care are unclear. We assessed the determinants of the quality of childbirth care along the continuum of care using different approaches.Methods: A health facility-based cross-sectional study with a direct observation of health care workers’ practices while caring for mother-newborn pairs was carried out in Burkina Faso and Côte d’Ivoire. The performance of a set of Essential Best Practices (EBPs) was assessed in each birth event at admission, pre-pushing and immediate post-partum stages. A quality score, in the form of the additive sum of EBPs effectively delivered was computed for each stage. We used negative binomial regression models and a structural equation modeling analysis to respectively assess the determinants of the quality of care at each stage and the relationships between the quality delivered at the different stages.Results: a total of 532 and 627 mother-newborn pairs were included respectively in Burkina Faso and Côte d’Ivoire. In both countries, the quality of delivery care varies significantly at all stages between health districts. The quality of predelivery care was consistently higher in referral hospitals as compared to primary health care facilities (IRR = 1.02; p < 0.05 and IRR = 1.10; p < 0.05 respectively for Burkina Faso and Côte d’Ivoire). The quality at admission was poorer in nurses as compared to midwives in Burkina Faso (IRR = 0.81; p < 0.001). The quality at admission and pre-delivery stages were positively correlated with the immediate post-partum quality (β = 0.48;p < 0.001 and β = 0.29;p < 0.001 respectively).Conclusion: Quality improvement strategies must target both providers and health facilities and different inputs are needed depending on the stage in the continuum of care.
The Comparison of the Effects of Β-Cyclodextrin Complex and Derivative Complex with Silver Nanoparticles on Cotton Fabric
Authors: SARI CAGLA , ARIK BUKET
Published: July 2021

In this study, sulfated β-cyclodextrin (S-β-CD) which is a β-cyclodextrin derivative was obtained by chemical treatment of natural β-cyclodextrin (β-CD) with sulfuric acid. Afterwards, β-CD and S-β-CD were applied to cotton fabrics. In different treatments, β-CD and S-β-CD were bonded to cotton fabrics with EDTA crosslinking agent. Then, all the fabrics were treated with antibacterial agent silver nanoparticles (AgNPs) and inclusion complexes were formed. The aims of this study were to increase the washing stability and the antibacterial activity against microorganisms and to compare the effects of β-CD complex and derivative complex with silver nanoparticles on treated cotton samples. So, for this purpose, the properties of the treated samples like antibacterial activity, washing stability, add-on, tensile strength, handle, thickness and color change were tested and compared to each other. In addition, characterization analyzes such as SEM, EDX and FT-IR were performed on the samples and XRD analysis was performed to characterize the AgNPs. As a result of the study, it was observed that AgNPs alone were not sufficient to obtain antibacterial textiles with strong antibacterial effect and good washing stability. The inclusion complexes formed with β-CD and S-β-CD had much more effective antibacterial activity and more robust washing stability. In addition, when the physical properties except stiffness and yellowness were considered besides antibacterial activity and washing stability, the treatment of derivative β-CD complex with AgNPs and crosslinking this complex to cotton sample by means of EDTA was found to be the most favorable method.
Impact of the COVID-19 Pandemic on the Conduct of Clinical Trials: A Quantitative Analysis
Authors: Margas Wojciech , Wojciechowski Piotr , Toumi Mondher
Published: July 2021

Background: Globally, healthcare has shouldered much of the socioeconomic brunt of the COVID-19 pandemic. In the area of clinical research, reports indicate that numerous clinical trials have had to be suspended or discontinued. However, these reports have been either qualitative in nature or limited in quantitative scope. The aim of the present analysis was to quantitatively estimate the impact of COVID-19 on the number of clinical trials worldwide. Methods: Data deposited by 219 countries in the ClinicalTrials.gov database between 2007 and 2020 were interrogated using targeted queries. A time series model was fitted to the data for studies ongoing, initiated, or ended between 2007 Quarter (Q) 1 and 2019 Q4 to predict the expected number of trials in 2020 in the absence of COVID-19. The predicted values were compared with the actual 2020 data to quantify the impact of the pandemic. Results: The number of ongoing registered trials showed continuous growth from 2007 Q1 to 2019 Q4 (from 33,739 to 80,319 trials). By contrast, there were markedly fewer ongoing trials in all four quarters of 2020 compared with forecasted values (1.6%–2.8% decrease). When excluding COVID-19-related studies, this disparity grew further (3.4%–5.8% decrease), to a peak of almost 5,000 fewer ongoing trials than estimated for 2020 Q2. Promisingly, however, the number of newly initiated non-COVID-19 trials was higher than predicted in 2020 Q4 (by 9.9%). Conclusions: This quantitative analysis confirmed that the pandemic has had an appreciable impact on clinical trials. Provided that current trends persist, clinical trial activities may soon recover to at least pre-COVID-19 levels.
Evaluation of Medical Certification of Cause of Death of Tertiary Cancer Hospitals of Northern India
Authors: Anand Akash , Khanna Divya , Singh Payal , Singh Anuj , Pandey Abhishek , Sumer Ram , Budukh Atul , Pradhan Satyajit
Published: July 2021

BackgroundMedical Certification of Cause of Death (MCCD) can provide valuable health status data regarding disease incidence, prevalence and mortality in a community. It can guide local health policy and help in setting priorities. On the contrary, incomplete and inaccurate MCCD data can significantly impair the precision of a national health information database. In the current study, the accuracy of death certificates at two tertiary cancer care hospitals in Northern India, has been evaluated.MethodsThis retrospective study has been conducted at Tata Memorial Centres namely, Mahamana Pandit Madan Mohan Malaviya Cancer Centre and Homi Bhabha Cancer Hospital, Varanasi, India on MCCD over a period of two and a half years. Medical records and death certificates of all the deceased were examined. The demographic characteristics, administrative details, co-morbidities and cause of death from death certificates were collected using an approved standardized form. The accuracy of this information was validated using the medical records. Errors in the death certificates were classified according to Haque’s grading scale.1Results778 deaths occurred during the study period between May 2018 to December 2020, and all certificates were accessed for analysis. Only 30 (4%) certificates were error-free. 591(75.9%) death certificates had an inappropriate immediate cause of death. 231(29.7%) death certificates had incorrectly labelled mode of death, such as cardiopulmonary arrest as the immediate cause of death. 585 (75.2%) death certificates had an incorrect underlying cause of death. Majority of the death certificates were prepared by the post MBBS junior residents and this was significantly associated with higher certification errors.ConclusionA high rate of errors was identified in the death certificates completed at our hospitals. Inaccurate death certificates related to cancers can potentially influence the cancer statistics of the defined region and thereby affect policymaking for cancer prevention and control. There is a pressing need for appropriate intervention/s to resolve this important issue. In an attempt to improve the quality of certification, it is envisaged to conduct training for all consultants and residents in proper death certification.
Diffusion Tensor Imaging of the Median Nerve: A Systematic Review and Meta-Analysis of Normal Values in Asymptomatic Adults and How They Change in Carpal Tunnel Syndrome
Authors: Rojoa Djamila , Raheman Firas , Rassam Joseph , Wade Ryckie George
Published: July 2021

Background: Carpal tunnel syndrome (CTS) leads to distortion of axonal architecture, demyelination and fibrosis within the median nerve. Diffusion tensor imaging (DTI) characterises tissue microstructure and generates reproducible proxy measures of nerve ‘health’ which are sensitive to myelination, axon diameter, fibre density and organisation. This meta-analysis summarises the normal DTI values of the median nerve, and how they change in CTS.Methods: This systematic review included studies reporting DTI of the median nerve at the level of the wrist in adults. The primary outcome was to determine the normal fractional anisotropy (FA) and mean diffusivity (MD) of the median nerve. Secondarily, we show how the FA and MD differ between asymptomatic adults and patients with CTS, and how these differences are independent of the acquisition methods.Results: 32 studies of 2643 wrists, belonging to 1575 asymptomatic adults and 1068 patients with CTS were included. The normal FA was 0·58 (95% CI 0·56, 0·59) and the normal MD was 1·138 x10-3 mm2/s (95% CI 1·101, 1·174). Patients with CTS had a significantly lower FA than controls (mean difference 0·12 [95% CI 0·09, 0·16]). Similarly, the median nerve of patients with CTS had a significantly higher mean diffusivity (mean difference 0·16 mm2/s x10-3 [95% CI 0·05, 0·27]). The differences were independent of experimental factors.Conclusion: We provide summary estimates of the normal FA and MD of the median nerve in asymptomatic adults. Furthermore, we show that diffusion throughout the length of the median nerve becomes more isotropic in patients with CTS.
Heterologous Overexpression of ZmHDZIV13 Enhanced Drought and Salt Tolerance in Arabidopsis and Tobacco
Authors: Wang Fang , Fang Peng , Yan Huiping , Ji Xiangzhuo , Peng Yunling
Published: July 2021

The homeodomain leucine zipper (HD-Zip) IV transcription factor is indispensable in the response of plants to abiotic stress. Systematic studies have been carried out in Arabidopsis, rice and other species from which a series of stress resistance-related genes have been isolated. However, the function of the HD-Zip-IV protein in maize is not clear. In this study, we cloned the HD-Zip-IV gene ZmHDZIV13 and identified its function in the stress response. Our phylogenetic analysis showed that ZmHDZIV13 and AtHDG11 had high homology and might have similar functions. The heterologous overexpression of ZmHDZIV13 in Arabidopsis resulted in sensitivity to abscisic acid (ABA), salt tolerance during germination and drought tolerance in seedlings. Under drought stress, the transgenic Arabidopsis showed stronger drought resistance than the wild-type showed (control). The malondialdehyde content of ZmHDZIV13 transgenic plants was lower than that of the control, and the relative water content and proline content were significantly higher than those of the control. After the drought was relieved, the expression of P5CS1, RD22, RD29B, RD29A, NCED3 and ERD1 were upregulated in transgenic Arabidopsis. Also, modified tobacco plants (35S::ZmHDZIV13) exhibited proper stomatal changes in response to drought conditions. These results show that ZmHDZIV13, as a stress-responsive transcription factor, plays a role in the positive regulation of abiotic stress tolerance and can regulate an ABA-dependent signaling pathway to regulate drought response in plants.
Study of Microbiocenosis of Canine Dental Biofilms
Authors: Kačírová Jana , Maďari Aladár , Mucha Rastislav , Fecskeová Lívia K. , Mujakic Izabela , Koblížek Michal , Nemcová Radomíra , Maďar Marián
Published: July 2021

Dental biofilm is a complex microbial community influenced by many exogenous and endogenous factors. Despite long-term studies, its bacterial composition is still not clearly understood. While most of the research on dental biofilms was conducted in humans, much less information is available from companion animals. In this study, we analyzed the composition of canine dental biofilms using both standard cultivation on solid media and amplicon sequencing, and compared the two approaches. The 16S rRNA gene sequences were used to define the bacterial community of canine dental biofilm with both, culture-dependent and culture-independent methods. After DNA extraction from each sample, the V3-V4 region of the 16S rRNA gene was amplified and sequenced via Illumina MiSeq platform. Isolated bacteria were identified using universal primers and Sanger sequencing. Representatives of 18 bacterial genera belonging to 5 phyla were isolated from solid media. Amplicon sequencing largely expanded this information identifying in total 284 OTUs belonging to 10 bacterial phyla. Amplicon sequencing revealed much higher diversity of bacteria in the canine dental biofilms, when compared to standard cultivation approach. In contrast, cultured representatives of several bacterial families were not identified by amplicon sequencing.
Magnetic resonance T1w/T2w ratio in multiple system atrophy: A combined study with voxel-based morphometry
Authors: Ponticorvo Sara , Manara Renzo , Russillo Maria Claudia , Erro Roberto , Picillo Marina , Salle Gianfranco Di , Salle Francesco Di , Barone Paolo , Esposito Fabrizio , Pellecchia Maria Teresa
Published: July 2021

Diagnosis of multiple system atrophy (MSA) may be improved by using multimodal imaging approaches. We investigated the use of T1-weighted/T2-weighted (T1w/T2w) images ratio combined with voxel-based morphometry to evaluate brain tissue integrity in MSA compared to Parkinson’s disease (PD) and healthy controls (HC). Twenty-six patients with MSA, 43 patients with PD and 56 HC were enrolled. Whole brain voxel-based and local regional analyses were performed to evaluate gray and white matter (GM and WM) tissue integrity and mean regional values were used for patients classification using logistic regression. Increased mean regional values of T1w/T2w in bilateral putamen were detected in MSA-P compared to PD and HC. The combined use of regional GM and T1w/T2w values in the right and left putamen showed the highest accuracy in discriminating MSA-P from PD and good accuracy in discriminating MSA from PD and HC. A good accuracy was also found in discriminating MSA from PD and HC by either combining regional GM and T1w/T2w values in the cerebellum or regional WM and T1w/T2w in the cerebellum and brainstem. The T1w/T2w image ratio alone or combined with validated MRI parameters can be further considered as a potential candidate biomarker for differential diagnosis of MSA.
Design, Synthesis, Molecular Docking and Biological Evaluation of Bromo-Pyridyl Containing 3-Chloro 2-Azetidinone Derivatives as Potential Antimycobacterial Agents
Authors: Kusurkar Rakesh V. , Rayani Rahul H. , Vala Anand G. , Parmar Deepa R. , Bhoi Manoj N , Zunjar Vishwanath , Soni Jigar Y.
Published: July 2021

A new class of β-lactam pharmacophore series of 2-Bromo-N-[4-(2-{[2-(substituted phenyl)-3-chloro-4-oxoazetidin-1-yl] amino}-2-oxoethyl) phenyl] pyridine-4-carboxamide derivatives were designed, prepared, and screened for their antimycobacterial activities. The hydrazone derivatives were first synthesized via conventional and microwave methods, and then the β-lactam ring could be constructed via a [2+2] ketenimine cycloaddition. The structure of all synthesized compounds was characterized by FTIR, 1H NMR, 13C NMR, and Mass spectroscopy techniques. All the newly synthesized derivatives were found to be effective in inhibiting M. tuberculosis H37RV strain infection at concentrations of 12.5, 25.0, and 50.0 µg/mL using the MABA method. Amongst, the compound (6e) was found to be good potent antitubercular activity at 12.5 mg/mL concentration in comparison with the rest of the compounds using the standard therapeutic agent Streptomycin. Molecular dynamics simulation studies and Molecular docking studies have been performed against mycobacterial InhA enzyme to gain an insight into the possible mechanistic action in search of good potent antitubercular candidates.
Analysis of Internal Transcribed Spacer Regions II Gene and Morphology of Paragonimus From Yunnan Province, China
Authors: Yang Binbin , Li Juan , Zhou Benjiang
Published: July 2021

For a long time, there is no clear-cut to identify some species of paragonimus in Yunnan Province, China. This paper involved the distribution of Paragonimus in Jinping country and Baoshan city, Yunnan province. In this experiment, the metacercariae, excysted metacercariae, eggs, adult worms were obtained from different hosts were observed and measured. Cats have been described as the appropriate definitive host of paragonimus sp., which are closed to P. cheni according to morphology. Especially the ovaries of adult worms are few and has no third branches. With SEM observation, their spines in the surface are single, a sharp-pointed knife or half-moon in shape and the end of a few of spines are bifurcate. While the clustered sequences strains of this study in the ITS2 tree clustered of Yunan is out sider of P. skirjabini complex and have the genetically greater distances than other isolates of the P. skrjabini complex. Therefore, the Paragonimus sp. of this study from Jinping County and Baoshan city are the same subspecies of P. skrjabini complex.
High Carriage of Plasmid-Mediated Quinolone Resistance (PMQR) Genes by Cefotaxime-Resistant Escherichia Coli Recovered from Surface-Leaking Sanitary Sewers
Authors: Adekanmbi Abimbola Olumide , Akinlabi Olabisi C. , Olaposi Adedolapo V.
Published: July 2021

There is a rapid rise in the incident of quinolone resistant bacteria in Nigeria. Most studies in Nigeria have focused on isolates from the clinical settings, with few focusing on isolates of environmental origin. This study aimed to investigate the antibiogram and carriage of plasmid-mediated quinolone resistance (PMQR) genes by quinolone-resistant isolates obtained from a pool of cefotaxime-resistant Escherichia coli (E. coli) recovered from sewage leaking out of some broken sanitary sewers in a University community in Nigeria. Isolation of E. coli from the sewage samples was done on CHROMagar E. coli after enrichment of the samples was done in Brain Heart Infusion amended with 6µg/mL of cefotaxime. Identification of presumptive E. coli was done using molecular methods (detection of uidA gene), while susceptibility to antibiotics was carried out using disc-diffusion method. Detection of PMQR genes (qnrA, qnrB, qnrS, aac(6')-lb-cr, qepA and oqxAB) was done using primer-specific PCR. A total of 32 non-repetitive cefotaxime-resistant E. coli were obtained from the sewage, with 21 being quinolone-resistant. The quinolone-resistant isolates showed varying level of resistance to the tested antibiotics, with imipenem being the only exception with 0% resistance. The PMQR genes: aac(6')-lb-cr, qnrA, qnrB, qnrS and qepA and oqxAB were detected in 90.5%, 61.9%, 47.6%, 38.1%, 4.8% and 0% respectively of the isolates. The findings of this study showed a high level of resistance to antibiotics and carriage of PMQR genes by quinolone-resistant E. coli obtained from the leaking sanitary sewers, suggesting a potential environmental and public health concern.
Inter-Kingdom Networks of Canola Microbiome Reveal Bradyrhizobium as Keystone Species and Underline the Importance of Bulk Soil in Microbial Studies to Enhance Canola Production.
Authors: Floc'h Jean-Baptiste , Hamel Chantal , Laterriere Mario , Tidemann Breanne , St-Arnaud Marc , Hijri Mohamed
Published: July 2021

The subterranean microbiota of plants are of great importance for plant growth and health, as root-associated microbes can perform crucial ecological functions. As the microbial environment of roots is extremely diverse, identifying keystone microorganisms in plant roots, rhizosphere and bulk soil is a necessary step towards understanding the network of influence within the microbial community associated with roots and enhancing its beneficial elements. To target these hot spots of microbial interaction, we used inter-kingdom network analysis on the canola growth phase of a long-term cropping system diversification experiment conducted at four locations in the Canadian prairies. Our aims were: to verify whether bacterial and fungal communities of canola roots, rhizosphere and bulk soil are related and influenced by diversification of the crop rotation system; to determine whether there are common or specific core fungi and bacteria in the roots, rhizosphere, and bulk soil under canola grown in different environments and with different levels of cropping system diversification; and to identify hub taxa at the inter-kingdom level that could play an important ecological role in the microbiota of canola. Our results showed that fungi were influenced by crop diversification but not by bacteria. We found no core microbiota in canola roots but identified three core fungi in the rhizosphere, one core mycobiota in the bulk soil and one core bacteria shared by the rhizosphere and bulk soil. We identified two bacterial and one fungal hub taxa in the inter-kingdom networks of the canola rhizosphere, and one bacterial and two fungal hub taxa in the bulk soil. Among these inter-kingdom hub taxa, Bradyrhizobium sp. and Mortierella sp. are particularly influential on the microbial community and the plant. To our knowledge, this is the first inter-kingdom network analysis utilized to identify hot spots of interaction in canola microbial communities.