bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Chemotherapy and Radiotherapy in Altering the Morphology of Subcortical Structures in Patients With Nasopharyngeal Carcinoma
Authors: Nan Feibiao , Zhang You-ming , Gao Jian-ming , Li Li , Zhang Yuanchao , Liao Wei-hua
Published: June 2021

Neuroimaging studies have found significant structural alterations of the cerebral cortex in patients with nasopharyngeal carcinoma (NPC) following radiotherapy (RT) or concomitant chemoradiotherapy (CCRT), while their effects on the morphology of subcortical structures remain largely unknown. In this study, we investigated the subcortical morphological alterations between three groups: 56 untreated NPC patients (pre-RT group), 37 RT-treated NPC patients (post-RT group), and 108 CCRT-treated NPC patients (post-CCRT group). Using FSL-FIRST, we found that, compared with the pre-RT group, the post-CCRT group exhibited morphological atrophy in the bilateral thalamus, bilateral putamen, left pallidum, and left caudate and morphological inflation in the left caudate, while the post-RT group only exhibited morphological atrophy in the bilateral thalamus. We also found a significant negative correlation between the maximum dosage of RT for temporal lobes and the morphological changes of the bilateral thalamus in treated NPC patients. These results indicated that there may be an interaction between RT and CT that can cause subcortical damage.
Sex Differences In The Association Between Hemoglobin A1c And Cerebral White Matter Lesions In The General Japanese Population
Authors: Li Honghao , Yu Jing , Guo Shougang
Published: June 2021

The influence of diabetes and associated sex differences on cerebral white matter lesions (WMLs) is unclear. We used data from a cross-sectional study uploaded to the DATADRYAD website by Shinkawa et al. to investigate differences in the association between hemoglobin A1c (HbA1c) levels and cerebral WMLs between men and women. The average age of all participants was56.4±11.5years old, and approximately 51.89 % of them were men. A linear relationship between HbA1c and cerebral WMLs was detected in men. Fully adjusted binary logistic regression showed no association of HbA1c with cerebral WMLs in men. A nonlinear relationship between HbA1c and cerebral WMLs was detected in women, whose cutoff point was 5.6%. The effect sizes and confidence intervals of the left and right sides of the inflection point were OR=0.21 (95%CI 0.06, 0.69, P=0.0098) and OR=3.5 (95%CI 1.50, 8.15, P=0.0037), respectively. In the higher HbA1c group, further subgroup analysis showed a stronger association between HbA1c and cerebral WMLs in women (OR=3.83, 95%CI 1.68, 8.72 P=0.0014) than in men (OR=1.02, 95%CI 0.76, 1.36 P=0.8986) (P for interaction with sex was 0.0004). A stronger effect of HbA1c on the risk of cerebral WMLs in women than in men was found in the higher HbA1c group.
Assessment of Spatiotemporal Variability and Rising Trends of Surface Ozone Over India
Authors: Kunchala Ravi Kumar , Singh Bhupendra Bahadur , Krishna Karumuri Rama , Attada Raju , Seelanki Vivek , Kumar Kondapalli Niranjan
Published: June 2021

With rising anthropogenic activities, surface ozone levels have increased across different parts of the world including India. Studies have shown that surface ozone shows distinct characteristics across India, however these studies are mostly based on isolated locations. Any comprehensive and spatiotemporally consistent study on surface ozone is lacking thus far. Keeping these facts in mind, we utilize ground-based observations and reanalysis datasets to investigate the surface ozone variability, seasonality, and linkages with meteorology over India. A validation exercise shows that the Copernicus Atmosphere Monitoring Service Reanalysis (CAMSRA) reasonably compares against the ground-based observations. Results show that the CAMSRA ozone is in good agreement with the observations across India, where it shows better correlations (r>0.7) over southern regions and relatively lesser (> 0.5) over northern and eastern regions indicating larger variability and spread over these regions. We further quantify this agreement in terms of range, mean absolute error (MAE), and root mean square error (RMSE). Time series analysis shows that the CAMSRA captures seasonal variations irrespective of location. Spatial distribution of surface ozone shows higher (lower) concentrations of about 40-60 ppb (15-20 ppb) during pre-monsoon (monsoon) months over a broad region covering northern and western parts, and peninsular India. A prominent increase during May is noted over the northern region especially over Indo-Gangetic Plains (IGP). These seasonal variations are linked to solar radiation (SR), temperature, low-level circulation, and boundary layer height (BLH). Furthermore, Principal Component Analysis (PCA) is performed to understand the dominant patterns of spatiotemporal variability for different seasons. It is seen that the first (second) mode shows a high percentage variance explained ranging between 30-50% (10-20%). The time series of PCA-1 mode indicates an overall increasing trend across India with a notable increase over south and central India. The second mode indicates prominent variability over the IGP (southern India) in the pre-monsoon (post-monsoon) season, which shows significant interannual variability. During the monsoon season, an interesting dipole pattern is seen which closely resembles the active and break spell patterns of the Indian summer monsoon. Overall, the spatiotemporal variations in surface ozone are closely tied to meteorology while the rising trends indicate the potential role of increasing precursors across India.
Geospatial Approach for Assessment of Groundwater Quality
Authors: Gauns Arvind Sharadchandra , Nagarajan M. , Lalitha R. , Baskar M.
Published: June 2021

Increasing population, erratic distribution of rainfall, and their rising demand for water in domestic and irrigation is fulfilled by groundwater resources. Due to overexploitation, there is the deterioration of groundwater quality and hence to evaluate the groundwater quality, a study was undertaken to understand the water suitability for drinking as well as for irrigation purposes. For this study, five villages namely Kumulur, Tachankurunchi, Pudurutamanur, Pandaravadai, and Poovalur were selected from Trichy District, Tamil Nadu, India with an areal extent of 45.1 km2. For the water quality assessment, samples were drawn from 53 locations from the sources like open well, bore well and hand pumps, etc., Parameters of pH, EC, TDS, Anions - CO3 2−, HCO3−, Cl−, SO4 2−, Cations - Ca2+, Mg2+, B3+, Na+ and potassium (K+) were estimated using the standard analytical procedure in three different seasons Viz., S-I (September 2019), S-II (December 2019) and S-III (March 2020). The WQI was computed for drinking water quality and it was found that 25% samples in S-I, 80% samples in S-II, and 83% samples in S-III were above the permissible limit for drinking purposes. Indices like Sodium Percentage, Sodium Adsorption Ratio, Permeability Index, Kelly’s Ratio, Magnesium Hazard Ratio, Potential Salinity, USSL Diagram, Wilcox Plot, Piper Diagram, and Gibbs plot were evaluated for examining irrigation water quality. The results revealed that 90% of the area, the water is suitable for irrigation purposes and a few locations (10%) wherein the salt content of water are relatively higher than the entire study area.
Stability of Fixed Points in an Approximate Solution of the Spring-mass Running Model
Authors: Wróblewska Zofia , Płociniczka Łukasz , Kowalczyk Piotr
Published: June 2021

We consider a classical spring-mass model of human running which is built upon an inverted elastic pendulum. Based on our previous results concerning asymptotic solutions for large spring constant (or small angle of attack), we construct analytical approximations of solutions in the considered model. The model itself consists of two sets of differential equations - one set describes the motion of the centre of mass of a runner in contact with the ground (support phase), and the second set describes the phase of no contact with the ground (flight phase). By appropriately concatenating asymptotic solutions for the two phases we are able to reduce the dynamics to a one-dimensional apex to apex return map. We find sufficient conditions for this map to have a unique stable fixed point. By numerical continuation of fixed points with respect to energy, we find a transcritical bifurcation in our model system.
Autologous Mesenchymal Stem Cell Therapy for Idiopathic Pulmonary Fibrosis and Comprehensive Assessment of Circulating Immune Populations Cells
Authors: Atanasova Elena , Milosevic Dragana , Bornschlegl Svetlana , Krucker Karen , Jacob Eapen , Porquera Eva Carmona , Anderson Dagny , Egan Ashley , Limper Andrew , Dietz Allan
Published: June 2021

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive pulmonary disease characterized by aberrant tissue remodeling, formation of scar tissue within the lungs and continuous loss of lung function. The areas of fibrosis seen in lungs of IPF patients share many features with normal aging lung with cellular senescence being one. The contribution of the immune system to the etiology of IPF remains poorly understood. Evidence obtained from animal models and human studies suggests that innate and adaptive immune processes can orchestrate existing fibrotic responses. Currently, there is only modestly effective pharmacotherapy for IPF. Mesenchymal stem cells (MSCs)-based therapies have emerged as a potential option treatment of IPF. This study explores the possibility of using autologous MSCs as an IPF therapy and present an attempt to determine if the disease occurring in the lungs can be reflected on peripheral blood immune status. MethodsComprehensive characterization of autologous adipose derived MSCs (aMSCs) from five IPF patients and five age and gender matched Healthy Controls (HC) was done using flow cytometry, Droplet Digital PCR (ddPCR), Multiplex Luminex xMAP technology and confocal microscopy. For assessing the self renewal capacity and osteogenic differentiation IncuCyte Live Cell Imaging technology was used. Multi-parameter quantitative flow cytometry of un-manipulated whole blood of another group of 15 IPF patients and 87 (30 age and gender matched) HC was used to analyze 110 peripheral phenotypes.ResultsThere are no differences between autologous aMSCs from IPF patients and HC in their stem cell properties, self renewal capacity, plasticity for osteogenic differentiation, secretome content, cell cycle inhibitor marker levels and mitochondrial health. IPF patients had altered peripheral blood immunophenotype including reduced B cells subsets, increased T cell subsets, and increased granulocytes among others demonstrating clear and significant differences.ConclusionsOur results indicate that there is no difference in aMSCs properties from IPF patients and HC, suggesting that autologous aMSCs may be an acceptable option for IPF therapy.Characterization of peripheral immune phenotype may be a valuable indicator for successful therapy, and for potentially staging the disease.
MiR-582-3p Participates in the Regulation of Biological Behaviors of A549 Cells by Ambient PM2.5 Exposure
Authors: Ju Liangliang , Yang Mei , Li Changlian , Cheng Han , Li Na , Zhang Qi , Sun Shu , Ding Liu , Sui Xinmiao , Zhang Chao , Yang Mingwei , Cao Jiyu , Ding Rui
Published: June 2021

Background Ambient fine particulate matter (PM2.5) is one of the main environmental air pollutants that closely related to the development of lung cancer, but the mechanisms are unclear. Results In this study, A549 cells were exposed to ambient PM2.5 to investigate the alterations of biological behaviors, and the possible role of miR-582-3p in the effects was further explored. The findings showed that that PM2.5 exposure could significantly enhance the biological behaviors of A549 cells, and promote their EMT transformation, especially at relatively low doses. Over-activation of Wnt/β-catenin signaling pathway and increased expression of miR-582-3p were also found in A549 cells after PM2.5 exposure. After the knockdown of miR-582-3p in A549 cells, the effects of PM2.5 on malignant biological behavior changes, EMT and the activation of Wnt/β-catenin signaling pathway were all significantly alleviated. Furthermore, the inhibition of Wnt/β-catenin signaling pathway also inhibited the EMT process of A549 cells, which was rescued by the overexpression of miR-582-3p. Conclusion This study showed that ambient PM2.5 can up-regulate the expression of miR-582-3p, consequently activate the Wnt/β-catenin signaling pathway, thereby enhance EMT transformation and promote the malignant biological behaviors of A549 cells. These findings provide evidence for further research into the mechanisms by which exposure to PM2.5 in the environment promotes lung cancer.
Assessment on Environmental Quality Management of Coal Stockpile for Environmental Sustainability
Authors: Ambarita Novitasari , Juniah Restu , Syarifudin Syarifudin , Zakir Syaifudin , Rahmi Hisni
Published: June 2021

The positive impact of coal mining has been reported to increase the country's economy and community income. However, the negative impact is found to be reducing the physical and chemical parameters of air, noise, soil and spontaneous combustion quality, therefore, having the potential to decrease environmental quality. Environmental management is often carried out to improve the physical and chemical parameters of societal quality, in order to match the required standards, therefore, resulting in sustainable coal mining. The management has also created environmental costs, as an externality of coal mining activities. Based on the technical assessment conducted, the results showed that environmental management at Tarahan Port Unit of PT BUKIT ASAM Persero Tbk, has been implemented in accordance with the Environmental Management/Monitoring Plan (RKL/RPL) documents, as well as the prevailing Indonesian laws and regulations. The physical and chemical parameters were observed to have met the standards of environmental quality, for a sustainable community. However, the economical assessment showed a mismatch between planned and realized environmental management costs. The funds used in the second quarter increased by IDR. 121,183,548 or 102.02%, compared to the realization program in that of the first. This increase was due to the construction of a dust suppression system and an operational chimney for the 2X8 MW Steam Power Plant, via the use of Electrostatic Precipitators. This research recommended a detailed inventory of environmental cost plans and escalation, in order to anticipate risk factors. And also help in carrying out machine maintenances, which are known to produce emissions on a regular basis. Therefore the emission produced were observed to be decreased, with the funds for managing and monitoring the environment also reduced.
Prognostic Utility of Optical Coherence Tomography for Visual Outcome After Extended Endoscopic Endonasal Surgery for Adult Craniopharyngiomas
Authors: Qiao Ning , Li Chuzhong , Xu Jing , Ma Guofo , Kang Jie , Jin Lu , Cao Lei , Liu Chunhui , Zhang Yazhuo , Gui Song-Bai
Published: June 2021

Optical coherence tomography (OCT) serving as a novel high resolution imaging technique can assess the retinal morphology. At present, a few studies are reported with limited evidence on the predictive value of OCT for visual outcome after optic nerve decompression. This study aims to utilize the largest series of adult craniopharyngiomas to evaluate the association between OCT parameters and visual outcome following the extended endoscopic endonasal surgery (EEES). From October 2018 to October 2020, one hundred and seventy eyes in 88 adult patients with craniopharyngiomas were retrospectively reviewed. Gross total resection was performed in 82 (93.2%) patients. The median follow-up time was 10.9 months. Our study showed that increased temporal circumpapillary retinal nerve fiber layer (cpRNFL) thickness was associated with higher odds of visual acuity (VA) improvement and maintenance (OR=1.070; P=0.035), and greater inferior cpRNFL thickness was significantly associated with visual field (VF) improvement and maintenance (OR=1.034; P=0.046). Tight adhesion was demonstrated as an independent adverse factor for either postoperative VA or VF (P=0.048, P=0.030, respectively). Receiver operating characteristic (ROC) analysis further verified the robustness of the prediction model either in VA (AUC=0.842; P<0.001) or VF (AUC=0.849; P<0.001). Preoperative OCT can effectively predict visual outcome after EEES for adult craniopharyngiomas. It can also serve as a reliable alternative to evaluate preoperative visual filed defects, especially for patients with lower compliance. Tight adhesion was confirmed as an independent risk factor for postoperative visual outcome. The OCT-based multivariable prediction models developed in present study may contribute to patient counseling on visual prognosis.
Spectral Behavior and Photophysical Parameters of Dihydrophenanthro[9,10-e][1,2,4]Triazine Derivative Dyes in Sol–gel and Methyl Methacrylate Polymer Matrices
Authors: Sakr Mahmoud , Kana Maram T. H. Abou , Elwahy Ahmed H.M. , El-Daly Samy A. El-Daly A. , Ebeid El-Zeiny M.
Published: June 2021

This paper deals the optical and photophysical properties of dihydrophenanthro [9,10-e] [1,2,4] triazine fluorescent derivative dyes doped in Silicate based sol–gel, homo-poly methyl methacrylate (PMMA). Solid hosts effect on the optical and photophysical parameters such as molar absorptivity, cross sections of singlet–singlet electronic absorption and emission spectra, excited state lifetime, quantum yield of fluorescence. Also the dipole moment of electronic transition, the length of attenuation and Oscillator strength of electronic transition from So →S1 have been detected. The dyes with different pumping power were pumped by 3rd harmonic Nd:YAG pulsed laser 8ns pulse duration, with a repetition rate at (10Hz). Good Photo stability of compound 1 and 2 were obtained that was decreased to 49%, 54% and 46%, 40% of the initial ASE of dyes in sol gel and PMMA respectively, after 55000 pumping pulses at (10 mJ/pulse). The dyes in sol-gel show improved Photo stability compared with those in organic polymeric matrices.
Latitudinal- and Height- Dependent Long-Term Climatology of Propagating Quasi-16-day in the Troposphere and Stratosphere
Authors: Tang Wentao , ZHANG Shao Dong , HUANG Chun Ming , HUANG Kai Ming , Gong Yun , Gan Quan
Published: June 2021

The global amplitude of the westward propagating quasi-16-day wave (16DW) with wavenumber 1 (Q16W1), the strongest component of 16DW, is derived from European Centre for Medium-Range Weather Forecasts ERA-Interim reanalysis temperature data set from February 1979 to January 2018. The strong climatological mean amplitudes of the Q16W1 appear in winter in the upper stratosphere at high latitudes in both hemispheres, and the wave amplitude is stronger in the Northern Hemisphere (NH) than in the Southern Hemisphere (SH). Multivariate linear regression is applied to calculate responses of the Q16W1 amplitude to QBO (quasi-biennial oscillation), ENSO (El Niño-Southern Oscillation), solar activity and the linear trend of the Q16W1 amplitude. The QBO signatures of the Q16W1 amplitude are mainly located in the stratosphere. In addition to the significant QBO response in the low latitude and low stratosphere, the largest QBO response occurs in the region with the strongest Q16W1 climatology amplitude. There no significant responses to ENSO and solar activity are observed. The linear trend of the monthly mean Q16W1 amplitude is generally positive, especially in the mid-high latitudes of the stratosphere. The trend is asymmetric about the equator and significantly stronger in the NH than in the SH. The trend shows obvious seasonal changes, that is, stronger in winter, weaker in spring and autumn. Further investigation suggests that the background and local instability trends contribute most of the increasing trend of the Q16W1 amplitude. In winter in both hemispheres, the weakening trend of eastward zonal wind provide more favourable background wind for Q16W1 upward propagation, in autumn and winter in the NH and in spring, autumn and winter in the SH, the increasing trend of local instability may enhance the wave excitation.
Molecular Epidemiology of Human Metapneumovirus Infection among Children with Severe Acute Respiratory Infection in Huzhou from 2016 to 2020
Authors: Ji Lei , Chen Liping , xu deshun , Wu Xiaofang
Published: June 2021

Background: Human metapneumovirus (hMPV) is one of the important pathogens of infant respiratory tract infection. However, the molecular epidemiological information relating to hMPV among children hospitalized patients with severe acute respiratory infection (SARI) have not been thoroughly studied as yet. To investigate the infection status and genotypes of hMPV among children hospitalized patients with SARI from January 2016 to December 2020 in Huzhou, China. Methods: A nasopharyngeal flocked swab, nasal wash or combination of nasopharyngeal swab and oropharyngeal swab samples were collected from children with SARI in Huzhou from January 2016 to December 2020. RT-PCR was used to detect the nucleic acid of hMPV. F gene was amplified and sequenced for the positive nucleic acid samples of hMPV. The obtained gene sequences were analyzed by MEGA software (version 7.0). Epidemiological data were analyzed using Microsoft Excel 2010 and service solutions (SPSS) 21.0 software.Results: A total of 1133 children with SARI were collected from 2016 to 2020. Among them, 56 cases were positive for hMPV nucleic acid, with a positive rate of 4.94%. Children under 5 years old accounted for 85.71% of the total positive cases. Higher activity of hMPV infection could be seen in the period in Spring and Winter. and the main epidemic months were December and January-March. The F gene sequences of 28 strains of hMPV were obtained by co-sequencing. Phylogenetic analysis showed that there were A1, B1 and B2 genotypes of hMPV prevalent in Huzhou, and the dominant genotype of hMPV during our study period varied according to surveillance year.Conclusions: HMPV is one of the important pathogens causing acute respiratory virus infection in children in Huzhou, with high incidence in winter and spring seasons and children under the age of 5，A1, B1 and B2 are three prevalent genotypes.
The Prevalence of Mild Cognitive Impairment Among the Elderly Population based on Spatio-temporal Data in the Yangtze River Delta Region of China
Authors: Shi Luping , Qiu Huiping , Zhou Min , Wang Wei
Published: June 2021

Background: With the development of China’s economy, China’s aging process has accelerated. The prevalence of mild cognitive impairment (MCI) in the elderly population showed a gradual increase. The Yangtze River Delta Economic Belt plays a very important role in China's economic development. China's seventh national census data show that the aging degree in the Yangtze River Delta is higher than the national average, and the dependency ratio of the elderly population in the Yangtze River Delta also presents the same characteristics. little is known about the prevalence of MCI in the Yangtze River Delta in recent years. It is necessary to summarize and analyze the prevalence and distribution of mild cognitive impairment in the elderly population in the Yangtze River Delta in the past 10 years. This can provide data support for formulating elderly care service policies and is of great significance for promoting healthy aging in China.Methods: By searching the Chinese and English databases to obtain the original research literature on the prevalence of MCI in the elderly population in China. Select the study about the Yangtze River Delta population. Extract relevant data on prevalence in the literature. According to the results of the heterogeneity test, a random-effect model was adopted to estimate the prevalence of MCI, followed by subgroup analyses and meta-regression.Results: A total of 18 articles were included in this study with a total sample size of 33042. In the past decade, the overall prevalence of MCI in the elderly population in the Yangtze River Delta was 18% (95% CI: 15-22%). Spatial distribution results: the prevalence difference between regions was (16%-23%). In the past 10 years, the prevalence of MCI has increased first and then decreased. Analyzed the demographic characteristics, the prevalence of women, low education, old age, rural areas, and no spouse groups was relatively higher. Conclusions: The prevalence of MCI in the Yangtze River Delta region was lower than the national average. There were differences between different regions. Besides, age, gender, and education level were all important factors affecting the prevalence of MCI.
Pancreas before Kidney Transplant in Diabetic Patients with Uremia
Authors: Shyr Bor-Uei , Shyr Bor-Shiuan , Chen Shih-Chin , Shyr Yi-Ming , Wang Shin-E
Published: June 2021

Theoretically, pancreas before kidney transplant (PBK) could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. This study is to clarify the justification and feasibility of PBK. There were 160 cases of pancreas transplant in this study, including 26 (16%) PBK. Rejection (3.8%) of pancreas graft was significantly lower in PBK group, followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). There was no chronic rejection in PBK and PAK groups. Fasting blood sugar and serum HbA1c levels after PBK were not significantly different from those by other subgroups. The serum C-peptide levels were significantly higher in PBK group than those by other subgroups. The 5-year pancreas graft survival was 100% for PBK and PAK, 97.0% for SPK and 77.9% for PTA. In conclusion, PBK could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes. However, given the inferior patient survival outcome, PBK is still not recommended unless SPK and PAK is not available.
Comparison of Complexity of the Switchable Chaotic Systems and its FPGA Implementation
Authors: Yan Shaohui , Wang Qiyu
Published: June 2021

A four-dimensional chaotic system with complex dynamical properties is constructed via introducing a nonlinear function term. The paper assesses complexity of the system employing equilibrium points, Lyapunov exponent spectrum and bifurcation model. Specially, the coexisting Lyapunov exponent spectrum and the coexisting bifurcation validate the coexistence of attractors. The corresponding complexity characteristics of the system can be analyzed by using C0 and spectral entropy(SE) complexity algorithms, and the most complicated integer-order system is obtained. Furthermore, the circuit which can switch the chaotic attractors is implemented. It is worth noting that the more sophisticated parameters are received by comparing the complexity of the most complicated integer-order chaotic system with corresponding fractional-order chaotic system. Finally, the results of simulation model built in the MATLAB are the same as the hardware verified on the Field-Programmable Gate Array(FPGA) platform, which verify the feasibility of the system.
Nociceptor neurons impair cancer immunosurveillance
Authors: Talbot Sébastien , Balood Mohammad , Ahmadi Maryam , Eichwald Tuany , Majdoubi Abdelilah , Merrison Hannah , Parrin Alexandre , Doyle Benjamin , Lucido Chris , Vermeer Daniel , Huang Siyi , Ji Lexiang , Dai Hongyue , Shu Chengyi , Roversi Katiane , Thomas Sini , Seehus Corey , Foster Simmie , Ahmadi Ali , Rafei Moutih , Rangachari Manu , Thibodeau Jacques , Ghasemlou Nader , Rincon Sonia del , Drapkin Ronny , Vermeer Paola , Woolf Clifford
Published: June 2021

Solid tumors are innervated by nerve fibers that arise from the autonomic and sensory peripheral nervous systems. In prostate cancer, doublecortin-expressing neural progenitors initiate autonomic adrenergic neurogenesis1 which facilitates tumor development and dissemination2, via an angiogenic switch that fuels cancer growth3,4. Similarly, a loss of TP53 drives the reprogramming of tumor-innervating sensory nerves into adrenergic neurons in head and neck tumors, which promotes tumor growth5. However, the impact of tumor neo-innervation by pain-initiating sensory neurons remains unclear. We show that melanoma cells interact with nociceptors, increasing neurite outgrowth, responsiveness to noxious ligands, and neuropeptide release. In turn, CGRP, a nociceptor-produced neuropeptide, directly increases exhaustion of cytotoxic CD8+ T-cells (PD1+Lag3+Tim3+IFNγ-), limiting their capacity to eliminate melanoma. Genetic NaV1.8 or TRPV1 lineage ablation, local pharmacological silencing or blockade of neuropeptide release from tumor-innervating nociceptors, and the antagonism of the CGRP receptor RAMP1, all blunt tumor-infiltrating leukocyte exhaustion, and tumor growth, nearly tripling survival of B16F10-inoculated mice. Inversely, CD8+ T-cell exhaustion increased following optogenetic activation of tumor-innervating NaV1.8 neurons+ and was rescued in sensory neuron depleted mice treated with recombinant CGRP. In comparison to wild-type CD8+ T-cells, RAMP1-/- CD8+ T-cells were protected from undergoing exhaustion when co-transplanted into tumor-bearing Rag1 deficient mice. Single-cell RNA sequencing of patient tumors revealed that intratumoral RAMP1-expressing CD8+ T-cells are more exhausted than their RAMP1 negative counterparts. RAMP1 expression in intratumoral CD8+ T-cells was also associated with resistance to immune checkpoint inhibitor treatment, while RAMP1 overexpression within the tumor correlated with a worse clinical prognosis. We conclude that reducing CGRP release from tumor-innervating nociceptors, by eliminating its immunomodulatory action on cytotoxic CD8+ T-cells, constitutes a useful strategy to safeguard anti-tumor immunity.
Mesenchymal Stem Cells for the Treatment of Intestinal Ischemia-reperfusion Injury: a Protocol of Systematic Review and Meta-analysis of Animal Models
Authors: Zhang Guangru , Suo Shenghong , Liu Zhenzhen , Liu Disheng , Zhao Zhiyu , Ge Long , Leng Yufang
Published: June 2021

Introduction: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event. Mesenchymal stem cells (MSCs) have been widely used to repair intestinal injury in animal models. However, the effects of MSCs on intestinal I/R injury therapy remain unclear. Thus, we will perform a systematic review and meta-analysis of controlled trials to evaluate the efficacy of MSCs in animal models of intestinal I/R injury.Methods and analysis: We will search PubMed, Web of Science, Embase, Cochrane Library, Science Citation Index, China National Knowledge Information database, Wanfang Database, and the Chinese Scientific and Technological Journal Database in May 2021. We will include studies that evaluate the two different interventions for target MSCs to be maintained for the degree of histopathologic changes, mortality rate of rats, tumour necrosis factor α, and diamine oxidase. Two reviewers will independently screen titles and abstracts, perform a full article review, and extract study data. We will also use the SYRCLE tool to assess the risk of bias in the included studies. Furthermore, a random-effects meta-analysis will be conducted. Dichotomous and continuous outcomes will be analysed using risk ratios with 95% confidence intervals (CIs) and weighted mean difference with 95% CIs, respectively. For outcomes where different scales or different measurement methods have been used, the standardised mean difference will be applied. Subgroup and sensitivity analyses will be performed to explore the heterogeneity. Stata (version 12.0, Stata Corp, College Station, Texas, USA) will be used to analyse and pool the individual research results.Ethics and dissemination: This systematic review and meta-analysis does not require an ethical approval because no human beings are involved. We aim to publish this systematic review in a peer-reviewed journal.PROSPERO registration number: CRD42021231826
Genome-wide Association Studies Reveal the Genetic Basis of Natural Ionomic Variation in Rice Grain Oryza Sativa Subsp. Indica
Authors: Cu Suong T. , Warnock Nicholas , Pasuquin Julie , Dingkuhn Michael , Stangoulis James
Published: June 2021

This study presents a comprehensive study of the genetic bases controlling variation in the rice ionome employing genome-wide association studies (GWAS) with a diverse panel of indica accessions, each genotyped with 5.2 million markers. GWAS was performed for twelve elements including B, Ca, Co, Cu, Fe, K, Mg, Mn, Mo, Na, P, and Zn and four agronomic traits including days to 50% flowering, grain yield, plant height and thousand grain weight (TGW). GWAS identified 128 loci associated with the grain elements and 57 associated with the agronomic traits. There were sixteen co-localization regions containing QTL for two or more traits. Fourteen grain element quantitative trait loci were stable across growing environments, which can be strong candidates to be used in marker-assisted selection to improve the concentrations of nutritive elements in rice grain. Potential candidate genes were revealed including OsNAS3 controlling the variation of Zn and Co concentrations. The effects of starch synthesis and grain filling on TGW and multiple grain elements were elucidated through the involvement of OsSUS1 and OsGSSB1 genes. Overall, our study provides crucial insights into the genetic basis of ionomic variations in rice and will facilitate improvement in breeding for trace mineral content.
Association of Blood Pressure With Stroke Risk in Chinese Population: A 6-Year Prospective Cohort Study
Authors: Yu Qi , Jin Qing-Dong , Chen Yan-Qing , Liu Xin-Ru , Lin Qing-Ying
Published: June 2021

Objective: Previous results on the association between blood pressure(BP) and stroke risk were controversial. We investigated the association of BP with stroke risk in China. Method: We included a total of 5,700 adults aged 40-90 years from the China Health and Nutrition Survey (CHNS) cohort. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs. Restricted cubic spline analyses were used to explore linear and nonlinear relationships of BP and stroke. Result: With a median follow-up of 6 years, a total of 5,700 individuals were enrolled in our study, of whom 178 developed stroke. Multivariable adjusted Cox models including systolic blood pressure(SBP) and diastolic blood pressure(DBP) showed a strong positive association between SBP and overall stroke. Compared with participants with SBP 0-130 mmHg, the multivariable adjusted HRs[95% CIs] in participants with SBP 130-140, 140-160, 160-180, and ≥180 mmHg were 1.08[0.62-1.89], 2.41[1.51-3.86], 2.21[1.16-4.20], and 3.90[1.78-8.55] for overall stroke; 0.65[0.21-2.04], 3.68[1.73-7.83], 2.51[0.84-7.47], and 5.91[1.69-20.60] for ischemic stroke; 1.26[0.50-3.20], 1.19[0.47-3.04], 2.06[0.66-6.41], and 5.10[1.36-19.20] for hemorrhagic stroke. Restricted cubic spline analyses including SBP and DBP showed linear relationships of SBP with overall, ischemic and hemorrhagic stroke. No linear or nonlinear relationships of DBP with overall, ischemic and hemorrhagic stroke were observed.Conclusion: SBP is independently and directly related to the risk of overall and its subtypes. Besides, the risk of ischemic and hemorrhagic stroke might be higher when SBP were more than 140 mmHg and 160 mmHg.
Assessment of Cleaning Methods on Bacterial Burden of Hospital Privacy Curtains: A Pilot Randomized Controlled Trial
Authors: Cadogan Kianna , Bashar Sabrin , Magnusson Saul , Patidar Rakesh , Embil John , Gawaziuk Justin , Gawthrop Monika Gawthrop , Liu Song , Kumar Ayush , Logsetty Sarvesh
Published: June 2021

Healthcare-associated infections (HAIs) are an important global issue, leading to poor patient outcomes. A potential route of transmission of HAIs is through contact with hospital privacy curtains. The aim of this study is to evaluate cleaning on reduction of curtain bacterial burden. In this pilot cluster randomized controlled trial we compared the bacterial burden between three groups of 24 curtains on a regional burn/plastic surgery ward. A control group was not cleaned. Two groups were cleaned at three to four day intervals with either disinfectant spray or wipe. The primary outcome was the difference in mean CFU/cm 2 between day 0 to day 21. The secondary outcome was the proportion of curtains contaminated with Methicillin-resistant Staphylococcus aureus (MRSA). By day 21, the control group was statistically higher (2.2 CFU/cm2) than spray (1.3 CFU/cm2) or wipe (1.5 CFU/cm2) (p < 0.05). After cleaning at three to four day intervals, the bacterial burden on the curtains reduced to near day 0 levels; however, this increased over the intervening three to four days. By day 21, 64% of control curtains were contaminated with MRSA compared to 10% (spray) and 5% (wipe) (p < 0.05). This study show that curtains start clean and progressively become contaminated with bacteria. Regularly cleaning curtains with disinfectant spray or wipes reduces bacterial burden and MRSA contamination.
In Vivo Optical Imaging-Guided Targeted Sampling for Precise Diagnosis and Molecular Pathology
Authors: Sahu Aditi , Peterson Gary , Cordova Miguel , Oh Yuna , Navarrete-Dechent Cristian , Gill Melissa , Alessi-Fox Christi , Gonzalez Salvador , Phillips William , Wilson Steven , Afzalneia Reza , Bello Danielle , Rotemberg Veronica , Marghoob Ashfaq , Rossi Anthony , Chen Chih Shan Jason , Rajadhyaksha Milind
Published: June 2021

Conventional tissue sampling used in disease and cancer diagnosis can lead to misdiagnoses and repeated biopsies, and the tissue processed for histopathology suffers from poor nucleic acid quality/quantity for molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity and complexity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of a 1-mm precision biopsy approach guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) imaging, and reflective metallic grids for accurate spatial targeting and sampling in 7 skin cancers lesions in 6 patients. Accurate sampling was confirmed by histopathology or successful molecular profiling using next generation sequencing (NGS) approaches. Imaging guided 1-mm biopsy enabled spatial targeting and sampling for in vivo diagnosis, feature correlation and predicted depth as confirmed on histopathology. High DNA quantity (680 ng) and quality (DIN: 8) were obtained from imaging-guided high melanoma cell density areas. Subsequent mutational profiling on a 505-gene panel revealed a missense BRAF V600E oncogenic mutations at 0.02 allelic frequency for guiding therapy. Our findings demonstrate accurate sampling of regions of interest that enables downstream diagnosis, molecular analysis and research in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in dermatological and mucosal settings currently accessible to RCM-OCT imaging.
Therapeutic Potential of Curcumin on the Cognitive Decline in Alzheimer’s Disease: A Study Integrated Meta-Analysis, Network Pharmacology, and Molecular Docking
Authors: Zhang Zheyu , Li Hongli , Hui Shan , Yi Min , Chen Xin , Huang Jianhua , Peng Weijun , Yang Jingjing
Published: June 2021

Background: Curcumin, a polyphenol derived from the herb turmeric, has emerged as a promising potential therapy in the management of Alzheimer’s disease (AD). However, the efficacy and potential therapeutic mechanisms remains largely unknown. Objective: To systematically meta-analysis the eﬀect and to investigate the potential pharmacological mechanisms of curcumin on cognitive deficits in AD. Methods: A systematic collection of curcumin studies was performed from MEDLINE’s database, PubMed, Web of Science, and Google Scholar until October 31th, 2020. Following quality assessment of study eligibility, stratified meta-analysis and meta-regression analyses were undertaken to recognize and control the heterogeneity in meta-analysis. An integrated network pharmacology and molecular docking approach were applied to decipher the potential pharmacological mechanisms of curcumin on AD. Results: A meta-analysis of 29 publications showed that curcumin exerts significantly positive eﬀects on cognitive performance. For acquisition, the global estimated effect of curcumin was -2.027 (95% CI: -2.435 to -1.619, p<0.001); For retention, the global estimated effect of curcumin was 1.606 (95% CI: 1.101 to 2.111, p<0.001). Stratified meta-analysis demonstrated that an increased effect size depended on various study characteristics. Network pharmacology analysis identified 63 genes targets, and STAT3, CHEK1, AKT1, EGFR, MMP9, hsp90AA1, and EP300 were core target proteins. Molecular docking showed that curcumin can closely bind with these seven targets. Besides, 69 potential pathways of curcumin were identified, like nitrogen metabolism.Conclusions: Our findings suggested that curcumin may reduce cognitive deficits in AD through multi-target and multi-pathway mechanism, providing a scientific basis for further experimental and clinical application.
Impact of Data-driven Methods for Causal Inference in Observational Studies: Simulations in Three Real-world Datasets
Authors: Pressat-Laffouilhère Thibaut , Massonnaud Clément , Bréard Hélène , Lefebvre Margaux , Falissard Bruno , Gillibert André
Published: June 2021

Background: Although data-driven methods for selecting covariates in multivariable models ignore confusion, mediation and collision, they are still used in causal inference. This study, through three real-world datasets, shows the impact of data-driven methods on causal inference. Methods: A research question leading to multivariate model was raised for each of three real-world datasets. Three covariate selection methods were compared on their performances to correctly answer the question: Augmented Backward Elimination with BIC criterion and “change-in-estimate” threshold set at 0.05, Backward Elimination with BIC criterion and a knowledge-based method relying on causal diagrams. The covariates were classified as indispensable, prohibited and optional, considering the potential bias they could cause on the estimate. For each dataset and sample size (N=75, 300 and 3,000), 10,000 Monte Carlo samples were drawn. Percentages of inclusion of each covariate in models were computed. Coverages of Wald’s 95% confidence interval of exposure effects were computed with two different theoretical values (the analysed method, the knowledge-based method).Results: Even with the largest sample size (n=3,000), data-driven methods were not reproducible, with 8.6% to 53% of covariates included in 20% to 80% of experiences. Prohibited covariates could be included in more than 80% of experiences and indispensable covariates missed in more than 80% of experiences even with n=3,000. With the largest sample sizes, coverages of the theoretical knowledge-based value by data-driven methods ranged from 0% to 83.7%; coverages of the theoretical value of the same data-driven method ranged from 73.2% to 91.1% and were asymmetrical. Conclusion: In conclusion, data-driven methods should not be used in causal inference.
Texture Analysis of Non-Contrast T2-Weighted Cardiovascular Magnetic Resonance Imaging to Discriminate Between Cardiac Amyloidosis and Hypertrophic Cardiomyopathy
Authors: Huang Shan , Shi Ke , Zhang Yi , Yan Wei-feng , Guo Ying-kun , Li Yuan , Yang Zhi-gang
Published: June 2021

BackgroundTo elucidate the value of texture analysis (TA) in detecting and differentiating myocardial tissue alterations on non-contrast T2-weighted CMR (cardiovascular magnetic resonance imaging) in patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM).MethodsIn this retrospective study, 100 CA (58.5±10.7 years; 41 (41%) females) and 217 HCM (50.7±14.8 years, 101 (46.5%) females) patients who underwent CMR scans were included. Regions of interest for TA were delineated by two radiologists independently on non-contrast T2-weighted imaging (T2WI). Stepwise dimension reduction and texture feature selection based on reproducibility, machine learning algorithms, and correlation analyses were performed to select features. Both the CA and HCM groups were randomly divided into a training dataset and a testing dataset (7:3). After the TA model was established in the training set, the diagnostic performance of the model was validated in the testing set and further validated in a subgroup of patients with similar hypertrophy.ResultsThe 7 independent texture features provided, in combination, a diagnostic accuracy of 86.0% (AUC=0.915; 95% CI: 0.879-0.951) in the training dataset and 79.2% (AUC=0.842; 95% CI: 0.759-0.924) in the testing dataset. The differential diagnostic accuracy in the similar hypertrophy subgroup was 82.2% (AUC=0.864, 95% CI: 0.805-0.922). The significance of the difference between the AUCs of the TA model and late gadolinium enhancement (LGE) was verified by Delong’s test (p=0.996). All seven texture features showed significant differences between CA and HCM (all p<0.001).ConclusionOur study demonstrated that texture analysis based on non-contrast T2-weighted images could feasibly differentiate CA from HCM, even in patients with similar hypertrophy. The selected final texture features could achieve a comparable diagnostic capacity to LGE.Trial registration:Since this study is a retrospective observational study and no intervention had been involved, trial registration is waived.
The transmission pattern and clinical course identified from 417 patients with COVID-19 pneumonia in Shenzhen, China: a retrospective and observational study
Authors: Huang Feijuan , Zhang Yu , Cai Yuanzhe , Ding Feng , Liu Zhanyan , Liu Jieren , Liu Yan , Huang Yaowei , Tian Xiaomiao , Lee Weldon , Wu Zhengzhi , Yang Shiwei
Published: June 2021

Background To help government formulating epidemic control strategies and spreading Shenzhen's experience. Methods 417 patients admitted to hospital with confirmed COVID-19 infection between 19 January and 21 February 2020 in Shenzhen, China.Observational study of COVID-19 outcomes using quality-assured public data from website of Shenzhen Municipal Health Commission and a COVID-19 diagnosis and treatment fixed-point hospital to transmission patterns and associated factors of sporadic and clustered COVID-19 cases and its critical time courses.Results We Compared the characteristics of clustered and non-clustered cases, found the clustered cases differed significantly from non-clustered cases in age and exposure history. Moreover, we analyzed the time intervals between symptom onset and recovery for three clinical conditions and different stages of transmission patterns, found the time intervals between illness onset and hospital discharge for all patients were no more than 30 days. Finally, we analyzed disease severity conditions, severe patients spent 4-5 more days of hospitalization and medical intervention than moderate and mild patients did.Conclusions The study confirms that severe patients spent 4-5 more days of hospitalization and medical intervention than moderate and mild patients did. Our results also provided robust evidence that timely and effective prevention measures were the key to quickly cut the transmission chains and prevent the transition from clustered transmission pattern to community transmission pattern.