bluuebunny/crossref_metadata_2025 huggingface dataset:
Abattoir-Based Serological Surveillance for Transboundary and Zoonotic Diseases in Cattle and Swine in Cambodia: A Pilot Study in Phnom Phen Province During 2019 and 2020.
Authors: Siengsanan-Lamont Jarunee , Tum Sothyra , Kong Lida , Selleck Paul W. , Gleeson Laurence J. , Blacksell Stuart D.
Published: August 2021

A pilot animal disease surveillance program was implemented at four abattoirs in Phnom Penh, Cambodia between October 2019 to January 2020. A total of 1,141 samples were collected from 477 cattle and 664 swine. Serological testing was performed using commercial antibody ELISA kits for zoonotic and high impact animal diseases, namely brucellosis, Q fever, CSF, PRRS and ASF. Only two samples tested positive for brucella antibodies (0.2% (0.4, 0.6), n = 1,141). The seroprevalences of Q fever was 0.8% (0.3, 2.1, n = 477) in the cattle samples while CSF, PRRS and ASF in pigs were 55.4% (51.6, 59.2, n = 655), 81.2% (78.1, 84.0, n = 655) and 2.6% (1.6, 4.1, n = 664), respectively. All 38 doubtful and 17 positive ASF antibody ELISA samples were negative when tested by real-time PCR. Statistical analyses demonstrated that the factors that were significantly associated with positive results of Q fever was sampling date (p-value = 0.04), and for ASF was the location of the abattoir (p-value = 0.002). Significant risk factors for both CSF and PRRS were the province of origin of the animals (CSF: p-value = 0.002; PRRS: p-value = 0.004) and sample collection month (CSF: p-value = 1.6 x 10− 6 ; PRRS: p-value = 4.8 x 10− 13). In conclusion, the prevalence of zoonotic diseases tested for in this study were very low. The high prevalences of CSF and PRRS antibodies were most likely the result of vaccination. All ASF seropositive pigs, including those that gave equivocal results, originated from large-scale Cambodian-based commercial farms, as well as Thailand, which raises questions about possible illegal vaccination or low-pathogenicity ASF variants. The pilot abattoir serosurveillance program described here has the potential to provide a sentinel for incursions of novel and endemic pathogens although further work is required to demonstrate its capacity to provide information on the longitudinal disease trends.
Environmental assessment of MSW collection/transport using biomethane in mid-sized metropolitan areas of developing countries
Authors: Ramalho José Carlos Martins , Calmon João Luiz , Colvero Diogo Appel , Siman Renato Ribeiro
Published: August 2021

The novelty of this paper is the focus solely on MSW collection/transport in mid-sized metropolitan regions of developing countries, using biomethane (which can be supplied by the MSW management system) an alternative fuel and different waste collection methods. The eight proposed scenarios, compared to the baseline scenario, combine diesel and biowaste, doorto-door and bring collection methods, as well as two different levels of sourceseparated collection. The results have shown if the collection vehicles use biomethane, the impacts will always be significantly lower than using diesel (between 68–98%, depending on the impact category and scenario), even accounting with the uncertainty of the results. In this particular case-study, increasing source-separated collection also reduced the transport impacts in 40–50%, as the transfer stations are closer to the recycling facilities than the landfills. This is because the fuel consumption of transport is a function of distance, so is the impact. Therefore, this study recommends: using biomethane produced from anaerobic digestion of organic waste instead of diesel to expand circular MSW management; establishing transfer stations for the municipalities located more than 25 km away from waste management facilities; expanding the collection coverage to 100%; increasing sourceseparated collection and recycling.
Biocides in Antifouling Paint Formulations Currently Registered For Use
Authors: Paz-Villarraga César Augusto , Castro Ítalo Braga , Fillmann Gilberto
Published: August 2021

Antifouling paints incorporate biocides in their composition seeking to avoid or minimize the settlement and growing of undesirable fouling organisms. Therefore, biocides are released into the aquatic environments also affecting several non-target organisms and, thus, compromising ecosystems. Despite global efforts to investigate the environment occurrence and toxicity of biocides currently used in antifouling paints, the specific active ingredients that have been used in commercial products are poorly known. Thus, the present study assessed the frequencies of occurrence and relative concentrations of biocides in antifouling paint formulations registered for marketing worldwide. The main data were obtained from databases of governmental agencies, business associations and safety data sheets from paint manufacturers around the world. Results pointed out for 25 active ingredients currently used as biocides, where up to six biocides have been simultaneously used in the examined formulations. Cuprous oxide, copper pyrithione, zinc pyrithione, zineb, DCOIT and cuprous thiocyanate were the most frequently ones, with mean relative concentrations of 35.9±12.8 %, 2.9±1.6 %, 4.0±5.3 %, 5.4±2.0 %, 1.9±1.9 % and 18.1±8.0 % (w/w) of respective biocide present in the antifouling paint formulations. Surprisingly, antifouling paints containing TBT as active ingredient are still being registered for commercialization nowadays. These results can be applied as a proxy of biocides that are possibly being used by antifouling systems and, consequently, released into the aquatic environment, which can help to prioritize the active ingredients that should be addressed in future studies.
Myopia Progress and Related Factors in School-Aged Children in Qingdao
Authors: An Meng , Liu Yuanyuan , Zhang Yan , Che Chengye , Zhang Jie , Sun Jintao
Published: August 2021

PurposeObjective to investigate the progress and related factors for myopia in school-aged children in the Economic and Technological Development Zone of Qingdao. MethodsA total of 320 myopic students (aged 10-15 years; grade 3 to 8), who were willing to cooperate for a long time follow-up, were enrolled in the longitudinal survey. Participants underwent a comprehensive ophthalmic examination included uncorrected visual acuity, corrected visual acuity, slit lamp examination, and cycloplegic autorefraction in January 2017 and 2019, respectively. At the end of the follow-up, the information of near work, outdoor activities and other related factors were collected through a questionnaire. Qualified questionnaires were obtained in 296 (92.50%) students. All the data were entered, cleaned and analyzed by EpiData3.0. SPSS 20.0 statistical software was used for data general description, univariate and multiple logistic regression analysis.Results1. The baseline mean spherical equivalent of all students decreased from -2.29±1.16D in 2017 to -3.45±1.34D at the end of 2 years follow-up in 2019. The annual average growth of myopia was -0.58D (t=7.708, P<0.001). The growth rate of myopia in Grade 6 was faster than that in other grades, and the difference was statistically significant (F=8.236, P=0.003). 2. Both boys and girls showed significant myopia progress after 2 year follow-up. (Boys: t=6.342, P<0.001; Girls: t=4.888, P<0.001). However, we have not found significant difference in the growth rate between them.3. The proportion of two myopic parent was the highest in this sample, followed by one myopic parent, and no myopic parent was the lowest (c2=27.919, P<0.001). 4. The higher the grade, the more time the students spend on near work (F=2.988, P=0.012) and the less time they spend on outdoor activities. (F=2.290, P=0.046). We did not find that the myopia progression was related with Age, Sex, Parent myopia, Near work time and Outdoor activity time.ConclusionsIn this study, the Grade 6 adolescents had relatively rapid progression for myopia than other age groups. There was no significant difference in the progression of myopia between girls and boys. We did not find that the progression of myopia was related with Age, Sex, Parental myopia, Near work time and Outdoor activities time.
Oral Hydration as a Safe Prophylactic Measure To Prevent Post-Contrast Acute Kidney Injury in Oncologic Patients with Chronic Kidney Disease (IIIb) Referred for Contrast-Enhanced Computed Tomography: Subanalysis of The Oncological Group of The NICIR Study.
Authors: Sebastia Carmen , Páez-Carpio Alfredo , Guillen Elena , Paño Blanca , Arnaiz JoanAlbert , de Francisco Angel Luís , Nicolau Carlos , Oleaga Laura
Published: August 2021

Background
The objective of this study is to evaluate oral hydration compared to intravenous (i.v.) hydration in the prevention of post-contrast acute kidney injury (PC-AKI) in the oncologic subgroup of patients with stage IIIb chronic kidney disease (CKD) included in the NICIR study referred for elective contrast-enhanced computed tomography (CE-CT).
Material and Methods
We performed a retrospective subanalysis of the oncological subgroup (174/228 patients, 74%) from a continuous prospective database of patients included in the recently published non-inferiority NICIR study. Patients received prophylaxis against PC-AKI with either oral hydration (500 mL of water two hours before and 2000 mL during the 24 hours after CE-CT) or i.v. hydration (sodium bicarbonate (166 mmol/L)3 mL/kg/h starting one hour before and 1 mL/kg/h during the first hour after CE-CT). The primary outcome was to compare the proportion of PC-AKI in the first 48 to 72 hours after CE-CT in the two hydration groups. Secondary outcomes were to compare persistent PC-AKI, the need for hemodialysis, and the occurrence of adverse events related to prophylaxis in each group.
Results
Of 174 patients included in the subanalysis, 82 received oral hydration and 92 received i.v. hydration. There were no significant differences in clinical characteristics or risk factors between the two study arms. Overall the PC-AKI rate was 4.6% (8/174 patients), being 3.7% in the oral hydration arm (3/82 patients) and 5.4% (5/92 patients) in the i.v. hydration arm. The persistent PC-AKI rate was 1.8% (1/82 patients) in the oral hydration arm and 3.3% (3/92 patients) in the i.v. hydration arm. No patient required dialysis during the first month after CE-CT or had adverse effects related to the hydration regime.
Conclusion
In oncological patients with stage IIIb CKD referred for elective CE-CT, the rate of PC-AKI in those receiving oral hydration did not significantly differ from that of patients receiving i.v. hydration.
Fecal Microbiota Analysis Exploring Taxonomic Diversity of Hindgut Microbial Communities in Kasaragod Dwarf and Holstein Friesian Cattle
Authors: M Deepthi , Arvind Kumar , Saxena Rituja , Pulikkan Joby , U Shamjana , Sharma Vineet K , Grace Tony
Published: August 2021

The indigenous cattle are efficient in converting low quality feeds and forage into animal products. Kasaragod Dwarf (K-Dwarf) cattle, a non-descriptive native cattle variety of Kerala, are noted for their unique qualities, like short stature, low feed intake, thermotolerance, greater resistance to diseases and A2 allelic variant milk. This study hypothesizes that K-Dwarf cow relies on their unique hindgut microbes to ferment the low quality feeds into the efficient animal product. To compare and contrast this unique microbiota and their relationship between the host, we performed microbial profiling of the two genetically distinct cattle-type viz., K-Dwarf, and Holstein utilizing 16S rRNA high-throughput sequencing. Principle Coordinate Analysis using weighted and unweighted UniFrac distance matrices showed significantly distinct clustering of K-Dwarf microbial community compared to Holstein, implying the distinct microbial architecture that K-Dwarf harbors. The dissimilarities observed between the two cattle types were further revealed from the signature taxa identified in each cattle type following Random Forest analysis. In addition, the study observed the predominance of feed efficiency associated genera viz., Anaerovibrio, Succinivibrio, Roseburia, Coprococcus, Anaerostipes, Paludibacter, Elusimicrobium, Sutterella, Oribacterium, Coprobacillus, and Ruminobacter in K-Dwarf cattle. The study highlights the abundance of unique and beneficial hindgut microflora found in K-Dwarf, which may attest its importance over exotic cattle breeds viz., Holstein. To our knowledge, this is the first report of K-Dwarf cattle gut microbiome profiling. Further molecular characterization is solicited to better understand the microbial role in the conversion of low-quality feeds into more efficient animal products, a well-defined characteristic of indigenous cattle.
Inter-Operator Reliability of an Onsite Machine Learning-Based Prototype to Estimate Ct Angiography-Derived Fractional Flow Reserve
Authors: Han Yushui , Ahmed Ahmed Ibrahim , Schwemmer Chris , Cocker Myra , Alnabelsi Talal S , Saad Jean michel , Giraldo Juan C Ramirez , Al-Mallah Mouaz H
Published: August 2021

Background: Advances in computed tomography (CT) and machine learning have enabled on-site non-invasive assessment of fractional flow reserve (FFRCT). Purpose: To assess the inter-operator variability of Coronary CT Angiography–derived FFRCT using a machine learning based post-processing prototype.Materials and Methods: We included 60 symptomatic patients who underwent coronary CT angiography. FFRCT was calculated by 2 independent operators after training using a machine learning based on-site prototype. FFRCT was measured 1 cm distal to the coronary plaque or in the middle of the segments if no coronary lesions were present. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate inter-operator variability effect in FFRCT estimates. Sensitivity analysis was done by cardiac risk factors, degree of stenosis and image quality. Results: A total of 535 coronary segments in 60 patients were assessed. The overall ICC was 0.986 per patient (95% CI: 0.977 - 0.992) and 0.972 per segment (95% CI: 0.967 - 0.977). The absolute mean difference in FFRCT estimates was 0.012 per patient (95% CI for limits of agreement: -0.035 - 0.039) and 0.02 per segment (95% CI for limits of agreement: -0.077 - 0.080). Tight limits of agreement were seen on Bland-Altman analysis. Distal segments had greater variability compared to proximal/mid segments (absolute mean difference 0.011 vs 0.025, p<0.001). Results were similar on sensitivity analysis. Conclusion: A high degree of inter-operator reproducibility can be achieved by onsite machine learning based FFRCT assessment. Future research is required to evaluate the physiological relevance and prognostic value of FFRCT.
Validation of the French translation of the Herth Hope Index assessment (HHI-F)
Authors: Aissaoui Djamel , Gronier Guillaume , Schwander Françoise , Cara-Nova Tanya
Published: August 2021

Objective

This article presents the french validation of a hope assessment scale for use in an international study on the mental health of Swiss and Portuguese students during a pandemic (Querido et al., 2021). is The original hope assessment scale is the Herth Hope Index (HHI) (Herth, 1991) which measures different dimensions of hope and assesses the state of motivation to overcome situations with strong stressful or life-threatening components.

Methods

Our methodology is divided into two main steps. The first step aims at evaluating the qualitative aspects of the assessment tool. We will use a literal translation and a cultural adaptation through cross-cultural validation. We will start with a back-translation method for the translation and preparation of a draft version. Then, we will evaluate the draft by selecting a committee of experts and a sample of "end-users" to correct the initial translation and produce a consensus version. The second part will concern the evaluation of the psychometric and metrological qualities of the instrument. We will set up a method of parallel/equivalent form reliability and tests of convergent/divergent validity with other tools assessing similar constructs.

Results

We obtained a consensus from our expert panel (n=7) after our back-translation. We then tested the translation on a pilot group of students (n=13) in order to highlight potential comprehension problems. We obtained CVIs >.80 for all of our items in the second test run, which indicates that the translation is understood and accepted by the subjects. We also measured the concurrent validity between the HHI-F (target instrument) and other scales (criterion instruments) measuring the same phenomena, which were administered simultaneously to our subjects (i.e. DASS-21, IES-R and BRCS). The results suggest good translation validity of the HHI-F: systematically negative correlations between the HHI-F and the DASS-21 (r= -.562; p=000); all correlations between the IES-R and the HHI-F are negative  (r= -.301; p=000) and all correlations between the HHI-F scale and the BRCS are positive (r= .552; p=000).

Discussion

The french version of the Herth Hope Index (HHI) is translated. Validation of the qualitative and quantitative criteria was carried out and the results show that the French version (HHI-F) has sufficiently strong fidelity and validity criteria to be used in practice.
Different Methods of Eubiotic Feed Additive Provision Affects Health, Performance, Fermentation, and Metabolic Status of Dairy Calves During The Preweaning Period
Authors: Stefańska Barbara , Katzer Frank , Golińska Barbara , Smulski Sebastian , Sobolewska Patrycja , Frankiewicz Andrzej , Nowak Włodzimierz
Published: August 2021

Background
The aim of this study was to evaluate whether different methods of providing eubiotic feed additives, to neonatal calves during the preweaning period, can improve the health, performance, rumen fermentation, and metabolic status of the calves. Forty-four Holstein-Friesian dairy calves, were divided into one of four treatment groups for the 8 week trial. The eubiotic feed additives consisted of a combination of probiotic Lactobacillus spp. (multiple-strains) at a dose of 250 mg/calf/d and phytobiotics containing rosmarinic acid, as the main bioactive compound, at a dose of 50 mg/calf/d. Treatment differed by the methods that the eubiotic feed additives were provided, and the groups were as follows: CON (control, without eubiotic feed additive in their milk replacer or their starter feed), MR (eubiotic feed additives added to the milk replacer), SF (eubiotic feed additives added to the starter feed), MRS (eubiotic feed additives added to the milk replacer and the starter feed). Individual intake of starter feed was measured daily and body weights weekly until 56 d of age.
Results
The body weight of the MR treatment group calves were higher on days 28 and 56. Including the eubiotic feed additive in the milk replacer affected increasing average daily gain, starter intake and total dry matter intake from d 29 to d 56 and the overall experimental period in comparison to the CON group. The calves of the MR treatment had lower fecal scores from d 3 to d 28, number of parasite oocysts/cysts per gram of feces on d 28, and the occurrences of faecal consistency scores of 3 (mild diarrhea) and 4 (confirmation diarrhea) were 3.2 and 3.0 times lower, respectively, compared with animals of the CON group. Also, in this group higher ruminal concentrations of total volatile fatty acids, propionate, and butyrate were noted on d 56 compared to CON group. Adding eubiotics into milk replacer resulted the highest concentrations of blood insulin-like growth factor-I and β-hydroxybutyrate from d 29 to 56 and through the entire experimental period.
Conclusion
The addition of eubiotic feed additives into the milk replacer can improve health, performance, rumen fermentation, and biochemical blood indices in dairy calves during the preweaning period.
CO2 uptake decreased and CH4 emissions increased in first two years of peatland seismic line restoration
Authors: Schmidt Megan , Davidson Scott J. , Strack Maria
Published: August 2021

Oil and gas exploration has resulted in over 300,000 km of linear disturbances known as seismic lines, throughout boreal peatlands across Canada. Sites are left with altered hydrologic and topographic conditions that prevent tree re-establishment. Restoration efforts have concentrated on tree recovery through mechanical mounding to re-create microtopography and support planted tree seedlings to block sightlines and deter predator use, but little is known about the impact of seismic line disturbance or restoration on peatland carbon cycling. This study looked at two mounding treatments and compared carbon dioxide and methane fluxes to untreated lines and natural reference areas in the first two years post-restoration. We found no significant differences in net ecosystem CO2 exchange, but untreated seismic lines were slightly more productive than natural reference areas and mounding treatments. Both restoration treatments increased ecosystem respiration, decreased net productivity by 6–21 gCO2m− 2d− 1, and created areas of increased methane emissions, including an increase in the contribution of ebullition, of up to 2000 mgCH4m− 2d− 1. Further research on this site to assess the longer-term impacts of restoration, as well as application on other sites with varied conditions, will help determine if these restoration practices are effective.
Analysis of Provincial Energy Consumption and Carbon Emissions Effect of West-to-East Gas Transmission Project: Based on PSM-DID Method
Authors: LUAN Xiaomei , Cui Danny Chunying , Zhang Dianping , XIE Junyue , YAN Ziwei
Published: August 2021

West-to-East gas transmission project (WEGTP) is a major energy construction programm in China. Evaluating its impacts on the energy consumption and carbon emissions(ECER) in involved provinces is of great significance for further achieve the goals of high-quality development. This paper takes WEGTP as a quasi-natural experiment, calculates the total energy consumption and carbon emissions by employing the provincial panel data of 1997-2017, and applies a counterfactual framework under Rubin Causal Model (RCM) to estimate the ECER policy effect of WEGTP Line I Subproject. It is found that WEGTP generates an overall carbon emissions reduction effect in the involved provinces. Further heterogeneity analysis points out that the project has an obvious energy conservation effect on the natural gas importer provinces, however the emissions reduction effect is not significant, while the project has significant positive effects on energy conservation and emissions reduction in the natural gas exporter provinces. Based on the results, WEGTP has played a long-term role in promoting energy structure optimization and carbon emissions reduction. It is still necessary to figure out the price mechanism of natural gas consumption, actively promote the structure of industrial, and meet the objective requirements of high-quality development with the actual effects of energy conservation and emissions reduction.
MAFB is a biomarker for cancer severity and prognosis, and is a potential cancer immunotherapy target
Authors: Samir Omar , Kobayashi Naohiro , Siyam Mennatullah , Yadav Manoj , Inoue Yuri , Takahashi Satoru , hamada Michito
Published: August 2021

MAFB is a transcription factor specifically expressed in macrophages. Tumor associated macrophages (TAMs) play a key role in the tumor microenvironment (TME) by inducing immunosuppression, angiogenesis, tumor invasion, and metastasis. However, finding a suitable specific biomarker and target for TAMs is challenging. Our previous study1 suggested that MAFB could be a suitable marker for tumor-associated macrophages (TAMs) besides MAFB is expressed in anti-inflammatory alternatively activated M2 macrophages in vitro. In the current study, in a cohort of patients with lung adenocarcinoma (n = 120), increased MAFB expression was related to increased metastasis and poor overall survival rate. Our findings indicate that MAFB can be used as a prognostic marker for assessing metastatic potential in patients with lung adenocarcinoma. Further, we showed that MAFB expression was positively correlated with the expression of CD204 and CD68 in hepatocarcinoma, colon and pancreatic cancers. We demonstrated that MAFB could be used as a biomarker for TAMs and consequently, for assessing severity in various human cancers, including lung, liver, colon, and pancreatic cancers, according to the immunohistochemical analysis of the expression of MAFB, CD68, and CD204. In addition, we showed that MAFB was expressed in TAMs expressing Programmed cell death protein-1 and/or Programmed cell death ligand 1 (TAM PD-1+ and TAM PD-L1+) cells in lung adenocarcinoma and Lewis lung carcinoma (LLC) mouse model. These findings indicate that MAFB can be a potential target for drug development against TAM PD-1+ and TAM PD-L1+ cells. In summary, transcriptional factor MAFB can be used as a specific biomarker, prognostic marker, and a potential target for cancer immunotherapy against TAMs.
Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants
Authors: Koehler Melanie , Ray Ankita , Silva Rodrigo Azevedo Moreira da , Juniku Blinera , Poma Adolfo , Alsteens David
Published: August 2021

Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observe a direct link between increased RBD—ACE2 complex stability and the greater transmissibility observed for the variants of concern. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.
Mapping the Effects of Pollution on Diabetes in Durham, NC
Authors: Zwecker Zoe L. , Spratt Susan E. , Granger Bradi B.
Published: August 2021

BackgroundThough the impact of environmental pollution on chronic disease remains largely unknown, previous case control studies have begun to examine the adverse effects of particulate matter (PM2.5) on prevalence of type 2 diabetes. Based on multivariate regression models in these studies, a 1% increase in diabetes prevalence is seen with a 10 μg/m3 increase in PM2.5 exposure due to impairment of vascular reactivity. Presentation of the hypothesis This study proposes the use of Geographic Information Systems (GIS) to illustrate the correlation of diabetes to the anthropogenic footprint to target healthcare delivery and policy for diabetes-related health mitigation. GIS is used to overlay variables of diabetes prevalence, social determinates of health, and particulate matter concentration as layers on a map allowing targeted prevention programming.Testing of the hypothesisThough PM2.5 can be harmful in many contexts, for adults with diabetes, it becomes adverse as it enters the bloodstream, placing the body under oxidative stress. The window of opportunity for testing the hypothesis is large in that ambient air pollution and patients with diabetes are abundant. Using a longitudinal, matched, family cohort design, we are able to assess the long and short-term exposure of PM2.5 to better understand the nature and timing of the onset of disease. Implications of the hypothesis The hypothesis has the potential to identify high risk patients and could provide the basis for future work to assess risk at the neighborhood level. Based on risk acceptance and aversion, targeted policy interventions within states, counties, and neighborhoods may advance the state of the science for improving health and reducing health risk at a population level.
Systems spatiotemporal dynamics of traumatic brain injury at single cell resolution reveals humanin as a therapeutic target
Authors: Arneson Douglas , Zhang Guanglin , Ahn In Sook , Ying Zhe , Diamante Graciel , Cely Ingrid , Palafox-Sanchez Victoria , Gomez-Pinilla Fernando , Yang Xia
Published: August 2021

The etiology of mild traumatic brain injury (mTBI) remains elusive due to the tissue and cellular heterogeneity of the affected brain regions that underlie cognitive impairments and subsequent neurological disorders. This complexity is further exacerbated by disrupted circuits within and between cell populations across brain regions and the periphery, which occur at different timescales and in spatial domains. We profiled three tissues (hippocampus, frontal cortex, and blood leukocytes) at the acute (24hr) and chronic (7days) phases of mTBI at single cell resolution and demonstrated that the coordinated gene expression patterns across cell types were disrupted and re-organized by TBI at different timescales with distinct regional and cellular patterns. Gene expression-based network modeling identified astrocytes as a key regulator of the cell-cell coordination following mTBI in both hippocampus and frontal cortex across timepoints, and mt-Rnr2, which encodes the mitochondrial peptide humanin, as a potential target for intervention based on its broad regional and dynamic dysregulation following mTBI. Treatment of a murine mTBI model with humanin reversed cognitive impairment caused by mTBI through the restoration of metabolic pathways within astrocytes. Our results offer a systems-level understanding of the dynamic and spatial regulation of gene programs by mTBI and pinpoint key target genes, pathways, and cell circuits that are amenable to therapeutics.
In vivo self-assembled siRNA: a new modality for combination therapy of ulcerative colitis
Authors: Zhou XinYan , Yu Mengchao , Fu JinYu , Ma Luzhen , Guo Jingwei , Lei Jieqiong , Fu Zheng , Fu Yong , Zhang Chen-Yu , Chen Xi
Published: August 2021

Given the complex nature of ulcerative colitis (UC), combination therapy targeting multiple pathogenic genes and pathways of UC may be required. Unfortunately, current therapeutic strategies based on independent chemical compounds or monoclonal antibodies are not applicable for combination therapy of UC. Here, we developed a synthetic biology strategy that integrates the naturally existing exosome-circulating system with artificial genetic circuits for self-assembly and delivery of multiple siRNAs for the combination therapy of UC. Intravenous injection of genetic circuit (in the form of DNA plasmid) designed for inhibition of TNF-α, B7-1 and integrin α4 successfully reprogrammed the host liver to direct the self-assembly of TNF-α, B7-1 and integrin α4 siRNA into secretory exosomes. The multitargeted genetic circuit could rapidly relieved intestinal inflammation and exert a synergistic therapeutic effect against UC through suppressing the proinflammatory cascade in colonic macrophages, inhibiting the costimulatory signal to T cells and blocking T cell homing to sites of inflammation. More importantly, we designed an AAV-driven genetic circuit to induce substantial and lasting inhibition of TNF-α, B7-1 and integrin α4. Overall, this study established a feasible combination therapeutic strategy for UC, which is superior to the conventional biological therapies requiring.
Genomic Expression in Peripheral Blood Mononuclear Cells (Pbmcs) of Patients with Hepatocellular Carcinoma (Hcc): Effect of Ablative Treatment
Authors: Gesualdo Annamaria , Passerini Francesca , D’Amore Simona , Grimaldi Lucia Donatella , Noto Antonino , Santovito Daniela , Graziano Giusi , Milella Michele , Marano Giuseppe , Puntillo Filomena , Mangia Alessandra , Palmieri Vincenzo Ostilio
Published: August 2021

Genome-wide association studies revealed potential driver genes involved in hepatocellular carcinoma (HCC) development thus providing putative therapeutic targets and predictive biomarkers for personalized therapy.In the present study, we analyzed changes in the gene expression profile of circulating peripheral mononuclear cells (PBMCs) of HCC patients undergoing treatment in order to identify the gene signatures useful as biomarkers for prognostic classification. Patients (24) diagnosed with HCC and staged according to BCLC criteria were enrolled. All patients underwent treatment by radiofrequency ablation or chemoembolization and the effect of treatment was evaluated three months later. Patients were stratified into 2 subgroups: 11 with complete response; 13 with partial response. Furthermore, we added six patients (with stable or progressive disease) to the initial cohort. Microarray expression profiling on PBMCs isolated before and three months after the therapeutic procedure was performed in order to identify upregulated and downregulated genesin each patient. In addition, quantitative real-time PCR was used to confirm differentially expressed genes on microarray analysis. The most intriguing results were the upregulation at baseline of ENTPD1 (ectonucleoside triphosphate diphosphohydrolase-1, able to suppress the immune system response to malignancies) and the down-regulation of ICOS (inducible co-stimulator, involved in anti-tumour T cell response) in patients with partial response to treatment. To the best of our knowledge, there are no study relating ENTPD1 and ICOS gene signatures to outcome of treatment in HCC. Our findings highlight a new role for ENTPD1 and ICOS as useful biomarkers for prognostic classification of patients with liver cancer.
WAC-A New GBM Tumour Suppressor- Induces GBM Cell Apoptosis and Promotes Autophagy
Authors: Wang Yixuan , Zhang Si , Sun Qian , Yuan Fan’en , Zhao Linyao , Ye Zhang , Li Yong , Wang Ronggui , Jiang Hongxiang , Hu Ping , Tian Daofeng , Liu Baohui
Published: August 2021

WAC is closely related to the occurrence and development of tumors. However, its role in human glioblastoma (GBM) and its potential regulatory mechanisms have not been investigated. This study demonstrated that WAC is downregulated in GBM, and its low expression predicts a poor prognosis. We investigated the effect of WAC on the proliferation of glioma cells through the CCK-8 assay, EdU incorporation and cell formation. The effects of WAC on apoptosis and autophagy in glioma were demonstrated by flow cytometry, TUNEL detection, immunofluorescence, q-PCR, WB and scanning electron microscopy. We found that overexpression of WAC inhibited proliferation of glioma cells, promoted apoptosis and induced autophagy. Therefore, WAC is likely to play a role as a new regulatory molecule in glioma.
Serum Prolactin Level to Tumor Size Ratio as a Potential Parameter for Preoperative Differentiation of Prolactinomas from Hyperprolactinemia-Causing Non-Functional Pituitary Adenomas.
Authors: Kim Jeong-Hwa , Hur Kyu-Yeon , Hong Sang-Duk , Choi Jung-Won , Seol Ho-Jun , Nam Do-Hyun , Lee Jung-Il , Kong Doo-Sik
Published: August 2021

Preoperative diagnosis of prolactinomas is critical because dopamine agonists have been regarded as a primary treatment. However, serum prolactin level alone is suboptimal for differentiating prolactinomas from hyperprolactinemia-causing non-functioning pituitary adenomas (NFPAs). By using the tumor size, we investigated a more effective parameter for the discrimination.223 patients with pituitary lesions of the histologic diagnosis were retrospectively reviewed. The prolactinoma group (n=48) showed higher serum prolactin (258.6㎍/L) and smaller maximal diameter (16.6mm) than those in the NFPA group (n=175) (44.4㎍/L and 23.9mm; both p-values < 0.001).Using receiver operating curve analyses, we compared diagnostic performances of serum prolactin levels (PRL), a ratio of PRL to maximal tumor diameter (PRL/MD; PDR1), and MD squared (PRL/(MD)2; PDR2) in preoperative diagnosis of prolactinomas. PDR2 exhibited better performance with the cutoff value of 0.83[㎍/L]/ mm2 (area under the curve [AUC] = 0.945), compared to the PDR1 (8.93[㎍/L]/ mm with AUC 0.938) and PRL (99.㎍/L with AUC 0.910). In the external validation study, PDR2 still maintained superiority over PDR1 and PRL (Accuracy of 94.8%, 91.8%, and 75.8%, respectively).In conclusion, PDR2 may be an effective parameter for preoperative discrimination of prolactinomas from NFPAs with hyperprolactinemia, and contribute to select patients who benefit from medical treatment primarily.
Impact of Prior to Intensive Care Unit Statin use on Patients with Acute Kidney Injury
Authors: Tu Bo-Xiang , Tang Yuan-Jun , Cheng Yi , Liu Xiao-Bin , Wu Cheng , Qian Di , Zhao Yan-Fang , Qin Ying-Yi , He Jia
Published: August 2021

Purpose: To evaluate if prior to intensive care unit (ICU) statin use improve the clinical outcomes, for critically ill patients with acute kidney injury (AKI).Materials and Methods: Patients with AKI were selected from the Medical Information Mart for Intensive Care IV v1.0 database for this retrospective observational study. The primary outcome was 30-day ICU mortality. 30-day in-hospital mortality and ICU length of stay (LOS) were considered as secondary outcomes. Comparison of mortality between pre-ICU statin users with non-users was conducted by multivariable cox proportional hazards model. Comparison of ICU LOS between two groups was implemented by multivariable linear model. Three propensity score methods were used to verify the results as sensitivity analyses. Stratification analyses were conducted to explore whether the association between pre-ICU statin use and mortality differed across various subgroups classified by sex and different AKI stages.Results: 3821 pre-ICU statin users and 9690 non-users were identified. In multivariable model, pre-ICU statin use was associated with reduced 30-day ICU mortality rate [Hazara ratio (HR) 0.68 (0.59,0.79); P<0.001], 30-day in-hospital mortality rate [HR 0.64 (0.57, 0.72); P<0.001] and ICU LOS [Mean Difference -0.51(-0.79, -0.24); P<0.001]. The conclusions were consistent in three propensity score methods. In Subgroup analyses, pre-ICU statin use was associated with decreased 30-day ICU mortality and 30-day in-hospital mortality in both sexes and AKI stages, only except for 30-day ICU mortality in AKI stage 1.Conclusions: Patients with AKI who were administered statins prior to ICU admission might have lower mortality rate during ICU or hospital stay and shorter ICU LOS.
Biodiversity risks and safeguards of China’s hydropower investments in Belt and Road Initiative (BRI) Countries
Authors: Narain Divya , Teo Hoong , Lechner Alex , Watson James , Maron Martine
Published: August 2021

The imperative of a global transition to renewables to achieve net-zero emissions by 2050 calls for an examination of the associated biodiversity risks. Hydropower is the biggest source of renewable energy globally, and its remaining untapped potential is concentrated in low and lower-middle income countries which are also among the world’s most biodiverse. China has emerged as a major overseas financier of hydropower dams under its flagship Belt and Road Initiative (BRI). We assess the biodiversity risk posed by proposed or under-construction hydropower dams being funded by China in BRI countries and compare it with that of dams being funded by Multi-lateral Development Banks (MDBs) – the other key overseas financiers of hydropower. We find that 48 hydropower dams are being financed by China in 18 BRI countries, likely impacting 14 free-flowing rivers and the ranges of 11 critically endangered freshwater fish species, and 130 km2 of critical terrestrial habitat(within a 1-km buffer distance). When compared to dams funded by MDBs, Chinese-funded dams are not located in riskier areas for biodiversity, but the total risk is higher due to their preponderance. We find that Chinese regulators and hydropower companies do not specify any enforceable biodiversity impact mitigation requirements. And while MDBs do specify binding safeguards, impacts on river connectivity do not form a part of the mitigation requirements, except in the case of the European Investment Bank (EIB). China is uniquely positioned to adopt a leadership role in specifying safeguards that will help BRI countries adopt an optimum renewable energy mix that minimizes biodiversity risks.
Relationship of Arterial Tonometry and Exercise in Patients With Chronic Heart Failure: a Systematic Review With Meta-analysis and Trial Sequential Analysis
Authors: Gong Xiaodan , Hu Mengwen , Li Mei , Wang Lishen
Published: August 2021

BackgroundArterial stiffness is a common characteristic in patients with chronic heart failure (CHF), and arterial tonometric technologies related to arterial stiffness are novel and effective methods and have an important value in the diagnosis and prognosis of CHF. In terms of ameliorating arterial stiffness in patients with CHF, exercise training is considered an adjuvant treatment and also an effective means in the diagnosis and judgment of prognosis. However, there are huge controversies and inconsistencies in these aspects. The objective of this meta-analysis was to systematically test the connection of arterial tonometry and exercise in patients with CHF.Methods and resultsMEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library were searched from inception to 2 June 2021. Eighteen articles were included, with a total of 876 participants satisfied the inclusion criteria. The pooling revealed that flow-mediated dilation (FMD) was lower in basal condition [standardized mean difference (SMD): -2.28%, 95% confidence interval (CI): -3.47 to -1.08, P<0.001] and improved significantly after exercise (SMD: 5.96%, 95%CI: 2.81 to 9.05, P<0.001) in patients with heart failure with reduced ejection fraction (HFrEF) compared with normal participants. High-intensity training exercise was more beneficial (SMD: 2.88%, 95% CI: 1.78 to 3.97, P<0.001) than moderate-intensity training exercise to improve FMD in patients with CHF. For augmentation index (AIx), our study indicated no significant differences (SMD: 0.50%, 95% CI: -0.05 to 1.05, p = 0.074) in patients with heart failure with preserved ejection fraction (HFpEF) compared with normal participants. However, other outcomes of our study were not identified after further verification using TSA, and more high-quality studies are needed to reach definitive conclusions in the future.ConclusionsThis review shows that FMD is lower in basal condition and improves significantly after exercise in patients with HFrEF compared with normal participants; high-intensity training exercise is more beneficial than moderate-intensity training exercise to improve FMD in patients with CHF; besides, there are no significant differences in AIx in patients with HFpEF compared with normal participants. More high-quality studies on this topic are warranted.
Neutralization of the emerging SARS-CoV-2 variant Lambda by antibodies elicited by inactivated virus and mRNA vaccines
Authors: Acevedo Mónica , Alonso-Palomares Luis , de Oca Marco Montes , Bustamante Andrés , Gaggero Aldo , Paredes Fabio , Cortés Claudia , Pantano Sergio , Navarrete Marcelo , Valiente-Echeverría Fernando , Soto-Rifo Ricardo
Published: August 2021

Here, we used pseudotyped viruses to characterize the neutralization capacity of antibodies elicited by the CoronaVac and BNT162b2 vaccines against the emerging variant of interest Lambda. We observed that BNT162b2 elicits higher neutralizing antibody titers than CoronaVac, ranging from 5.8-fold for the ancestral spike to 9.4-fold for the Lambda variant. Neutralization against D614G, Alpha, Gamma, and Lambda variants was reduced between 1.78 to 3.05-fold for CoronaVac and 1.10 to 1.87-fold for BNT162b2. Structural analyses of the Lambda spike show significant changes in antigenic sites including the 246–252 deletion in an antigenic supersite at the NTD loop and, L452Q/F490S within the RBD that may account for immune escape. Our analysis of pseudotyped viruses also suggests increased infectivity driven by the Lambda spike. Together, our data indicate that inactivated virus and mRNA vaccines elicit different levels of neutralizing antibodies with different potency to neutralize SARS-CoV-2 variants, including the emergent variant Lambda.
Patients with Stable Coronary Artery Disease and Type 2 Diabetes But Without Prior Myocardial Infarction or Stroke and THEMIS-like Patients: Real-World Prevalence and Risk of Major Outcomes from the SNDS French Nationwide Claims Database
Authors: Blin Patrick , Darmon Patrice , Henry Patrick , Guiard Estelle , Bernard Marie-Agnès , Dureau-Pournin Caroline , Maizi Hélène , Thomas-Delecourt Florence , Lassalle Regis , Droz-Perroteau Cécile , Moore Nicholas
Published: August 2021

Aim and hypotheses: The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the corresponding population in a real-world setting, i.e. CAD-T2DM population without prior MI or stroke, and more specifically, the THEMIS-like population, as well as their risk of major outcomes in current practice.Methods: A 2-year follow-up cohort study included all CAD-T2DM prevalent patients without prior MI or stroke on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan-Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death.Results: From a population of about 50 million adults, the prevalence of CAD-T2DM without prior MI or stroke and THEMIS-like populations was respectively at 6.17 and 1.53 per 1,000 adults. Both populations had similar general characteristics with the same mean age of 72 years, 68% and 66% men, respectively, and less comorbidities and diabetic complications for the THEMIS-like population. The 2-year cumulative incidence was respectively 1.7% and 1.3% for MI, 1.7% and 1.5% for stroke, 4.8% and 3.1% for major bleeding, 13.6% and 9.7% for all-cause death, and 16.2% and 12.0% for the composite outcome.Conclusion: The THEMIS-like prevalence was estimated to 1.53 per 1,000 adults, representing about a quarter of CAD-T2DM patients without prior MI or stroke. In current French practice, the median age of the THEMIS-like population was 6 years older than in the THEMIS trial (i.e. 72 vs. 66 years), with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions.Registration n° EUPAS27402 (http://www.ENCEPP.eu).