bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA expression profile of Chicken cecal in different stages during Histomonas meleagridis infection
Authors: Zhang Yu-Ming , Chen Qiao-Guang , Chen Chen , Wang Shuang , Li Zai-Fan , Hou Zhao-Feng , Liu Dan-Dan , Tao Jian-Ping , Xu Jin-jun
Published: March 2022

Background: Histomonas meleagridis is an anaerobic, intercellular parasite, which infects gallinaceous birds such as turkeys and chickens. In recent years, the reemergence of Histomoniasis has caused serious economic losses as drugs to treat the disease have been banned. At present, H. meleagridis research focuses on virulence, gene expression analysis, and the innate immunity of the host. However, there are no studies on the differentially expressed miRNAs (DEMs) associated with the host inflammatory and immune responses induced by H. meleagridis. In this research, high-throughput sequencing was used to analyze the expression profile of cecal miRNA at 10 and 15 days post-infection (DPI) in chickens infected with Chinese JSYZ-F strain H. meleagridis.Results: Compared with the controls, 94 and 127 DEMs were found in cecal of infected chickens at 10 DPI (CE vs CC) and 15 DPI (CEH vs CCH), respectively, of which 60 DEMs were shared at two-time points. Gene Ontology (GO) functional enrichment analysis of the target genes of DEMs indicated that 881 and 1027 GO terms were significantly enriched at 10 and 15 DPI, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the target genes of DEMs demonstrated that 5 and 3 KEGG pathways were significantly enriched at 10 and 15 DPI, respectively. The integrated analysis of miRNA–gene network revealed that the DEMs played important roles in the host inflammatory and immune responses to H. meleagridis infection by dynamically regulating expression levels of inflammation and immune-related cytokines. Conclusion: This article not only suggested that host miRNA expression was dynamically altered by H. meleagridis and host but also revealed differences in the regulation of T cell involved in host responses to different times H. meleagridis infection. This article contributes to future research into miRNA-target interactions during H. meleagridis infection in chickens and provides new ideas for H. meleagridis treatment and control.
Universal health coverage and the poor: To what extent are health financing policies making a difference? Evidence from a Benefit Incidence Analysis in Zambia
Authors: Ridde Valery , Chitah Bona , Rudasingwa Martin , De Allegri Manuela , (Deceased) Chrispin Mphuka , Chansa Collins , Yeboah Edmund , Bonnet Emmanuel
Published: March 2022

Background: Zambia has invested in several healthcare financing reforms aimed at achieving universal access to health services. Several evaluations have investigated the effects of these reforms on the utilization of health services. However, only one study has assessed the distributional incidence of health spending across different socioeconomic groups, but without differentiating between public and overall health spending and between curative and maternal health services. Our study aims to fill this gap by undertaking a quasi-longitudinal benefit incidence analysis of public and overall health spending between 2006 and 2014. Methods: We conducted a Benefit Incidence Analysis (BIA) to measure the socioeconomic inequality of public and overall health spending on curative services and institutional delivery across different health facility typologies at three time points. We combined data from household surveys and National Health Accounts. Results: Results showed that public (concentration index of -0.003; SE 0.027 in 2006 and -0.207; SE 0.011 in 2014) and overall (0.050; SE 0.033 in 2006 and -0.169; SE 0.011 in 2014) health spending on curative services tended to benefit the poorer segments of the population while public (0.241; SE 0.018 in 2007 and 0.120; SE 0.007 in 2014) and overall health spending (0.051; SE 0.022 in 2007 and 0.116; SE 0.007 in 2014) on institutional delivery tended to benefit the least-poor. Higher inequalities were observed at higher care levels for both curative and institutional delivery services.Conclusion: Our findings suggest that the implementation of UHC policies in Zambia led to a reduction in socioeconomic inequality in health spending, particularly at health centres and for curative care. Further action is needed to address existing barriers for the poor to benefit from health spending on curative services and at higher levels of care.
Epidemiological Status of Malaria in Karimganj District of Assam, India (2001-2020)
Authors: Dey Ankita , Dey Debojit
Published: March 2022

In the present study Epidemiological status of Malaria in Karimganj disctrict of Assam is monitored from 2001–2020. Plasmodium falciparum accounts for 81% disease burden in the the district but survey also revealed that 41% & 32% cases caused by P. vivax in Block Primary Health Centre (BPHC)- Patharkandi & R.K. Nagar respectively. As per 20 years data from 2001–2020 it was noticed that the Slide Falciparum Rate (SFR) declined from 0.54% (2001) to 0% (2020) but contrastingly high intensity of P. vivax positive cases reported in 2018, 2019 & 2020 with Pv% 60, 45 & 100 respectively, indicating P. vivax as threat in future years. Out of 5 BPHCs in the district 3 BPHCs- Kachuadam, R.K. Nagar & Grishganj viewed mortality zero in last 5 years (2016–2020). In 2016, total 4 mortality recorded in Assam out of which 2 deaths reported from Karimganj district 1 each from BPHCs- Patharkandi and Nilambazar. In 2019 Assam witnessed 6 mortality of which 2 again reported from Karimganj district under same BPHC Nilambazar. From the survey it is also noted that malaria cases are temperature, humidity and rainfall dependent. Favourable temperature is 20-35o & humidity 57–76%. Thus, maximum cases recorded between between April to July. Study also revealed that gradual decrease in Annual Parasite Index in the district in past 20 years with only 4 mortality in last five years (2016–2020). Hence, from the survey it can be presumed that the National Centre for Vector Borne Disease Control Programme working sincerely towards malaria free district in future years.
AquiferLevel_PredicT: Predictability of Groundwater Level Dynamics in Aquifers Through Causal Reasoning Modelling
Authors: Molina Jose-Luis , García-Aróstegui Jose-Luis
Published: March 2022

The analysis of causal relationships of hydrological processes is a very unexplored field. It is even less investigated the usage of Causal Reasoning modelling for the study of groundwater hydrodynamic processes. This paper is aimed to analyse and model the relationship of the binomial Rainfall-Piezometry. For that, the inherent causality contained in temporal data records has been captured, analysed and interpreted. This has been done through Bayesian Causal Reasoning (BCR) which is technique belonging to Artificial Intelligence (AI) based on Bayesian Theorem. The data for Rainfall and Groundwater levels (piezometry) has been taken in hourly data records. The methodology comprises two main stages, first an analytical method from classic regression analysis, and second, a Bayesian Causal Modelling Translation (BCMT) that itself comprises several iterative steps. This research ultimately become a tool for aquifers management that comprises a bivariate function made of two variables Rainfall and piezometry (Temporal Groundwater level evolution). This innovative methodology has been successfully applied in the Quaternary aquifer of the Campo de Cartagena groundwater body, which is an aquifer system that directly is connected to Mar Menor coastal lagoon (Murcia region, SE Spain). This system has been in the spotlight worldwide due to major environmental problems, closely related to the lack of groundwater management.
Modeling and Simulation of the Automated Lane Change Process, Taking Into Account Freeplay and Friction in the Vehicle Steering System
Authors: Żardecki Dariusz , Gidlewski Mirosław , Jaśkiewicz Marek , Jemioł Leszek
Published: March 2022

The paper reports rather unique research on the influence of freeplay and friction in the car steering mechanism on automatically controlled process of lane change. The developed controller algorithm was based on very simplified (and thus effective in on-line calculations) reference models of the car dynamics, obviously without taking into account the nonlinearities of its steering system. Extensive simulation investigations of the developed controller algorithm carried out in a very wide range of changes in road and operational conditions, with regard to two-axle medium-duty truck, confirmed its advantages. The research presented in this article concerns the unpublished area of analyzes concerning the sensitivity of the lane change controller to freeplay and friction occurring in the steering mechanism of a controlled car. Some results of the simulation tests turned out to be surprising The piecewise-linear luz(...) and tar (...) projections used in these studies to describe the freeplay and friction effects facilitated modeling and simulation calculations.
Transplanted Allogeneic Stem Cells Secrete GDF-15 and stimulate an Active Immune Remodeling Process in the Ischemic Myocardium
Authors: Mishra Rachana , Saha Progyaparamita , Datla Srinivasa Raju , Mellacheruvu Pranav , Gunasekaran Muthukumar , Fu Xuebin , Guru Sameer Ahmad , Chen Ling , Bolli Roberto , Kaushal Sunjay , Sharma Sudhish
Published: March 2022

Background: Despite promising results in clinical studies, the mechanism for the beneficial effects of allogenic cell-based therapies remains unclear. Macrophages are not only critical mediators of inflammation but also critical players in cardiac remodeling. We hypothesized that transplanted allogenic rat cardiac progenitor cells (rCPCs) augment T-regulatory cells which ultimately promote proliferation of M2 like macrophages by an as-yet undefined mechanism.Methods and Results: To test this hypothesis, we used crossover rat strains for exploring the mechanism of myocardial repair by allogenic CPCs. Human CPCs (hCPCs) were isolated from adult patients undergoing coronary artery bypass grafting, and rat CPCs (rCPCs) were isolated from male Wistar-Kyoto (WKY) rat hearts. Allogenic rCPCs suppressed the proliferation of T-cells observed in mixed lymphocyte reactions in vitro. Transplanted syngeneic or allogeneic rCPCs significantly increased cardiac function in a rat myocardial infarct (MI) model, whereas xenogeneic CPCs did not. Allogeneic rCPCs stimulated immunomodulatory responses by specifically increasing T-regulatory cells and M2 polarization, while maintaining their cardiac recovery potential and safety profile.Mechanistically, we confirmed the inactivation of NF-kB in Treg cells and increased M2 macrophages in the myocardium after MI by transplanted CPCs derived GDF15 and it’s uptake by CD48 receptor on immune cells.Conclusion: Collectively, these findings strongly support the active immunomodulatory properties and robust therapeutic potential of allogenic CPCs in post-MI cardiac dysfunction.
Effect of exfoliated MoS2 on the Microstructure, Hardness, and Tribological properties of Copper matrix nanocomposite via hot pressing method
Authors: Mohamed Hossam , Abd-Elhameed Ehab , Ali Ahmed I.
Published: March 2022

This study aims to exfoliate the molybdenum disulfide to flakes and use it in strengthening copper matrix to reduce the rate of mechanical wear and reduce the coefficient of friction, consequently increasing the life of copper composites that are used as self-lubricating bushings. Three samples by mixing for 15 hrs were prepared: pure copper, copper with 10% alumina, and copper with a mixture of alumina and molybdenum disulfide in a ratio of 1:1 (Cu, Cu/10 Al2O3, and Cu/ hybrid (10 Al2O3-10 MoS2)). Before adding the hybrid of alumina/MoS2 with copper, they were mixed for 40 hrs to peel the molybdenum disulfide and cover the alumina particles with it. The Hot-pressing method was used to manufacture prepared samples. The crystal structure of the compositions, microstructure, density, and Raman spectra have been studied. Mechanical properties, including hardness, mechanical wear rate, and coefficient of friction, were investigated for the fabricated pieces. The mixing for 15 hrs improves the exfoliation of the MoS2 flakes inside the copper matrix. The hardness measurements showed a clear improvement by adding alumina and the mixture of alumina/MoS2. The copper sample reinforced with the hybrid of alumina/MoS2 gave the lowest mechanical wear rate and the lowest average friction coefficient of 0.17.
Climate Related Trends in U.S. Hazardous Material Releases Caused by Natural Hazards
Authors: Santella Nicholas
Published: March 2022

Natural hazards are the underlying cause of between 1 and 7 percent of federally reported hazmat releases in the US every year. During the period from 1990 through 2019 the fraction of releases caused by natural hazards has increased, in large part due to increased releases from hurricanes as well as floods, storms and wind. Many of these events are minor, but some have resulted in large and expensive releases as well as deaths, injuries, and evacuations. Inter annual variability of these releases are correlated with occurrence of extreme weather and associated climate indices. Given observed and future predicted increases in extreme weather events, it is likely many of these types of releases will continue to increase. Greater attention to management of natural hazard risk to industry, and in particularly to bulk storage facilities, is required to prevent further increase in the frequency and severity of these events.
A Fractional Model Approach for Drug Concentration in Blood
Authors: AWADALLA MUATH , NOUPOUE YVES YANNICK YAMENI , ABUASBEH KINDA , GHILOUFI NOUREDDINE
Published: March 2022

This article studies a pharmacokinetics problem which is the mathematical modeling of a drug concentration in a human blood over time, starting from when the drug is administered. Results are obtained using fractional calculus theories. A fractional derivative known as Psi-Caputo plays a substantial role in the study. We proved existence and uniqueness of the solution to the problem using the psi-Caputo fractional derivative. Application of the results on a data set showed that a psi-Caputo with the kernel ψ = x + 1 was the best approach as it leaded to mean square error of 0.04065. The second best was the simple fractional method whose error was 0.05814 and, finally the classical approach with an error of 0.07299.
Spinal transection switches the effect of metabotropic glutamate receptor subtype 7 from the facilitation to inhibition of ejaculation
Authors: Masugi-Tokita Miwako , Kubota Shigehisa , Kobayashi Kenichi , Yoshida Tetsuya , Kageyama Susumu , Sakamoto Hirotaka , Kawauchi Akihiro
Published: March 2022

Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of the group III mGluRs, which localize to presynaptic active zones of the central nervous system. We previously reported that mGluR7 knockout (KO) mice exhibit ejaculatory disorders, although they have normal sexual motivation. We hypothesized that mGluR7 regulates ejaculation by potentiating the excitability of the neural circuit in the lumbosacral spinal cord, because administration of the mGluR7-selective antagonist into that region inhibits drug-induced ejaculation. In the present study, to elucidate the mechanism of impaired ejaculation in mGluR7 KO mice, we eliminated the influence of the brain by spinal transection (spinalization). Unexpectedly, sexual responses of mGluR7 KO mice were stronger than those of wild-type mice after spinalization. Histological examination indicated that mGluR7 controls sympathetic neurons as well as parasympathetic neurons. In view of the complexity of its synaptic regulation, mGluR7 might control ejaculation by multi-level and multi-modal mechanisms. Our study provides insight into the mechanism of ejaculation as well as a strategy for future therapies to treat ejaculatory disorders in humans.
Enhancing the properties of PVDF/ MFe2O4; (M: Co-Zn and Cu-Zn) nanocomposite for the Piezoelectric Optronic applications.
Authors: El-Masry Mai M. , Ramadan Rania
Published: March 2022

Polyvinylidene fluoride (PVDF) polymer is considered as an encouraging piezoelectric material whose optical properties need to be enhanced. Zinc ferrite is an excellent photoelectric material, in the present work it was doped separately by (cobalt and copper) ferrite. Co-ZnFe2O4 and Cu-ZnFe2O4 nanoparticles were synthesized and characterized to be used as PVDF fillers, aiming to improve its optical properties. The optical properties as well as, the piezoelectric response of the prepared PVDF/ (Co-ZnFe2O4 and Cu-ZnFe2O4) nanocomposites were investigated. A significant improvement in the PVDF relative permittivity, optical conductivity, refractive index, non-linear susceptibility, and a great reduction in the band gap energy value is obtained by adding Co-ZnFe2O4 nanoparticles to it. However, Cu-ZnFe2O4 nanoparticles have limited improvement of the PVDF optical properties compared to the Co-ZnFe2O4 nanoparticles. as Co-ZnFe2O4 nanoparticles increases the PVDF optical conductivity σopt. four times its original value as well as the dielectric values was increased from 0.05 for neat PVDF to 2. The piezoelectric response of the PVDF polymer is clearly increased by the addition of both Co-ZnFe2O4 and Cu-ZnFe2O4 nanoparticles.
Climate change impact on the geographic distribution of Nepeta glomerulosa, medicinal species endemic to southwestern and central Asia
Authors: Karami Sahar , Ejtehadi Hamid , Moazzeni Hamid , Vaezi Jamil , Behroozian Maryam
Published: March 2022

Medicinal plants are valuable species, but their geographic distributions may be limited or exposed to extinction by climate change. Therefore, research on medicinal plants in the face of climate change is fundamental for developing conservation strategies. Distributional patterns for a semi-endemic medicinal plant species, Nepeta glomerulosa, distributed in southwestern and central Asia was determined based on a maximum–entropy algorithm. We evaluated potential geographic shifts in suitability patterns for this species under two scenarios (RCP 4.5 and RCP 8.5) of climate change for 2050. Our models indicate that the species occupies montane areas under current conditions; transfer of the model to future climate scenarios indicated that suitable areas for the species will decrease, and the species will likely shift towards higher elevations. But the types and degrees of these shifts differ among areas. Our findings can be used to inform conservation management programs for medicinal, endemic, and endangered species in southwestern and central Asia.
Pseudoprogression and peritumoral edema due to intratumoral necrosis after gamma knife radiosurgery for meningioma
Authors: Jung In-Ho , Chang Kyung Won , Park So Hee , Jung Hyun Ho , Chang Jong Hee , Chang Jin Woo , Chang Won Seok
Published: March 2022

Objective: Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. Methods: This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant.Results: After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p=0.009) greater. When a 70% dose volume ≥1 cc was used, the possibility of ITN was 5.892-fold (p<0.001) higher. On average, meningiomas with ITN increased in volume by 128.5% at 6 months after GKRS and then decreased to 94.6% at 12 months.Conclusions: When performing GKRS in meningioma, a 70% dose volume ≥1 cc is a risk factor for ITN. At 6 months after GKRS, meningiomas with ITN may experience a transient volume expansion and PTE, which are characteristics of pseudoprogression. These characteristics typically improve at 12 months following GKRS.
Flood Vulnerability Characteristics Considering Environmental Justice and Urban Disaster Prevention Plan in Seoul, Korea
Authors: Son Cheol Hee , Ban Yong Un
Published: March 2022

This study aimed to evaluate environmental injustice and analyze flood vulnerability characteristics in consideration of environmental justice and urban flood disaster prevention planning. We investigated various urban disaster prevention factors applied to the urban development process in Seoul from the perspective of environmental justice. Flood risk areas were identified and flood damage data from 2000 to 2018 were collected. Furthermore, a panel analysis was performed and the final model was selected. The flood vulnerability characteristics were found to be detached houses having basements, aged detached houses, land area for detached houses, public assistance recipients, and population aged 65 years or above, which had impact factors of 8.323, 3.781, -2.877, 3.257, and 2.637, respectively. The results indicate that not only the socially vulnerable population lacks the ability to respond to floods, but buildings and areas with poor residential environments also suffer from flood damage. This implies that there is socioeconomically disproportionate exposure (termed as environmental injustice) in the process of urban flood prevention planning and urban development. Our results can contribute qualitatively and quantitatively to prepare a flood prevention plan based on environmental justice paradigm.
The Prehospital to Emergency Department Hand Over Model (PEDHOM): a conceptual model addressing content, process, and communication in prehospital to Emergency Department handover
Authors: Makkink Andrew William , Stein Christopher Owen Alexander , Bruijns Stevan Raynier
Published: March 2022

Background: Patient handover is closely linked to patient safety. As the first interaction with the healthcare system, emergency department handovers are critically significant. Addressing content, process and communication aspects of handover has the potential to improve patient safety and decrease the incidence of adverse events. Methods: We used a sequential explanatory mixed methods study to gather data in Study One (quantitative) and Study Two (qualitative). Study One gathered questionnaires from 175 prehospital and 50 emergency department personnel. Study Two drew from the data in Study One and involved conducting face-to-face, semi-structured interviews from 15 prehospital and 15 emergency department personnel. Results: Study One provided quantitative data related to the importance of variables included in handover content and additional information related to handover within the ED from the perspectives of both prehospital and ED personnel. Study Two provided qualitative data on experiences and perceptions related to handover within the ED from the perspectives of both prehospital and ED personnel. These data were used to develop the Prehospital to Emergency Department Hand Over Model (PEDHOM) conceptual model that was synthesized from the findings. Conclusion: This PEDHOM addresses some of the content, process and communication aspects in prehospital to ED handover. The PEDHOM identifies barriers to effective ED handover and postulates potential solutions or strategies to addressing these barriers. The PEDHOM has potential for implementation in the ED and in healthcare environments other than the ED where interprofessional handover is practiced.
A Study On Prescriptions Contributing To The Risk Of High Anticholinergic Burden In Adults With Intellectual Disabilities: Retrospective Record Linkage Study
Authors: Ward Laura , Cooper Sally-Ann , Henderson Angela , Stanley Bethany , Greenlaw Nicola , Pacitti Christine , Kinnear Deborah
Published: March 2022

Background: People with intellectual disabilities face a disproportionate risk of experiencing high anticholinergic burden, and its negative sequalae, at younger ages than the general population. Our aim was to determine the source of that burden from prescribed medication. Methods: Retrospective matched observational study using record linkage. Adults with (n=4,305), and without (n=12,915), intellectual disabilities matched by age-, sex- and neighbourhood deprivation. The main outcome measure was the prescription of long-term (approximately 9 months use) anticholinergic medications overall, by drug class, individual drugs, and polypharmacy.Results: 38.4% and 23.6% of adults with, and without, intellectual disabilities were prescribed medications long-term with anticholinergic properties. Of those on such drugs, adults with intellectual disabilities were most likely to be on central nervous system (62.6%), gastrointestinal (46.7%), and cardiovascular (28.4%) medications. They were prescribed more central nervous system, gynaecological/urinary tract, musculoskeletal, and respiratory medications, and less cardiovascular, infection, and endocrine medications than their matched comparators. Regardless of age, sex, or neighbourhood deprivation, adults with intellectual disabilities had greater odds of being prescribed antipsychotics (OR=5.37 [4.40-6.57], p<0.001), antiepileptics (OR=2.57 [2.22-2.99], p<0.001), and anxiolytics/hypnotics (OR=1.28 [1.06-1.56], p=0.012). Adults with intellectual disabilities were more likely to be exposed to overall anticholinergic polypharmacy (61.3% (n=1,013), 54.7% (n=1,668) respectively, OR=1.48 [1.33-1.66], p<0.001), and to psychotropic polypharmacy than adults without intellectual disabilities (33.7% (n=558), 14.3% (n=435) respectively, OR=2.79 [2.41-3.23], p<0.001).Conclusions: Adults with intellectual disabilities are exposed to a greater risk of having very high anticholinergic burden through polypharmacy from several classes of medications, which may be prescribed by several different prescribers. Clinicians need to be cognisant of this issue, and the potential adverse consequences. These findings highlight the need for regular medication reviews to reduce inappropriate prescribing and adverse anticholinergic effects.
Protective effects of MSC-conditioned medium on DFO-induced mimetic-hypoxia injury of renal tubular epithelial cells
Authors: Zhou Tianbiao , Liao Chunling , Weng Wenjuan , Yang Lujun , Liu Yiping , Yang Qian , Chen Guangyong
Published: March 2022

Background: Acute kidney injury (AKI) is mainly characterized by inflammatory infiltration, the damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) inducing cells’ mimetic-hypoxia injury is a well-accepted renal injury model in vitro. Mesenchymal stem cell - conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect of MSC-CM on RTECs under DFO mimetic-hypoxia and its possible molecular mechanism. Methods: NRK-52E cells with the treatment of DFO25uM for 24 hours could be well-accepted RTECs’ injury model using Cell Counting Kit-8 (CCK-8) to detect cell viability and Western Blot to evaluate the expression of transforming growth factor-beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells with the treatment of different concentrates of DFO for 24 hours. Then three groups of NRK-52E cells were used in experiments, including normal control (NC), DFO25uM, DFO25uM+MSC-CM. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and DFO 25uM cocultured cells for another 24 hours. Then the cell samples were collected. Results: Using Western Blot and cellular immunofluorescence, we found MSC-CM could reverse the DFO-induced up-regulation of TGF-β1, α-SMA, HIF-1α and steroid receptor coactivator 1 (SRC-1). DFO 25uM coculturing NRK-52E cells for 24 hours could simulate hypoxia well; HIF-1α and SRC-1 might be the harmful factors promoting EMT in NRK-52E cells during DFO mimetic-hypoxia.Conclusions: Our results suggest that MSC-CM have a protective effect on RTECs under DFO mimetic-hypoxia by down-regulating HIF-1α and SRC-1 which may be the harmful factors in renal injury.
Decreased expression of miR-23b is associated with poor survival of endometrial cancer patients
Authors: Włodarski Paweł K. , Klicka Klaudia , Grzywa Tomasz M. , Klinke Alicja , Mielniczuk Aleksandra , Wejman Jarosław , Ostrowska Joanna , Gondek Agata
Published: March 2022

Endometrial cancer (EC) is one of the most common types of cancer of the female reproductive system. EC is classified into two types (EC1 and EC2). MiRNAs are single-stranded RNA molecules that regulate gene expression posttranscriptionally. They have aberrant expression profiles in cancer, including EC. This study aimed to assess the level of expression of a panel of 16 miRNAs in both types of EC and healthy endometrium (HE). A total of 45 patients were enrolled into the study, 18 patients diagnosed with EC1, 12 diagnosed with EC2, and 15 HE controls. Tumor tissues or healthy endometrial tissues were dissected from archival formalin-fixed paraffin-embedded (FFPE) using laser capture microdissection (LCM). RNA was isolated from collected material and the expression of selected miRNAs was determined using the real-time qPCR. We found that miR-23b, miR-125b-5p, miR-199a-3p, miR-221-3p, and miR-451a were downregulated in EC in comparison to HE. Moreover, the expression of miR-34a-5p and miR-146-5p was higher in EC1 compared to EC2. Analysis of The Cancer Genome Atlas (TCGA) database confirmed decreased levels of miR-23b, miR-125b-5p, and miR-199a-3p in EC. Decreased miR-23b expression was associated with worse survival of EC patients.
Development and validation of an extended Cox prognostic model for patients with ER/PR+ and HER2‒ breast cancer: a retrospective cohort study
Authors: XIE YIQUN , LI XIZHOU , WU YING , CUI WENTING , LIU YANG
Published: March 2022

Background
The purpose of this study was to explore a new ER/PR + and HER2 − breast cancer prognostic model, called the extended Cox prognostic model, for determining the cutoff values for multiple continuous prognostic factors and their interaction via the new model concept and variable selection method.
Methods
A total of 335 patients with ER/PR + and HER2– breast cancer were enrolled for the final analysis. The primary endpoint was breast cancer-specific mortality. Prognostic factors (histological grade, histological type, stage, T, N, lymphovascular invasion, P53, Ki67, ER, PR, and age) were included in this study. The four continuous variables (Ki67, ER, PR, and age) were partitioned into a series of binary variables that were fitted in the multivariate Cox analysis. A smoothly clipped absolute deviation variable selection method was used. Model performance was expressed in discrimination and calibration.
Results
We developed an extended Cox model with a time threshold of 164 weeks (more than 3 years) postoperation and developed a user-friendly nomogram based on our extended Cox model to facilitate clinical application. We found that the cutoff values for PR, Ki67, and age were 20%, 60%, and 41–55 years, respectively. There was an interaction between age and PR for patients aged ≥ 41 years and PR ≥ 20% at 164 weeks postoperation: the older the patients with ER/PR+, HER2-, PR ≥ 20% were, the lower survival and more likely to recur and metastasize exceeding 164 weeks (more than 3 years) after surgery.
Conclusions
Our study offers guidance on the prognosis of patients with ER/PR + and HER2‒ breast cancer in China. The new concept can inform modeling and the determination of cutoff values of prognostic factors in the future.
Demographic history of two endangered Atlantic eel species, Anguilla anguilla and A. rostrata
Authors: Feng Xiu , Liu Shenglin , Hansen Michael M.
Published: March 2022

European (Anguilla anguilla) and American eel (A. rostrata) are panmictic catadromous fish species, which have experienced recent drastic population declines amounting to just a few percent recruitment relative to levels prior to 1980. However, little is known about the extent of recent population declines relative to historical fluctuations. We analyzed demographic histories of the species using a method for reconstructing skyline plots based on site frequency spectra, in this case derived from restriction site-associated DNA (RAD) markers. The results showed very high effective population sizes ranging in the millions for most of the time range covered. Both species experienced ancient declines coinciding with the time of speciation (ca. 170,000 generations ago) and at a later stage where secondary contact occurred (ca. 90,000 generations ago). Whereas the demographic histories of the species were similar most of the time, they followed widely different trajectories from ca. 70,000 to 40,000 generations ago. However, for the past ca. 30,000 generations both species have shown demographic stability, even across glacial and interglacial periods. We discussed the possible environmental factors, including ocean current changes and geomagnetism reversal that could have affected demographic history and further suggest that southward displacement of spawning regions and continental distribution could explain the apparent stability even during glaciations. The recent declines appear unprecedented against a backdrop of long-term demographic stability, underpinning concerns that low density of spawners in the huge spawning region could lead to detrimental Allee Effects.
Polish Adaptation of the TOS Scale in the Adult Population and Comparison with the ORTO-15 Scale
Authors: Gortat Mateusz , Samardakiewicz Marzena
Published: March 2022

BackgroundOrthorexia nervosa (ON) is a concept introduced in 1997. It is defined as excessive concentration on healthy eating. Orthorexia can lead to health loss and disrupt the psychosocial functioning of a person. A significant and current research problem on nervous orthorexia is the lack of appropriate diagnostic tools. One of the promising tools for studying orthorexia behavior is the Teruel Orthorexia Scale (TOS). This scale allows distinguishing pathological orthorexia (Ne) from healthy orthorexia (He), defined as an interest in healthy eating free from psychopathology. There are still no tools to measure orthorexia-related behavior with good psychometric properties. Therefore, this study aimed to adapt and validate Teruel Orthorexia Scale (TOS) in Poland. MethodsThe research involved the evaluation of 680 questionnaires collected in a group of adult Poles (18-68 years old). The research was conducted in the period from June 2019 to March 2020. The diagnostic survey method was used to collect the data. The study used the TOS scale translated into Polish and the Polish adaptation of the ORTO-15 scale. The obtained results were statistically analyzed. The validation procedure included three primary methods: assessment of the discriminant power, reliability, and validity of the tool compared to the ORTO-15 scale. ResultsAlmost all items of the validated scale achieved a satisfactory value of discriminant power >0.3. The individual TOS subscales were characterized by high reliability (TOS He = 0.87; TOS Ne = 0.78). The validity analysis of the validated tool consisting in correlating the obtained results with the results of the ORTO-15 questionnaire showed a significant correlation between the scales (healthy orthorexia r = -0.36; pathological orthorexia r = -0.19). ConclusionsThe Polish version of the TOS scale is a reliable and valuable tool for measuring orthorexia-related behavior in the Polish adult population.
Microbial Extracellular Alkaline Phosphatase Revealed the Linkage Between Carbon and Phosphorus Cycles in the Deepest Ocean
Authors: Fang Jiasong , Cao Junwei , Liu Ying , Deng Junhao , Li Zhenzhen , Luo Min , Yu Xi , Wang Li , Li Jiangyan , Xu Yunping , Wang Jiahua , Li Yongqi , Wang Guangyi , Zhang Li
Published: March 2022

We present the first dataset of microbial extracellular alkaline phosphatase activities (APA) and community compositions measured in the entire water column of the Challenger Deep (CD), Mariana Trench. We show that there existed two distinct P-APA regimes in the CD water column, reflecting different nutrient use strategies of the microbes; that in surface water (50 m) where microorganisms were P-limited (110 nmol L-1) and expressed extremely high APA (average 23.8 nmol h-1) for generating inorganic P, and that in the deep waters (1,000–10,918 m) which were P-replete (average 2.2 mmol L-1), yet microorganisms were carbon-starved and also expressed high levels of APA (average 17.0 nmol h-1). We suggest that microorganisms in the deep waters likely utilized a piggyback strategy to satisfy carbon requirements by expressing elevated APA to decompose dissolved organic phosphorus and concurrently, leading to high concentrations of P in the deep. Our results implicate the intimate connection and coupling between P- and C-cycling mediated by microbes in the hadal biosphere.
Carcinogenic risk in the biliary epithelium of children with congenital biliary dilatation via the DNA damage repair pathway
Authors: Mori Hiroki , Morine Yuji , Yokota Noriko , Ishibashi Hiroki , Shimada Mitsuo
Published: March 2022

Background: Congenital biliary dilatation (CBD) is a high-risk factor for biliary tract cancer (BTC). We have previously reported the potential for carcinogenesis in the biliary epithelium of patients with CBD. In this study, we investigated potential carcinogenetic pathways, focusing on the DNA damage repair response, in children with CBD and compared the findings with adults.Methods: We enrolled six children with CBD and 10 adults with CBD without BTC who underwent extrahepatic bile duct resections, plus four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. Levels of phosphorylated histone H2AX (γH2AX), MRE11, and Ku-70 in the biliary tract epithelium were evaluated by immunohistochemistry.Results: Levels of γH2AX, MRE11, and Ku-70 were significantly higher in the gallbladder epithelium and bile duct epithelium of both children and adults compared with in controls. Conclusions: Children and adults with CBD might develop BTC via the DNA damage repair pathway, as evidenced by increased γH2AX, MRE11, and Ku-70 expression.
Impaired sensitivity to thyroid hormones is associated with elevated blood glucose in coronary heart disease — a RCSCD-TCM study in China
Authors: Yu Lu , Li Zhu , Yang Rongrong , Pan Guangwei , Cheng Qi , He Yuanyuan , Liu Yijia , Liu Fanfan , Ma Mei , Yang Tong , Wang Yang , Su Jinyu , Zheng Yanchao , Gao Shan , Xu Qiang , Li Lin , Yu Chunquan
Published: March 2022

BackgroundThyroid hormone influences glucose homeostasis through central and peripheral regulations. So far, the association between thyroid hormone sensitivity and elevated blood glucose (EBG) in patients with coronary heart disease (CHD) remains unknown. The purpose of this study is to investigate the association between thyroid hormone sensitivity and risk of EBG in patients with CHD, and to further explore their association in different sexes and ages.MethodsThis large multicenter retrospective study included 30,244 CHD patients (aged from 30 to 80) between January 1, 2014 and September 30, 2020. The study calculated the parameters representing central and peripheral sensitivity to thyroid hormones. Central sensitivity to thyroid hormones was assessed by calculating the thyroid feedback quantile-based index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotropin thyroxine resistance index (TT4RI), and peripheral sensitivity to thyroid hormones was evaluated by the ratio of FT3/FT4. Taking normal glucose tolerance (NGT) as a reference, participants with diabetes or prediabetes were assigned to the EBG group. The study used logistic regression to analyze the relationship between central and peripheral thyroid hormone sensitivity and EBG in CHD patients.ResultsAmong the 30,244 participants, 15,493 (51.23%) had EBG. The risk of EBG was negatively associated with TSHI (OR: 0.86; 95%CI: 0.85 to 0.87; P < 0.001), TT4RI (OR: 0.99; 95% CI: 0.99 to 0.99; P<0.001), TFQI (OR: 0.72; 95%CI: 0.70 to 0.73; P <0.001) and PTFQI (OR: 0.60; 95%CI: 0.58 to 0.61; P<0.001). Compared to males and people aged 60 and below, the OR value for EBG was lower in females and those aged over 60 years old. Conversely, EBG risk was positively associated with FT3/FT4 (OR: 1.25; 95% CI: 1.24 to 1.26; P <0.001) and in the sex-categorized subgroups, males had higher OR values than females.ConclusionsThis study shows that the increase in central thyroid hormone sensitivity is associated with the reduced risk of EBG in CHD patients, among which females and people aged over 60 years old are at higher risk.
Balamuthia mandrillaris trophozoites ingest human neuronal cells via a trogocytosis-independent mechanism
Authors: Pengsart Worakamol , Thongkrachang Nongnat , Whangviboonkij Narisara , Sarasombath Patsharaporn Techasintana , Kulkeaw Kasem
Published: March 2022

Background: Environmental protozoa need an adaptation mechanism to survive drastic changes in niches in the human body. In the brain parenchyma, Balamuthia mandrillaris trophozoites, which are causative agents of fatal brain damage, must acquire nutrients through ingestion of the surrounding cells. However, the mechanism the trophozoites deploy for cellular uptake remains unknown.Methods: Amoebic ingestion of human neural cell components was investigated using a coculture of clinically isolated B. mandrillaris trophozoites with human neuroblastoma SH-SY5Y cells. Cell-to-cell interactions were visualized in a three-dimensional manner using a confocal and holotomographic microscope.Results: The B. mandrillaris trophozoites attached themselves to human neuroblastoma SH-SY5Y cells, followed by twisting themselves around the cytoplasmic bridge. Based on fluorescence-based cell tracking, the B. mandrillaris trophozoites inserted invadopodia into the cytoplasm of the human cells. Subsequently, the human protein-enriched components were internalized into the trophozoites in the form of nonmembranous granules, whereas the human lipids were dispersed in the cytoplasm. Intervention of trogocytosis, a process involving nibbling on the parts of target cells, failed to inhibit this cellular uptake.Conclusions: In summary, human cell ingestion by B. mandrillaris trophozoites likely differs from trogocytosis, suggesting that a pathogen-specific strategy can be used to ameliorate brain damage.
Analysis and construction of an exosome derived competing endogenous RNA network for small cell lung cancer in the exoRbase database
Authors: Zhu Kangle , Wang Lian , Chen Zanhao , Ding Jianing , Dong Jixuan , Chen Jinliang
Published: March 2022

A competing endogenous RNA (ceRNA) regulatory network in the blood exosomes of small cell lung cancer (SCLC) patients was constructed by bioinformatics methods to explore the pathogenesis. Blood exosomal gene sequencing data of SCLC patients and normal controls were downloaded from the exorbase 2.0 database, and the expression profiles of exosomal mRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) were differentially analyzed using the R language, miRNAs binding to differentially expressed lncRNAs were predicted using the miRcode database, and miRNAs binding to differentially expressed circRNAs were predicted using the Starbase database. The associated mRNAs, circRNAs, lncRNAs, and their corresponding miRNA prediction data were imported into the cytoscape software to visualize the ceRNA network. Enrichment analysis of Go and KEGG was performed and visualized using the R language and Kobas. Cytohubba has used Plug-in identified hub genes. 13 differentially expressed mRNAs, 59 differentially expressed circRNAs, and 40 differentially expressed lncRNAs were filtered out. A ceRNA network was constructed by cytoscape software, and a total of 5 mRNA nodes, 5 lncRNA nodes, 7 circRNA nodes, and 41 miRNA nodes were identified. KEGG enrichment analysis showed that the differentially expressed mRNAs in the regulatory network were mainly enriched on non-small cell lung cancer pathways, and rassf3 was the pathway Among the key genes. Cytohubba to find the most critical hub gene oip5-as.in this study, we successfully constructed a ceRNA regulatory network in the blood exosomes of SCLC patients to provide exact targets for the diagnosis and treatment of SCLC.
miR-124-3p and miR-181a-5p Mediate AT1-Receptor Autoantibody Induced Fetal Rat Cardiac Remodeling via Increased VCAN Expression
Authors: Yue Mingming , Sun Yan , Li Yang , Wang Pengli , He Chunyu , Bai Lina , Wu Ye , Lan Shuhai , Lau Wayne , Ma Xin-Liang , Zhang Suli , Liu Huirong
Published: March 2022

Autoantibodies against angiotensin II type 1 receptor (AT1-AA) are prevalent in preeclampsia. They induce fetal cardiac structural remodeling in late pregnancy via still unknown mechanisms, the subject of this study’s investigation. MicroRNA array revealed differential expression of microRNAs in fetal hearts exposed to AT1-AA. miR-124-3p and miR-181a-5p, the most significantly altered microRNAs, were significantly enriched in the myocardium. Gain- and loss-of-function experiments demonstrated that miR-124-3p and miR-181a-5p governed cardiomyocyte phenotype. Overexpression of miR-124-3p or inhibition of miR-181a-5p activated neonatal rat cardiomyocyte proliferation and size (the converse also being true). Moreover, miR-124-3p overexpression and miR-181a-5p inhibition acted in concert to exacerbate the effects of AT1-AA (increasing the size and proliferation of neonatal rat cardiomyocytes). Through TMT™ quantitative proteomics and luciferase reporter gene assay, miR-181a-5p and miR-124-3p respectively target the 3’ UTR and 5’UTR of VCAN, and oppositely regulate its expression. VCAN knockdown in neonatal rat cardiomyocytes blocked the pathological effect of AT1-AA. Furthermore, ELISA demonstrated positive correlation between AT1-AA expression and VCAN level in preeclamptic patient umbilical cord blood. Our study demonstrates that upregulation of miR-124-3p promotes VCAN expression, and miR-181a-5p downregulation decreases VCAN inhibition, thereby co-mediating AT1-AA induced fetal cardiac remodeling.