bluuebunny/crossref_metadata_2025 huggingface dataset:
A case report of a severe neonatal systemic vasculitis on the first day of life
Authors: Wong Stephanie , Demirkaya Erkan , Berard Roberta
Published: March 2021

BACKGROUND: Transmission of autoantibodies across the placenta has been associated with neonatal cutaneous vasculitis and lupus syndromes. Here we report a novel association of a case of new-onset maternal seronegative inflammatory arthritis associated with a transient systemic vasculitis in a neonate. CASE PRESENTATION: In the first 24 hours of life, a preterm baby boy was noted to have blue discoloration to all four extremities. A workup for sepsis and thrombosis were negative. Despite antibiotics, fresh frozen plasma and anticoagulation, the discoloration remained, particularly in the left index finger. This was associated with fever and a maximum C-reactive protein (CRP) of 148 mg/L. Two doses of intravenous immunoglobulin (IVIG) were given with short-term improvement. Echocardiogram was normal. The fever, elevated CRP and finger discoloration responded to high dose steroid administration. MRI angiography (MRA) of body and heart showed tortuosity of arteries in the upper and lower extremities with gadolinium uptake, suggestive of vasculitis. Autoantibody profile negative. Genetic panel for hereditary autoinflammatory diseases was negative as was as whole exome sequencing performed on the trio. The baby was weaned off steroids by 5 months of age. A small distal autoamputation of the left index finger occurred. He was born to a 28-year-old woman who developed new onset severe symmetrical polyarthritis at 8 weeks gestation. It was presumed this was reactive arthritis secondary to a dental infection. Infectious work up and autoantibodies were negative. She was treated with high dose prednisone for the remainder of her pregnancy. The mother was weaned off prednisone and treated with hydroxychloroquine for 8 months post-partum and remains in remission. A repeat MRA done at 1 year old showed mild residual tortuosities of the arteries in the forearms. The remainder of the medium and large vessels were within normal limits with no gadolinium enhancement to suggest active disease. The child is now 4 years old with normal growth and development. CONCLUSION: This is a unique case of new-onset seronegative presumed reactive arthritis in a mother with the rare development of a successfully treated medium vessel vasculitis in an infant.
GIS-Based Risk Mapping of Cutaneous Leishmaniasis: A Survey in an Endemic Area of Central Iran
Authors: Maracy Mohammad , Jaffary Fariba , Ebrahimi Afshin , Sokhanvari Fatemeh , Heidari Asieh , Koupaiee Hanieh Sharifian , Fadaei Reza , Ramazanpour Javad , Moazeni Malihe
Published: March 2021

Introduction: [Cutaneous Leishmaniasis (CL)] is Vector-borne infectious disease that is affected by various environmental agents. The main objective of this study was to determine the spatial distribution of CL incidence by using [Geographical Information System (GIS)].Materials and Methods: This is a cross-sectional study that was conducted during 5 years from 2014 to 2018 in Isfahan, Iran. We used the required data on each leishmaniasis patient that were recorded from 44 counties of Isfahan in databases and archive of provincial Health Centre. We used GIS for determining the incidence of CL in the high-risk foci. Moran index was used to identify high risk points (clustering in similar values) compared to the values of neighborhood points. Hot spot analysis was conducted by Getis-Ord-Gi. Results: The highest incidence of the disease occurred in the age group of 18-64 years and 61.6% of patients were male. According to seasonal distribution, autumn (58.6%) had the highest frequency. Time-trend of incidence showed that it had both decreasing and increasing, and there was a sudden upward trend of disease in 2018 except only two counties. The hot spots were involved the central areas of the Isfahan province slightly toward to the north and southeast of the province. Moran index showed that the differences for all points were not significant (p-value>0.05).Conclusions: Varzaneh (placed in southeast of Isfahan) was the hottest spot and had the worst position for leishmaniasis compared to all years and all cities.
Impact of cognitive reserve on dance intervention-induced changes in brain plasticity
Authors: Mitterová Kristína , Klobušiaková Patrícia , Minsterová Alžběta Šejnoha , Kropáčova Sylvie , Balážova Zuzana , Točík Jaroslav , Vaculíková Pavlína , Skotáková Alena , Grmela Roman , Rektorová Irena
Published: March 2021

Dance is a complex sensorimotor activity with positive effects on physical fitness, cognition, and brain plasticity in the aging population. We explored whether individual levels of cognitive reserve (CR) proxied by education moderate dance intervention (DI)-induced plasticity assessed by resting-state functional connectivity (rs-FC) changes of the sensorimotor network (SMN), and between the dorsal attention network (DAN) and anterior default mode network (aDMN). Our cohort consisted of 99 subjects, randomly assigned to either a DI group who underwent a 6-month intervention (n = 49, Mage = 69.02 ± 5.40) or a control group (n = 50, Mage = 69.37 ± 6.10). Moderation analyses revealed that CR moderated DI-induced increases of the SMN rs-FC with significant changes observed in participants with ≥ 13 years of education (b = .05, t(64) = 3.20, p < .001). Only DI alone was a significant predictor of the DAN-aDMN crosstalk change (b = .06, t(64) = 2.16, p = .03). The rs-FC increases in the SMN were correlated with an improved physical fitness measure, and changes in the DAN-aDMN connectivity were linked to better performance on a cognitive task. Consistent with the passive CR hypothesis, we observed that CR correlated only with baseline behavioral scores, not their change.
What You Don’t Know Might Hurt You: Cost Variations for Fecal Immunochemical Tests in Primary Care Practices
Authors: Coury Jennifer , Ramsey Katrina , Gunn Rose , Judkins Jon , Davis Melinda
Published: March 2021

Background

Colorectal cancer (CRC) screening can improve health outcomes, but screening rates remain low across the US. Fecal immunochemical testing (FIT) is an effective way to screen more people for colorectal cancer, but barriers exist to implementation in clinical practice. Little research examines the impacts of cost on FIT selection and implemention.
Methods

We administered a multi-modal, cross-sectional survey to 252 primary care practices to assess readiness and implementation of direct mail fecal testing programs, including the cost and types of FIT used. We analyzed the range of costs for the tests, and identified practice and test procurement factors. We examined the distributions of practice characteristics for FIT use and costs answers using the non-parametric Wilcoxon rank-sum test. We used Pearson's chi-squared test of association and interpreted a low p-value (e.g. <0.05) as evidence of association between a given practice characteristic and knowing the cost of FIT or fecal occult blood test (FOBT).
Results

Among the 84 practice survey responses, more than 10 different types of FIT/FOBTs were in use; 76% of practices used one of the five most common FIT types. Only 40 practices (48%) provided information on the cost of their FIT/FOBTs. Thirteen (32%) of these practices received the tests for free while 27 (68%) paid for their tests; median reported cost of a FIT was $3.04, with a range from $0.83 to $6.41 per test. Costs were not statistically significant different by FIT type. However, practices who received FITs from vendors were more likely to know the cost (p = 0.0002) and, if known, report a higher cost (p = 0.0002).
Conclusions

Our findings indicate that most practices without lab or health system supplied FITs are spending more to procure tests. Cost of FIT may impact the willingness of practices to distribute FITs in clinic-based encounters as well as through population outreach strategies, such as mailed FIT. Differences in the ability to obtain FIT tests in a cost-effective manner could have far reaching consequences for addressing colorectal cancer screening disparities in primary care practices.
Histologic findings of the dura mater at the level of the foramen magnum in 121 CKCS with Chiari-like malformation
Authors: Holdsworth Jaclyn P. , Marino Dominic J. , Loughin Catherine A. , Miller Andrew D. , Sackman Joseph J. , Lesser Martin L , O’Donnell Marissa
Published: March 2021

Background: To describe histopathologic features found in dural biopsies of Cavalier King Charles Spaniels (CKCS) with Chiari-like malformation (CM) and identify any associations between age, duration of clinical signs, syrinx location or syringomyelia (SM) and quality of life (QOL). The medical records of 121 consecutive client owned CKCS with CM and SM, confirmed by whole body magnetic resonance imaging (MRI), that underwent foramen magnum decompression (FMD) with cranioplasty and durectomy with biopsy from 2006 to 2016 were retrospectively reviewed. Dura biopsies were submitted to a board-certified veterinary pathologist for histopathologic interpretation. The chi-square test was used to analyze associations between diagnosis and categorical variables. For continuous measures, the Kruskal-Wallis non-parametric test was used to compare distributions across pathology categories. A result was considered statistically significant at the P<0.05 level of significance. Results: The mean age, duration of pre-surgical clinical signs, and pre-operative QOL (1-5 scale) were 44.27 months, 44.78 weeks, and 2.72 respectively. Syringomyelia was found in the cervical region only in thirty-nice of one hundred twenty-one (32.23%) of dogs, in the cervical and thoracic region only in seventeen of one hundred twenty-one (14.05%) of dogs, and in the cervical, thoracic and lumbar region combined in sixty-five of one hundred twenty-one (53.72%) of dogs. Sixty-six of one hundred twenty-one (54.55%) dural biopsy specimens had histopathology changes; fifty-five (45.45%) did not. Forty-three of one hundred twenty-one (35.54%) dural biopsy specimens had osseous metaplasia, sixteen of one hundred twenty-one (13.22%) had evidence of fibrosis, four of one hundred twenty-one (3.31%) had arachnoid hyperplasia, and three of one hundred twenty-one (2.48%) had evidence of mineralization. Conclusions: The majority of dogs with CM were found to have histopathologic changes in the dura at the time of FMD cranioplasty was performed. These dural changes can be observed in dogs experiencing clinical signs for a time period as short as four weeks prior to presentation. Histopathologic changes were not associated with age, breed, duration of clinical signs, the location of syringomyelia or preoperative QOL. The influence of histopathologic changes on long term prognosis in dogs without dural decompression is unknown since all dogs in this study had dural resection.
An asymmetric mode-localized mass sensor based on the electrostatic coupling of different structural modes with distributed electrodes
Authors: Song Jiahao , Lyu Ming , Kacem Najib , Zhao Jian , Liu Pengbo , Huang Yu , Fan Kefeng
Published: March 2021

Mode-localization sensor with amplitude ratio as output metric has shown excellent potential in the field of micro-mass detection. In this paper, an asymmetric mode -localized mass sensor with a pair of electrostatically coupled resonators of different thickness is proposed. Partially distributed electrodes are introduced to ensure the asymmetric mode coupling of second and third order modes while actuating the thinner resonator by the distributed electrode. The analytical dynamic model is established by Euler–Bernoulli theory and solved by harmonic balance method (HBM) combined with asymptotic numerical method (ANM). Detailed investigations on the linear and nonlinear behavior, critical amplitude as well as the sensitivity of the sensor are performed. The sensitivity of the proposed sensor can be enhanced by about 20 times compared to first order mode-localized mass sensors. Furthermore, by exploiting the nonlinearities while driving the device beyond the critical amplitude for the in-phase mode, the sensor performs a great improvement in sensitivity up to 1.78 times. Besides, the influence of the decrease of coupling voltage is studied, which gives a good reference to avoid mode aliasing.
Sub-second multi-channel magnetic control of select neural circuits in behaving flies
Authors: Sebesta Charles , Torres Daniel , Wang Boshuo , Li Zhongxi , Duret Guillaume , Jiang Kaiyi , Xiao Zhen , Zhang Qingbo , Colvin Vicki , Goetz Stefan , Peterchev Angel , Dierick Herman , Bao Gang , Robinson Jacob
Published: March 2021

Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or “magnetogenetics” using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we demonstrate that by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A) it is possible to achieve sub-second behavioral responses in Drosophila melanogaster. Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve fast, multi-channel stimulation, analogous to optogenetic stimulation with different wavelengths of light. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.
Dabigatran Treatment Increased Closure Device-Related Thrombosis by Platelet Activation in Patients Undergoing Percutaneous Left Atrial Appendage Closure
Authors: Li Xiaoye , Zhang Xiaochun , Jin Qinchun , Li Yanli , Ge Junbo , Zhou Daxin , lv qianzhou
Published: March 2021

Background

This study was designed to evaluate the platelet reactivity of different antithrombotic regimens under the condition of occluder implantation.
Methods

A single, prospective cohort study was conducted among patients who received anticoagulation with either dabigatran (N = 33) or rivaroxaban (N = 72) between January 2018 and December 2019. We applied thromboelastogram (TEG) to evaluate platelet aggregation induced with thrombin receptor activating peptide (TRAP) after anticoagulation for 3 months. Plasma coagulation markers mediate platelet activation including TAT, P-selectin, vWF and CD40L were tested by the method of ELISA kit on the day of LAAC and at 3 months after operation procedure. Repeated transesophageal echocardiographic were scheduled to evaluate device related thrombosis (DRT) formation on occluders at 3-month after discharge.
Results

There was 3(4.2%) in rivaroxaban and 4(12.1%) in dabigatran group experiencing DRT events (OR = 0.315, 95%CI:0.066–1.489, P = 0.129) during follow-ups. The TRAP induced platelet aggregation was higher for patients medication with dabigatran as compared to rivaroxaban group (62.9% vs. 59.7%, P = 0.028*). The plasma levels of TAT, P-selectin, vWF expression was significant higher after 3 months intake of dabigatran compared with that on the day LAAC operation, meanwhile, no significant difference was found in the changes of CD40L plasma levels. After receiving 3 months anticoagulation with rivaroxaban, the expressions of plasma platelet activation of TAT, P-selectin, vWF and CD40L showed no significant changes. We observed significant higher expressions of plasma platelet activation markers for DTR patients in terms of the P-selectin and vWF compared with non-DRT patients. Multivariate regression shwed that anticoagualtion regimen (P = 0.022; OR = 4.366, 95%CI: 0.434–10.839) was an independent predictor for DRT in patients after LAAC operation, while non of the plasma platelet activation included was associated with DRT.
Conclusions

By avoiding peri-procedure DRT occurrence, it is possible that dabigatran usage might even be reduced, as they had been shown to increase expressions of platelet reactivity.
Protection From Distributed Denial of Service Attack Using Fuzzy Logic
Authors: S Hemalatha , N Vasantha Gowri , A vani , Qaiyum Sana , P vijayakumar , Haleem Sulaima Lebbe Abdul
Published: March 2021

Distributed Denial of Service (DDoS) attacks represent an important challenge for public cloud as they invade the offender and completely delete Cloud service in order to serve the correct user and at the same time against the targets that cause system and service lack of access on infected devices. DDoS (Distributed Denial of Service) attacks are usually specific efforts to drain the resources of the victim or interrupt connections to networks by legitimate users. Traditional internet infrastructure is susceptible to DDoS assaults, and through leveraging their flaws to set up assault networks or Botnets, it offers an opening for an intruder to reach a wide number of infected machines. In order to identify and sustain improved detection accuracy, this work focuses on evaluating the different works and recommending a better solution to accommodate the cloud environment. A fuzzy logic for the detection and safety of DDOS attacks is proposed in this paper. The Fuzzy logic is used to dynamically select an algorithm from a collection of defined supervised learning that distinguish various DDoS variations and ultimately choose the relevant traffic algorithm.
Electrospun Fibrous Sponge via Short Fiber for Mimicking 3D ECM
Authors: Li Yan , Wang Juan , Qian Dejian , Chen Liang , Mo Xiumei , Wang Lei , Wang Yan , Cui Wenguo
Published: March 2021

BackgroundMost of the natural extracellular matrix (ECM) is a three-dimensional (3D) network structure of micro/nanofibers for cell adhesion and growth of 3D. Electrospun fibers distinctive mimicked 2D ECM, however, it is impossible to simulate 3D ECM because of longitudinal collapse of continuous micro/nanofibers. Herein, 3D electrospun micro/nanofibrous sponge was fabricated via electrospinning, homogenization, short fiber and thermal crosslinking for 3D tissue regeneration of cells and vascular. ResultsFibrous sponge exhibited high porosity, water absorption and compression resilience and no chemical crosslinked agent was used in preparation process. In vitro studies showed that the 3D short fiber sponge provided an oxygen-rich environment for cell growth, which was conducive to the 3D proliferation and growth of HUVECs, stimulated the expression of VEGF, and well promoted the vascularization of HUVECs. In vivo studies showed that the 3D short fiber sponges had a good 3D adhesion to the chronic wound of diabetes in rats. Furthermore, 3D short fibrous sponges were better than 2D micro/nanofiber membranes in promoting the repair of diabetic full-thickness skin defects including wound healing, hair follicle regeneration, angiogenesis, collagen secretion. ConclusionTherefore, electrospun short fibrous sponges are special candidates for mimicking the 3D ECM and promoting 3D regeneration of tissue.
Ethnobotanical Survey of Medicinal Herbs in the Western Region in Syria (Latakia and Tartus)
Authors: Khatib Chadi , Nattouf Abdulhakim , Agha Mohamad Isam Hasan
Published: March 2021

ContextThe use of traditional Arabic medicine (TAM) has spread to treat various diseases in Syria since ancient time. They are cost-effective with fewer side effects and are more suitable for long-term use compared with chemically synthesized medicines.ObjectiveWe conducted ethnobotanical and ethno-medicine research on plants traditionally used to treat various diseases in Western region of Syria. MethodsField surveys were conducted during July 2019-December 2020 to document ethnobotanical information through oral interviews and designed semi-structured questionnaire from local herbalists (Tabib Arabi) and the elderly people and others who were familiar with traditional uses of plants particularly for medicinal. The queries were repeatedly made to increase the reliability of the data, during the field survey of 475 local inhabitants of 70 villages. ResultsIn this research we listed 258 medicinal plants belonging to 83 families in alphabetical order with the parts used and the method of preparation according to their therapeutic use. Of these studied plants, 185 are used to treat digestive disorders, 118 for respiratory diseases, 91 for several skin diseases, 87 for kidney and urinary tract disorders, 78 for diabetes, 18 for nervous system disorders, and a few plants for treatment the other diseases which are commonly spread in study area. The calculated results of medicinal use-value (MUV) showed that Olea europaea L., Origanum syriacum L. was ranked first (MUV= 0.934), while the lowest value was found for Fumana thymifolia (L.) Spach and Cistus creticus L. (MUV= 0.003).ConclusionA large portion of the uses of medicinal plants mentioned in the research are still under study. There is no doubt that its study will provide many new data that could contribute to further pharmacological discoveries by identifying the active ingredients and their mechanism of effect by doing a lot of pharmacological work to confirm the alleged biological activities of these plants.
PAX5 Haploinsufficiency Induces Immune Inhibitory-Related Molecules Expressions of CD8 + T Cells in the Tumor Microenvironment
Authors: liang mi , gong duanhao , wang lei , liang xue , meng jiao , huang wei , zhou jianfeng
Published: March 2021

Loss of function of PAX5 plays an important role in PAX5 mutation tumor, and PAX5 haploinsufficiency promoting tumorigenesis is related to immune escape. But the mechanisms of PAX5 mutations inducing tumor immune escape have not been clarified. We estimated the proportions of 22 immune cell types and the expressions of immune inhibitory-related molecules based on gene expression profiles (GEPs) from B- acute lymphoblastic leukemia(B-ALL) with PAX5 mutations by CIBERSORT, an established algorithm. We constructed the PAX5 haplodeletion A20 cell lines, built allografted A20 tumor models and evaluated the effect of PAX5 haplodeletion on immune inhibitory-related molecules in the tumor microenvironment (TME). Our results indicated the percentages of T cells in bone marrow of B-ALL with PAX5 mutations were not statistically different from that in bone marrow of B-ALL without PAX5 mutations, except for T follicular helper (Tfh) cells. But a variety of up-regulated immune inhibitory-related molecules in bone marrow of B- ALL with PAX5 mutations were identified. By different approaches, we found that several immune inhibitory-related molecules of CD8+ T cells in TME of PAX5 haplodeletion clones such as TIM3, NR4A1 and BATF, were increased significantly compared with that of PAX5 wild type control. The IFN-ɤ of CD8+ T cells in TME of PAX5 haplodeletion tumors was decreased significantly compared with that of PAX5 wild type control. Our study showed that PAX5 haploinsufficiency induced high expressions of TIM3, NR4A1 and BATF in the TME and was involved in CD8+ T cells dysfunction or exhaustion.
Carbapenem-Resistant Klebsiella Pneumoniae in Southwest China: Molecular Characterizations and Risk Factors Caused by NDM and KPC Producers
Authors: Li Zhaoyinqian , Ding Zixuan , Yang Jia , Liu Yao , Jin Xinrui , Xie Jingling , Li Tingting , Ding Yinhuan , Zeng Zhangrui , Liu jinbo
Published: March 2021

Background: Klebsiella pneumoniae is one of the most common Enterobacteriaceae. In recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has become one of the most important carbapenem-resistant Enterobacteriaceae. CRKP are usually resistant to antibiotics. Up to this day, the emergence of carbapenemase-producing K. pneumoniae has been a challenge for treatment of clinical infection.Methods: (i) 66 non-repetitive clinical CRKP isolates were identified by matrix-assisted laser analytical ionization time-of-flight mass spectrometer (MALDI-TOF-MS) and drug sensitivity analysis was performed by Vitek2 Compact. EDTA-synergy test and mCIM / eCIM test were used to detect drug-resistant phenotypes. (ii) Carbapenemase genes, extended-spectrum β-lactamase genes (ESBLs), cephalosporinase gene (AmpC), virulence genes, integron and resistance gene cassettes were amplified by PCR. (iii) Plasmid typing was performed by plasmid conjugation assay and PCR-based replicon typing (PBRT) method. (iv) The genetic environments of KPC-2 and NDM-1 were analyzed by using overlapping PCR. (v) MLST was used to analyze the molecular epidemiological characteristics of CRKP. (vi) Risk factors of CRKP infection by logistic regression model.Results: Our study revealed that 42 of the 66 CRKP isolates obtained from patients were identified as blaKPC-2, 24 blaNDM-1-positive strains were identified (20 blaNDM-1 and 4 blaNDM-5), of which 18 were from the neonatal departments. And CRKP strains were ESBL (extended-spectrum β-lactamases) and AmpC enzymes producer, Notably, we found two CR-hvKp (carbapenem-resistant hypervirulent klebsiella pneumoniae) strains, which contains blaKPC-2 gene and other resistant genes. Two of the 42 KPC-2-producing CRKP strains were positive for transconjugants, and the plasmid typing was the IncFII type. And two NDM-producing CRKP strains tested positive for transconjugants, which belonged to the lncX3 plasmid. Analysis of the genetic environment of these two genes has revealed that the highly conserved regions (tnpA-tnpR-ISkpn8-blaKPC-2) and conserved regions (blaNDM−1-bleMBL-trpF-tat) are associated with the dissemination of KPC-2 and NDM-1. Intl1 carrying drug resistance gene cassettes were widely distributed in CRKP. According to the MLST results, a total of 13 ST types were measured in 66 CRKP strains, ST11 and ST4495 were the main ST types, and the latter was the newly discovered ST type. Hematological disease, tracheal cannula and prior use of β-lactams and β-lactamase inhibitor combination were identified as independent risk factors for CRKP infections.Conclusion: These findings manifested the need for intensive surveillance and precautions to monitor the further spread of KPC and NDM in southwest China.
GDF11 alleviates pathological myocardial remodeling in diabetic cardiomyopathy through SIRT1-dependent regulation of oxidative stress and apoptosis
Authors: Zhu Hanzhao , Zhang Liyun , Zhai Mengen , Xia Lin , Cao Yu , Xu Lu , Li Kaifeng , Jiang Liqing , Shi Heng , Li Xiang , Zhou Yenong , Ding Wei , Wang Dongxu , Gao Erhe , Liu Jincheng , Yu Shiqiang , Duan Weixun
Published: March 2021

Background

Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte injury, which induced by metabolic disorder. Nowadays, there is still a lack of drugs for the treatment of DCM. Growth differentiation factor 11 (GDF11) is a novel member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in DCM remain largely unknown.
Methods

In this study, we sought to determine whether GDF11 could prevent DCM. The mouse model of diabetes was established by administering a high-fat diet and intraperitoneal injecting streptozotocin. After that, intramyocardial injection of an adeno-associated virus carrying GDF11 gene was used to achieve myocardium-specific overexpression.
Results

Our data showed that GDF11 overexpression remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression was observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were also eliminated by SIRT1 depletion.
Conclusion

Our results demonstrated for the first time that GDF11 protected against DCM by regulating SIRT1 signaling pathway, and GDF11 had the potential to become a novel target for reversing cardiac dysfunction in diabetic patients.
A novel proposal for ultra-fast all optical half subtractor based on nonlinear ring resonators
Authors: Khajeheian Niloofar , Jamali Jasem , Fatehi-Dindarlou Mohammadhossein , Taghizadeh Mehdi
Published: March 2021

Optical half subtractors are required for designing any optical computation system. Operation speed and the on/off contrast ratios are very important characteristics for any optical logic device. A novel structure composed of three nonlinear ring resonators and some optical waveguides are used for designing for the proposed half subtractor with improved operation speed and on/off contrast ratio. The simulation results show that the rise time for this structure is 1.5 ps. Also the on/off contrast ratios for B and D are 13.7 dB and 14.5 dB respectively.
Effects of Seasonal Freezing-thawing on the Protistan Communities in a Mountain Lake
Authors: Liu Jinxian , Li Xiaoqi , Chai Baofeng
Published: March 2021

Background: Freezing-thawing cycles are common phenomena in temperate regions. Such events may have a significant influence on the composition of the protistan communities in a mountain lake. Protists are single-celled eukaryotic microorganisms that act as links in the aquatic microbial food web, affecting the transfer of substances and energy transformation. Yet little is known about the effects of freezing and thawing on the protistan community in a mountain lake. Results: The protistan communities in the lake were mainly composed of Ochrophyta, Ciliophora, Choanoflagellida, Cryptophyta, Chlorophyta, Stramenopiles_X, Cercozoa, Dinophyta, and Haptophyta. Seasonal freezing and thawing affected the community composition and diversity of protists. The change in the protistan community structure resulted from a significant change in organic carbon from the ice-covered to ice-free period. During the ice-covered and ice-free periods, temperature and nitrate were the main causes, respectively, for the changes in protistan community structure at different depths. Water depth also affected the structure of the protistan community, but it was not the most important factor. Conclusions: This study revealed that duration of lake surface icing might affect the function of subalpine lake ecosystems, including the rate of nutrient cycling and energy flow, owing to changes in the structure and biodiversity of the microbial community.
Can Conventional MRI Features Predict H3K27M Mutation Status of Diffuse Midline Gliomas?
Authors: Chauhan Richa Singh , Kulanthaivelu Karthik , Kathrani Nihar , Kotwal Abhishek , Bhat Maya Dattatraya , Saini Jitender , Prasad Chandrajit , Chakrabarti Dhritiman , Santosh Vani , Uppar Alok Mohan , Srini Dwarakanath
Published: March 2021

Purpose Pre-surgical prediction of H3K27M mutation in diffuse midline gliomas (DMG) on MRI is desirable. The purpose of the study is to elaborate conventional MRI (cMRI) of H3K27M-mutant DMGs and identify features that could discriminate them from WT (wild type)-DMGs.Methods cMRI features of 123 patients with DMG were evaluated conforming to the institutional research protocols. Multimodality MRI was performed on 1.5 or 3.0 Tesla MR Scanners with imaging protocol including T1w, T2w, FLAIR, diffusion-weighted, susceptibility-weighted and post- contrast T1w sequences. Pertinent cMRI features were annotated along the lines of Visually AcceSAble Rembrandt Images (VASARI) features and Intra Tumoral Susceptibility Signal score (ITSS) were evaluated. R software was used for statistical analysis.Results Sixty-one DMGs were H3K27M-mutant (mutant DMGs). The patients in the H3K27M-mutant DMG group were younger compared to the WT-DMG group (WT DMGs) (mean age 24.13+13.13 years vs. 35.79+18.74 years) (P= 0.016). The two groups differed on 5 cMRI features– i) enhancement quality (P=0.032), ii) thickness of enhancing margin (P=0.05), iii) proportion of edema (P=0.002), iv) definition of non-contrast enhancing tumor (NCET) margin (P=0.001) and v) cortical invasion (P=0.037). The mutant DMGs showed greater enhancement and greater thickness of enhancing margin while the WT DMGs exhibited significantly larger edema proportion with poorly defined NCET margins and cortical invasion. ITSS was not significantly different among the groups. Conclusion cMRI features like enhancement quality, thickness of the enhancing margin, proportion of edema, definition of NCET margin and cortical invasion can discriminate between the H3K27M-mutant and WT DMGs.
Evolution of the Illegal Substances Market and Substance Users’ Social Situation and Health During the Covid-19 Pandemic
Authors: Gaume Jacques , Schmutz Elodie , Daeppen Jean-Bernard , Zobel Frank
Published: March 2021

Background: The outbreak of the Covid-19 pandemic and the measures taken for tackling it had the potential to lead to deep modifications in the supply of illegal drugs and to impact substance users’ health and social situation. Methods: To investigate this, we used mixed methods, i.e. quantitative data collected with a brief questionnaire from substance users receiving opioid agonist treatment in a treatment centre in Switzerland (N=49), and qualitative data obtained using semi-structured phone interviews among a sub-group of participants (N=17). We repeated data collection twice over four weeks to investigate trends over time (N=51 and 14 at wave 2). Results: Findings consistently showed limited impact of the Covid-19 outbreak on the illegal substance market. Over the two waves, the supply, price and purity of three main illegal substances did not significantly vary. Substance use was estimated as usual by most, trending toward decrease. The impact of the pandemic on participants’ social situation and health was appraised as low to medium. Nevertheless, a minority of participants reported higher impact related to anxiety, boredom, depression and lack of social contacts. Multivariate analyses also nuanced overall findings and showed a more important impact for those who were female, younger, and not using multiple substances. Conclusions: This process could be implemented quickly and provided an understanding of the short-term impact of the pandemic and related lockdown on drug markets and users. Findings are limited by our sample and further research should address the plight of more vulnerable populations, as well as the long-term effects of this crisis.
Ancestry Specific Associations of a Genetic Risk Score, Dietary Patterns and Metabolic Syndrome: A Longitudinal ARIC Study
Authors: Hardy Dale Sharon , Racette Susan B. , Garvin Jane T. , Gebrekristos Hirut T. , Mersha Tesfaye B.
Published: March 2021

Background: Associations have been observed among genetic variants, dietary patterns, and metabolic syndrome (MetS). A gap in knowledge is whether a genetic risk score (GRS) and dietary patterns interact to increase MetS risk among African Americans. We investigated whether MetS risk was influenced by interaction between a GRS and dietary patterns among Whites and African Americans. A secondary aim examined if molecular genetic clusterings differed by racial ancestry.Methods: We used longitudinal data over 4-visits (1987-1998) that included 10,681 participants aged 45-64y at baseline from the Atherosclerosis Risk in Communities study (8,451 Whites and 2,230 African Americans). We constructed a simple-count GRS as the linear weighted sum of high-risk alleles (0, 1, 2) from cardiovascular disease polymorphisms from the genome-wide association studies catalog associated with MetS risk. Three dietary patterns were determined by factor analysis of food frequency questionnaire data: Western, healthy, and high-fat dairy. MetS was defined according to the 2016 National Cholesterol Education Program Adult Treatment Panel III criteria but used 2017 American Heart Association/American College of Cardiology criteria for elevated blood pressure. Analyses included generalized linear model risk ratios (RR), 95% confidence intervals (CI), and Bonferroni correction for multiple testing.Results: The Western dietary pattern was associated with higher risk for MetS across increasing GRS tertiles among Whites (p<.017). The high-fat dairy pattern was protective against MetS, but its impact was most effective in the lowest GRS tertile in Whites (RR=0.62; CI:0.52-0.74) and African Americans (RR=0.67; CI:0.49-0.91). Among each racial group within GRS tertiles, the Western dietary pattern was associated with development and cycling of MetS status between visits, and the high-fat dairy pattern with being free from MetS (p<.017). The healthy dietary pattern was associated with higher risk of MetS among African Americans which may be explained by higher sucrose intake (p<.0001). Fewer genes, but more metabolic pathways for obesity, body fat distribution, and lipid and carbohydrate metabolism were identified in African Americans than Whites. Some polymorphisms were linked to the Western and high-fat dairy patterns.Conclusion: A dietary pattern characterized by high-fat dairy foods may be protective against MetS among individuals with a genetic predisposition.
Identification of differentially expressed genes, biological pathways and prognostic signature in bladder cancer
Authors: Tang Fucai , Qian Xiayan , Lu Zeguang , Lai Yongchang , Li Zhibiao , He Chengwu , He Zhaohui
Published: March 2021

Background

Bladder cancer (BC) is one of the most common malignant cancer of urinary system in the worldwide. The purpose of the present study was to analysis differentially expressed genes (DEGs), biological pathways and prognostic significance BC by bioinformatics analysis.
Methods

The gene expression dataset GSE7476 and the mRNA Seq sequencing data were downloaded respectively from GEO and TCGA. A total of 220 DEGs were obtained in BC. GO analysis and KEGG pathway analysis were performed for up- and down-regulated DEGs. Then, a protein-protein interaction (PPI) networks and module were constructed by Cytoscape software. Survival analysis of hub genes was performed.
Results

The result of GO analysis revealed that the up-regulated DEGs were enriched mainly in sister chromatid segregation, while the down-regulated DEGs were enriched mainly in muscle contraction. The result of KEGG pathway analysis showed that up-regulated DEGs were enriched mainly in cell cycle, while down-regulated DEGs enriched in IL-17 signaling pathway. 41 hub gene and 3 crucial modules were identified in the PPI network. 15 genes significantly associated with patient prognosis in BC were obtained by Kaplan-Meier analysis.
Conclusions

In summary, the present study identified hub genes, crucial pathways and provide possible the molecular targets and prognostic biomarkers for targeted therapy and prognostic assessment of BC.
The Effectiveness of a Balanced Salt Solution on Dry Eyes in Comatose Patients: A Randomized Trial
Authors: sadeghi-hasanvand Hengameh , Kordestani-Moghadam Parastou , irandoost Farnoosh , ali Seyed hadi , Toulabi Tahereh , Ebrahimzadeh Farzad , heidari Fardin
Published: March 2021

Objective: Dry eye is one of the complications of hospitalization in ICUs. This study was conducted to assess the effectiveness of a Balanced Salt Solution (BSS) on dry eyes in comatose patients. This clinical trial was conducted in 2019 on 34 patients admitted to the ICUs. The control group received sterile eye ointment with artificial tears (2 drops every 6 hours) and a tape over the eye. The trial group also received BSS (2 drops every 6 hours) in the opposite eye over five days. The patients' dry eye was examined on first day and sixth day of the study using Schirmer’s Test (ST) and the Tear Breakup Time Test (TBUT). The data were analyzed in SPSS-21.Results: The results of the paired T-test based on ST and TBUT showed no significant change from first day one to sixth day in the BSS-receiving group (P>0.999 and P=0.187, respectively). Furthermore, no significant difference was observed between the two groups in the mean score of dry eye after eliminating the effect of the demographic and clinical variables (P=0.947). The administration of this solution by nurses seems to be an effective method for preventing the progression of dry eye in ICU patients.
Performance evaluation of the KRYPTOR Compact PLUS analyzer-based B.R.A.M.S CgA II KRYPTOR assay for chromogranin A measurement
Authors: CHOI Yu Jeong , Roh Juhye , Kim Sinyoung , Lee Kyung-A , Park Younhee
Published: March 2021

Background: Numerous immunoassays have been developed to measure the levels of chromogranin A (CgA), a useful biomarker for diagnosing and monitoring generally heterogeneous neuroendocrine tumors (NETs). Here, we evaluated the imprecision and linearity of three such assays: KRYPTOR (ThermoFisher Scientific), NEOLISA (EuroDiagnostica), and CgA-RIA (CisBio) using 123 samples for each assay.Results: The correlation coefficients between the assays were 0.932 (CgA-RIA versus NEOLISA), 0.956 (KRYPTOR versus CgA-RIA), and 0.873 (NEOLISA versus KRYPTOR). KRYPTOR showed good precision, with percent coefficients of variation less than 5% for low and high concentration quality controls. Linearity was maintained over a wide concentration range. Comparison of CgA levels from three disease entities (NETs, non-NET pancreatic tumors, and prostate cancer) and healthy controls showed that patients with NETs had significantly higher CgA levels (n = 57, mean: 1.82 ± 0.43 log ng/mL) than healthy individuals (n = 20, mean: 1.51 ± 0.23 log ng/mL; P = 0.018). No other significant differences between groups were observed.Conclusion: All three immunoassays showed strong correlations in measured CgA levels. Because KRYPTOR operation uses a fully automated random-access system and requires shorter incubation times and smaller sample volumes, the KRYPTOR assay may improve laboratory workflow while maintaining satisfactory analytical performance.
Associations of Gene Expressions in Liver and Blood Cells and Circulating Proteins With Coronary Artery Disease
Authors: Chai Tianci , Wan Zhisheng , Yang Xiaojie , Qiu Zhihuang , Chen Liangwan
Published: March 2021

Background: Circulating low-density lipoprotein cholesterol (LDL-C) plays a causal role in coronary artery disease (CAD). However, genetic risk factors of CAD were not yet fully understood. The aim of the study was to identify additional factors that contributed to CAD.Methods: We conducted integrative analysis on publicly available data from genome-wide association studies and quantitative trait locus studies by employing two-sample Mendelian randomization methods to examine the associations of gene expression and circulating protein levels with LDL-C and CAD.Results: We found that mRNA expression levels of SORT1, PSRC1 and CELSR2 in liver cells were significantly associated with both LDL-C and CAD (P < 5.0 × 10-8). Higher expression levels of SORT1, PSRC1 and CELSR2 in the liver were significantly associated with lower circulating LDL-C level (beta= -0.142, -0.138 and -0.171, respectively) and CAD risk (beta= -0.10, -0.097 and -0.121, respectively). Expression levels of 31 genes in blood cells associated with LDL-C level were found. Expressions of PSRC1, IL6R, GGCX, VAMP8, LIPA, NT5C2, SWAP70, EIF2B2, FURIN, FES and ATP5G1 in blood cells were significantly associated with CAD. Higher circulating granulins and apolipoprotein B levels, which were strongly affected by PSRC1 and APOB variants, were significantly associated with higher LDL-C level (beta = 0.22 and 1.35) and CAD risk, with odds ratios of 1.15 (1.10-1.19) and 1.45 (1.21-1.74), respectively. Conclusions: This study identified gene expressions in liver and blood cells and circulating granulins and apolipoprotein B that were genetically associated with LDL-C and CAD and provided evidence for exploring the potential causal relationship.
Meta-analysis With Zero-event Studies: A Comparative Study With Application to COVID-19 Data
Authors: Wei Jiajin , Lin Enxuan , Shi Jiandong , Yang Ke , Hu Zongliang , Zeng Xian-Tao , Tong Tiejun
Published: March 2021

Background: Meta-analysis is a statistical method to synthesize evidence from a number of independent studies, including those from clinical studies with binary outcomes. In practice, when there are zero events in one or both groups, it may cause statistical problems in the subsequent analysis. Methods: In this paper, by considering the relative risk as the effect size, we conduct a comparative study that consists of four continuity correction methods and another state-of-the-art method without the continuity correction, namely the generalized linear mixed models. To further advance the literature, we also introduce a new method of the continuity correction for estimating the relative risk. Results: From the simulation studies, the new method performs well in terms of mean squared error when there are few studies. In contrast, the generalized linear mixed model performs the best when the number of studies is large. In addition, by reanalyzing a recent COVID-19 data, it is evident that the double-zero-event studies impact on the estimate of the mean effect size.Conclusion: We recommend the new method to handle the zero-event studies when there are only few studies in the meta-analysis, or instead use the GLMM when the number of studies is large. The double-zero-event study may beinformative, and so we suggest not excluding them.
QuantiFERON-TB Gold Plus Testing for the Detection of LTBI in Health Care Workers in the Kyrgyz Republic
Authors: Corbett Caroline Susan , Kalmambetova Gulmira , Umetalieva Nagira , Ahmedov Sevim , Antonenka Uladzimir , Myrzaliev Bakyt , Sahalchyk Evgeni , Vogel Monica , Kadyrov Abdylat , Hoffmann Harald
Published: March 2021

Background: Health care workers (HCW) are at increased risk of TB infection due to their close contact with infected patients with active TB. The objectives of the study were (1) to assess the prevalence of LTBI among HCW in major TB hospitals of the Northern Kyrgyz Republic, and (2) to determine the association of LTBI with certain job positions, hospital units, or hospitals. Methods: HCWs from 4 TB hospitals in the Northern Kyrgyz Republic were tested with the interferon-gamma release assay (IGRA) Quantiferon-TB Gold plus (QFT) for the detection of an immune response to TB as marker of TB infection. Age was controlled for as a confounder. Univariate and multivariable analysis were performed using logistic regression to assess the association of the risk factors (age, job position, and hospital unit) with having a QTF positive result. Firth’s penalized-likelihood estimates were used for determining the odd’s of QFT positivity to account for the small-sample size. Pairwise comparisons using the Bonferroni correction (conservative) and comparisons without adjusting for multiple comparisons (unadjusted) were used to identify the categories where differences occurred.Results: QFT yielded valid results for 404 HCW, with 189 (47%) that had a positive test. In the National Tuberculosis Center, there was an increased odds to have a positive QFT test for the position of physician (OR=8.7, 95%, CI=1.2-60.5, p=0.03) and laboratory staff (OR=19.8, 95% CI=2.9-135.4, p<0.01) when administration staff was used as the baseline and controlling for age. No job position was found to have a significantly higher odds of positivity following a pairwise analysis controlling for multiple comparisons. Fifteen of the 49 HCW with follow-up tests converted from negative to positive at follow-up testing. Conclusions: This is the first report on prevalence and risk factors of LTBI for HCW in the Kyrgyz republic, and results indicate an increased risk for LTBI among physicians and laboratory personnel.