bluuebunny/crossref_metadata_2025 huggingface dataset:
Apatinib combined with PD-L1 blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer
Authors: Zhang Yu , Wang Fei , Sun Haoran , Huang Yakai , Gao Jianpeng , Huang Hua
Published: October 2020

Background: Apatinib, an antiangiogenic drug, has showed beneficial effects only in a fraction of advanced gastric cancer (GC) patients. Given the recent success of immunotherapies, combination of apatinib with immune checkpoint inhibitor may provide sustained and potent antitumor responses.Methods: Immunocompetent mice with subcutaneous MFC tumors grown were given combination of apatinib and anti-PD-L1 antibody therapy. GC tissues from patients undergoing curative resection in China were collected, and the density of HEVs, MSI status and tumor-infiltrated lymphocytes were analyzed by immunohistochemical staining.Results: Combined apatinib and PD-L1 blockade therapy synergistically delayed tumor growth and increased survival in MFC-bearing immunocompetent mice. The combination therapy promoted antitumor immunity by increasing the ratio of CD8+ cytotoxic T cells to Foxp3+ Treg cells, the accumulation of CD20+ B cells and the Th1/Th2 cytokine ratio (IFN-γ/IL-10). The combination therapy induced the formation of HEVs through activation of LTβR signaling mediated by DCs, thus promoting CD8+ cytotoxic T cell and CD20+ B cell infiltration in tumors. In clinical GC samples, the density of HEVs positively correlated with the intratumoral infiltration of CD8+ cytotoxic T cells and CD20+ B cells. MSI-high GC showed a higher density of HEVs, CD8+ cytotoxic T cells and CD20+ B cells than MSS/MSI-low GC. GC patients with high densities of HEVs, CD8+ cytotoxic T cells and CD20+ B cells had an improved prognosis with superior overall survival.Conclusions: Combining apatinib with PD-L1 blockade treatment synergistically enhances antitumor immune responses and promotes HEV formation in GC.
Pathogenic Functions of Tumor Necrosis Factor Receptor-associated Factor 6 Signaling Following Traumatic Brain Injury
Authors: Huang Huan , Xia Anqi , Sun Li , Lu Chun , Liu Ying , Zhu Zhenjie , Wang Siye , Cai Junyan , Zhou Xiaoyun , Liu Su
Published: October 2020

BackgroundNeuroinflammation contributes to delayed (secondary) neurodegeneration following traumatic brain injury (TBI). Tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling may promote post-TBI neuroinflammation, thereby exacerbating secondary injury.MethodsThis study investigated the pathogenic functions of TRAF6 signaling following TBI in vivo and in vitro. A rat TBI model was established by air pressure contusion while lipopolysaccharide (LPS) exposure was used to induce inflammatory-like responses in cultured astrocytes. Model rats were examined for cell-specific expression of TRAF6, NF-κB, phosphorylated (p)-NF-κB, MAPKs (ERK, JNK, p38), p-MAPKs, chemokines (CCL2 and CXCL1), and chemokine receptors (CCR2 and CXCR2) by immunofluorescence, RT-qPCR, western blotting, and ELISA, for apoptosis by TUNEL staining, and spatial cognition by Morris water maze testing. These measurements were compared between TBI model rats receiving intracerebral injections of TRAF6-targeted RNAi vector (AAV9-TRAF6-RNAi), empty vector, MAPK/NF-κB inhibitors, or vehicle. Primary astrocytes were stimulated with LPS following TRAF6 siRNA or control transfection, and NF-κB, MAPKs, chemokine, and chemokine receptor expression levels evaluated by western blotting and ELISA. ResultsTRAF6 was expressed mainly in astrocytes and neurons of injured cortex, peaking 3 days post-TBI. Knockdown by AAV9-TRAF6-RNAi improved spatial learning and memory, decreased TUNEL-positive cell number in injured cortex, and downregulated expression levels of p-NF-κB, p-JNK, p-ERK, p-p38, CCL2, CCR2, CXCL1, and CXCR2 post-TBI. Inhibitors of NF-κB, ERK, JNK, and p38 significantly suppressed CCL2, CCR2, CXCL1, and CXCR2 expression following TBI. Furthermore, TRAF6-siRNA inhibited LPS-induced NF-κB, ERK, JNK, p38, CCL2, and CXCL1 upregulation in cultured astrocytes.ConclusionsTargeting TRAF6-MAPK/NF-κB-chemokine signaling pathways may provide a novel therapeutic approach for reducing post-TBI neuroinflammation and concomitant secondary injury.
Obesity and Metabolic Comorbidity in Bipolar Disorder: Do Patients on Lithium Comprise A Subgroup? A Naturalistic Study.
Authors: Prillo Jake , Soh Jocelyn Fotso , Dols Annemick , Park Haley , Beaulieu Serge , Linnaranta Outi , Rej Soham
Published: October 2020

Background: Bipolar disorders (BD) are associated with increased prevalence of obesity and metabolic syndrome (MetS). Nevertheless, there is a wide range in prevalence estimates, and little is known about the relative contributions of medications, especially lithium. We hypothesized that lithium use is not associated with increased body mass index (BMI), metabolic syndrome, and type II diabetes (DM II), when compared to non-lithium users (those on anticonvulsants (ACs) or second-generation antipsychotics (APs)). Methods: Cross-sectional study of 129 patients aged 18-85 with bipolar disorder, followed at tertiary care clinics in Montreal. Patients using lithium were compared with those not on lithium, for body mass index and metabolic syndrome. Results: The prevalence of obesity and MetS in the sample of lithium-using bipolar patients was 42.4% and 34.9%, respectively, with an average BMI of 29.10 (+/-6.70). Lithium and non-lithium groups did not differ in BMI or prevalence of MetS. However, compared to the non-lithium group, lithium users had lower hemoglobin A1C (5.24 +/- 0.53 versus 6.01 +/- 1.83, U=753.5, p=0.006) and lower triglycerides (1.46 +/- 0.88 versus 2.01 +/-1.25, U=947, p=0.020). Conclusions: There is a high prevalence of obesity and metabolic syndrome among bipolar disorder patients. However, this did not appear to be associated with lithium use, when compared to those not on lithium. The lithium subgroup was also associated with lower prevalence of type II diabetes. Future prospective and intervention studies with larger sample sizes are necessary to further explore the association between lithium and insulin resistance, as well as its underlying mechanisms.
Brucellosis Spinal Epidural Abscess: A Case Series of Fourteen Patients
Authors: Su WeiLiang , Dai GuoHua , Guo Zhu , Liu Chang , Yang Shuai , Wu XiaoLin , Qiu ChenSheng , Xiang HongFei , Chen BoHua
Published: October 2020

Objective: In the present study, we aimed to describe the clinical features, diagnosis, treatment and prognosis of Brucellosis spinal epidural abscess (BSEA). Methods: The complete clinical data of 14 BSEA patients who were treated in our hospital system from January 2014 to February 2019 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment and prognosis of 60 BSEA cases collected from the English literature from 1994 to 2019 were also investigated. Results: 3 cases were positive for blood culture, 6 cases were positive for Brucella latex agglutination test, and 9 cases were positive for tissue culture. All 14 cases showed focal spinal pain, 11 cases showed neurological deficits, and 7 cases showed fever. Of the 14 cases, 12 involved the lumbosacral spine and 2 involved the cervical spine. 13 cases were cured, 1 case left limb numbness, and the follow-up time was 12-20 months. Conclusion: The classic diagnosis of triad (focal spinal pain, neurological deficit and fever) is less specific for the diagnosis of BSEA. MRI examination can find epidural abscess, brucella latex agglutination test, blood culture, tissue culture and biopsy can be used for etiological diagnosis. Brucellosis is an uncommon cause of epidural abscess. For BSEA, early detection, early diagnosis, and early treatment should be performed, and the most suitable treatment method should be selected through comprehensive evaluation.
Associations of Indoor Carbon Dioxide Concentration and Symptoms of Sick Building Syndrome in Air-Conditioned Lecture Halls
Authors: Jayasooriya V M , Rajapaksha R M D H , Ng A W M , Muthukumaran S
Published: October 2020

Indoor Carbon Dioxide (CO 2 ) concentrations and its impacts on health and wellbeing of the occupants is a widely discussed topic in building science. Although there is an abundance of knowledge on relationships between the Sick Building Syndrome (SBS) of office environments and naturally ventilated buildings, there is yet a limited knowledge available on associations’ of SBS in the students of higher educational facilities especially in air-conditioned lecture halls. To fill this research gap, present study has analyzed indoor CO 2 levels of 5 air-conditioned lecture halls with varying occupant densities for ongoing lectures of 2 hours. Statistically significant (α<0.05) strong positive correlation (R= 0.856) was shown between the occupant density and the CO 2 levels of the selected lecture halls. The results from the ordinal logistic regression shows significant odds ratios (OR>1, at 95% confidence interval) for the prevalence of symptoms such as headache, difficulties in concentration, dry throat, cough and tiredness/lethargy for certain lecture halls with high occupant densities. The results of the present study highlight the importance of adhering to proper design standards of lecture halls, optimum occupant control and selection of efficient air conditioning systems to maintain the health and wellbeing of higher education students.
Domain Multiplexed Computer-generated Holography by Embedded Wavevector Filtering Algorithm
Authors: Wu Lin , Zhang Ziyang
Published: October 2020

Computer-generated holography can obtain the wavefront required for constructing arbitrary intensity distributions in space. Currently, speckle noises in holography remain an issue for most computational methods. In addition, there lacks a multiplexing technology by which images from a single hologram and light source can be switched by a lens. In this work, we first come up with a new algorithm to generate holograms to project smoother images by wavevector filtering. Thereupon, we propose a unique multiplexing scheme enabled by a Fourier lens, as the incident light can be decomposed either by a superposition of spherical waves or plane waves. Different images are obtained experimentally in the spatial and wavevector domains, switchable by a lens. The embedded wavevector filtering algorithm provides a new prospective for speckle suppression without the need for postprocessing. The multiplexing technology can double the capacity of current holographic systems and exhibits potential for various interesting display applications.
Preoperative C-Reactive Protein as A Predictor of Postoperative Complications in Patients Undergoing Surgery for Colorectal Neoplasia
Authors: Alsaif Sufana , Rogers Ailín C , Pua Priscilla , Casey Paul T , Aherne Geoff G , Brannigan Ann E , Mulsow Jurgen J , Shields Conor J , Cahill Ronan A
Published: October 2020

Background: Inflammatory markers are measured following colorectal surgery to detect postoperative complications. However, the association of these markers preoperatively with subsequent postoperative course has not yet been usefully studied. Aim: The aim of this study is to assess the ability of preoperative C-reactive protein (CRP) and other inflammatory marker measurements in the prediction of postoperative morbidity after elective colorectal surgery. Methods: This retrospective study catalogues 218 patients undergoing elective, potentially-curative surgery for colorectal neoplasia. Preoperative laboratory results of the full blood count (FBC), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were recorded. Multivariable analysis was performed to examine preoperative variables against 30-day postoperative complications by type and grade (Clavien-Dindo (CD)), adjusting for age, sex, BMI, smoking status, medical history, open versus laparoscopic operation, and tumor characteristics. Results: Elevated preoperative CRP (≥ 5 mg/L) was significantly predictive of all-cause mortality, with an OR of 17.0 (p < 0.001) and was the strongest factor to predict a CD morbidity grade ≥ 3 (OR 41.9, p < 0.001). Other factors predictive of CD morbidity grade ≥ 3 included smoking, elevated preoperative platelet count and elevated preoperative neutrophil-lymphocyte ratio (OR 15.6, 8.6 and 6.3 respectively, all p < 0.05). CRP values above 5.5 mg/L were indicative of all-cause morbidity (AUC=0.871), and values above 17.5 mg/L predicted severe complications (AUC=0.934). Conclusions: Elevated preoperative CRP predicts increased postoperative morbidity in this patient cohort. The results herein aid risk and resource stratification and encourage preoperative assessment of inflammatory propensity besides simple sepsis exclusion.
CYP 3A5*3 Gene Polymorphism Among Sudanese Patients With Chronic Myeloid Leukemia 
Authors: Abdallah Elharam Ibrahim , M.Alamin Nazic Ibrahim , Elradi Wala Eldin Osman , Elzaki Salah Eldin G. , Shrif NassrEldin Mohamed Ahmed
Published: October 2020

Introduction: Interaction of environmental and genetic elements plays a vital role in the pathogenesis of CML and other types of cancer. CYP 3A5 is enzyme responsible of metabolizing of approximately 50 % of therapeutic drugs and xenobiotics. So polymorphism variation may genetically predispose individuals to CML.Objective: The purpose of this study was to determine CYP3A5*3 Polymorphism among Sudanese patients with Chronic Myeloid Leukemia (CML).Materials and Methods: This case control study was conducted among 50 patients with chronic myeloid leukemia among both genders at different ages and 42 apparently healthy control subjects. The CYP3A5*3 genotype was determined using (PCR-RFLP) method.Results: Paerson`s chi-square test was used to assess the possible link between CYP3A5*3 genotype and CML. The percentage of CYP3A5*3*3 genotype in CML patients was significantly higher than in control (OR = 11.71, 95% CI: 4.30 –31.83; p =0.000). The frequency of mutant genotype was higher among CML patients with advance phase compared with chronic phase, 100% versus 80% respectively.Conclusion: CYP3A5*3/*3 genotype associated with CML development and progression.
Alleviatory Effects of Danshen, Salvianolic Acid A and Salvianolic Acid B on Pc12 Neuronal Cells and Drosophila Melanogaster Model of Alzheimer’s Disease
Authors: TAN Florence Hui Ping , Ting Andrew Chung Jie , Najimudin Nazalan , WATANABE Nobumoto , LEOW Ban Guan , AZZAM Ghows
Published: October 2020

Background: Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder worldwide. Its pathogenesis involves the hallmark aggregation of amyloid-beta (Aβ). Of all the Aβ oligomers formed in the brain, Aβ42 has been found to be the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. Danshen water extract (DWE), obtained from the root of Salvia miltiorrhiza Bunge, was found to have a vast array of beneficial properties. In this study, DWE, and its major components, Salvianolic acid A (SalA) and Salvianolic acid B (SalB) were tested for their abilities to attenuate Aβ42’s toxic effects.Methods: The compounds were first verified for their ability to diminish Aβ42 fibrillation using an in vitro activity assay. Since Aβ42 aggregation results in neuronal degeneration, the potential Aβ42 inhibitors were next evaluated on Aβ42-exposed PC12 neuronal cells as well as the Drosophila melanogaster model organism. Results: DWE, SalA and SalB were shown to be able to reduce fibrillation of Aβ42. When tested on PC12 neuronal cells, DWE, SalA and SalB ameliorated cells from cell death associated with Aβ42 exposure. Next, DWE and its components were tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. When human Aβ42 was expressed, the Drosophila exhibited degenerated eye structures known as the rough eye phenotype (REP), reduced lifespan and deteriorated locomotor ability. Administration of DWE, SalA and SalB partially reverted the REP, increased the age of AD Drosophila and improved most of the mobility of AD Drosophila. Conclusion: Collectively, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.Trial Registration: Not applicable
Impact of Surface Modification on Cellular Uptake and Cytotoxicity of Silica Nanoparticles
Authors: Vranic Sandra , Watanabe Eri , Miyakawa Kayoko , Takeuchi Sakie , Osada Yurika , Ichihara Sahoko , Zong Cai , Wu Wenting , Sakurai Toshihiro , Sato Akira , Hara Yasushi , Suzuki Toshihiro , Abe Ryo , Boland Sonja , Tran Lang , Ichihara Gaku
Published: October 2020

Background: Silica nanoparticles (SiO2 NPs) are widely used in industrial products as additives for rubber and plastics or as filler strengthening concrete, as well as being used in the biomedical field for drug delivery and theranostic purposes. The present study investigated the effects of amino or carboxyl functionalization of rhodamine-labeled SiO2 NPs on cellular uptake and cytotoxicity. Methods: Male mice were randomly divided into seven groups (n=6, each) and exposed to non-functionalized (plain), carboxyl or amino-functionalized rhodamine-labeled SiO2 NPs at 2 or 10 mg/kg bw, or endotoxin-free water, by pharyngeal aspiration. At 24 hours after administration, the mice were euthanized and bronchoalveolar lavage fluid (BALF) was collected for differential cell count and identification of silica nanoparticle uptake using confocal microscopy. In the in vitro studies, murine RAW264.7 macrophages were exposed to non-functionalized, amino- or carboxyl-functionalized Rhodamine-labeled SiO2 NPs. Nonspecific caspase inhibitor and necrostatin-1 were used to determine the involvement of caspase or receptor-interacting protein 1 kinase domain in the cytotoxicity. Results: The in vivo study demonstrated that the neutrophil and macrophage counts and the percentage of macrophages with internalized particles was highest in the order of carboxyl >= amino- > > non-functionalized particles. The in vitro study demonstrated greater cytotoxicity for non-functionalized silica nanoparticles, compared to the others. Treatment with non-specific caspase or necroptosis inhibitor did not attenuate MTS cytotoxicity of non-functionalized silica nanoparticles. Conclusion: We conclude that carboxyl-functionalzed SiO2 NPs are internalized by macrophages more efficiently but less cytotoxic than plain SiO2 NPs. The cytotoxic effect of plain SiO2 NPs, which cannot be explained by apoptosis or necroptosis, can be avoided by carboxyl- or amino- functionalization.
Potential Health Impact of Increasing Adoption of Sustainable Dietary Practices in Sweden
Authors: Patterson Emma , Colombo Patricia Eustachio , Milner James , Green Rosemary , Elinder Liselotte Schäfer
Published: October 2020

BackgroundAn urgent transition to more sustainable diets is necessary for the improvement of human and planetary health. One way to achieve this is for sustainable practices to become mainstream. We estimated the potential health impact of wider adoption of dietary practices deemed by consumers, researchers and stakeholders in Sweden to be niche, sustainable and with the potential to be scaled up.MethodsA life table method was used to estimate the impact - changes in years of life lost (YLL) - over periods of 20 and 30 years in the Swedish population had the practices been adopted in 2010-11, when the last national adult dietary survey was conducted. The practices modelled were reducing red and processed meat (by 25%, 50% and 100%), and assuming, for each stage, replacement by an equal weight of poultry/fish and vegetables +/- legumes; reducing milk intake (by 25%, 50% and 100%); and reducing sugar-sweetened beverage intake (by 25%, 50% and 100%). Using population data together with data on cause-specific mortality and relative risks for diet-disease outcomes, impacts were estimated for each scenario separately and in combination, for the outcomes ischaemic heart disease (IHD), ischaemic stroke, diabetes type 2 and colorectal cancer.ResultsFor a “moderate” combination of scenarios (changes at the 50% level), reductions of 513,200 YLL (lower-upper uncertainty estimate 59,400-797,900) could have been achieved over 20 years and 1,148,500 YLL (135,900-1,786,600) over 30 years. The majority (over 90%) of YLLs prevented were related to IHD, and the majority were in men. The singular practice that had the most impact was reducing the intake of red and processed meat and replacing it with a mixture of vegetables and legumes. Reducing milk intake resulted in an increase in YLL, but this was compensated for by other scenarios. ConclusionIf these practices were more widely adopted, they would be expected to lead to improvements in public health in Sweden. Over the long term, this would translate to many premature deaths postponed or prevented from a number of chronic diseases, to the benefit of individuals, society, the climate and the economy.
Neural Correlates of the Impulse Dyscontrol Domain of Mild Behavioral Impairment
Authors: Gill Sascha , Wang Meng , Mouches Pauline , Rajashekar Deepthi , Sajobi Tolulope , MacMaster Frank P , Smith Eric E , Forkert Nils D , Ismail Zahinoor
Published: October 2020

Background: Agitation and aggression are common in dementia and pre-dementia. The dementia risk syndrome mild behavioral impairment (MBI) includes these symptoms in the impulse dyscontrol domain. However, the neural circuitry associated with impulse dyscontrol in neurodegenerative disease is not well understood. The aim of this work is to investigate if regional micro- and macro-structural brain properties are associated with impulse dyscontrol symptoms in older adults with normal cognition, mild cognitive impairment, and Alzheimer’s disease. Methods: Clinical, neuropsychiatric, and T1-weighted and diffusion-tensor MRI (DTI) data from 80 individuals with and 123 individuals without impulse dyscontrol, were obtained from the Alzheimer’s Disease Neuroimaging Initiative. Linear mixed effect (LME) models were used to assess if impulse dyscontrol was related to regional DTI and volumetric parameters. Results: Impulse dyscontrol was present in 17% of participants with NC, 43% with MCI, and 66% with AD. Impulse dyscontrol was associated with: 1) lower fractional anisotropy, and greater mean, axial, and radial diffusivity in the fornix; 2) lesser fractional anisotropy, and greater radial diffusivity in the superior fronto-occipital fasciculus; 3) greater axial diffusivity in the cingulum; 4) grey matter atrophy, specifically, lower cortical thickness and greater surface area in the parahippocampal gyrus. Conclusion: Our findings provide evidence that well-established atrophy patterns of AD are prominent in the presence of impulse dyscontrol, even when disease status is controlled for, and possibly in advance of dementia. Our findings support the growing evidence base for impulse dyscontrol symptoms as an early manifestation of Alzheimer’s disease.
Morphological Study of Embryonic Chd8+/- Mouse Brains Using Light-Sheet Microscopy
Authors: Gómez Harold , Hodel Leonie , Michos Odyssé , Iber Dagmar
Published: October 2020

ObjectiveAutism spectrum disorder (ASD) encompasses a group of neurodevelopmental conditions that remain poorly understood due to their genetic complexity. CHD8 is a risk allele strongly associated with ASD, and heterozygous Chd8 loss-of-function mice have been reported to exhibit macrocephaly in early postnatal stages. In this work, we sought to identify measurable brain alterations in early embryonic development.ResultsWe performed light-sheet fluorescence microscopy imaging of N-cadherin stained and optically cleared Chd8+/- and wild-type mouse brains at embryonic day 12.5 (E12.5). We report a detailed morphometric characterization of embryonic brain shapes and cortical neuroepithelial apical architecture. While Chd8+/- characteristic expansion of the forebrain and midbrain was not observed this early in embryogenesis, a tendency for a decreased lateral ventricular sphericity and an increased intraocular distance in Chd8+/- brains was found compared to controls. This study advocates the use of high-resolution microscopy technologies and multi-scale morphometric analyses of target brain regions to explore the etiology and cellular basis of Chd8 haploinsufficiency.
A Data Fusion Method in Wireless Sensor Network Based on Belief Structure
Authors: Long Chenfeng , Liu Xinxing , Yang Yakun , Zhang Tao , Tan Siqiao , Tang Xiaoyong , Yang Gelan
Published: October 2020

Considering the issue with respect to the high data redundancy and high cost of information collection in wireless sensor nodes, this paper proposes a data fusion method based on belief structure to reduce attribution in multi-granulation rough set. By introducing belief structure, attribute reduction is carried out for multi-granulation rough sets. From the view of granular computing, this paper studies the evidential characteristics of incomplete multi-granulation ordered information systems. On this basis, the positive region reduction, belief reduction and plausibility reduction are put forward in incomplete multi-granulation order information system, and analyze the consistency in the same level and transitivity in different levels. The positive region reduction and belief reduction are equivalent, and the positive region reduction and belief reduction is unnecessary and sufficient conditional plausibility reduction in the same level; if the cover structure order of different levels are the same, the corresponding equivalent positive region reduction. The algorithm proposed in this paper not only performs three reductions, but also reduces the time complexity largely. The above study fuses the node data which reduces the amount of data that needs to be transmitted and effectively improves the information processing efficiency.
Synthesis and Characterization of Commercial Pure Titanium-nickel Alloy Behavior Reinforced With Titanium Diboride
Authors: Falodun O.E. , Oke Samuel R , Olubambi Peter A
Published: October 2020

Commercial pure titanium alloy with Ni-TiB2 ceramic additions (5, 10, 15 and 20 vol.%) were synthesized through the spark plasma sintering approach with sintering temperature of 1000 oC, the heating rate of 100 oC/min, holding time of 5 min at a constant pressure of 50 MPa. The study investigated the effect of Ni-TiB2 on the densification, phase change, microhardness, microstructure, and wear properties of the sintered titanium-based composites. Results showed that Ti-Ni-TiB2 composites relative density ranges from 97 to 99 %, while microhardness values increase with addition of nickel and titanium diboride from 228 to 587 HV0.1. The microstructural evolution shows that pure titanium transformed from lamellar phase to equiaxed alpha phase upon addition of nickel alloy and further get refined with a distinct grain boundary comprises of titanium diboride around the boundaries. The average coefficient of friction for the titanium-based composite was higher for commercially pure titanium (0.73) while the addition of TiB2 exhibit (0.66, 0.63, 0.58, 0.55 and 0.46 respectively) improvement in the wear behavior.
Artificial intelligence for reduced dose 18F-FDG PET examinations: A real-world deployment through a standardized framework and business case assessment
Authors: Katsari Katia , Penna Daniele , Arena Vincenzo , Polverari Giulia , Ianniello Annarita , Italiano Domenico , Milani Rolando , Roncacci Alessandro , Illing Rowland , Pelosi Ettore
Published: October 2020

Background To determine whether artificial intelligence (AI) processed PET/CT images of reduced by 33% administered 18-F FDG activity acquired in a single center, were non-inferior to native scans and if so to assess the potential impact of commercialization. Methods SubtlePET™ AI was introduced in a PET/CT center in Italy. Eligible patients referred for 18F-FDG PET/CT were prospectively enrolled. Administered 18F-FDG was reduced to two-thirds of standard dose. Patients underwent one low-dose CT and two sequential PET scans; ‘PET-processed’ with reduced dose and standard acquisition time, and ‘PET-native’ with an elapsed time to simulate standard acquisition time and dose. PET-processed images were reconstructed using SubtlePET™. PET-native images were defined as the standard of reference. The datasets were anonymized and independently evaluated in random order by four blinded readers. The evaluation included subjective image quality (IQ) assessment, lesion detectability and assessment of business benefits. Results From February to April 2020, 61 patients were prospectively enrolled. Subjective IQ was not significantly different between datasets (4.62±0.23, p=0.237) for all scanner models, with ‘almost perfect’ inter-reader agreement. There was no significant difference between datasets in lesions’ detectability, target lesion mean SUVmax value and liver mean SUVmean value (182.75/181.75 [SD:0.71], 9.8/11.4 [SD:1.13], 2.1/1.9 [SD:0.14] respectively). No false-positive lesions were reported in PET-processed examinations. Agreed SubtlePET™ price per examination was 15-20% of FDG savings. Conclusion This is the first real-world study to demonstrate the non-inferiority of AI processed 18F-FDG PET/CT examinations obtained with 66% standard dose and a methodology to define the AI solution price.
Treatment of Microglia with Anti-PrP Antibodies Induces Neuronal Allergenicity
Authors: Adhikari Utpal Kumar , Sakiz Elif , Habiba Umma , Kumar Sachin , Mikhael Meena , Guillemin Gilles J. , Ooi Lezanne , David Monique , Karl Tim , Tayebi Mourad
Published: October 2020

Background: Previous reports identified proteins associated with ‘apoptosis’ following cross-linking PrPC with motif-specific anti-PrP antibodies in vivo and in vitro. The molecular mechanisms underlying this IgG-mediated neurotoxicity and the role of the activated proteins in the apoptotic pathways leading to neuronal death has not been properly defined. Previous reports implicated a number of proteins, including apolipoprotein E, cytoplasmic phospholipase A2, prostaglandin and calpain with anti-PrP antibody-mediated ‘apoptosis’, however, these proteins are also known to play an important role in allergy. In this study, we investigated whether cross-linking PrPC with anti-PrP antibodies stimulates a neuronal allergenic response.Methods: Initially, we predicted the allergenicity of the epitope sequences associated with ‘neurotoxic’ anti-PrP antibodies using allergenicity prediction servers. We then investigated whether anti-PrP antibody treatment of neuronal (N2a) and microglia (N11) cell lines leads to a neuronal allergenic response.Results: We found that both tail- and globular-epitopes were allergenic. Specifically, binding regions that contain epitopes for ‘neurotoxic’ antibodies such as ICSM18 (146-159), ICSM35 (91-110), POM 1 (138-147), POM 2 (57-88) and POM 3 (95-100) lead to activation of allergenic related proteins. Following direct application of anti-PrPC antibodies on N2a cells, mass spectrometry analysis identified 4 neuronal allergenic-related proteins when compared with untreated cells. Furthermore, mass spectrometry analysis identified 8 neuronal allergenic-related proteins following cross-linking N11 cells with anti-PrPC antibodies prior to co-culture with N2a cells, when compared with untreated cells. Of importance, we showed that the allergenic effects triggered by the anti-PrP antibodies were more potent when antibody-treated microglia were co-cultured with the neuroblastoma cell line. Furthermore, in both direct and co-culture with antibody-treated microglia, we demonstrate that the allergenic proteome was part of the PrPC-interactome. Conclusions: This study showed for the first time that anti-PrP antibody binding to PrPC triggers a neuronal allergenic response (we termed ‘IgG-Mediated Neuronal Allergenic Toxicity’) and highlights the important role of microglia in triggering IgG-mediated neuronal allergenic toxicity. Moreover, this study provides an important impetus for including allergenic assessment of therapeutic antibodies for neurodegenerative to derive safe and targeted biotherapeutics.
Dose approach matter?A Meta-analysis of outcomes following transfemoral versus transapical transcatheter aortic valve replacement
Authors: Guo Ruikang , Xie Minghui , Yim Wai Yen , Wu Wenconghui , Jiang Weiwei , Wang Yin , Hu Xingjian
Published: October 2020

Background: Transcatheter aortic valve replacement (TAVR) has gained increasing acceptance for patients with aortic disease. Both transfemoral (TF-TAVR) and transapical (TA-TAVR) approach were widely adopted while their performances are limited to a few studies with controversial results. This meta-analysis aimed to compare the mortality and morbidity of complications between TF- versus TA-TAVR based on the latest data. Methods: Electronic databases were searched from January 2005 to December 2019. RCTs and observational studies comparing the outcomes between TF-TAVR versus TA-TAVR patients were included. Heterogeneity assumption was assessed by an I2 test. The pooled odds ratios(OR) or mean differences with corresponding 95% confidence intervals (CI) were used to evaluate the difference for each end point using a fixed-effect model or random-effect model based on I2 test. Results: The meta-analysis included 1 RCT and 18 observational studies, enrolling 12,953 patients (TF-TAVR, n=8,649 and TA-TAVR, n=4,304). Compared with TA-TAVR, TF-TAVR patients showed significantly lower rate of postoperative in-hospital death (OR=0.63, 95%CI 0.54-0.74, P<0.001) and 1-year death(OR=0.53, 95%CI 0.41-0.69, P<0.001). Incidence of major bleeding and acute kidney injury were lower, whereas those of permanent pacemaker and major vascular complication were higher in TF-TAVR patients. There were no significant differences between TF-TAVR versus TA-TAVR for stroke and mid-term mortality.Conclusions: There were fewer early deaths in patients with transfemoral approach, whereas the number of mid-term deaths and stroke was not significantly different between two approaches. TF-TAVR was associated with lower risk of bleeding, acute kidney injury as well as shorter in-hospital stay, but higher incidence of vascular complication and permanent pacemaker implantation.
Evaluation the effectiveness of Abridged IMNCI (7-Day) Course v standard (11-Day) Course in Pakistan
Authors: Ariff Shabina , Ahmed Khalil , Sadiq Kamran , Nuzhat Khadija , Ahmed Shakeel , Jiwani Uswa , Nizami Qamruddin , Khan Iqtidar A , Ali Nabila , Soofi Sajid Bashir , Bhutta Zulfiqar A
Published: October 2020

Background: The conventional IMCI training for healthcare providers is delivered in 11 days, which can be expensive and disruptive to the normal clinical routines of the providers. An equally effective, shorter training course may address these difficulties.Methods: This was a quasi-experimental study that was conducted in two provinces (Sindh and Punjab) of Pakistan. 104 healthcare providers were conveniently selected to receive either the abridged (7-day) or the standard (11-day) training. Knowledge and clinical skills of the participants were assessed before, immediately on conclusion of, and six months after the training.Results: The improvement in mean knowledge scores of the 7-day and 11-day training groups was 31.6 (95% CI: 24.3, 38.8) and 29.4 (95% CI: 23.9, 34.9) respectively, p = 0.630 while the improvement in mean clinical skills scores of the 7-day and 11-day training groups was 23.8 (95% CI: 19.3, 28.2) and 23.0 (95% CI: 18.9, 27.0) respectively, p = 0.784. The decline in mean knowledge scores six months after the training was -12.4 (95% CI -18.5, -6.4) and -6.4 (95% CI: -10.5, -2.3) in the 7-day and 11-day groups respectively, p = 0.094. The decline in mean clinical skills scores six months after the training was -6.3 (95% CI -11.3, -1.3) in the 7-day training group and -9.1 (95% CI -11.5, -6.6) in the 11-day group, p = 0.308.Conclusion: An abridged IMNCI training is equally effective as the standard training. However, training for certain illnesses may be better delivered by the standard course.
Transhumanizam – filozofska osnova
Authors: Furjanić Lovro
Published: October 2020

Članak donosi pregled najosnovnijih postavki transhumanističkog pokreta. Transhumanistički pokret počinje krajem 20. stoljeća i zalaže se za korištenje tehnologije u svrhu unapređivanja ljudskog stanja. S obzirom na izvjesnu razinu sličnosti s posthumanizmom, pregled transhumanizma počinje analizom osnovnih pojmova: transhumanizam, posthumanizam, transhumano biće i posthumano biće. Nakon toga, transhumanizam se proučava iz perspektive različitih disciplina. Te su discipline: filozofija znanosti, metafizika, etika, filozofija uma, filozofija religije i filozofija politike.
Postsmrtno stanje: metafizičko-eshatološke ambicije transhumanizma
Authors: Singbo Odilon-Gbènoukpo
Published: October 2020

U radu se ispituju metafizičke i eshatološke implikacije transhumanizma, osobito u svjetlu njegove ideje o besmrtnosti ljudske vrste. Kroz jezgrovit prikaz povijesnog okvira pojave transhumanističkog pokreta, rad ističe njegove glavne karakteristike kao što su poboljšanje čovjeka, nadilaženje ljudskoga i pobjeda inherentnih čovjekovih nedostataka pomoću suvremenih grana znanosti te suvremene tehnike. Navedene karakteristike pomažu u shvaćanju metafizike i eshatologije na način kako ih formiraju neki aspekti transhumanizma. Upravo su ti aspekti po svojim načelima nedvojbeno tehničke i sekularne naravi jer se odmiču od religioznog shvaćanja ljudskih čežnji i smrti. Često se smrt shvaća kao greška, a proces starenja kao patološko, ponižavajuće, ali izlječivo stanje. Transhumanizam na taj način označava kraj humanističko-transcendentalne perspektive o slobodnom subjektu stvorenom dobrotom i spašenom ljubavlju Boga u otajstvu Isusa Krista. Kroz rad se argumentira da tehnokratska rješenja ne mogu ispuniti temeljne ljudske čežnje.
Za etiku kontinuuma prirode i čovjeka
Authors: Jakovljević Dragan
Published: October 2020

U ovom se članku sagledava pitanje odnosa čovjeka i prirode, polazeći od drevne nereflektirane upotrebe izraza ethos u smislu naviknutog mjesta življenja koje od strane njega nastanjujućih živih bića biva u određenoj mjeri (su)oblikovano. To se polazište dalje razrađuje kroz pojmove obitavalište i zavičaj (Milan Kangrga), odnosno zavičajni svijet i domovina (Bernhard Waldenfels). Drevni pojam ethos ne može zamijeniti odgovarajući moderni pojam, ali ipak može biti shvaćen kao njegova upotpunjavajuća primjesa smisla. Ona pokazuje neočekivanu aktualnost, s obzirom na suvremenu problematiku ekologije i biodiverziteta. Pritom se, prije svega, otvara pitanje o tome koje načine nastanjivanja i kultiviranja tla svakidašnjeg obitavališta treba preferirati, a koje izostaviti. Kao imperativ autor ističe neophodnost jednog obzirnog odnošenja prema drugim živućim bićima s kojima dijelimo planetarno obitavalište, ali i prema vegetaciji i prirodnom okruženju, uz poštovanje prema drugim, ne-ljudskim oblicima života i njihovoj dobrobiti.
Barochronous shear gas motion
Authors: Yulmukhametova Yu.V.
Published: October 2020

The equations of ideal gas dynamics admit an 11-dimensional Lie algebra of first-order differentiation operators. All subalgebras of this algebra are listed. Khabirov S.V. for all 48 types of 4-dimensional subalgebras, the bases of point invariants are calculated and three 4-dimensional subalgebras are considered that produce regular partially invariant solutions in Cartesian, cylindrical and spherical coordinates, respectively. In this paper, we pose the problem of finding the solution of 3-dimensional equations of gas dynamics in a Cartesian coordinate system with an arbitrary equation of state, built on invariants of a 4-dimensional subalgebra. The basic operators of the considered subalgebra are combinations of translations and Galilean transfers. The invariants of this subalgebra define a representation of the solution for unknown hydrodynamic functions. Speed components are linear functions in terms of spatial variables. Moreover, density and pressure depend only on time. After substituting the solution representation, we studied the compatibility of the resulting system of differential equations. The system is collaborative and has an exact solution. Such a solution describes the isentropic barochronous shear motion of a gas. The equations of the world lines of motion of gas particles are found. The moments of particle collapse are established. There were two of them. The equations of collapse surfaces are found and written. For the flat case, several statements about the nature of the motion of gas particles are proved.
Pharmacological and In-Silico Investigations of Anxiolytic-like Effects of Phyllanthus Fraternus: A Probable Involvement of GABA-A Receptor
Authors: Chopade Atul R. , Pol Rahul P. , Patil Pramod A. , Dharanguttikar Vyankatesh R. , Naikwade Nilofar S. , Dias Remeth J. , Mali Suraj N.
Published: October 2020

Background::

Phyllanthus fraternus Webster Linn (family, Euphorbiaceae) is used as a traditional
medication for the treatment of various disorders and has therapeutic implications.

Objective::

This study intends to investigate the anxiolytic potential of Phyllanthus fraternus standardized
extract and prediction of the probable role of its marker phytoconstituents.

Methods::

We tested the standardized hydro-ethanolic extract of Phyllanthus fraternus (whole plant)
for the Elevated plus-maze model (EPM) and Light & Dark Exploration test as classical models for
anxiety. Phyto-chemical HPTLC fingerprint analysis was performed for the detection of two classes of
compounds lignans and tannins. HPTLC analysis of the standardized extract was performed using phyllanthin
hypophyllanthin and corilagin as marker compounds. Additionally, GABA receptor antagonism
was studied in other sets of experiments to assess the involvement of this receptor in the anxiolytic-
like effects produced by Phyllanthus fraternus.

Results::

The lower doses of the lignan and tannin-rich extract of the Phyllanthus fraternus possess
significant anxiolytic-like activity compared to the standard diazepam. Additionally, the results of the
present study suggested that high doses (400mg/kg) of Phyllanthus fraternus have exerted some sedative-
like effects. Phytochemical screening and HPTLC fingerprint analysis indicate the presence of
lignans and tannins, whereas HPLC analysis of the standardized extract revealed the presence of marker
lignan (Hypophyllanthin) and Tannin (Corilagin). The anxiolytic-like effect of Phyllanthus fraternus
observed in the mice models were blocked by Flumazenil indicating the involvement of GABAA receptors
in the modulation of this effect. Our molecular docking studies also supported probable anxiolytic
and sedative effects.

Conclusion::

To summarize, results support the use of Phyllanthus fraternus in the anxiety-like symptoms/
disease condition and suggest its anxiolytic-like effect governed by the GABA-A receptors.
Role of Genes and Treatments for Parkinson’s Disease
Authors: Naz Falaq , Siddique Yasir Hasan
Published: October 2020

Parkinson’s Disease (PD) is a complex neurodegenerative disorder that mainly results due to the loss of dopaminergic neurons in the substantia nigra of the midbrain. It is well known that dopamine is synthesized in substantia nigra and is transported to the striatumvianigrostriatal tract. Besides the sporadic forms of PD, there are also familial cases of PD and number of genes (both autosomal dominant as well as recessive) are responsible for PD. There is no permanent cure for PD and to date, L-dopa therapy is considered to be the best option besides having dopamine agonists. In the present review, we have described the genes responsible for PD, the role of dopamine, and treatment strategies adopted for controlling the progression of PD in humans.
Underwater Image Enhancement Method Combining color and Luminance
Authors: Baiting Zhao , Feng Wang , Xiaofen Jia , Yongcun Guo , Chengjun Wang
Published: October 2020

Background::

Aiming at the problems of color distortion, low clarity and poor visibility of underwater image caused by complex underwater environment, a wavelet fusion method UIPWF for underwater image enhancement is proposed.

Methods::

First of all, an improved NCB color balance method is designed to identify and cut the abnormal pixels, and balance the color of R, G and B channels by affine transformation. Then, the color correction map is converted to CIELab color space, and the L component is equalized with contrast limited adaptive histogram to obtain the brightness enhancement map. Finally, different fusion rules are designed for low-frequency and high-frequency components, the pixel level wavelet fusion of color balance image and brightness enhancement image is realized to improve the edge detail contrast on the basis of protecting the underwater image contour.

Results::

The experiments demonstrate that compared with the existing underwater image processing methods, UIPWF is highly effective in the underwater image enhancement task, improves the objective indicators greatly, and produces visually pleasing enhancement images with clear edges and reasonable color information.

Conclusion::

The UIPWF method can effectively mitigate the color distortion, improve the clarity and contrast, which is applicable for underwater image enhancement in different environments.
Nanovesicle Ethosome: A Potential Carrier of Microwave Assisted Polyherbal Extracts as Cosmecueticals
Authors: Jena Jasma , Mahendrakar Sushma , Sahu Dipika , Sahu Baby , Patro Niranjan , Sahoo Biswa M. , Sruti Jammula
Published: October 2020

Background::

Deep rooted mission for long life and having a sound skin has apparently achieved uncommon statures in our time of stamped populace maturing, aging alludes to the different procedures of mileage that influence us ceaselessly. Therefore, three primary ideal models such as ‘packed dismalness’, ‘decelerated maturing’ and ‘captured maturing’ are recognized in organic research on ageing. Various examinations have announced that ceaseless introduction to receptive free radicals can invigorate skin maturing and that over the top fat testimony can cause a hindered skin hindrance and tissue structure modifications.

Objectives::

Safe and effective formulations deliver active substances to the desired site of action with negligible discomfort and side effects. Herbal cosmetics have a restorative effect and are an important endowment of nature. Different innovative advances have been created to beat the problems raised in the penetration of cosmetic ingredients. One such procedure is the utilization of ethosomes.

Methods::

Development product of liposome have less ethanol content. Ethosomes are mainly the transdermal course of medication which facilitates good skin penetration. It can be used for developing various cosmeceuticals to overcome various skin ailments.

Conclusion::

Ethosomes are nanophospholipid vesicular systems of an average size of 1.112 micrometre produced by combinations of phospholipid, ethanol, and water. Clitorea ternatea separates are usually utilized in the traditional system of medicine as a restoring formula. Trigonella foenum-graecum Linn has various medical advantages and physiological characteristics taken together; our findings may provide scientific evidence supporting the development of various cosmetic preparations.