bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Tolerability Study of Sotrovimab (VIR-7831) Prophylaxis Against COVID-19 Infection in Immunocompromised Individuals with Impaired SARS-CoV-2 Humoral Immunity
Authors: Gonzalez-Bocco Isabel H , Beluch Katherine , Cho Alyssa , Unger-Mochrie Gillian M , Lahoud Chloe , Reyes Fabiola A , Moshovitis Dimitrios G , Wang Wei , Hammond Sarah P , Manne-Goehler Jennifer , Koo Sophia
Published: August 2022

Background: Since August 2021, multiple vaccines have been approved to prevent infection with SARS-CoV-2; however, 20-40 % of immunocompromised people fail to develop SARS-CoV-2 spike antibodies after COVID-19 vaccination and remain at an exceptionally high risk of infection and more severe illness than non-immunocompromised hosts. Sotrovimab (VIR-7831) is an engineered monoclonal antibody that targets a highly conserved epitope on the SARS-CoV-2 spike glycoprotein. It is neither renally excreted nor metabolized by P450 (CYP) enzymes; therefore, interactions with concomitant medications are unlikely, which is an important consideration for patients receiving multiple immunosuppressive medications. In this Phase II open-label safety and tolerability study protocol, we propose to evaluate the safety and tolerability of sotrovimab as pre-exposure prophylaxis for immunocompromised individuals.Methods: We will enroll a total of 93 eligible immunocompromised adults with a negative or low-positive (<50 U/mL) SARS-CoV-2 spike antibody. In Phase 1, the first 10 patients will participate in a lead-in pharmacokinetics (PK) cohort study to determine the optimal dosing interval between two sequential doses of sotrovimab. Phase 2 will expand this population to 50 participants to examine rates of infusion-related reactions (IRR) with a 30-minute 500mg sotrovimab IV infusion. Phase 3 will be an expansion cohort for further assessment of the safety and tolerability of sotrovimab in this patient population. In Phase 4, the first 10 patients receiving 2000mg IV of sotrovimab on the second sotrovimab infusion day (Treatment Day 2) will comprise a lead-in safety cohort that will inform the duration of observation following administration of the drug, with the observation period being reduced from two hours to one hour for the remaining study population if none of these patients have a grade 3-4 infusion-related reaction. The patients will be followed for safety and COVID-19 events for an additional 36 weeks after the second dose.Discussion: In a previous Phase III randomized, placebo-controlled pivotal trial, there were no significant differences in the prevalence of adverse events in patients receiving sotrovimab vs. placebo. Thus, we propose to study the safety and tolerability of sotrovimab (VIR-7831) prophylaxis against COVID-19 infection and evaluate its PK in immunocompromised individuals with impaired SARS-CoV-2 humoral immunity. We also aim to determine COVID-19 infections over the study period and self-reported quality of life measures over the course of the study.Trial registration: ClinicalTrials.gov Identifier: NCT05210101
Plant-soil interactions of an invasive plant species and its non-invading congener differ in soil from their original range
Authors: Florianová Anna , Hanzelková Věra , Drtinová Lucie , Pánková Hana , Cajthaml Tomáš , Münzbergová Zuzana
Published: August 2022

The aim of this study was to compare plant-soil feedback (PSF) of globally invasive Cirsium vulgare in its native range with its non-invading congener C. oleraceum. We assessed changes in soil nutrients and biota following soil conditioning by each species and compared performance of plants grown in self-conditioned and control soil, from which all, some or no biota was excluded. The invasive species depleted more nutrients than the non-invasive species and coped better with altered nutrient levels. The invasive species had higher seedling emergence which benefited from the presence of unconditioned (non-specific) microbes. Biomass of the invasive species increased less in presence of self-conditioned microbiota and decreased more in presence of self-conditioned larger-sized biota compared to unconditioned biota than biomass of the non-invasive species. The invasive species showed greater ability to decrease its root-shoot ratio in presence of harmful biota and thus reduce their negative effects on its performance.The results show that the invasive species is more limited by self-conditioned pathogens in the native range and benefits more from unconditioned mutualists, and thus may benefit more from loss of specialized soil biota in a secondary range. Our study highlights the utility of detailed PSF research in the native range of species for understanding the factors that regulate performance of invasive and non-invasive species in their native range, and for pinpointing the types of biota involved in their regulation and how this regulation changes across the plants life cycle.
Power Spectrum Inception of F2 Layer at Solar Terrestrial Region of Pakistan
Authors: Jan Bulbul , Afridi Faisal Ahmed Khan , Nawaz Faisal , Yousufzai Muhammad Ayub Khan , Ahmed Arsalan , Mehmood Faraz , Baig Mirza Jawwad
Published: August 2022

In this study, we introduce a recent approach to implement the wavelet analysis of ionospheric parameters and anomaly detection during ionospheric irregularities over Pakistan. The most important aspect of the wavelet analysis is the timefrequency distribution representation of the signal. This study investigates the variability of ionospheric F2 layer and utilizes critical frequency (foF2) of F2 layer during the year 2008-2017 in Pakistan region. The results of this study identify the most important bands of low frequency variations, which are very relevant for study of periodicities measurements of F2 layer. Moreover, Morlet wavelet has revealed that generally the global wavelet power spectrum (GWPS) is the most prominent in the annual cycles. The multifaceted interactions of ionospheric fluctuations with different time scales, e.g. annual, biannual, become significant due to higher peaks appear during the periods 128-256, 256-512 and 512-1024 days in daily data sets. The wavelet trend revales a noticeablel power range between the 2–16 day bands, representing an annual fluctuation for daily observations of F2 layer. The low deviation in a frequency range highlights the existence of seasonality in the F2 layer during the study period. These results emphasize that foF2 observations exhibit irregular distrabances with non-stationary power at different frequencies.The study will be helpful for stakeholders and government authorities because high frequency sky-waves users schedule their programs one month in advance, but they also need day by day information about the ionospheric conditions in order to revise programs.
Pre-treatment with IL-6 potentiates β-cell death induced by pro-inflammatory cytokines
Authors: Oliveira Viviane Rosa , Paula Carolina Cavalcante , Ortis Fernanda
Published: August 2022

Background: Type I Diabetes mellitus (T1D) is characterized by a specific destruction of β-cells by the immune system. During this process pro-inflammatory cytokines are released in the pancreatic islets and contribute for β-cells demise. Cytokine-induced iNOS activation, via NF-B, is implicated in induction of β-cells death, which includes ER stress activation. Physical exercise has been used as an adjunct for better glycemic control in patients with T1D, since it is able to increase glucose uptake independent of insulin. Recently, it was observed that the release of IL-6 by skeletal muscle, during physical exercise, could prevent β-cells death induced by pro-inflammatory cytokines. However, the molecular mechanisms involved in this beneficial effect on β-cells are not yet completely elucidated. Our aim was to evaluate the effect of IL-6 on β-cells exposed to pro-inflammatory cytokines. Results: Pre-treatment with IL-6 sensitized INS-1E cells to cytokine-induced cell death, increasing cytokine-induced iNOS and Caspase-3 expression. Under these conditions, however, there was a decrease in cytokines-induced, p-eIF2-α and p-IRE1expression, proteins related to ER stress. To address if this prevention of adequate UPR response is involved in the increase in β-cells death markers induced by IL-6 pre-treatment, we used a chemical chaperone (TUDCA), which improves ER folding capacity. Use of TUDCA increased cytokines-induced Caspase-3 expression in the presence of IL-6 pre-treatment. However, there is no modulation of p-eIF2-α expression by TUDCA in this condition. Conclusion: Treatment with IL-6 alone is not beneficial for β-cells, leading to increased cell death markers and impaired UPR activation. In addition, TUDCA has not been able to restore ER homeostasis or improve β-cells viability under this condition, suggesting that other mechanisms may be involved.
The Asymmetric Correlation and Causality between the European Union Carbon Market and Fossil Energy Markets before and after COVID-19
Authors: Wang Shuo , Chen Xuesheng , Yuan Di , Yan Xiaodong
Published: August 2022

This paper analyzes the correlation and causality between the European Union carbon emission allowance market and international fossil energy markets. Asymmetric correlation is examined using local Gaussian correlation and asymmetric causality is assessed using a quantile Granger causality test. Empirical results show that, after the COVID-19 outbreak, the EU carbon emission market is more correlated to the crude oil market, but it is less linked to the coal futures market. In contrast to the UK natural gas futures market, the EU carbon emission market shows contagion with the US natural gas market. During the COVID-19 pandemic, unidirectional causality from the EU carbon emission market to the fossil energy market has been becoming bidirectional.JEL classification: C22, I18, O13, O52, Q43
Aniline-naphthylamine copolymer as sorbent for needle trap device
Authors: Roostaie Ali , Haddad Reza , Mohammadiazar Sirwan
Published: August 2022

In current work, aniline-naphthylamine copolymers were prepared using electrochemical technique and then applied as a new sorbent for needle trap extraction of some volatile organic compounds from aqueous solution in headspace mode. The scanning electron microscopy and infrared spectrometry techniques were used to characterization of synthesized aniline-naphthylamine copolymers of aniline and naphthylamine. The results showed that aniline-naphthylamine copolymer compared to unmodified polymer, has higher porosity and non-uniform structures. The significant parameters of the sorbent preparation and extraction process such as the type and concentration of polymer, time and voltage of electrochemical deposition, the extraction time and temperatures and salt content were studied and optimized. The modified device is sensitive and fast providing good analytical parameters so that the detection limit of 0.9-2 ng L− 1 and the quantification limit of 3–7 ng L− 1 along with equilibrium time of 20 minutes were obtained. The linearity of method was obtained in the range of 15-1500 ng L− 1 with R2 > 0.9996. The method repeatability was considered at 50 ng L− 1 and relative standard deviations of 3–5% were obtained. To finish, the performance of proposed device was studied via the extraction of selected analytes in real water samples and the relative recovery values were found to be in the range of 94–102%, showing no matrix effect.
Construction of ceRNA network mediated by circRNAs screening from microarray and identification of novel biomarkers for myasthenia gravis
Authors: Kong Xiaotong , Wu Tao , Chen Zhimin , Cai Hanlu , Wang Yu , He Ping , Liu Peifang , Li Lei , Peng Shanshan , Tian Kuo , Wang Jianjian , Zhang Huixue , Wang Lihua
Published: August 2022

Background:
Recent studies have revealed that circRNA can serve as ceRNA to participate in the development of multiple autoimmune diseases. However, the ceRNA regulatory mechanism mediated by circRNA in myasthenia gravis is not yet investigated in detail. Our study aims to explore the key circRNA as ceRNA and biomarker for the progression of MG.
Methods:
We used circRNA microarray to explore DECs from MG compared with control. Then we predicted the target miRNA asscociated with DECs and screened miRNAs by the algorithm of random walk with restart. DECM network was constructed to present the relationship of miRNA and circRNA. Based on the miRNAs in DECM, we predicted the target genes from different database. Next, we constructed the circRNA-miRNA-mRNA ceRNA regulated network (CMMC) to identify the hub objects. Protein–protein interaction (PPI) network analysis and module analysis were performed using the genes from CMMC. The GO and KEGG pathway enrichment analysis were carried out to analyze the function of the circRNA via targeting genes. Hypergeometric test was calculated to identify the significant circRNA-gene pairs. Following, we detected the expression of hub-circRNAs by RT-PCR.
Results:
5 up-regulated circRNAs and 16 down-regulated circRNAs were obtained from microarray. 16 circRNAs and 184 miRNAs were screening by RWR algorithm and used to construct DECM. Then, 16 DECs, 184 miRNAs and 127 genes were integrated to construct the CMMC network. Based on CMMC, we identified 5 hub circRNA (hsa_circ_0004183; hsa_circ_0089153; hsa_circ_0035381; hsa_circ_0046669 and hsa_circ_0048764). We found that the expression level of hsa_circ_0004183 and hsa_circ_0035381 were upregulated and hsa_circ_0089153 had the low expression level in MG compared with control. In the end, we considerd that hsa_circ_0004183 or hsa_circ_0089153 may play key roles in the occurence of MG through miR-145-5p/SMAD4 axis.
Conclusions:
We found that hsa_circ_0004183, hsa_circ_0035381 and hsa_circ_0089153 can be seen as the valuable potential novel biomarker for MG. hsa_circ_0004183 or hsa_circ_008915 may participate the pathology of MG via miR-145-5p/SMAD4 axis.
Contextualizing policy implementation, challenges, and plans for improving breast cancer early detection programs in Indonesia
Authors: Yuniar Popy , Kardinah Kardinah , Sinulingga Dian , Kartikawati Anggi , Sirait Lady , Widyastuti Widyastuti , Utomo Budi , Moorin Rachael , Norman Richard , Makate Marshall , Robinson Suzanne
Published: August 2022

Background
Late-stage breast cancer (BC) is commonly diagnosed in limited-resource countries such as Indonesia. The lack of information for decision-making emphasizes the need for efforts to support evidence-informed practice for improving BC early detection in Indonesia. This study attempts to understand the local context evidence on policy implementation, challenges, and plans for enhancing BC early detection programs in Indonesia. The evidence gained from this study will help harness the power of scientific reasoning that shapes theories of how BC early detection intervention works and its operationalization in practice.
Methods
This study engaged three interrelated phases of qualitative methods. Phase I involved a document analysis in determining the predominant strategy and approach to the landscape of BC early detection programs. Phase II was an in-depth interview to clarify the operationalization of the technical aspect, eliciting stakeholder experiences and their perceptions about the factors supporting or hindering goal achievement. In phase III, two consecutive collaborative expert workshops and a collaborative learning process nested with the Indonesia Project ECHO team for Knowledge Summaries for Comprehensive Breast Cancer Control.
Results
Current BC early detection strategies to downstage women's symptomatic breast abnormalities are considered an essential preparatory step before starting a screening program at the enhanced or maximal level of resources. However, the absence of an integrated cancer registry system renders it impossible to measure the full effect of the program implementation as a public health policy. Emphasis on improving structural barriers during the follow-up of abnormalities, patient navigation for referrals, and a surveillance system to track the times from presentation to diagnosis and diagnosis to treatment is needed for Indonesia's early detection services continuum.
Conclusion
The local context presented in this research increased the usability and usefulness of relevant evidence for decision-makers, thus bridging the gap in translating research findings into healthcare practice for BC early detection in Indonesia. Importantly, attention to providing a clear national guideline, developing a highly interoperable screening registry system, and ensuring the sustainability of pilot sites on mammography screening is critical to the success of expected outcomes.
Comparison of a human acellular dermal matrix and a polypropylene mesh for pelvic floor reconstruction: a randomized trial study in a rabbit model
Authors: Peró Marta , Castells-Sala Cristina , Alserawan Leticia , Casani Laura , Babot Josep Oriol Juan , Jorba Ignasi , Pérez Maria Luisa , Moga Esther , Otero Jorge , López-Chicón Patricia , Badimon Lina , Serrat Anna Vilarrodona , Roda Oriol Porta
Published: August 2022

Non-absorbable polypropylene (PP) meshes have been widely used in surgical reconstruction of the pelvic floor disorders. However, they are associated with serious complications. Human acellular dermal matrices (hADM) have demonstrated safety and efficacy in reconstructive medicine, but their suitability and efficacy at vaginal level is not known. This study compares the biological performance of PP mesh and a newly developed hADM. 20 rabbits were randomized to receive the hADM graft or the PP mesh. Grafts were surgically implanted in the abdominal wall and vagina. After 180 days, grafts were explanted and evaluated. The vaginal mesh extrusion rate was higher in the PP group (33% vs 0%, p = 0.015). Full integration of the vaginal grafts was more frequent in the hADM group, where 35% of the grafts were difficult to recognize. In the PP group, the vaginal mesh was identified in 100% of the animals (p = 0.014). In PP group, the infiltrates had a focal distribution and were mostly located in the internal part of the epithelium, while in the hADM group, the infiltrates had a diffuse distribution. Additionally, the hADM group also presented more B-lymphocytes and less T-lymphocytes. Biomechanical analysis showed that hADM had lower resistance to stress. Moreover, PP mesh stiffness and elasticity were higher. Then, hADM is associated with fewer clinical complications, as well as better tissue integration. However, it shows greater incorporation into the surrounding native tissue, especially in the vaginal location, undergoing a reduction in its biomechanical properties 6 months after implantation.
Allele variation in the ferrochelatase gene in a Chinese pedigree of erythropoietic protoporphyria
Authors: Li Dongliang , Lin Xiaoqing , Ao Xiulan , Fang Jian , Zhang Zhiqiang , Zheng Zhiyong , YAN Yongqin
Published: August 2022

Background: Erythropoietic protoporphyria (EPP) is characterized by photosensitive skin lesions and various liver injuries. EPP is an inherited disease closely related to single nucleotide polymorphisms (SNPs) in the ferrochelatase gene ( FECH ). We aim to analyze FECH mutations in a Chinese pedigree in order to help clarify the disease’s pattern of inheritance. Results: We genotyped the FECH gene in a male proband with EPP with liver injury and in his family members in Fujian, China. Since the FECH allele (IVS3-48C) has been associated with up to 98% of patients with EPP, we investigated this mutation in 200 unrelated controls in Fujian. The deletion shift mutation c.757_761delAGAAG was detected in the proband and his brother, father, two uncles, and grandmother. The proband, his brother and two uncles, all of whom showed photosensitive lesions, carried both the c.757_761delAGAAG allele and the IVS3-48C allele. We also detected the mutant allele IVS8-61_-62delCT in this pedigree. In the 200 unrelated subjects, 31.47% carried the IVS3-48C allele. In a pedigree of EPP, we detected the deletion shift mutation c.757_761delAGAAG, which is the first report of such a mutation in China . Conclusions: Based on our data, the mode of inheritance requires a haplotype formed by two loci, IVS3-48T>Cand c.757_761delAGAAG.
Mitigating local human impacts promotes coral reef persistence under climate change
Authors: Gove Jamison , Williams Gareth , Lecky Joey , Brown Eric , Conklin Eric , Counsell Chelsie , Davis Gerald , Donovan Mary , Falinski Kim , Kramer Lindsey , Kozar Kelly , Li Ning , Maynard Jeffrey , Mccutcheon Amanda , McKenna Sheila , Neilson Brian , Safaie Aryan , Teague Christopher , Whittier Robert , Asner Gregory
Published: August 2022

Coastal ecosystems are disproportionally inhabited by global human population. Consequently, human impacts originating from land and sea combine with climate-driven disturbances to fundamentally restructure nearshore marine ecosystems. These coincident human stressors are especially acute in the tropics where population centres concentrate along shorelines and marine heatwaves increasingly trigger mass coral bleaching and mortality. However, despite decades of research, we lack consensus as to whether local management supports coral reef resilience under climate change. Here we combined recurring reef surveys with a unique time series of land-sea human impacts over a 20-year period that encompassed an unprecedented marine heatwave in Hawaiʻi. Reefs with high fish biomass and reduced land-based impacts such as wastewater pollution had positive coral trajectories pre-disturbance and experienced minimal coral loss following severe heat stress. Concurrent land-sea management resulted in a 3- to 7-fold increase in the probability of a reef having high reef-builder cover four years post-disturbance. International efforts to conserve 30% of Earth’s ecosystems are gaining momentum, but do not intrinsically link land and ocean conservation targets. Our findings suggest coupled land-sea policy measures are required to realise global conservation goals and provide coral reefs with the best opportunity for persistence in our changing climate.
N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability
Authors: Liu Deyin , Li Zhong , Zhang Kun , Jiao Ning , Lu Daigang , Zhou Dawen , Meng Yibin
Published: August 2022

N6-methyladenosine (m6A) modification is pivotal transcripts chemical modification of eukaryotic, which has been identified to play critical roles on tumor metabolic reprogramming. However, the functions of m6A reading protein YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) in osteosarcoma is still unclear. This research planed to investigate the bio-functions and mechanism in osteosarcoma tumorigenesis. Results indicated that YTHDF3 up-regulated in the osteosarcoma tissue samples and cells, and closely correlated to the poor prognosis of osteosarcoma patients. Functionally, gain and loss-of-functional assays illustrated that YTHDF3 promoted the proliferation and aerobic glycolysis of osteosarcoma cells in vitro, and accelerated the tumor growth in vivo. Mechanistically, a m6A-modified PGK1 mRNA functioned as the target of YTHDF3, and YTHDF3 enhanced the PGK1 mRNA stability via m6A-dependent manner. In conclusion, these findings indicated that YTHDF3 functioned as an oncogene in osteosarcoma tumorigenesis through m6A/PGK1 manner, providing a therapeutic strategy for human osteosarcoma.
Healthcare resource utilization and costs among patients with heart failure with preserved, mildly reduced, and reduced ejection fraction in Spain
Authors: Escobar Carlos , Palacios Beatriz , Varela Luis , Gutiérrez Martín , Duong Mai , Chen Hungta , Justo Nahila , Cid-Ruzafa Javier , Hernández Ignacio , Hunt Phillip , Delgado Juan F.
Published: August 2022

Aims
To describe healthcare resource utilization (HCRU) of patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF) in Spain.
Methods
Adults with ≥ 1 HF diagnosis and ≥ 1 year of continuous enrolment before the corresponding index date (1/January/2016) were identified through the BIG-PAC database. Rate per 100 person-years of all-cause and HF-related HCRU during the year after the index date were estimated using bootstrapping with replacement.
Results
21,297 patients were included, of whom 48.5% had HFrEF, 38.6% HFpEF and 4.2% HFmrEF, with the rest being of unknown EF. Mean age was 78.8 ± 11.8 years, 53.0% were men and 83.0% were in NYHA functional class II/III. At index, 67.3% of patients were taking renin angiotensin system inhibitors, 61.2% beta blockers, 23.4% aldosterone antagonists and 5.2% SGLT2 inhibitors. Rates of HF-related outpatient visits and hospitalization were 968.8 and 51.6 per 100 person-years, respectively. Overall, 31.23% of patients were hospitalized, mainly because of HF (87.88% of total hospitalizations); HF hospitalization length 21.06 ± 17.49 days (median 16; 25th, 75th percentile 9–27). HF hospitalizations were the main cost component: inpatient 73.64%, pharmacy 9.67%, outpatient 9.43%, and indirect cost 7.25%. Rates of all-cause and HF-related HCRU and healthcare cost were substantial across all HF subgroups, being higher among HFrEF compared to HFmrEF and HFpEF patients.
Conclusions
HCRU and cost associated with HF are high in Spain, HF hospitalizations being the main determinant. Medication cost represented only a small proportion of total costs, suggesting that an optimization of HF therapy may reduce HF burden.
An Efficient and Intelligent Conference Management System- Desired Services and Features
Authors: Deutschland Aboli H. Patil Livanova , pune Parikshit N. Mahalle VIIT , MCERC Varsha H. Patil , MCERC Swati A. Bhavsar
Published: August 2022

Conferences and Journals serve as a strong platform and media for research work. Organizing a conference is an extensive, difficult and complex process involving many stakeholders. Due to the increasing number of conferences held worldwide and huge submissions at both conferences and journals, quality has become a highly coveted topic. Today number of systems and platforms for organizing conferences with a varying set of services and features are available. Conference organizer has to choose one of the Conference Management System (CMS) for managing the whole event efficiently. This paper presents a set of desired services and features of efficient CMS; and a comparative study of 30 CMS. The key features desired to be included in efficient CMS include-fair reviews, accurate, reliable, fast, online/web-based, fully automatic, secure assuring confidentiality, user-friendly, and scalable system. Though services and features contribute to overall management and performance of the event it is observed that the overall performance of any conference management mainly depends on the peer review process. For fair reviews integration of intelligent reviewer assignment module in the conference management system is need of the day.
Lipin2 ameliorates diabetic encephalopathy via suppressing JNK/ERK-mediated NLRP3 inflammasome overactivation
Authors: Zhang Xiaochen , Huang Shan , Zhuang Ziyun , Han Xiaolin , Yu Shuyan , Hua Mengyu , Liang Zhonghao , Meng Chao , Yin Ling , Zhuang Xianghua , Chen Shihong
Published: August 2022

OBJECTIVES: Diabetic encephalopathy (DE) is a common complication of diabetes in the central nervous system, which can cause cognitive dysfunction in patients. However, its pathophysiological mechanism has not been elucidated, and thus effective prevention and treatment methods are still lacking. Previous studies reported that neuroinflammation involved in the central neuropathy, while lipin2 plays an important role in inflammatory response. Therefore, we aimed to investigate the effects of lipin2 on regulating inflammatory response in the pathogenesis of DE. METHODS: BV2 cells were treated with high glucose and infected with lipin2 overexpression or knockdown virus to observe the cell viability. Then, we constructed a mouse model of DE, and constructed a lipin2 knockdown or overexpression model by injecting lentivirus into the brain with stereotaxis. The expression of lipin2 in inflammatory bodies and related inflammatory factor signaling pathway-related proteins were examined by western blot and quantitative real-time PCR. Morris water maze was used to evaluate the spatial learning and memory of mice.RESULTS: High glucose decreased the expression of lipin2 in BV2 cells, while overexpression of lipin2 in BV2 cells significantly suppressed the inflammatory response and apoptosis induced by high glucose. Meanwhile, the expression of lipin2 was down-regulated in the hippocampus in a DE mice model. Up-regulation of lipin2 in the hippocampus of DE mice inhibited JNK/ERK signaling pathway, reduced NLRP3 inflammasome-mediated inflammatory response, down-regulated IL-1/TNF-α expression, and improved synaptic plasticity and cognitive dysfunction in mice. Conversely, knockdown of lipin2 increased NLRP3 inflammasome overactivation, caused neuronal abnormalities and cognitive impairment in mice. CONCLUSIONS: Lipin2 may play a neuroprotective role in DE by inhibiting JNK/ERK-mediated NLRP3 inflammasome overactivation and subsequent inflammatory responses. It may be a potential therapeutic target for DE therapy.
A Pair-Task Heuristic for Scheduling Tasks in Heterogeneous Multi-Cloud Environment
Authors: Krishnasamy Kamalam Gobichettipalayam , Periasamy Suresh , Periasamy Keerthika , Veerappan Prasanna Moorthy , Thangavel Gunasekaran , Lamba Ravita , Muthusamy Suresh
Published: August 2022

Heterogeneous multi-cloud environments make use of a collection of varied performance rich cloud resources, linked with huge-speed, performs varied applications which are of computational nature. Applications require distinct computational features for processing. Heterogeneous multi-cloud domain well suits to satisfy the computational need of very big diverse nature of collection of tasks. Mapping problem provides an optimal solution in scheduling tasks to distributed heterogeneous clouds is termed NP-complete, which leads to the ultimate establishment of heuristic problem solving technique. Identifying the heuristic which is appropriate and best still exists as a complicated problem. In this paper, to address scheduling collection of ‘n’ tasks in two groups among a set of 'm' clouds, we propose three heuristics PTL (Pair-Task Threshold Limit), PTMax-Min, and PTMin-Max. Firstly to determine the tasks scheduling order, proposed heuristics based on the tasks attributes calculate tasks threshold value. Tasks sorted in descending value of threshold. Group G1 comprises tasks ordered in descending value of threshold. Group G2 comprises remaining tasks ordered in ascending value of threshold. Secondly, tasks form Group 1 are scheduled first based on minimum completion time, and then tasks in Group 2 are scheduled. The proposed heuristicsare compared with existing heuristics, namely MCT, MET, Min-Min using benchmark dataset. Heuristics PTL, PTMax-Min, and PTMin-Max bring out reduced makespan compared to MCT, MET, and Min-min.
Machines Sounding like Older People: Investigating how older adults perceive an emphatic voice assistant in their first interactions
Authors: Yücel Yeliz , Rızvanoğlu Kerem
Published: August 2022

Universal usability is an essential constituent of HCI, but new technologies are not usable by all populations. This deficit highlights the importance of improving the conversational agents' abilities for disadvantaged populations like older adults. Conversational agents hold a great potential to support older adults, which were affected mainly by the Covid-19 pandemic and were the most psychologically damaged population caused by fear and isolation during the outbreak. In this research, we present the results of a mixed study investigating the potential of voice assistants (VA) for older adults. This study aims to identify older adults’ (ranging in age from 65 to 75) perceptions, needs and challenges when interacting with a smart speaker based voice assistant (Google Home) during the first-time user interaction. We aim to explore the effects of VA’s voice characteristics (mature vs young) and the presence of empathic expression (high empathic expression vs low empathic expression) on the social (perceived support and trust) and functional (perceived self-efficacy toward voice assistants) outcomes of 60 (30 male- 30 female) older adults. This study used a voice-based CA prototype through the Wizard of Oz technique and adopted a multi-method approach. Using CASA (Computers are Social Actors) Paradigm and Similarity Attraction Theory as a foundation, our research revealed that expression of high empathy is a powerful motivator for older adults to perceive a VA as a discreet social companion due to their cultural beliefs and biases. However, we found no evidence that the similarity attraction effect works on older adults when the similarity is mediated since a mature voice has no significant impact on perceived support or trust both qualitatively and quantitatively.
Angiotensin II Type I Receptor -168A/G Polymorphism is Associated withIncreased the Risk of Glioma
Authors: TURAN Taylan , ÖZAYDIN Burak , EMMEZ Ömer Hakan , KAYMAZ Ahmet Memduh , GÖNÜL İpek Işık , BOZKURT Melih , GÖNENÇ Aymelek
Published: August 2022

The authors have requested that this preprint be removed from Research Square.
Design of a Quantum circuit for 4-Qubit multiplier using IBM Quantum Computer
Authors: Gudivada A Arunkumar , Panigrahy Asisa Kumar
Published: August 2022

Reversible gates have been one of the emerging research areas in these days. The reversible gates have several applications in the fields of low power CMOS, DNA computing, optical, nanotechnology etc. Quantum computing is one of the fastest and upcoming nanotechnologies that can implement the digital logical circuits using reversible logic gates. In this paper, CNOT, TOFFOLI, FREDKIN and PERES reversible logic gates have been implemented on IBM quantum computer. An efficient one-bit full adder is going to be proposed using the reversible gates like CNOT and TOFFOLI. Later, a 4x4 multiplier will be developed using the proposed one-bit full adder. The proposed multiplier is proved to perform faster calculations compared to the earlier multipliers. The simulation of the presented modules will be done on IBM Quantum computer and the respective probabilities can be observed for different inputs.
Too close for comfort? Attitudes of gynecologic oncologists toward caring for dying patients
Authors: Hmaidan Sarah , Goulder Alison , Bos Lia , Shen Megan , Wellman JD , Prescott Lauren , Brown Alaina
Published: August 2022

PurposeTo assess the association between gynecologic oncologists’ stigma and palliative care referrals among advanced cancer patients. MethodsGynecologic oncologists were surveyed using validated measures to assess stigmatizing attitudes toward palliative care, anticipated stigma of palliative care, acceptance of palliative care, and willingness to refer to palliative care. Descriptive statistics were calculated. Analysis was performed using linear regression.Results1200 physicians received the survey and 108 (9%) completed it. Most were female (69.4%) and white (82.4%). Most practiced in academics (64.8%) in urban environments (71.3%). Respondents did not have anticipated stigma surrounding palliative care referral (mean score 1.89, range 1-7, higher score indicating more stigma), were accepting of palliative care (mean score 1.45, range 1-7, higher score indicating less acceptance), and were willing to refer patients to palliative care (mean score 5.75, range 1-7, higher score indicating more willingness to refer). Linear regression demonstrated females had less anticipated stigma surrounding palliative care (B=-0.213, p=0.04) and higher acceptance of palliative care (B=-0.244, p=0.01). Most surveyed derived satisfaction from work with advanced cancer patients (83%). Nineteen percent were depressed by managing advanced cancer patients. One fourth felt emotionally burned out by dealing with too many deaths. ConclusionsMost gynecologic oncologists did not exhibit stigma surrounding palliative care and derive satisfaction from their work. Some gynecologic oncologists experience depression and burnout related to their profession. This close connection with patients as they transition to the end of life may take a toll on providers.
Factors associated with the oral health-related quality of life of patients with temporomandibular disorder after occlusal splint treatment
Authors: Limpuangthip Nareudee , Potewiratnanond Prangtip , Karunanon Varangkana , Buritep Ansaya , Thawai Athitaya
Published: August 2022

Objectives
To determine the oral health-related quality of life (OHRQoL) of temporomandibular disorder (TMD) patients after occlusal splint treatment, and to investigate the associated factors.
Materials and methods
This cross-sectional study comprised 227 TMD patients. The dependent variable was OHRQoL determined by telephone interview using the 14-item Oral Health Impact Profile (OHIP-14) questionnaire. The independent variables were collected from dental record, comprising age, sex, treatment duration, clinical diagnosis, clinical parameters, and pain perception. The TMD patients were diagnosed as having masticatory muscle disorders (TMDM), temporomandibular joint (TMJ) disorders (TMDJ), or combined muscle and TMJ disorders (TMDC). Bivariate analyses were performed and multivariable linear regression was used to analyze the factors associated with the OHIP-14 score.
Results
The bivariate analyses demonstrated higher OHIP-14 scores in being younger, females, having TMDC, and lower mouth opening distance. The multivariable analysis demonstrated the association of higher OHIP-14 scores with being younger and having TMDC. The participants with TMDC demonstrated greater improvement in unassisted mouth opening distance, compared with the other clinical diagnosis groups.
Conclusions
After TMD treatment, oral health impact problems remained, but with low frequency. Better OHRQoL after TMD treatment was found in older and TMDC patients.
Correlation between systolic blood pressure and alanine aminotransferase in children and adolescents with short stature based on growth hormone peak
Authors: Jiang Mingming , Zhang Xinran , Zhao Qianqian , Zhang Mei
Published: August 2022

Objective: This study aimed to investigate the relationship between systolic blood pressure (SBP) and alanine aminotransferase (ALT) in children and adolescents with short stature based on growth hormone peak (peak GH).Methods: In this study, 1151 patients diagnosed with short stature in the Shandong Growth and Developmental Disease Follow-up Study Cohort were included and anthropometric and biochemical parameters were measured. In accordance with the peak GH level in the growth hormone challenge test, all subjects were divided into three groups to determine the correlation between SBP and ALT in children and adolescents with schizophrenia: peak GH < 5 ng/mL, 5 ng/mL ≤ peak GH < 10 ng/mL and peak GH ≥ 10 ng/mL. Cross-sectional analysis of the correlation between SBP and ALT in children and adolescents with short stature.Result: The serum ALT levels in the GH peak <5 ng/mL and 5 ng/mL ≤GH < 10 ng/mL groups were elevated compared with those in the GH peak ≥10 ng/mL group. Univariate analysis showed a significant positive correlation between SBP and ALT in subjects with peak GH <5 ng/mL and 5 ng/mL ≤ peak GH < 10 ng/mL (P < 0.05). After adjusting for possible confounding factors, further smooth curve fitting found a nonlinear relationship between SBP and ALT. Further analysis of threshold effects showed that in the GH peak < 5 ng/mL group, the serum ALT levels increased with SBP when SBP reached 116 mmHg (β 0.35; 95% CI 0.04, 0.67; P = 0.029). In the 5 ng/mL ≤ GH < 10 ng/mL group, the serum ALT levels increased with SBP when SBP reached 106 mmHg (β 0.19; 95% CI 0.05, 0.34; P = 0.010). However, in subjects with peak GH <5 ng/mL and 5 ng/mL ≤ peak GH <10 ng/mL, no correlation was observed when the SBP levels does not reach the inflection point. The relationship between serum ALT levels and SBP was not significant in the GH peak ≥10 ng/mL group (β 0.05; 95% CI −0.02, 0.11; P = 0.140).Conclusion: The serum ALT levels in the GH peak < 5 ng/mL and 5 ng/mL ≤GH peak < 10 ng/mL groups were elevated compared with those in the GH peak ≥ 10 ng/mL group and a nonlinear relationship was found between SBP and ALT. When SBP reached the inflection point, the serum ALT levels were positively correlated with the increase in SBP. Future research is required to explore this relationship and mechanism.
Complete genome sequence of a novel mycovirus from Pleurotus citrinopileatus
Authors: Li Xuefei , Li Shiyu , Yin Weiqi , Sossah Frederick Leo , Song Bing , Li Yu , Bo Zhang
Published: August 2022

The complete genome sequence of a novel single-stranded [+ssRNA] positive-sense (+) RNA mycovirus, designated as "Pleurotus citrinopileatus ourmiavirus 1" (PcOV1), isolated from the Pleurotus citrinopileatus strain CCMJ2141, was determined. The complete genome of PcOV1 is composed of 2,535 nucleotides long. It contains a single open reading frame (ORF), which encodes a protein of 657 amino acids (aa) showing conserved domains of RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis based on the RdRp revealed that PcOV1 is a new member of the genus ourmiavirus in the family Botourmiaviridae. This is the first virus characterized in P. citrinopileatus.
Bilimbi (Averrhoa bilimbi) fruit derived carbon dots for dual sensing of Cu(II) and quinalphos
Authors: Venugopalan P. , Vidya N.
Published: August 2022

Synthesis of highly fluorescent carbon dots from an agro crop through facile one-pot microwave method has been reported. Bilimbi fruit derived carbon dots named as BCDs, exhibited excellent photoluminescent properties and stability. Fluorescence of the system selectively quenched on interaction with Cu(II), due to the complex formation between amine, hydroxyl and carboxyl groups in the surface of the BCDs with Cu(II). The non-fluorescent complex displayed a selective and sensitive turn-on fluorescence behavior on adding organophosphorus pesticide quinalphos. And hence, the prepared system is used for dual sensing purposes with nanomolar level of detection limits. The limit of detection of Cu(II) and quinalphos was estimated as 115 nM and 510 nM, respectively. The entire detection process was visible under UV light of 365 nm. Moreover, the BCDs@Cu(II) nanoprobe was effectively applied as fluorescence sensor of quinalphos in real samples of rice and tea where its presence is frequently reported, with good level of recovery percentages.
Early urate-lowering therapy in gouty arthritis with acute flares: a double-blind placebo controlled clinical trial
Authors: Yang Deng-Ho , Chen Hsiang-Cheng , Wei James Cheng-Chung
Published: August 2022

Background
Gouty arthritis (GA) is a chronic systemic disease with recurrent acute monoarthritis. In a previous study, a higher incidence of acute flares was observed during the initial marked decrease in serum urate level. Our study evaluated the effect of early urate-lowering therapy in patients with acute GA flares.
Methods
This study included 40 patients with acute GA; of them, 20 received colchicine 0.5 mg colchicine twice daily, while 20 received probenecid 500 mg and colchicine 0.5 mg twice daily. We evaluated GA severity and laboratory data for two weeks after the initial therapy.
Results
Rapidly decreasing serum uric acid levels was found in the patients treated with probenecid and colchicine compared with the patients treated with colchicine alone on day 8 (-1.77 ± 2.037 vs 1.24 ± 2.084; P < 0.0001). However, the mean decrease in visual analog scale score did not differ significantly between the two groups (-5.20 ± 3.09 vs -3.63 ± 2.38; P = 0.079).
Conclusion
No significant increase was noted in acute gout flare severity or duration among GA patients treated with early aggressive control of hyperuricemia using probenecid plus colchicine.
Leisure time activities in adolescents predicts problematic technology use
Authors: Ibabe Izaskun , Albertos Aranzazu , Burgo Cristina López-del
Published: August 2022

Introduction. The problematic use of technology of children and adolescents is becoming a growing problem. Research has shown that excessive technology use predict a variety of psychological and physical health problems. The aim of this study was to analyze the role of leisure time activities (structured and unstructured) in adolescents as a predictor of problematic technology use. Method. Participants were 7,723 adolescents of which 55% were girls from four Spanish-speaking countries (Chile, Spain, Mexico, and Peru) between the ages of 13 and 18 years. The evaluation instrument applied was the YOURLIFE project self-report questionnaire. Two executive functions were measured: goal setting and inhibitory control. Results. Using structural equation modeling, findings indicated that structured leisure time activities predicted less PTU, whereas unstructured activities predicted more PTU, MLχ2 (69, N = 7,723) = 806.60; CFI= .929, RMSEA= .042, and the model had good predictive capacity for PTU (R2 = .46). Structured and unstructured activities also showed indirect effects on PTU through executive functions. Conclusions. As adolescents spent more time in unstructured leisure activities, poorer goal setting, inhibitory control skills, and more PTU were found. The opposite was right for structured leisure time activities. Implications of structured leisure activities to develop executive functioning and to prevent PTU for adolescents are discussed.
E - RiCoBiT – II : A High Performing RiCoBiT (Ring Connected Binary Tree) Topology With Fully Adaptive Routing Algorithm
Authors: Sanju V , Manvi Sunilkumar
Published: August 2022

Network on Chip (NoC) is very useful in connecting the different components of a chip. Many NoC topologies like 2D mesh, torus etc. are already in use. RiCoBiT (Ring Connected Binary Tree) is a new topology which was recently proposed and studied. RiCoBiT is a topol-ogy where performance parameters like maximum hop and average hop are better than the other topologies. Area parameters like wire-length and number of wire segments are approximately the same as compared to other topologies, but one of the biggest problems with this topology was the lack of an adaptive routing algorithm. Thus, we propose a new routing algorithm which is adaptive in nature. The algorithm is tested for all cases: destination and source in the same ring, destination is above the source ring, and the destination is below the source ring. The testing of the algorithm was performed by using a simulation setup for E-RiCoBiT-II (Enhanced RiCoBiT). It is observed that the topology is 100The average hop, maximum hop, and total time are studied for the proposed architecture and algorithm.