bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding consumer preferences for integration between mobility-as-a-service (MaaS) and tourism transport in China
Authors: LI Wanying , Guan Hongzhi , Han Yan , Wang Hongfei , Liang Weiwei
Published: October 2022

Mobility-as-a-Service can be customized in various forms depending on the regional and activity travel contexts. Unlike the previous studies dealing with the daily trip and general characteristics of MaaS, this study focuses on more specific contexts like MaaS in tourism transport. An online survey and stated preference experiments were conducted for the first time in China to evaluate consumer preference for different MaaS packages bundled with tourism service, and six discrete choice models were constructed which reflects the interaction of propensity to consume with other attributes. Survey results indicate that MaaS in tourism will find a promising market in China, and more than 50 percent of respondents would choose to use MaaS packages. MaaS consumers can be divided into three categories based on average propensity to consume that conservative consumer group has the highest proportion of the sample, followed by moderate consumer group and aggressive consumer group. Model estimations illustrate those factors affecting whether to subscribe to the MaaS package mainly include MaaS app-related attributes, social environment, and the living location of the respondents; individual socio-demographics, tour preference, and daily travel habits have influences on their choice behaviors of MaaS service pattern. It also reveals that the interaction items of propensity to consume and package-related attributes (i.e., subscription price, period of validity, and tourism preferential price) play significant and heterogeneous roles to consumer interests and preferences for MaaS in tourism.
Combined effect of sarcopenia and osteoporosis on the prevalence of mild cognitive impairment in Chinese community-dwelling old adults
Authors: Sun Yuechao , Zheng Yue , Chen Xiaoyu , Han Peipei , Zhang Xinyue , Meng Shixing , Zhao Chenyang , Xu Che , Zheng Yaqing , Zhang Ziwei , Li Ming , Guo Qi
Published: October 2022

Purpose: The study aimed to explore the single and combined effects of sarcopenia and osteoporosis on the prevalence of mild cognitive impairment (MCI) in a Chinese community-dwelling elderly population.
Patients and methods: A total of 1268 community-dwelling participants aged ≥ 60 in Shanghai of China from 2019 to 2020. The dual-energy X-ray image of forearm bone of each participant whose T score is less than -2.5 is defined as osteoporosis. Sarcopenia was diagnosed according to the 2019 Asian sarcopenia working group (AWGS) standard. The Mini Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scales were used to diagnose MCI patients.
Results: This study was conducted on 1,268 (30.4% male) Chinese community-dwelling participants with a mean age of 71.8±5.8 years. The prevalence of MCI was significantly greater in the cooccurring group (OR=3.11, 95% CI=1.88-5.17) than in the sarcopenia alone group (OR=1.80, 95% CI=1.04-3.10) or osteoporosis alone group (OR=1.67, 95% CI=1.16-2.41) in unadjusted model. After adjusting for potential confounding factors, the results remained the same (OR=2.51, 95% CI=1.36-4.64).
Conclusion: In our study, although sarcopenia and osteoporosis did not independently affect the prevalence of MCI, the joint of the osteoporosis and sarcopenia can synergistically increase the prevalence of MCI in Chinese community-dwelling older adults.
HSP90/c-Myc Axis regulated by lncRNA LINC00461 upregulation inhibited the ubiquitination of c-Myc and promotes glucose Metabolism and proliferation through LDHA in Triple-negative Breast Cancer
Authors: Feng Xiulai , Liu HuiFang , Lu Zinan , Qiao Lei , Ma Bin , Guo Wenjia , Sun Gang
Published: October 2022

LINC00461 represents a new long noncoding RNA. However, it is unclear whether LINC00461 is associated with glucose metabolism and proliferation in triple-negative breast cancer. Here, we show that LINC00461 overexpression induces glucose metabolism and proliferation in TNBC, whereas its downregulation markedly reduces glucose metabolism and proliferation. Mechanistically, LINC00461 might function in TNBC by binding with HSP90. Then, it enhances the interaction between HSP90 and c-Myc and inhibits ubiquitination and degradation of c-Myc to regulate c-Myc target genes-LDHA. Clinically, LINC00461 has tight associations with tumor grade and TNM in cancer patients. There is compelling evidence LINC00461 may be exploited as a possible novel molecular marker and therapeutic target in TNBC.
The Ecuadorian extract -BIRM- induces in vitro antitumor effects on CF41.Mg canine mammary carcinoma cells
Authors: Gallmeier Michelle , Guzmán Sofía , Cruz Pamela , Reyes Fernando , Torres Cristian G.
Published: October 2022

Mammary tumors are the most frequent tumor disease in female dogs. Since conventional therapies as surgery and chemo are of partial utility, especially in histological high-grade carcinomas, are non-selective and can trigger potential adverse effects, it is necessary to study new and harmless antitumor treatment alternatives. Commercial herbal extract derived from Kalanchoi gastonis-bonnieri -BIRM- has been used empirically for cancer, however, there are few studies that reveal its antitumor potential. BIRM induces an antiproliferative and pro-apoptotic effect, mainly on androgen-dependent human prostate carcinoma cells. It attractive to analyze whether BIRM also induces antiproliferative effects on CF41.Mg canine mammary carcinoma cells, a cell line representative of high-grade mammary tumors. For this purpose, proliferation of CF41.Mg and non-tumorigenic MDCK cells were studied in the presence of herbal extract. In addition, the effect of BIRM on apoptosis and invasive ability of tumor cells was analyzed. BIRM decreased cell proliferation on both cell types, effects that were concentration dependent. Moreover, the extract induced apoptosis and a decrease in the invasiveness of CF41.Mg cells. In conclusion, BIRM triggers a non-selective antiproliferative effect on CF41.Mg cells, diminishing their invasion ability. These outcomes may support future clinical trials involving this plant extract in dogs with high-grade mammary carcinoma.
Ultrafast, autonomous self-healable iontronic skin exhibiting piezo-ionic dynamics
Authors: Boahen Elvis K. , Pan Baohai , Kweon Hyukmin , Kim Joo Sung , Choi Hanbin , Kong Zhengyang , Zhu Jin , Ying Wu Bin , Lee Kyung Jin , Kim Do Hwan
Published: October 2022

The self-healing properties and ionic sensing capabilities of the human skin offer inspiring groundwork for the designs of stretchable iontronic skins. However, from electronic to ionic mechanosensitive skins, simultaneously achieving autonomously superior self-healing properties, superior elasticity, and effective control of ion dynamics in a homogeneous system is rarely feasible. Here, we report a Cl-functionalized iontronic pressure sensitive material (CLiPS), designed via the introduction of Cl-functionalized groups into a polyurethane matrix, which realizes an ultrafast, autonomous self-healing speed (4.3 µm/min), high self-healing efficiency (91% within 60 min), and mechanosensitive piezo-ionic dynamics. This strategy promotes both an excellent elastic recovery (100%) and effective control of ion dynamics because the Cl groups trap the ions in the system via ion-dipole interactions, resulting in excellent pressure sensitivity (7.36 kPa-1) for tactile sensors. The skin-like sensor responds to pressure variations, demonstrating its potential for touch modulation in future wearable electronics and human–machine interfaces.
Temporal Evolution and Differential Patterns of Cellular Reconstitution after Therapy for Childhood Cancers
Authors: Hofmann Gina , Zierk Jakob , Sobik Bettina , Wotschofsky Zofia , Sembill Stephanie , Krumbholz Manuela , Metzler Markus , Karow Axel
Published: October 2022

The cellular reconstitution after childhood cancer therapy is associated with the risk of infection and efficacy of revaccination. Many studies have described the reconstitution after stem cell transplantation (SCT). The recovery after cancer treatment in children who have not undergone SCT has mainly been investigated in acute lymphoblastic leukemia (ALL), less for solid tumors. Here, we have examined the temporal evolution of total leukocyte, neutrophil and lymphocyte counts as surrogate parameters for the post-therapeutic immune recovery in a cohort of n = 52 patients with ALL in comparison to n = 58 patients with Hodgkin`s disease (HD) and n = 22 patients with Ewing sarcoma (ES). Patients with ALL showed an efficient increase in blood counts reaching the age-adjusted lower limits of normal between 4 and 5 months after the end of maintenance therapy. The two groups of patients with HD and ES exhibited a comparably delayed recovery of total leukocytes due to a protracted post-therapeutic lymphopenia which was most pronounced in patients with HD after irradiation. Our results underline that the kinetics of cellular reconstitution after therapy for HD and ES differ significantly from ALL and depend on treatment regimens and modalities. This suggests a need for disease- and treatment-specific recommendations concerning the duration of infection prophylaxis and the timing of revaccination.
Prevalence of arterial stiffness and factors associated with arterial stiffness in rheumatoid arthritis patients without cardiovascular disease symptoms: a cross- sectional study
Authors: Nilmoje Thanapon , Aiewruengsurat Duangkamol , Tirasathit Pawita , Juthong Siriporn , Hiranyachattada Siriphun , Chongsuvivatwong Virasakdi
Published: October 2022

Asymptomatic peripheral arterial stiffness is an intermediary outcome of atherosclerosis which leads to cardiovascular morbidity and mortality in rheumatoid arthritis (RA) patients. We conducted this study to determine the prevalence of arterial stiffness as measured by cardio-ankle vascular index (CAVI) in RA patients compared to controls, and to assess factors associated with arterial stiffness in RA patients. This stratified cross-sectional study was performed on 48 confirmed RA patients without overt cardiovascular disease and 51 controls matched for age and sex. All subjects underwent CAVI and ankle-brachial index (ABI). Arterial stiffness prevalence measured by CAVI was significantly high in the RA group (18.8%) than that in the control (17.6%). So was the respective difference in mean (SD) 8.2 (1.1) vs 7.7 (1.2). No subject in either group had abnormal ABI. Independent variables associated with high CAVI values included low and moderate disease activity, high age and high systolic blood pressure (SBP). This study may imply cardiovascular benefit to reduce RA disease activity especially among those with existing other cardiovascular risk factor.
Diagnosis of Serious Conditions Delayed in Association with Ondansetron Treatment for Vomiting in the Pediatric Emergency Department
Authors: Soffer Gili Palnizky , Schnapp Zeev , Miroluz Dana , Rimon Ayelet
Published: October 2022

We evaluated the characteristics and sought risk factors for hospitalization in children who return to the emergency department (ED) within 7 days of discharge after oral or intravenous ondansetron treatment for vomiting. The secondary aim was to determine whether the diagnosis of any serious condition had been delayed as the result of discharge after ondansetron treatment. This retrospective analysis of the medical records of children who had been treated for vomiting with ondansetron in a tertiary care pediatric ED and revisited the ED within 7 days was performed between 2017 and 2019. We compared demographic and clinical features as well as management between hospitalized and discharged patients, focusing upon potentially delayed diagnoses of serious conditions. Fifty of the 89 ondansetron treated children (56.2%) who revisited the ED were discharged home after their second ED visit and the remaining 39 (43.8%) were hospitalized. No parameter of the management of the first visit was predictive of the outcome of the revisit. Five revisit patients (5.6%) were newly diagnosed with a serious condition, with intussusception and ovarian torsion being the most substantial time-sensitive delays (the other diagnoses were pneumonia and aseptic meningitis).
Conclusion: Physicians assessing patients who had been treated with ondansetron as supportive care for vomiting at an earlier visit to the pediatric ED should consider alternative diagnoses despite initial clinical improvement. No definitive risk factor for readmission was identified, but a high level of alertness to a possible meningeal or acute abdominal source is imperative.
Overlapping filter-bank convolutional neural network for multisubject multicategory motor imagery BCI
Authors: Luo Jing , Mao Qi , Shi Zhenghao , Ren Xiaorong , Hei Xinhong
Published: October 2022

Background
Recently, CNN-based models have been widely used in motor imagery brain-computer interfaces (BCIs) due to their powerful feature representation ability. However, in multisubject motor imagery BCI, the discriminative frequency bands vary from subject to subject. Thus, using CNNs to extract discriminative features from EEG signals of different frequency components is a promising method in multisubject EEG recognition.
Methods
This paper presents a novel overlapping filter-bank CNN to incorporate discriminative information from multiple frequency components in multisubject motor imagery recognition. Specifically, two overlapping filter banks with fixed low-cut frequency or sliding low-cut frequency are employed to obtain multiple frequency component representations of EEG signals. Then, multiple CNN models are trained separately. Finally, the output probabilities of multiple CNN models are integrated to determine the predicted EEG label.
Results
Experiments were conducted based on three popular CNN backbone models and two public datasets. We compared the performance of overlapping filter-bank CNN with the state-of-the-art methods and traditional nonoverlapping-based CNN, and the results showed that the overlapping filter-bank CNN was efficient and universal in improving multisubject motor imagery BCI performance.
Conclusion
The proposed overlapping filter bank CNN framework with fixed low-cut frequency is an efficient and universal method to improve the performance of multisubject motor imagery BCI.
A randomized clinical trial of innate immunity restoration by branched-chain amino acid granules in cirrhosis patients
Authors: Chamroonkul Naichaya , Rujeerapaiboon Natthapat , Sripong Pimsiri , Kaewdech Apichat , Piratvisuth Teerha
Published: October 2022

Background

Infection among cirrhotic patients results in major morbidity and mortality. Reduction in phagocytic activation, as part of immunoparesis, is a distinctive key component of cirrhosis-associated immune dysfunction (CAID) and predicts the development of infection. However, there are limited data on immunotherapeutic approaches to restore phagocytosis. We aimed to determine the effect of branched-chain amino acid (BCAA) granules on phagocytic activity in patients with CAID.

Method

In this double-blind randomized controlled trial, participants were randomly assigned (1:1 ratio stratified by Child–Pugh status) to receive either BCAA granules or placebo. In the 3rd and 6th months, phagocytic activity was assessed by flow cytometry. The primary endpoint was the restoration of innate immunity at the 6th month, defined as ≥ 75% phagocytic activity; the secondary endpoints were the accretion of phagocytic activity and hospitalization due to infection.

Results

Thirty-seven patients were included. There were no differences among the patients in the baseline characteristics and phagocytic activity. At the 6th month, a higher proportion of patients with phagocytic restoration was observed in the BCAA granule group than in the placebo group (68% vs. 5.6%, p < 0.001). The mean phagocytic activity was 75.4% and 63.4% in the BCAA granule and placebo groups, respectively (p < 0.001). Progressive accretion of phagocytic activity was observed during the 3rd and 6th months. There was no difference in hospitalization due to infection (3 vs. 2 events, p = 0.487).

Conclusion

BCAA granules significantly restore phagocytic activity across various stages of cirrhosis. A longer follow-up period is required to demonstrate infection prevention.
Trial registration: www.clinicaltrials.in.th (TCTR20190830005)
Health oil preparation from gardenia seeds by aqueous enzymatic extraction combined with puffing pre-treatment and its properties analysis
Authors: Jin Chengyu , Wang Lingyun , Liu Xiaoying , Lu Yuanchao , Yu Ningxiang , Ye Qin , Nie Xiaohua , Meng Xianghe
Published: October 2022

Gardenia jasminoides Ellis, a typical representative for “homology of medicine and food”, can be used to produce gardenia yellow and edible oil. Here, aqueous enzymatic extraction (AEE) combined with puffing pre-treatment was explored to prepare oil from gardenia seeds. Free oil yield (FOY) by AEE was evaluated in term of selection of enzyme, enzyme combination, as well as puffing ways and conditions. Results suggested that seeds taken as raw materials were better than whole fruit, sequential hydrolysis was superior to single enzymatic hydrolysis. Both wet-heating puffing at 90℃ and dry-heating puffing at 1.0MPa facilitated the release of free oil by AEE, while FOY produced the highest oil yields of 21.8% and 23.2% within 3h, and 58.3%, 68.4% higher than that of un-puffed group, active crocin and geniposide were also completely released. The FOY obtained in this study was far higher than pressing method (10.44%), and close to solvent extraction (25.45%). Also, microstructure analysis indicated that gardenia seeds expanded by dry-heating puffing (1.0MPa) had larger and rougher surface and porous structure than other groups. Moreover, there was no significant difference between oils prepared by various methods in term of nutritional and safety characteristics. AEE coupled with puffing pre-treatment developed is an eco-friendly extraction technology with high efficiency that can be employed to oil preparation enriched with active crocin and geniposide from gardenia seeds.
Cost analysis of hospital-at-home services vs. in-patient medical wards
Authors: Frvd Natalia , Weinstein Orly , shiber shachaf
Published: October 2022

Objective: Hospital-at-home schemes have been widely adopted as an alternative to in-hospital treatment for acutely ill patients. However, their impact on hospital costs remains unclear.
Study setting: we calculated the costs during the index admission and 30 days later of 131 randomly selected acutely ill patients attending a tertiary medical center in 2011-2021 who met the inclusion criteria for hospital-at-home care. study design: findings were compared to a simulation of the same cohort based on assumptions of potential costs and outcomes under a hospital-at-home program.
principal findings: hospital-at-home care was found to incur higher costs during the index admission (+30%) and 30 days after (+14%). It remained costlier on most subpopulation and sensitivity analyses, except when patients were readmitted within 30 days of the index admission (-27%), owing to 30% lower hospital-at-home labor costs, and if the predicted index admission days were decreased by 10% in the hospital-at-home scheme (-11%).
Conclusions: under the assumptions made, there may not be a clear and robust cost reduction to hospitals by the mere application of a hospital-at-home scheme.
Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes
Authors: Liu Zhijie , Xu Yue , Wang Wenxuan , Guo Bin , Guo Xiaolan , Zhang Guoyuan , Luo Guangcheng , Wang Qiang
Published: October 2022

Background and aims

Hepatocellular carcinoma (HCC) is difficult to diagnose and has a low survival rate. The survival of patients with HCC is closely related to the stage of diagnosis. Using logistic regression model, this study aimed to identify risk factors associated with HCC and establish a risk prediction model based on clinical characteristics and liver-related indicators to predict the presence of HCC.

Methods

The clinical data of patients in Affiliate Hospital of North Sichuan Medical College from 2016 to 2020 were collected. Based on the time of admission, the cases were divided into training cohort (n = 1739) and validation cohort (n = 467). Using HCC as a dependent variable, the research indicators were incorporated into logistic univariate and multivariate analysis. An HCC risk prediction model, which was called NSMC-HCC model, was then established in training cohort and verified in validation cohort.

Results

The area under receiver operating characteristic curve (AUC) of NSMC-HCC model in HCC diagnosis was 0.960, with sensitivity 94.40% and specificity 95.35% in training cohort, and AUC was 0.966, with sensitivity 90.00% and specificity 94.20% in validation cohort. In early-stage HCC diagnosis, the AUC of NSMC-HCC model was 0.946, with sensitivity 85.93% and specificity 93.62% in training cohort, and AUC was 0.947, with sensitivity 89.10% and specificity 98.49% in validation cohort.

Conclusions

NSMC-HCC model was an effective risk prediction model in HCC and early-stage HCC diagnosis.
Phosphorylation disrupts long-distance electron transport in cytochrome c
Authors: Gomila Alexandre , Pérez-Mejías Gonzalo , Hill Alba Nin , Guerra Alejandra , Casas-Ferrer Laura , Ortiz-Tescari Sthefany , Díaz-Quintana Antonio , Samitier Josep , Rovira Carme , Rosa Miguel A. De la , Díaz-Moreno Irene , Gorostiza Pau , Giannotti Marina , Lagunas Anna
Published: October 2022

It has been recently shown that electron transfer (ET) between mitochondrial cytochrome c (Cc) and the cytochrome c1 subunit of the cytochrome bc1 (Cc1) and Cc can proceed at long-distance through the aqueous solution. Cc is thought to adjust its activity by changing the affinity for its partners via Tyr48 phosphorylation, but it is unknown how it impacts the nanoscopic environment, interaction forces, and long-range ET. Here, we constrain the orientation and separation between Cc1 and Cc or the phosphomimetic Y48pCMF Cc, and deploy an array of single-molecule, bulk, and computational methods to investigate the molecular mechanism of ET regulation by Cc phosphorylation.. We demonstrate that phosphorylation impairs long-range ET, shortens the long-distance charge conduit between the partners, strengthens their interaction, and departs it from equilibrium. These results unveil a nanoscopic view of the interaction between redox protein partners in electron transport chains and its mechanisms of regulation.
Age and Sex Differences in the Eμ-TCL1 adoptive transfer mouse model of CLL
Authors: Sharpe Chia , Perry Elizabeth , Muthusamy Natarajan , Hertlein Erin , Byrd John C.
Published: October 2022

Background:The Eμ-TCL1 syngeneic model is the most widely used mouse model of chronic lymphocytic leukemia and has been extensively used to understand the pathogenesis of select genes, the effect of the immune microenvironment and for pre-clinical drug development studies. Recently there has been an increasing awareness of the impact of age and sex differences on not only the development of cancers but also the efficacy and toxicity of specific cancer therapies. However, despite the predominance of older males in CLL patient demographics, the Eμ-TCL1 adoptive transfer studies have used almost exclusively young female recipient mice.
Methods:In this study we performed primary and secondary adoptive transfer experiments in order to understand the impact of recipient age and sex on the development of disease as assessed by flow cytometry and survival in the Eμ-TCL1 adaptive transfer model.
Results:We found that young female recipients had pro-longed survival in a primary adoptive transfer, however sex differences were not observed in a subsequent secondary adoptive transfer experiment. Furthermore, while recipient age did not have a significant effect on the rate of disease establishment or survival in female mice, aged male mice had a significantly decreased rate of Eμ-TCL1 tumor engraftment.
Conclusions:These findings suggest that age and sex differences must be considered in the experimental design of studies using the Eμ-TCL1 adaptive transfer model of CLL.
Rapid combinatorial rewiring of metabolic networks for enhanced poly(3- hydroxybutyrate) production in Corynebacterium glutamicum
Authors: Yim Sung Sun , Choi Jae Woong , Lee Yong Jae , Jeong Ki Jun
Published: October 2022

Background: The disposal of plastic waste is a major environmental challenge. With recent advances in microbial genetic and metabolic engineering technologies, microbial polyhydroxyalkanoates (PHAs) are being used as next-generation biomaterials to replace petroleum-based synthetic plastics in a sustainable future. However, the relatively high production cost of bioprocesses hinders the production and application of microbial PHAs on an industrial scale.
Results: Here, we describe a rapid strategy to rewire metabolic networks in an industrial microorganism, Corynebacterium glutamicum, for the enhanced production of poly(3-hydroxybutyrate) (PHB). A three-gene PHB biosynthetic pathway in Rasltonia eutropha was refactored for high-level gene expression. A fluorescence-based quantification assay for cellular PHB content using BODIPY was devised for the rapid fluorescence-activated cell sorting (FACS)-based screening of a large combinatorial metabolic network library constructed in C. glutamicum. Rewiring metabolic networks across the central carbon metabolism enabled highly efficient production of PHB up to 29% of dry cell weight, which is the highest PHB content ever reported in C. glutamicumusing a sole carbon source.
Conclusions: We successfully constructed a heterologous PHB biosynthetic pathway and rapidly optimized metabolic networks across central metabolism in C. glutamicum for enhanced production of PHB using glucose or fructose as the sole carbon source in minimal medium. We expect that this FACS-based metabolic rewiring framework will accelerate strain engineering processes for the production of diverse biochemicals and biopolymers.
Charectarization of Groundwater Level Zones Using Innovative Trend & Regression Analysis: Case Study at Rechna Doab-Pakistan
Authors: Abbas Muhammad , Arshad Muhammad , Shahid Muhammad Adnan
Published: October 2022

The authors have requested that this preprint be removed from Research Square.
Combined Non-convex Second-order Total Variation with Overlapping Group Sparsity for Full Waveform Inversion
Authors: fu Hongsun , Qi Hongyu , Gu Ruixue
Published: October 2022

Full Waveform Inversion (FWI) can provide an accurate velocity modelby matching observed and simulated seismograms. Mathematically, FWIis a highly ill-posed inverse problem that the inversion results lackdependence on the observed data. For a stable and reasonable inversion,proper regularization methods have to be taken into account.We proposea novel composite regularization for frequency-domain FWI problem,which uses a non-convex second-order total variation (TV) term and anoverlapping group sparse TV (OGS-TV) regularization term. Comparedwith the conventional TV regularization, our method has better accuracyand robustness, and could effectively make use of the structuralsparsity in the velocity model. Furthermore, the alternating directionmultiplier algorithm with the adaptive selection of the penalty parametersis developed to solve this composite constraint problem, which canimprove the stability of the FWI process. To illustrate the superior performanceof the proposed FWI method both visually and quantitatively,we present several numerical examples through the comparison betweenour FWI method and conventional FWI method with TV regularization.
Phosphoethanolamine reverses aberrant DNA methylation in non-alcoholic steatohepatitis caused by Pcyt2 deficiency
Authors: Grapentine Sophie , Agarwal Prasoon , Dolinsky Vern , Bakovic Marica
Published: October 2022

Background Accumulating evidence links disruptions in phospholipid homeostasis to obesity, type 2 diabetes, and fatty liver diseases. Mice with a heterozygous ablation of the phosphatidylethanolamine (PE) synthesizing enzymePcyt2+/−show reduced PE synthesis and turnover and develop an age-dependent metabolic syndrome that is characterized by impaired fatty acid and glucose metabolism, hypertriglyceridemia, insulin resistance, obesity, and all characteristics of NASH. Aberrant DNA methylation can lead to the onset of pathological phenotypes and is increasingly being implicated in age-related metabolic diseases, including NASH. The methylation of PE to phosphatidylcholine (PC) is a major consumer of liver S-adenosyl methionine (SAM) and thus, alterations in PE metabolism have the potential to influence DNA methylation by modulating SAM availability. Here, we hypothesize that abnormal DNA methylation patterns underly the development ofPcyt2+/−NASH. We conduct an epigenome-wide methylation analysis to determine differential methylation and investigate whether treatment with the Pcyt2 substrate phosphoethanolamine (PEtn) for 8 weeks can reverse aberrant DNA methylation through the stimulation PE synthesis. ResultsPcyt2+/−NASH liver experiences significant alterations in DNA hypo- and hypermethylation relative toPcyt2+/+. Differentially methylated genes belong to pathways including PI3K-Akt signalling pathway, Foxo signalling pathway, oxidative phosphorylation and insulin signalling/secretion indicating that epigenetic regulation underlies many of our previously established pathological mechanisms ofPcyt2+/−NASH. Previously unidentified pathways during Pcyt2 deficiency are highlighted such as cell cycle regulation and cellular senescence that may contribute to NASH development. Treatment with PEtn dramatically reverses aberrant total and protein-coding DNA methylation patterns by 96%. PEtn treatment restored the methylation status of key genes involved in epigenetic modifications and induced differential methylation of genes associated with obesity and T2DM such asAdyc3, Celsr2, Fam63b.Conclusion ThePcyt2+/−liver methylome and transcriptome is altered and likely underlies much of the pathology inPcyt2+/−NASH phenotype. PEtn significantly attenuates aberrant DNA methylation inPcyt2+/−liver by stimulating the CDP:Ethanolamine Kennedy pathway and corrects the epigenetic regulation of genes involved in the pathogenesis of NASH, showing its therapeutic potential. This analysis provides critical insight into the epigenetic basis of NASH pathophysiology and suggests diagnostic markers and therapeutic targets.
Diagnostic performance of total PSA an its derivatives for clinically significant prostate cancer and high-grade prostate cancer
Authors: Wang Changming , Zhang Bin , Zhang Qi , Wang Lei , Wang Ling , Xu Siqin , Tao Tao , Xiao Jun
Published: October 2022

Background: Diagnostic value of total PSA an its derivatives for prostate cancer is still controversial. Our aim is to explore the diagnostic performance of total prostate-specific antigen (tPSA) and its derivatives for clinically significant prostate cancer (csPCa) and high-grade prostate cancer (hgPCa).
Methods: Data of qualified 423 patients who received prostate biopsy from October 2020 to July 2022 was used to accomplish this study. Patient’s clinical characteristics were compared by Mann Whitney U test. Spearman rank correlation analysis was performed to calculate correlation coefficients. Univariate logistic regression analysis was used to screen the related variables of csPCa and hgPCa. Receiver-operating characteristic (ROC) curves and diagnostic tests were performed for assessing the diagnostic value of clinical variables.
Results: Of these 423 patients, 131/423 (31.0%) were diagnosed with csPCa and 103/423 (24.3%) were diagnosed with hgPCa. By plotting ROC curves, PSAD had highest diagnostic accuracy for both csPCa (AUC: 0.840, 95%CI: 0.802-0.874) and hgPCa (AUC: 0.825, 95%CI: 0.785-0.860), tPSA and prostate volume had fair diagnostic value after PSAD, then, f/t PSA only had mediocre performance, but fPSA alone had very low diagnostic value. After stratifying patients into different subgroups of tPSA, prostate volume, PSA density (PSAD) and free/total PSA (f/t PSA). We found the detection rate will obvious rise following by increased tPSA, PSAD and decreased prostate volume, f/tPSA. The results of diagnostic tests found the sensitivity and negative predictive value were 79.4%, 83.0% for tPSA<10ng/ml, 80.8%, 76.2% for f/tPSA>0.20, 95.4%, 93.2% for prostate volume≥70ml and 96.9%, 96.0% for PSAD<0.15 ng/ml2 respectively.
Conclusions: In this study, we evaluated the diagnostic value of tPSA and its derivatives for identification of prostate cancer. For patients with suspected prostate cancer, lower tPSA and PSAD, bigger prostate volume and higher f/tPSA value may mean smaller probability of csPCa.
Aerobic biodegradation of untreated polyester-polyether urethanes by newly isolated yeast strains Exophilia sp. NS-7 and Rhodotorula sp. NS-12
Authors: Giyahchi Minoo , Moghimi Hamid
Published: October 2022

In this study, two polyester-polyether urethane degrading yeasts were isolated from forest soil and wastewater. These isolates were identified through ITS region gene sequencing as two new strains of Exophilia sp. NS-7 and Rhodotorula sp. NS-12. The polyurethanes (PUs) biodegradation ability of two strains was evaluated by urease, protease, esterase, and Impranil® degradation activity assays, Fourier transformed infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM), Sturm test, and Proton nuclear magnetic resonance (H-NMR) spectroscopy. The results showed that Exophilia sp. NS-7 is esterase, protease, and urease positive, and Rhodotorula sp. NS-12 can produce esterase and urease. Both strains can degrade Impranil® as the sole source of carbon with the highest growth rate in 4–6 and 8–12 days, respectively. SEM micrograph revealed PU degradation ability in both strains by showing so many pits and holes in treated films. The Sturm test showed that these two isolates can mineralize PU to CO2, and significant decreases in N-H stretching, C-H stretching, C = O stretching, and N-H/ C = O bending absorption in the molecular structure of PU were revealed by the FT-IR spectrum. The detection of new signals in the H-NMR spectrum after the treatment also confirmed the destructive effects of both strains on PU films.
Renewable Composite Quantile Method and Algorithm for Nonparametric Models with Streaming Data
Authors: Chen Yan , Fang Shuixin , Lin Lu
Published: October 2022

We are interested in renewable estimations and algorithms for nonparametric models with streaming data. In our method, the nonparametric function of interest is expressed through a functional depending on a weight function and a conditional distribution function (CDF). The CDF is estimated by renewable kernel estimations combined with function interpolations, based on which we propose the method of renewable weighted composite quantile regression (WCQR). Then we fully use the model structure and obtain new selectors for the weight function, such that the WCQR can achieve asymptotic unbiasness when estimating specific functions in the model. We also propose practical bandwidth selectors for streaming data and find the optimal weight function minimizing the asymptotic variance. The asymptotical results show that our estimator is almost equivalent to the oracle estimator obtained from the entire data together. Besides, our method also enjoys adaptiveness to error distributions, robustness to outliers, and efficiency in both estimation and computation. Simulation studies and real data analyses further confirm our theoretical findings.
Novel Ultra-Energy-Efficient Reversible Designs of Sequential Logic Quantum-Dot Cellular Automata Flip-Flop Circuits
Authors: Alharbi Mohammed , Edwards Gerard , Stocker Richard
Published: October 2022

Quantum-dot cellular automata (QCA) is a technological approach to implement digital circuits with exceptionally high integration density, high switching frequency, and low energy dissipation. QCA circuits are a potential solution to the energy dissipation issues created by shrinking microprocessors with ultra-higher integration densities. Current QCA circuit designs are nonreversible, yet reversible circuits are known to increase energy efficiency. Thus, the development of reversible QCA circuits will further reduce energy dissipation. This paper presents novel reversible and nonreversible sequential QCA set/reset (SR), data (D), Jack Kilby (JK), and toggle (T) flip-flop designs based on the majority gate that utilizes the universal, standard, and efficient (USE) clocking scheme, which allows the implementation of feedback paths and easy routing for sequential QCA-based circuits. The simulation results confirm that the proposed reversible QCA USE sequential flip-flop circuits exhibit energy dissipation less than the Landauer energy limit. Nonreversible QCA USE flip-flop designs, although having higher energy dissipation, sometimes have floorplan areas and delay times less than those of reversible designs; therefore, they are also explored. The trade-offs between the energy dissipation versus the area cost and delay time for the reversible and nonreversible QCA circuits are examined comprehensively.
CD146+ umbilical cord mesenchymal stem cells exhibit higher immunomodulatory activity and therapeutic efficacy in septic mice
Authors: Zhang Lin , Zhang Xiaoxu , Liu Yubin , Zhang Weiyuan , Wu Chu-Tse , Wang Lisheng
Published: October 2022

Background
Several animal studies have shown that MSCs can significantly improve the survival of sepsis. CD146 + MSCs, a subpopulation of mesenchymal stem cell (MSCs), correlate with high therapeutic and secretory potency. However, their therapeutic effect on sepsis and detail mechanisms about regulation of macrophage have not been explored.
Methods
The effect of CD146+/-MSCs on differentiation of Treg,Th1,Th17 subsets was evaluated by flow cytometry. The paracrine effects of CD146+/-MSCs on RAW264.7 phagocytosis and LPS-stimulated polarization were studied using a co-culture protocol. In addition, we employed Luminex bead array and RNA sequencing analysis to determine the mechanisms of MSCs on LPS-stimulated RAW264.7. The Arg1 protein was detected by Western blot. CD146+/-MSCs were injected into LPS-induced sepsis mice by tail vein. The treatment effect was assessed by organ HE staining, T-cell subsets, cytokine in plasma, peritoneal macrophages, infiltrating monocytes subpopulations.
Results
In vitro, CD146 + MSCs could significantly increase the Treg cells proportion in PBMCs stimulated by PHA. Both CD146+/-MSCs can reduce the proportion of Th1 and Th17 subsets. CD146 + MSCs can increase the phagocytic rate of raw264.7. The RNA sequencing data indicated that UC-MSCs therapy improved LPS-induced raw264.7 through PPAR and cytokine receptor pathways. The differences between the CD146 + and CD146- groups were clustered in arginine metabolism. CD146 + MSCs decreased NO production and increased agr1 expression. CD146 + MSCs secreted higher IL15,IFNγ, VEGF and lower IL1β, IL8 under LPS. In vivo, CD146+/-MSCs treatment can improve the pathological damage of organs caused by LPS. CD146+/-MSCs therapy significantly decreased CD4 expression, increased CD8 expression, and decreased CD4/CD8 ratios, which was similar to that in the normal group. CD146+/-MSCs can reduce IL1β,IL6 content in plasma. The level of IL10 at 24h and CXCL1 at 12h in CD146 + MSCs group was the highest. The phagocytic capacity of peritoneal macrophages in CD146 + MSCs group was better than that in CD146- group and LPS group at 12h. The CD146+/-MSCs had significantly reduced numbers of monocytes in the peritoneal cavity. CD146 + MSCs enhanced the ratios of CD11b + Ly6Clo reparative monocytes and CD11b + Ly6Chi inflammatory monocytes until 24h.
Conclusions
Compared with CD146-MSCs, CD146 + MSCs can accelerates the end of the inflammatory response and have robust anti-inflammatory effects, by increasing the Treg cells, promoting macrophage phagocytosis, enhancing the reparative macrophage, secreting more VEGF, etc.
De novo transcriptome analysis and development of novel EST-SSR markers in Bergenia ciliata (Haw.) Sternb. (Saxifragaceae) through Illumina sequencing
Authors: Singh Harish Chandra , Tiwari Vandana , Tiwari Avinash , Rana Tikam Singh
Published: October 2022

Bergenia ciliata (Haw.) Sternb. is an important herb predominantly found in Indian Himalayan Region (IHR). It is widely used in medicines and healthcare system, cosmetics, food, fodder, and ornamental purposes. Illumina sequencing and de novo transcriptome assembly were carried out in B. ciliata to develop and identify simple sequence repeat markers for genetic diversity and conservation studies. The assembled data generated a total of 65,010 unigenes that showed significant similarities when compared with seven functional databases including 53,577 (Non-Redundant Protein Sequence Database: 82.41%), 44,297 (Nucleotide Sequence Database: 68.14%), 42,287 (Swiss Prot: 65.05%), 15,027 (Eukaryotic Orthologous Groups: 23.11%), 22,540 (KEGG Orthology: 34.67%), 29,477 (Gene Ontology: 45.34%) and 20,609 (Pfam: 31.7%) unigenes. In this study, a total of 18,226 SSRs and 14,497 SSR containing sequences were identified. Dinucleotides were found to be abundant (47.88%) in B. ciliata followed by mononucleotides (35.04%), and trinucleotides repeat (15.90%). AG/CT was the most common di-nucleotide repeat (40.33%). A total of 11,839 EST-SSR primers were designed, of which 96 primer pairs were synthesized randomly. Finally, 18 primer pairs were selected that revealed clear, distinct polymorphic bands when examined in eight diverse B. ciliata accessions. Furthermore, the transcriptome data and the EST-SSR markers will be an important resource for investigating genetic diversity in B. ciliata and other species of the family Saxifragaceae.
Treatment of herpes zoster with brivudin in immunocompromised children
Authors: Vogel Clara , Wetzel Laura , Wutzler Peter , Gruhn Bernd
Published: October 2022

Purpose: Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increases during immunosuppression. Especially immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudin), one of the most potent oral inhibitors of VZV replication, is widely used in therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudin in immunocompromised children to provide an outpatient treatment option.
Methods: In this prospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudin was administered orally at a single dose of 2-5 mg/kg per day. We monitored the patients’ response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred.
Results: Patients received medication for 7-21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications.Crusting of lesions was reached after 3-14 days (median: 6 days). Full healing of skin lesions was ascertained within 7-21 days (median: 12 days). Overall, brivudin therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner.
Conclusion: Oral brivudin was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers potential for outpatient treatment of HZ in these patients.
Optimization of job shop scheduling problem based on deep reinforcement learning
Authors: Qiao Dongping , Duan Lvqi , Li HongLei , Xiao Yanqiu
Published: October 2022

Aiming at the optimization problem of minimizing the maximum completion time in job shop scheduling, a deep reinforcement learning optimization algorithm is proposed. First, a deep reinforcement learning scheduling environment is built based on the disjunctive graph model, and three channels of state characteristics are established. The action space consists of 20 designed combination scheduling rules. The reward function is designed based on the proportional relationship between the total work of the scheduled operation and the current maximum completion time. The deep convolutional neural network is used to construct action network and target network, and the state features are used as inputs to output the Q value of each action. Then, the action is selected by using the action validity exploration and exploitation strategy. Finally, the immediate reward is calculated and the scheduling environment is updated. Experiments are carried out using benchmark instances to verify the algorithm. The results show that it can balance solution quality and computation time effectively, and the trained agent has good generalization ability to the scheduling problem in the non-zero initial state.
Keywords
Deep reinforcement learning · Job shop scheduling · Scheduling rules · Agent
Introducing the E100: Will the improvement make a significant difference? Financial analysis based on sleeve gastrectomy
Authors: Guevara Oriana , Lam Victoria , Sanchez Alexis , Arias Simon , Teixeira Andre , Ghanem Muhammad
Published: October 2022

Robotic Assisted surgery has proven to show significant advantages in surgery, for patients and surgeons alike. Nontheless the elevated cost remains a barrier to its acceptance in the medical field. Strategies to reduce cost should be implemented as a way to ensure cost-effectiveness in robotic-assisted procedures. The aim of this article was to compared the performance of the new generator E100 (Intuitive Surgical, Inc.) vs. VIO dV 2.0 (Erbe Elektromedizin GmbH) by analyzing the number of times the generators were activated, the average time per seal, total sealing time, and console time. Financial impact based on annual volume was determined. A total of 1,457 sleeves gastrectomies (Erbe:746, E100:711) were analyzed, the average activation per case was similar in both groups. The sealing time dropped by 42.3% and the average console time dropped by 8 minutes in cases with the E100. The financial analysis concluded that transitioning to the E100, will in fact save $33K to $34K/year. Proving that Introducing the new generator is a successful strategy to reduce costs.