bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid shear stress enhances T cell activation through Piezo1
Authors: Hope Jacob M. , Dombroski Jenna A. , Pereles Rebecca S. , Lopez-Cavestany Maria , Greenlee Joshua D. , Schwager Samantha C. , Reinhart-King Cynthia A. , King Michael R.
Published: March 2022

Background

T cell activation is a mechanical process as much as it is a biochemical process. In this study, we used a cone-and-plate viscometer system to treat Jurkat and primary human T cells with fluid shear stress (FSS) to enhance the activation of the T cells through mechanical means.

Results

The FSS treatment of T cells in combination with soluble and bead-bound CD3/CD28 antibodies increased the activation of signaling proteins essential for T cell activation, such as zeta-chain-associated protein kinase-70 (ZAP70), nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), and AP-1 (activator protein 1). The FSS treatment also enhanced the expression of the cytokines tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), and interferon gamma (IFN-γ), which are necessary for sustained T cell activation and function. The enhanced activation of T cells by FSS was calcium dependent. The calcium signaling was controlled by the mechanosensitive ion channel Piezo1, as GsMTx-4 and Piezo1 knockout reduced ZAP70 phosphorylation by FSS.

Conclusions

These results demonstrate an intriguing new dynamic to T cell activation, as the circulatory system consists of different magnitudes of FSS and could have a proinflammatory role in T cell function. The results also identify a potential pathophysiological relationship between T cell activation and FSS, as hypertension is a disease characterized by abnormal blood flow and is correlated with multiple autoimmune diseases.
Severe α1-antitrypsin deficiency associated with lower blood pressure and reduced risk of ischemic heart disease: a cohort study of 91,540 individuals and a meta-analysis
Authors: Winther Sine Voss , Ahmed Dunia , Al-Shuweli Suzan , Landt Eskild Morten , Nordestgaard Børge Grønne , Seersholm Niels , Dahl Morten
Published: March 2022

Background

Increased elastase activity in α1-antitrypsin deficiency may affect elasticity of the arterial walls, and thereby blood pressure and susceptibility to cardiovascular disease. We hypothesized that severe α1-antitrypsin deficiency is associated with reduced blood pressure and susceptibility to cardiovascular disease.

Methods

We genotyped 91,353 adults randomly selected from the Danish general population and 187 patients from the Danish α1-Antitrypsin Deficiency Registry and recorded baseline blood pressure, baseline plasma lipids and cardiovascular events during follow-up. 185 participants carried the ZZ genotype, 207 carried the SZ genotype and 91,148 carried the MM genotype.

Results

α1-Antitrypsin deficiency was associated with decreases in blood pressure of up to 5 mmHg for systolic blood pressure and up to 2 mmHg for diastolic blood pressure, in ZZ vs SZ vs MM individuals (trend test, P’s ≤ 0.01). Plasma triglycerides and remnant cholesterol were reduced in ZZ individuals compared with MM individuals (t-test, P’s < 0.001). α1-Antitrypsin deficiency was associated with lower risk of myocardial infarction (trend test P = 0.03), but not with ischemic heart disease, ischemic cerebrovascular disease or hypertension (trend test, P’s ≥ 0.59). However, when results for ischemic heart disease were summarized in meta-analysis with results from four previous studies, individuals with versus without α1-antitrypsin deficiency had an odds ratio for ischemic heart disease of 0.66 (95% CI:0.53–0.84).

Conclusions

Individuals with severe α1-antitrypsin deficiency have lower systolic and diastolic blood pressure, lower plasma triglycerides and remnant cholesterol, reduced risk of myocardial infarction, and a 34% reduced risk of ischemic heart disease.
Citizens’ opinions and experiences related to costs and reimbursements for medications in times of retrenchment: cross-sectional population surveys in 2015 and 2017
Authors: Aaltonen Katri , Niemelä Mikko , Prix Irene
Published: March 2022

Background

Finland has universal coverage for prescription medications under the National Health Insurance. Eligibility schemes target higher reimbursements to individuals with chronic illness. Nevertheless, co-payments always apply, and austerity reforms implemented in 2016 and 2017 led to further increases in co-payments. We examined the extent to which people with chronic illness experienced financial difficulties in purchasing medications, how perceptions of fairness regarding the national reimbursements differs by exposure to policies and medicine use, and in what way do these experiences and opinions vary between surveys collected before and after the reforms.

Methods

We used two waves of Medicines Barometer (2015 and 2017, pooledn = 10,801), a national, biennial, cross-sectional population survey. Logistic regression analyses were performed with experiences of financial difficulties and perceptions of fairness as dependent variables. We compared people with and without prescription medication use, eligibilities, and/or diabetes (exposure groups), controlling for age, gender, survey type and geographic area (NUTS2). To examine the modifying effect of study year, we fitted models with an interaction term between group and year.

Results

Respondents with diabetes or eligibility based on chronic illness had a notably higher risk than other respondents with at least some prescription medication use to have experienced financial difficulties in affording medications. The share of respondents experiencing difficulties increased the most among people with diabetes. Three-quarters of respondents were either critical or unsure of whether the reimbursements for medications were fair and just. People with recent prescription medication use tended to be more sceptical than people without. Overall, scepticism tended to be more prevalent in 2017 than in 2015.

Conclusions

Despite the protective policies in place, individuals with chronic illness were disproportionately burdened by costs of medications already before the reforms. Among individuals with diabetes, financial difficulties were even more prevalent in 2017 than in 2015, which is likely attributed to the particularly high co-payment increases targeted to type 2 diabetes medicines. Perceived fairness of the processes and outcomes of policies and regulations is a key dimension of trust in public policy. Thus, increasing scepticism implies that retrenchment may also have implications in terms of public legitimacy.
Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease
Authors: An Jong Hun , Hong Sang-Eun , Yu Seong-Lan , Kang Jaeku , Park Chang Gyo , Lee Hoi Young , Lee Sung-Ki , Lee Dong Chul , Park Hwan-Woo , Hwang Won-Min , Yun Sung-Ro , Park Yohan , Park Moon Hyang , Yoon Kuk Ro , Yoon Se-Hee
Published: March 2022

Background

Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid–polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD.

Results

Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old maleB6;129-Glatm1Kul/J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved.

Conclusions

PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease.

Graphical Abstract
RETRACTED ARTICLE: Artificial photoactive chlorophyll conjugated vanadium carbide nanostructure for synergistic photothermal/photodynamic therapy of cancer
Authors: Lu Huiting , Zada Shah , Tang Songsong , Yaru Cheng , Wei Wei , Yuchun Qiao , Yang Qiqi , Du Jinya , Fu Pengcheng , Dong Haifeng , Zhang Xueji
Published: March 2022

Optically active nanostructures consisting of organic compounds and metallic support have shown great promise in phototherapy due to their increased light absorption capacity and high energy conversion. Herein, we conjugated chlorophyll (Chl) to vanadium carbide (V2C) nanosheets for combined photodynamic/photothermal therapy (PDT/PTT), which reserves the advantages of each modality while minimizing the side effects to achieve an improved therapeutic effect. In this system, the Chl from Leptolyngbya JSC-1 extracts acted as an efficient light-harvest antenna in a wide NIR range and photosensitizers (PSs) for oxygen self-generation hypoxia-relief PDT. The available large surface of two-dimensional (2D) V2C showed high Chl loading efficiency, and the interaction between organic Chl and metallic V2C led to energy conversion efficiency high to 78%. Thus, the Chl/ V2C nanostructure showed advanced performance in vitro cell line killing and completely ablated tumors in vivo with 100% survival rate under a single NIR irradiation. Our results suggest that the artificial optical Chl/V2C nanostructure will benefit photocatalytic tumor eradication clinic application.

Graphical Abstract
Visualization of the process of a nanocarrier-mediated gene delivery: stabilization, endocytosis and endosomal escape of genes for intracellular spreading
Authors: Ma Zhongzheng , Zheng Yang , Chao Zijian , Chen Hongtao , Zhang Yunhui , Yin Meizhen , Shen Jie , Yan Shuo
Published: March 2022

Nanoparticles have been widely applied as gene carrier for improving RNA interference (RNAi) efficiency in medical and agricultural fields. However, the mechanism and delivery process of nanoparticle-mediated RNAi is not directly visualized and elucidated. Here we synthesized a star polymer (SPc) consisted of a hydrophilic shell with positively-charged tertiary amine in the side chain, which was taken as an example to investigate the mechanism in gene delivery. The SPc could assemble with dsRNA spontaneously through electrostatic force, hydrogen bond and van der Waals force. Interestingly, the SPc could protect dsRNA from degradation by RNase A and insect hemolymph, thus remarkably increasing the stability of dsRNA. Meanwhile, the SPc could efficiently promote the cellular uptake and endosomal escape for intracellular spreading of dsRNA. Transcriptome analysis revealed that the SPc could up-regulate some key genes such asChc,AP2S1andArf1for activating clathrin-mediated endocytosis. Furthermore, the suppression of endocytosis hindered the cellular uptake of SPc-delivered dsRNA in vitro, and the subsequent RNAi effect was also disappeared in vivo.To our knowledge, our study is the first direct visualization of the detailed cellular delivery process and mechanism of nanocarrier-mediated gene delivery. Above mechanism supports the application of nanocarrier-based RNAi in gene therapy and pest management.

Graphical Abstract
Integrative metabolomic profiling reveals aberrations in myometrium associated with adenomyosis: a pilot study
Authors: Song Wei , Zhang Zhibo , Jiang Ying , Cao Yang , Zhang Bo , Wang Yujie , Shi Honghui , Zhu Lan
Published: March 2022

Background

Uterine adenomyosis is a common gynecologic disease in premenopausal women, the pathological mechanism of which remains largely unknown. The aim of this study was to identify metabolic biomarkers significantly altered in the myometrium of adenomyosis patients.

Methods

The comprehensive metabolomic profiles of 17 myometrium specimens from adenomyosis patients and 25 control specimens were analyzed using untargeted approach by combination of gas chromatography–mass spectrometry and high performance liquid chromatography-mass spectrometry. Metabolic data were filtered using orthogonal partial least square-discriminant analysis and univariate statistics.

Results

We firstly demonstrated that the myometrial metabolome of women with adenomyosis is distinct from that of women without adenomyosis. A total of 106 metabolites, mainly including nucleosides, lipids (including acylcarnitines), amino acids, organic acids and carbohydrates, were found to be differentially expressed in myometrium of uteri with adenomyosis compared to the control subjects. Functional inferences of these perturbed metabolites indicated that inflammation, oxidative stress, cell proliferation and apoptosis, and energy metabolism appeared to be involved in the progress of adenomyosis.

Conclusion

This study firstly described the integrated metabolic signatures of the adenomyosis uterus, which provided novel insights for the pathogenesis study of this disease.
Changes in the intestinal expression of drug metabolism-related genes in a piglet model of parenteral nutrition
Authors: Dai Li-Na , Zhao Yu-Ling , Jiang Lu , Yan Jun-Kai
Published: March 2022

Background

Parenteral nutrition (PN) may serve as a nutritional supportive therapy accompanied by oral medication, but the effect of PN on intestinal expression of drug metabolism-related genes remains unknown.

Methods

Twelve Bama piglets receiving PN for 14 days were used as in vivo model. Changes in intestinal drug metabolism-related genes were examined by proteomic analysis. Serum levels of fibroblast growth factor 19 (FGF19) were determined by ELISA, and the effect of FGF19 on the expression of drug metabolism-related genes was examined using murine ileum organoids.

Results

A total of 1063 differentially expressed proteins were identified in PN group. Of note, two drug transporters (Abcb1 and Abcc2) were significantly decreased in PN group, along with two glutathione-related drug-metabolizing enzymes, glutathione peroxidase (Gpx2) and glutathione S-transferase (Gsta1). Serum FGF19 levels were dramatically reduced in PN group. Treatment with recombinant FGF19 in vitro dose-dependently up-regulated the expression of Abcb1, Abcc2, Gpx2 and Gsta1 in organoids.

Conclusion

Our data indicated that intestinal drug metabolism-related genes were significantly dysregulated under PN, and some of the changed genes were attributed to gut-derived FGF19.
Quantification of biological range uncertainties in patients treated at the Krakow proton therapy centre
Authors: Garbacz Magdalena , Gajewski Jan , Durante Marco , Kisielewicz Kamil , Krah Nils , Kopeć Renata , Olko Paweł , Patera Vincenzo , Rinaldi Ilaria , Rydygier Marzena , Schiavi Angelo , Scifoni Emanuele , Skóra Tomasz , Skrzypek Agata , Tommasino Francesco , Rucinski Antoni
Published: March 2022

Background

Variable relative biological effectiveness (vRBE) in proton therapy might significantly modify the prediction of RBE-weighted dose delivered to a patient during proton therapy. In this study we will present a method to quantify the biological range extension of the proton beam, which results from the application of vRBE approach in RBE-weighted dose calculation.

Methods and materials

The treatment plans of 95 patients (brain and skull base patients) were used for RBE-weighted dose calculation with constant and the McNamara RBE model. For this purpose the Monte Carlo tool FRED was used. The RBE-weighted dose distributions were analysed using indices from dose-volume histograms. We used the volumes receiving at least 95% of the prescribed dose (V95) to estimate the biological range extension resulting from vRBE approach.

Results

The vRBE model shows higher median value of relative deposited dose and D95 in the planning target volume by around 1% for brain patients and 4% for skull base patients. The maximum doses in organs at risk calculated with vRBE was up to 14 Gy above dose limit. The mean biological range extension was greater than 0.4 cm.

Discussion

Our method of estimation of biological range extension is insensitive for dose inhomogeneities and can be easily used for different proton plans with intensity-modulated proton therapy (IMPT) optimization. Using volumes instead of dose profiles, which is the common method, is more universal. However it was tested only for IMPT plans on fields arranged around the tumor area.

Conclusions

Adopting a vRBE model results in an increase in dose and an extension of the beam range, which is especially disadvantageous in cancers close to organs at risk. Our results support the need to re-optimization of proton treatment plans when considering vRBE.
Prevalence of bacterial species associated with ovine footrot and contagious ovine digital dermatitis in Swedish slaughter lambs
Authors: Rosander Anna , Albinsson Rebecka , König Ulrika , Nyman Ann , Frosth Sara
Published: March 2022

Background

Ovine footrot and contagious ovine digital dermatitis (CODD) are contagious mixed bacterial infections with major impacts on animal health and production. In Sweden, ovine footrot and CODD were first detected in 2004 and 2019, respectively. In 2009, a voluntary control programme for footrot was established, and a prevalence study in slaughter lambs was conducted, however, the distribution of footrot and CODD-associated bacteria is still unknown. This study examined the prevalence of Dichelobacter nodosus, Fusobacterium necrophorum and Treponema spp., as well as the current prevalence of footrot and CODD, in Swedish slaughter lambs.

Results

A total of 2048 feet, from 512 slaughter lambs, were collected from eight slaughterhouses throughout Sweden in autumn 2020. All feet were visually examined for lesions of footrot and CODD and sampled for subsequent real-time polymerase chain reaction (PCR) analysis. Nine lambs (1.8%) had at least one foot affected with footrot (footrot score ≥ 2). A CODD grade 1 lesion was detected in a single lamb (0.2%). The prevalence of D. nodosus, F. necrophorum and Treponema spp. was 6.1%, 7.6% and 90.6%, respectively. The D. nodosus detected were benign strains.

Conclusions

The prevalence of footrot in Swedish slaughter lambs has been significantly reduced, from 5.8 to 1.8%, during the past 11 years. This indicates that preventive measures, such as the national control programme and elimination of footrot from affected flocks, have been effective. A single lamb (0.2%) was found with a CODD lesion (grade 1). In Sweden, benign rather than virulent strains of D. nodosus seem to be the most common. Neither D. nodosus nor F. necrophorum were widespread among Swedish slaughter lambs, but both were more likely to be found in lambs with footrot. Treponema spp. was very commonly found in lambs with and without footrot, but there is a lack of information on the individual Treponema spp. present in Swedish slaughter lambs and their potential pathogenicity.
BCL-XL PROTAC degrader DT2216 synergizes with sotorasib in preclinical models of KRASG12C-mutated cancers
Authors: Khan Sajid , Wiegand Janet , Zhang Peiyi , Hu Wanyi , Thummuri Dinesh , Budamagunta Vivekananda , Hua Nan , Jin Lingtao , Allegra Carmen J. , Kopetz Scott E. , Zajac-Kaye Maria , Kaye Frederic J. , Zheng Guangrong , Zhou Daohong
Published: March 2022

KRAS mutations are the most common oncogenic drivers. Sotorasib (AMG510), a covalent inhibitor of KRASG12C, was recently approved for the treatment of KRASG12C-mutated non-small cell lung cancer (NSCLC). However, the efficacy of sotorasib and other KRASG12C inhibitors is limited by intrinsic resistance in colorectal cancer (CRC) and by the rapid emergence of acquired resistance in all treated tumors. Therefore, there is an urgent need to develop novel combination therapies to overcome sotorasib resistance and to maximize its efficacy. We assessed the effect of sotorasib alone or in combination with DT2216 (a clinical-stage BCL-XL proteolysis targeting chimera [PROTAC]) on KRASG12C-mutated NSCLC, CRC and pancreatic cancer (PC) cell lines using MTS cell viability, colony formation and Annexin-V/PI apoptosis assays. Furthermore, the therapeutic efficacy of sotorasib alone and in combination with DT2216 was evaluated in vivo using different tumor xenograft models. We observed heterogeneous responses to sotorasib alone, whereas its combination with DT2216 strongly inhibited viability of KRASG12C tumor cell lines that partially responded to sotorasib treatment. Mechanistically, sotorasib treatment led to stabilization of BIM and co-treatment with DT2216 inhibited sotorasib-induced BCL-XL/BIM interaction leading to enhanced apoptosis in KRASG12C tumor cell lines. Furthermore, DT2216 co-treatment significantly improved the antitumor efficacy of sotorasib in vivo. Collectively, our findings suggest that due to cytostatic activity, the efficacy of sotorasib is limited, and therefore, its combination with a pro-apoptotic agent, i.e., DT2216, shows synergistic responses and can potentially overcome resistance.
Italian intersociety consensus on management of long covid in children
Authors: Esposito Susanna , Principi Nicola , Azzari Chiara , Cardinale Fabio , Di Mauro Giuseppe , Galli Luisa , Gattinara Guido Castelli , Fainardi Valentina , Guarino Alfredo , Lancella Laura , Licari Amelia , Mancino Enrica , Marseglia Gian Luigi , Leonardi Salvatore , Nenna Raffaella , Zampogna Stefania , Zona Stefano , Staiano Annamaria , Midulla Fabio
Published: March 2022

Background

Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed.

Main findings

Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type.

Conclusions

Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.
DNA demethylation affects imprinted gene expression in maize endosperm
Authors: Xu Qiang , Wu Leiming , Luo Zhixiang , Zhang Mei , Lai Jinsheng , Li Lin , Springer Nathan M. , Li Qing
Published: March 2022

Background

DNA demethylation occurs in many species and is involved in diverse biological processes. However, the occurrence and role of DNA demethylation in maize remain unknown.

Results

We analyze loss-of-function mutants of two major genes encoding DNA demethylases. No significant change in DNA methylation has been detected in these mutants. However, we detect increased DNA methylation levels in the mutants around genes and some transposons. The increase in DNA methylation is accompanied by alteration in gene expression, with a tendency to show downregulation, especially for the genes that are preferentially expressed in endosperm. Imprinted expression of both maternally and paternally expressed genes changes in F1 hybrid with the mutant as female and the wild-type as male parental line, but not in the reciprocal hybrid. This alteration in gene expression is accompanied by allele-specific DNA methylation differences, suggesting that removal of DNA methylation of the maternal allele is required for the proper expression of these imprinted genes. Finally, we demonstrate that hypermethylation in the double mutant is associated with reduced binding of transcription factor to its target, and altered gene expression.

Conclusions

Our results suggest that active removal of DNA methylation is important for transcription factor binding and proper gene expression in maize endosperm.
Sports injuries patterns in children and adolescents according to their sports participation level, age and maturation
Authors: Costa e Silva Lara , Teles Júlia , Fragoso Isabel
Published: March 2022

Background

Growth can make young athletes more vulnerable to sports injuries. Increased knowledge about injury profile and its predictors is an important part of an overall risk management strategy but few studies have produced information.

Methods

Information about injury profile and sports participation (SP) level was obtained by LESADO and RAPIL II questionnaires. They were distributed to 651 participants aged between 10 and 18 years attending four schools. Maturity measures were evaluated through maturity offset (MO) and Tanner-Whitehouse III method. Bivariate analysis was used to identify the set of candidate predictors for multinomial logistic regression analysis that was used to determine significant predictors of injury type and body area injury location.

Results

Regarding injury type predictors recreative boys had more chances of having a sprain or a fracture than a strain. Also, recreative and scholar girls had more chances of having a sprain than a strain. As MO decreased, the chances of girls having a strain or a fracture when compared to sprains were higher. For body area location boys with 10–11 years were more likely to have upper limbs injuries than boys of other ages. This was also confirmed by MO. Spine and trunk injuries were more likely to occur in federate and no sports participation girls.

Conclusions

Injury type and body area injury location differed significantly by SP level, age group and MO.
Some remarks on α-admissibility in S-metric spaces
Authors: Priyobarta Ningthoujam , Rohen Yumnam , Thounaojam Stephen , Radenović Stojan
Published: March 2022

The concept of α-admissible mapping introduced by Samet et al. (Nonlinear Anal. 75:2154–2165, 2012) has various generalizations. In this paper, we introduce the concept of $\alpha _{s}$

α
s

-admissible mapping and its various forms by generalizing the concept of α-admissible mapping in the setting of S-metric spaces. Further, we also introduce generalized rational $\alpha _{s}$

α
s

-Geraghty contraction type mappings and study the existence of fixed point theorems in S-metric spaces. Examples are also given to verify the main results.
Validation of the coping self-efficacy scale: Vietnamese version for adolescents
Authors: Tran Thach , La Nga , Nguyen Huong , Shochet Ian , Nguyen Nga , Wurfl Astrid , Orr Jayne , Nguyen Hau , Stocker Ruby , Fisher Jane
Published: March 2022

Background

This study aimed to examine the construct validity of the Coping Self-Efficacy Scale-Vietnamese Version (CSES-V) among Vietnamese adolescents.

Methods

This study selected Grade 10 students from eight schools in Hanoi using a multiple-stage sampling method. Multiple aspects of the construct validity were examined including: factorial structure (evaluated using exploratory factor analysis); internal consistency (tested using Cronbach’s alpha coefficient); measurement invariance between male and female participants and longitudinal measurement invariance (tested by employing multiple group confirmatory factor analysis) and external aspect (tested using Pearson’s correlation coefficients between CSES-V and the Depression Anxiety and Stress Subscales of Depression (DASS21-D), Anxiety (DASS21-A), and Stress (DASS21-S) and a measure of mental well-being, Mental Health Continuum Short Form (MHC-SF)).

Results

A total of 1082 adolescents (aged 14–16 years) was included in this study. Data supported a three-factor structure (comprising 24 items) that explained 97.6% of the total variance of the CSES-V. Cronbach’s alpha coefficients of all three factors were acceptable. All levels of measurement invariance between male and female participants and longitudinal measurement invariance were well-supported. The three factors of the CSES-V were positively correlated with MHC-SF and were negatively correlated with the DASS21 subscales at a low or moderate level, supporting the external aspect of the construct validity.

Conclusions

CSES-V is recommended to assess coping self-efficacy among Vietnamese adolescents who are attending school.
Modelling the perspectives of distance education students towards online learning during COVID-19 pandemic
Authors: Segbenya Moses , Bervell Brandford , Minadzi Vincent Mensah , Somuah Beatrice Asante
Published: March 2022

This study examined perspectives of distance education students on online learning based on their access gadgets (availability and functionality), online presentation or teaching methods, actual use of online learning coupled with its challenges. A quantitative approach and descriptive survey design were adopted for the study. A sample of 1061 was drawn from a study population of 44,134 distance learners across sixteen administrative regions and data collected using a questionnaire. Partial least squares structural equation modelling (PLS-SEM) was used to analyse the hypotheses of the study, and descriptive statistics were deployed to analyse students perceived challenges. The study found a statistically significant relationship between the availability and functionality of online gadgets, availability of online gadgets and online presentation methods, functionality and online presentation methods and functionality and online learning usage. Thus, these factors are necessary for successful online learning. Four main perceived challenges identified were unreliable power/electricity and internet connectivity, lack of collaboration and motivation during online learning. Therefore, it was recommended that steps are taken to resolve the perceived challenges while adopting the blended approach comprising face-to-face and online learning. The blended learning approach would enable students to adjust better and appreciate its usefulness in distance education.
Fast cortical surface reconstruction from MRI using deep learning
Authors: Ren Jianxun , Hu Qingyu , Wang Weiwei , Zhang Wei , Hubbard Catherine S. , Zhang Pingjia , An Ning , Zhou Ying , Dahmani Louisa , Wang Danhong , Fu Xiaoxuan , Sun Zhenyu , Wang Yezhe , Wang Ruiqi , Li Luming , Liu Hesheng
Published: March 2022

Reconstructing cortical surfaces from structural magnetic resonance imaging (MRI) is a prerequisite for surface-based functional and anatomical image analyses. Conventional algorithms for cortical surface reconstruction are computationally inefficient and typically take several hours for each subject, causing a bottleneck in applications when a fast turnaround time is needed. To address this challenge, we propose a fast cortical surface reconstruction (FastCSR) pipeline by leveraging deep machine learning. We trained our model to learn an implicit representation of the cortical surface in volumetric space, termed the “level set representation”. A fast volumetric topology correction method and a topology-preserving surface mesh extraction procedure were employed to reconstruct the cortical surface based on the level set representation. Using 1-mm isotropic T1-weighted images, the FastCSR pipeline was able to reconstruct a subject’s cortical surfaces within 5 min with comparable surface quality, which is approximately 47 times faster than the traditional FreeSurfer pipeline. The advantage of FastCSR becomes even more apparent when processing high-resolution images. Importantly, the model demonstrated good generalizability in previously unseen data and showed high test–retest reliability in cortical morphometrics and anatomical parcellations. Finally, FastCSR was robust to images with compromised quality or with distortions caused by lesions. This fast and robust pipeline for cortical surface reconstruction may facilitate large-scale neuroimaging studies and has potential in clinical applications wherein brain images may be compromised.
Default rules in investment decision-making: trait anxiety and decision-making styles
Authors: Gambetti Elisa , Zucchelli Micaela Maria , Nori Raffaella , Giusberti Fiorella
Published: March 2022

This study investigates the role of default options in the relationship between trait anxiety, and decision-making styles and financial decisions. One hundred and ninety-four participants were divided into three groups and subjected to three different conditions. Under each experimental condition, they had to decide whether to accept or reject investment proposals. In the first group, they had been enrolled in investment plans by default (opt-out condition), in the second group, they had not been automatically enrolled in these plans (opt-in condition), and in the third group they had to choose whether to enroll or not (control condition). The results showed that the investment decisions of anxious, avoidant, rational and dependent individuals could be facilitated by default options. In conclusion, using default options as a “nudge” can support specific groups of people to improve their financial decisions.
Effect of gas blowing on the head of thermal ablation vehicle
Authors: Li Qing , Yuan Xianxu , Chen Jianqiang , Bi Lin
Published: March 2022

The reentry vehicle will encounter thermal ablation, especially at the stagnation point regime. A theoretical work has been done to analyze the thermal effect of gas blowing due to thermal ablation of surface material on the head of a general hypersonic vehicle. By deriving the formulation, research takes into account the effect of gas blowing on the thermal dynamics balance, and then solves them by numerical discretization. It is found that gas blowing will increase the temperature and heat flux at the surface of stagnation point regime.
Cerebrospinal fluid biomarkers and genetic factors associated with normal pressure hydrocephalus and Alzheimer’s disease: a narrative review
Authors: Afrashteh Fatemeh , Ghafoury Roya , Almasi-Doghaee Mostafa
Published: March 2022

Background

Normal pressure hydrocephalus is a neurologic disease leading to enlargement of ventricles which is presented with gait and balance disturbance, cognitive decline, and urinary incontinence. Diagnosis of normal pressure hydrocephalus is challenging due to the late onset of signs and symptoms. In this review, we summarize the cerebrospinal fluid, plasma, pathology, and genetic biomarkers of normal pressure hydrocephalus and related disorders.

Body

Recently, cerebrospinal fluid and serum biomarkers analysis alongside gene analysis has received a lot of attention. Interpreting a set of serum and cerebrospinal fluid biomarkers along with genetic testing for candidate genes could differentiate NPH from other neurological diseases such as Alzheimer's disease, Parkinson's disease with dementia, and other types of dementia.

Conclusion

Better understanding the pathophysiology of normal pressure hydrocephalus through genetic studies can aid in evolving preventative measures and the early treatment of normal pressure hydrocephalus patients.
Analysis and modeling for illuminance and signal-to-noise of smart traffic information system
Authors: Chen Yaoting , Chen Huanting
Published: March 2022

The traffic lights using by light emitting diode (LED) are able to indicate and provide the information about the ambient. The signal transimission performance of traffic system is related to a variety of factors such as the signal-to-noise ratio (SNR), illuminance. Several factors are influence on illumiance and SNR, such as eatsink temperature and driver parameters. It has not been any substantial investigate on the operated effects of traffic light with sinusoidal waveform driver on illuminance and SNR. With the use of heatsink temperature and driver parameters of the LED source with sinusoidal waveform driver, prediction modeling for the illuminance and SNR of the mixed white LED sources with heatsink temperature, frequency, amplitude voltage, bias voltage and amplification factors are proposed in this paper to enhance the illuminance and SNR model of LED source inside smart traffic information system. The proposed model should carry out a series of calibration step for illuminance, heatsink temperature and driver parameters, which are easy for traffic designer and source system designers to follow in the traffic information system. The proposed model has been measured for the mixed white LED sources, with reasonably good agreements between theoretical and practical results.
Bidirectional recurrent neural networks for seismic event detection
Authors: Birnie Claire , Hansteen Fredrik
Published: March 2022

Real-time accurate passive seismic event detection is a critical safety measure across a range of monitoring applications, from reservoir stability to carbon storage to volcanic tremor detection. The most common detection procedure remains the short-term average to long-term average (STA/LTA) trigger developed in the 1970s, in part due to its easy implementation and real-time processing capability. However, it has several well-documented limitations, such as requiring a signal-to-noise ratio greater than one and being highly sensitive to trigger parameters. Although numerous alternatives have been proposed, they often are tailored to a specific monitoring setting and therefore cannot be widely applied, or they are too computationally expensive and therefore cannot be run in real time. This work introduces a deep learning approach to event detection that is an alternative to the STA/LTA trigger. A bidirectional, long short-term memory, neural network (NN) is trained solely on synthetic traces. Evaluated on synthetic and field data, the NN approach significantly outperforms the STA/LTA trigger on the number of correctly detected arrivals as well as on reducing the number of falsely detected events. Its applicability is proven with 600 traces processed in real time on a single processing unit.
Adoption of Telemedicine for Postoperative Follow-Up After Inpatient Cancer-Related Surgery
Authors: Uppal Abhineet , Kothari Anai N. , Scally Christopher P. , Roland Christina L. , Bednarski Brian K. , Katz Matthew H.G. , Vauthey Jean-Nicholas , Chang George J. ,   in collaboration with the D3CODE Team
Published: March 2022

PURPOSE:

The COVID-19 pandemic has resulted in significant changes in health care delivery, including the rapid adoption of telemedicine across multiple specialties and practice environments. This includes postoperative visits (POV), despite limited data on outcomes following these telemedicine POV. We sought to determine whether these types of visits successfully identify and address postoperative complications when compared with in-person POV.

METHODS:

This was a retrospective cohort study of patients undergoing elective inpatient cancer-related surgery from March 2020 through December 2020. The exposure variable was type of POV (telemedicine v in-person). The primary outcome was unplanned hospital readmission within 90 days, and secondary outcomes included 30-day readmission, length of stay of first readmission, and mortality.

RESULTS:

Five-hundred thirty-five patients underwent elective inpatient operations and met our inclusion criteria. Of these, 98 (18.5%) had an initial telemedicine POV. There was no difference in 90-day readmission on the basis of POV type (16.3% telemedicine v 16.5% in-person, P = .99). Reasons for readmission did not differ between patients who underwent a telemedicine POV compared with in-person POV (all P > .05). After adjustment for patients' demographic and clinical factors, telemedicine POV was not associated with 90-day readmission (odds ratio, 0.89; 95% CI, 0.43 to 1.70; P = .77).

CONCLUSION:

Telemedicine POV use adopted during the COVID-19 pandemic did not increase risk of readmission when compared with in-person visits following inpatient oncologic surgery. These data can help inform policy on the continued use and application of telemedicine after the pandemic.
Comparative Study of Bayesian Information Borrowing Methods in Oncology Clinical Trials
Authors: Su Liwen , Chen Xin , Zhang Jingyi , Yan Fangrong
Published: March 2022

PURPOSE

With deeper insight into precision medicine, more innovative oncology trial designs have been proposed to contribute to the characteristics of novel antitumor drugs. Bayesian information borrowing is an indispensable part of these designs, which shows great advantages in improving the efficiency of clinical trials. Bayesian methods provide an effective framework when incorporating information. However, the key point lies in how to choose an appropriate method for complex oncology clinical trials.

METHODS

We divided the borrowing information scenarios into concurrent and nonconcurrent scenarios according to whether the data to be borrowed are observed at the same time as in the current trial or not. Then, we provided an overview of the methods in each scenario. Performance comparison of different methods is carried out with regard to the type I error and power.

RESULTS

As demonstrated by the simulation results in each borrowing scenario, the Bayesian hierarchical model and its extensions are more appropriate for concurrent borrowing. The simulation results demonstrate that the Bayesian hierarchical model shows great advantages when the arms are homogeneous. However, such a method should be adopted with caution when heterogeneity exists. We recommend the other methods, considering heterogeneity. Borrow information from informative priors is more suggested for nonconcurrent borrowing scenarios. Multisource exchangeability models are more suitable for multiple historical trials, while meta-analytic-predictive prior should be carefully applied.

CONCLUSION

Bayesian information borrowing is useful and can improve the efficiency of clinical trial designs. However, we should carefully choose an appropriate information borrowing method when facing a practical innovative oncology trial, as an appropriate method is essential to provide ideal design performance.
The Effects of Common Genetic Variation in 96 Genes Involved in Thyroid Hormone Regulation on TSH and FT4 Concentrations
Authors: Sterenborg Rosalie B T M , Galesloot Tessel E , Teumer Alexander , Netea-Maier Romana T , Speed Doug , Meima Marcel E , Visser W Edward , Smit Johannes W A , Peeters Robin P , Medici Marco
Published: March 2022

Objective

While most of the variation in thyroid function is determined by genetic factors, single nucleotide polymorphisms (SNPs) identified via genome-wide association analyses have only explained ~5% to 9% of this variance so far. Most SNPs were in or nearby genes with no known role in thyroid hormone (TH) regulation. Therefore, we performed a large-scale candidate gene study investigating the effect of common genetic variation in established TH regulating genes on serum thyrotropin [thyroid-stimulating hormone (TSH)] and thyroxine (FT4) concentrations.

Methods

SNPs in or within 10 kb of 96 TH regulating genes were included (30 031 TSH SNPs, and 29 962 FT4 SNPs). Associations were studied in 54 288 individuals from the ThyroidOmics Consortium. Linkage disequilibrium-based clumping was used to identify independently associated SNPs. SNP-based explained variances were calculated using SumHer software.

Results

We identified 23 novel TSH-associated SNPs in predominantly hypothalamic-pituitary-thyroid axis genes and 25 novel FT4-associated SNPs in mainly peripheral metabolism and transport genes. Genome-wide SNP variation explained ~21% (SD 1.7) of the total variation in both TSH and FT4 concentrations, whereas SNPs in the 96 TH regulating genes explained 1.9% to 2.6% (SD 0.4).

Conclusion

Here we report the largest candidate gene analysis on thyroid function, resulting in a substantial increase in the number of genetic variants determining TSH and FT4 concentrations. Interestingly, these candidate gene SNPs explain only a minor part of the variation in TSH and FT4 concentrations, which substantiates the need for large genetic studies including common and rare variants to unravel novel, yet unknown, pathways in TH regulation.
Obesity and COVID-19: Mechanistic Insights From Adipose Tissue
Authors: Yu Lili , Zhang Xiaoying , Ye Sarah , Lian Hongkai , Wang Hui , Ye Jianping
Published: March 2022

Obesity is associated with an increase in morbidity and mortality from coronavirus disease 2019 (COVID-19). The risk is related to the cytokine storm, a major contributor to multiorgan failure and a pathological character of COVID-19 patients with obesity. While the exact cause of the cytokine storm remains elusive, disorders in energy metabolism has provided insights into the mechanism. Emerging data suggest that adipose tissue in obesity contributes to the disorders in several ways. First, adipose tissue restricts the pulmonary function by generation of mechanical pressures to promote systemic hypoxia. Second, adipose tissue supplies a base for severe acute respiratory syndrome coronavirus 2 entry by overexpression of viral receptors [angiotensin-converting enzyme 2 and dipeptidyl peptidase 4]. Third, impaired antiviral responses of adipocytes and immune cells result in dysfunction of immunologic surveillance as well as the viral clearance systems. Fourth, chronic inflammation in obesity contributes to the cytokine storm by secreting more proinflammatory cytokines. Fifth, abnormal levels of adipokines increase the risk of a hyperimmune response to the virus in the lungs and other organs to enhance the cytokine storm. Mitochondrial dysfunction in adipocytes, immune cells, and other cell types (endothelial cells and platelets, etc) is a common cellular mechanism for the development of cytokine storm, which leads to the progression of mild COVID-19 to severe cases with multiorgan failure and high mortality. Correction of energy surplus through various approaches is recommended in the prevention and treatment of COVID-19 in the obese patients.