bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1
Authors: Kuo Feng-Chih , Wang Yu-Ting , Liu Chia-Hsin , Li Yao-Feng , Lu Chieh-Hua , Su Sheng-Chiang , Liu Jhih-Syuan , Li Peng-Fei , Huang Chia-Luen , Ho Li-Ju , Lin Chien-Ming , Lee Chien-Hsing
Published: December 2022

Purpose

Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells.

Methods

We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues.

Results

We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues.

Conclusions

Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.
Potential of Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, as a hot tumor inducer
Authors: Horii Takayuki , Orikawa Yuki , Ohira Yuta , Eta Runa , Kobayashi Nobuyoshi , Sato Takanori , Watanabe Takeshi , Tanaka Takao
Published: December 2022

The tumor microenvironment is one of the most important factors determining the efficacy of cancer immunotherapy. In particular, variability in efficacy has been linked to whether tumors are hot or cold, with hot tumors exhibiting greater T cell infiltration and responding better to immunotherapy. Z-100 extracted from Mycobacterium tuberculosis Aoyama B strain has been reported to increase cytokine production from immune cells. In this study, we examined its effect on the tumor microenvironment and its potential as a hot tumor inducer. The antitumor effect of Z-100 was confirmed in a mouse oral squamous cell carcinoma (Sq-1979) tumor model by starting administration before tumor injection. Treated tumors were collected to identify infiltrating CD8+ T cells. The antitumor effects of Z-100 were additionally examined in mice treated with anti-CD8 antibody and in IL-12p40 knockout (KO) mice. We found that Z-100 had strong antitumor effects and increased the proportion of CD8+ T cells in tumors. Moreover, the CD8+ T cells infiltrating tumors were identified as effector memory CD8+ T cells. Furthermore, the antitumor effects of Z-100 were abolished in mice treated with an anti-CD8 antibody and in IL-12p40 KO mice. Thus, Z-100 induces its antitumor effects by increasing tumor-infiltrating CD8+ T cells, suggesting that Z-100 may be a useful cancer therapy by acting as a hot tumor inducer.
Disseminated Mycobacterium chimaera infection favoring the development of Kaposi’s sarcoma: a case report
Authors: Clemente Tommaso , Spagnuolo Vincenzo , Bottanelli Martina , Ripa Marco , Del Forno Benedetto , Busnardo Elena , Di Lucca Giuseppe , Castagna Antonella , Danise Anna
Published: December 2022

Background

Disseminated Mycobacterium chimaera infection is an emerging disease in people undergone to cardiothoracic surgery, which need to be suspected also with atypical presentations.

Case presentation

We report the case of a 74-year-old man with fever of unknown origin, purple nodules on both feet and a history of open-heart surgery. Imaging investigations showed an abscess near aortic bioprosthesis but screening for endocarditis resulted negative and pyrexia did not respond to antibiotic therapy. A biopsy of cutaneous lesions showed HHV8-related Kaposi’s sarcoma, so bone marrow biopsy was executed with evidence of HHV8 localization. Bone marrow and urine mycobacterial cultures resulted positive for M. chimaera and a specific antimicrobial therapy was started, with apyrexia after 7 weeks.

Conclusions

M. chimaera infection should be always investigated as a possible etiology of fever of unknow origin in people with a history of open-heart surgical intervention, even with negative mycobacterial blood cultures. The possible role of disseminated infection in inducing immunodepression with the occurrence of other opportunistic diseases (such as Kaposi’s sarcoma) cannot be excluded.
TSPAN4-positive migrasome derived from retinal pigmented epithelium cells contributes to the development of proliferative vitreoretinopathy
Authors: Wu Liangjing , Yang Shuai , Li Hui , Zhang Yao , Feng Le , Zhang Conghui , Wei Jiayi , Gu Xunyi , Xu Guotong , Wang Zhaoyang , Wang Fang
Published: December 2022

Background

Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-β families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration.

Results

Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-β1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-β1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-β1/Smad2/3 signaling pathway.

Conclusion

In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.
Cystic angiomatosis in children: clinical experience and review of literature
Authors: Li Wen Chao , Liu Li , Wang Zhen Dong , Chen Hui , Liu Guang , Feng Zhi Chun
Published: December 2022

Background

Cystic angiomatosis is a rare benign disease manifesting as multiple lytic and sclerotic bone lesions, described as the proliferation of vascular and lymphatic channels lined by a single layer of endothelial cells. However, the potential pathogenetic mechanism of the disease still remains unknown. Here, we reported a case of cystic angiomatosis with multifocal bone lesion evaluated by whole exome sequencing.

Case description

In this presentation, we reported a case of an 11-year-old boy with pain in his chest. Computed tomography (CT) revealed the multiple lytic of the bone in the ribs, clavicle, vertebra thoracalis, skull, mandibula, shoulder blade, etc. The blood test showed ALP to be 393U/L and VEGF to be 287.26 pg/ml. The patient was performed with an open biopsy in the ribs and was diagnosed with cystic angiomatosis. Besides, the whole exome sequencing reported the single-nucleotide substitutions in the coding region of BRIP1, CHEK2, GRM4, and MUC16. Then, the upregulated genes involved CASC15, CENPF, ABCA13, ALK, BLM, and FGFR3.

Conclusions

In this article, we report a rare case of cystic angiomatosis in a child with abnormal VEGF and ALP reported by peripheral blood examination. The whole exome sequencing could provide the reference for the potential molecular mechanism in the diagnosis and treatment of cystic angiomatosis.
Observed and personally experienced discrimination: findings of a cross-sectional survey of physicians and nursing staff
Authors: Yolci Arda , Schenk Liane , Sonntag Pia-Theresa , Peppler Lisa , Schouler-Ocak Meryam , Schneider Anna
Published: December 2022

Background

Discrimination against hospital staff based on ascribed features is prevalent in healthcare systems worldwide. Detrimental effects on health and quality of patient care have been shown. Our study aims to describe and analyse the discrimination experiences of both physicians and nurses, specifically for the German hospital context.

Methods

A cross-sectional online survey on observed and personally experienced discrimination at work addressed staff from 22 hospitals of two organizations in Germany. Sociodemographic and occupational as well as institutional characteristics served as independent variables. In multivariable analyses, block- and stepwise logistic regressions were calculated for the two dependent variables (witness and victim of discrimination). Sensitivity analyses with imputed data for missings were performed.

Results

N = 800 healthcare professionals (n = 243 physicians, n = 557 nurses; response rate: 5.9%) participated in the survey. 305 respondents (38.1%) were witnesses of discrimination, while 108 respondents (13.5%) were victims of discrimination in their wards. Reasons for observed discriminatory acts were predominantly attributed to the ethnicity of the person concerned, their appearance and language, whereas personally affected staff most frequently cited gender as a reason, followed by ethnicity, and physical appearance. In multivariable models, cultural competence significantly increased the likelihood of witnessing discrimination (β = .575; p = .037). In terms of the likelihood of being a victim of discrimination, in addition to cultural competence (β = 2.838; p =  < .001), the interaction of the effects of gender and professional group was statistically significant (β = .280; p = .010).

Conclusions

Given the extent of experienced and observed discrimination, appropriate institutional responses are needed. Further research on discriminatory structures in the German-speaking health care system should focus on discrimination at the intersection of ethnicity, gender and occupation.
Cook like a Boss Online: an adapted intervention during the COVID-19 pandemic that effectively improved children’s perceived cooking competence, movement competence and wellbeing
Authors: Hollywood Lynsey , Issartel Johann , Gaul David , McCloat Amanda , Mooney Elaine , Collins Clare Elizabeth , Lavelle Fiona
Published: December 2022

Background

The COVID-19 pandemic has further exacerbated physical inactivity, poor dietary intake and reduced mental wellbeing, contributing factors to non-communicable diseases in children. Cooking interventions are proposed as having a positive influence on children’s diet quality. Motor skills have been highlighted as essential for performance of cooking skills, and this movement may contribute to wellbeing. Additionally, perceived competence is a motivator for behaviour performance and thus important for understanding intervention effectiveness. Therefore, this research aimed to assess the effectiveness of an adapted virtual theory-based cooking intervention on perceived cooking competence, perceived movement competence and wellbeing.

Methods

The effective theory-driven and co-created ‘Cook Like A Boss’ was adapted to a virtual five day camp-styled intervention, with 248 children across the island of Ireland participating during the pandemic. Pre- and post-intervention assessments of perceived cooking competence, perceived movement competence and wellbeing using validated measurements were completed through online surveys. Bivariate Correlations, paired samples t-tests and Hierarchical multiple regression modelling was conducted using SPSS to understand the relationships between the variables and the effect of the intervention.

Results

210 participants had matched survey data and were included in analysis. Significant positive correlations were shown between perceived cooking competence, perceived movement competence and wellbeing (P < 0.05). Children’s perceived cooking competence (P < 0.001, medium to large effect size), perceived movement competence (P < 0.001, small to medium effect size) and wellbeing (P = 0.013, small effect size) all significantly increased from pre to post intervention. For the Hierarchical regression, the final model explained 57% of the total variance in participants’ post-intervention perceived cooking competence. Each model explained a significant amount of variance (P < 0.05). Pre-intervention perceived cooking competence, wellbeing, age and perceived movement competence were significant predictors for post-intervention perceived cooking competence in the final model.

Conclusion

The ‘Cook Like A Boss’ Online intervention was an adapted virtual outreach intervention. It provides initial evidence for the associations between perceived cooking competence, perceived movement and wellbeing as well as being effective in their improvement. This research shows the potential for cooking to be used as a mechanism for targeting improvements in not only diet quality but also movement and wellbeing.

Trial Registration

NCT05395234. Retrospectively registered on 26th May 2022.
A bispecific, crosslinking lectibody activates cytotoxic T cells and induces cancer cell death
Authors: Rosato Francesca , Pasupuleti Rajeev , Tomisch Jana , Meléndez Ana Valeria , Kolanovic Dajana , Makshakova Olga N. , Wiltschi Birgit , Römer Winfried
Published: December 2022

Background

Aberrant glycosylation patterns play a crucial role in the development of cancer cells as they promote tumor growth and aggressiveness. Lectins recognize carbohydrate antigens attached to proteins and lipids on cell surfaces and represent potential tools for application in cancer diagnostics and therapy. Among the emerging cancer therapies, immunotherapy has become a promising treatment modality for various hematological and solid malignancies. Here we present an approach to redirect the immune system into fighting cancer by targeting altered glycans at the surface of malignant cells. We developed a so-called “lectibody”, a bispecific construct composed of a lectin linked to an antibody fragment. This lectibody is inspired by bispecific T cell engager (BiTEs) antibodies that recruit cytotoxic T lymphocytes (CTLs) while simultaneously binding to tumor-associated antigens (TAAs) on cancer cells. The tumor-related glycosphingolipid globotriaosylceramide (Gb3) represents the target of this proof-of-concept study. It is recognized with high selectivity by the B-subunit of the pathogen-derived Shiga toxin, presenting opportunities for clinical development.

Methods

The lectibody was realized by conjugating an anti-CD3 single-chain antibody fragment to the B-subunit of Shiga toxin to target Gb3+cancer cells. The reactive non-canonical amino acid azidolysine (AzK) was inserted at predefined single positions in both proteins. The azido groups were functionalized by bioorthogonal conjugation with individual linkers that facilitated selective coupling via an alternative bioorthogonal click chemistry reaction. In vitro cell-based assays were conducted to evaluate the antitumoral activity of the lectibody. CTLs, Burkitt´s lymphoma-derived cells and colorectal adenocarcinoma cell lines were screened in flow cytometry and cytotoxicity assays for activation and lysis, respectively.

Results

This proof-of-concept study demonstrates that the lectibody activates T cells for their cytotoxic signaling, redirecting CTLs´ cytotoxicity in a highly selective manner and resulting in nearly complete tumor cell lysis—up to 93%—of Gb3+tumor cells in vitro.

Conclusions

This research highlights the potential of lectins in targeting certain tumors, with an opportunity for new cancer treatments. When considering a combinatorial strategy, lectin-based platforms of this type offer the possibility to target glycan epitopes on tumor cells and boost the efficacy of current therapies, providing an additional strategy for tumor eradication and improving patient outcomes.
Associated factors and global adherence of cervical cancer screening in 2019: a systematic analysis and modelling study
Authors: Zhang Wanting , Gao Kai , Fowkes Freya J. I. , Adeloye Davies , Rudan Igor , Song Peige , Jin Mingjuan , Chen Kun
Published: December 2022

Background

Cervical cancer screening is vital for its prevention. Adherence is a crucial indicator that implies the individual willingness to take cervical cancer screening. We aimed to estimate the global and regional adherence rates of cervical cancer screening in 2019 and identify its associated factors among general women.

Method

We searched studies in PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, ProQuest theses database and Google Web, without a lower time limit and until 23 June, 2021. Survey studies were considered eligible if they investigated cervical cancer screening adherence among general women, with data on sample size, the number of adherent subjects, and/or adherence rate. Random-effects were used to pool the odds ratios (ORs) of associated factors of adherence. Using modelling analysis, we estimated 2019 overall and age-specific adherence rates at the global and regional levels in women aged 20–69 years.

Results

Eight thousand two hundred ninety records were identified, and 153 articles were included. Being married (vs not married: OR, 1.34; 95% confidence interval [CI]: 1.23–1.46), higher educational attainment (higher than high school vs less than high school: OR, 1.44; 95% CI: 1.35–1.53), having healthcare (OR, 1.64; 95% CI: 1.43–1.88), former smoking (OR, 1.20; 95% CI: 1.07–1.34), physical activity (OR, 1.19; 95% CI: 1.05–1.36), parity (OR, 1.07; 95% CI: 1.01–1.12), and chronic disease (OR, 1.17; 95% CI: 1.04–1.32) were associated with better adherence, whereas obesity (vs normal: OR, 0.85; 95% CI: 0.74–0.97) and current smoking (vs former/never: OR, 0.64; 95% CI: 0.54–0.76) were associated with worse adherence. In 2019, the adherence was at 33.66% (95% CI: 23.34–39.30%) worldwide, and was higher in high-income countries (HICs) (75.66, 95% CI: 66.74–82.81%) than in low and middle-income countries (LMICs) (24.91, 95% CI: 14.30–30.24%). It varied across regions, the highest in the European region (65.36, 95% CI: 55.40–74.19%), but the lowest in the African region (5.28, 95% CI: 3.43–8.03%).

Conclusions

Cervical cancer screening adherence remained low globally, exhibiting geographical discrepancy with HICs higher than LMICs. Further implementations of screening programs should comprehensively consider the local economy, social benefits, and demographic structure to adapt delivery for vulnerable or underserved women to boost screening adherence.
Exploring alternative financing models and early access schemes for orphan drugs: a Belgian case study
Authors: Abdallah Khadidja , Claes Kathleen , Huys Isabelle , Follon Lennert , Calis Charlotte , Simoens Steven
Published: December 2022

Background

Although some jurisdictions have implemented particular adjustments to accommodate often-expensive orphan drugs in their healthcare systems, availability of these drugs remains complex. This study investigates alternative financing models and early access schemes for orphan drugs in the context of the Belgian healthcare system.

Methods

Three focus group discussions were held with a panel of eleven experts from the Belgian Drug Reimbursement Committee, the Colleges for Orphan Drugs, the pharmaceutical industry, physicians, ethicists and pharmacists. Retrieved data were pseudonymised, analysed and coded according to the Qualitative Analysis Guide of Leuven.

Results

Experts disfavoured the insulated fund as well as private insurance for financing orphan drugs, as, respectively, isolation of a separate budget and a mostly profit-driven mechanism would contradict the Belgian fundamental principle of solidarity. Moreover, an insulated fund could, albeit on a smaller scale, reproduce the same budgetary constraints as the general reimbursement system. As the Special Solidarity Fund is intended for urgent care and exclusively accommodates financial needs subject to eligibility criteria, its design would not allow general financing of orphan drugs. Overall, implementation of an alternative financing model was not endorsed, instead, improving the current reimbursement system was preferred. Suggestions mentioned were; increased collaboration and transparency, robust and quality real-world evidence but also digitalization of data. Alleviating administrative burden and simplifying the admission process of compassionate use program, medical need program and early treatment reimbursement should be prioritized to facilitate early access. Furthermore, a legal framework for off-label use could stimulate proper implementation. Efforts on collaboration of expertise centres and coordination of orphan drug databases across Europe could foster a robust data network to support orphan drug availability in individual countries.

Conclusions

This research reveals that reassessing current financing models and early access schemes by eliminating inadequacies, may be more conducive than establishing alternative systems to increase availability of orphan drugs in Belgium. Other jurisdictions may rely on this information to review their own models of early access and financing to cultivate a more sustainable delivery of orphan drugs.
Associations of aspirin and other anti-inflammatory medications with breast cancer risk by the status of COX-2 expression
Authors: Yaghjyan Lusine , Eliassen A. Heather , Colditz Graham , Rosner Bernard , Schedin Pepper , Wijayabahu Akemi , Tamimi Rulla M.
Published: December 2022

Background

We investigated the associations of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with breast cancer risk by the status of COX-2 protein expression.

Methods

This study included 421 cases and 3,166 controls from a nested case–control study within the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) cohorts. Information on medication use was first collected in 1980 (NHS) and 1989 (NHSII) and was updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users using data collected from all biannual questionnaires preceding the reference date. Immunochemistry for COX-2 expression was performed using commercial antibody (Cayman Chemical and Thermo Fisher Scientific). We used polychotomous logistic regression to quantify associations of aspirin and NSAIDs with the risk of COX2+ and COX2− breast cancer tumors, while adjusting for known breast cancer risk factors. All tests of statistical significance were two-sided.

Results

In multivariate analysis, we found no differences in associations of the aspirin exposures and NSAIDs with breast cancer risk by COX2 expression status. In stratified analyses by COX2 status, significant associations of these medications with breast cancer risk were observed for dosage of aspirin among current users in COX2- tumors (OR for > 5 tablets per week vs. none 1.71, 95% CI 1.01–2.88, p-trend 0.04). Regular aspirin use was marginally associated with the risk of COX2- tumors (p-trend = 0.06).

Conclusions

Our findings suggested no differences in associations of aspirin and other NSAIDs with COX2+ and COX2− tumors.
Detailed statistical analysis plan for the neurological complications in endoscopic versus open radial artery harvest (NEO) randomised clinical trial
Authors: Carranza Christian L. , Ballegaard Martin , Werner Mads U. , Hasbak Philip , Kjaer Andreas , Kofoed Klaus , Olsen Markus Harboe , Gluud Christian , Jakobsen Janus Christian
Published: December 2022

Introduction

Coronary artery bypass grafting can be conducted using the radial artery as a bypass graft. However, it remains unclear which harvesting method is superior, i.e. endoscopic or open radial artery, and which site for proximal anastomosis of the radial artery has the greatest benefits?

Methods

The NEO Trial is a single site randomised clinical trial with a 2 × 2 factorial design. The first comparison assesses endoscopic versus open radial artery harvest with a primary outcome of hand function and secondary outcomes of neurological deficits through clinical exams and neurophysiological studies. The primary outcome is postoperatively hand function at three months. We anticipate a mean difference of 3 points with a standard deviation of 8 points, a power of 90%, and a type I error of 5%, resulting in a required sample size of 300 participants randomised 1:1. Secondary outcomes are neurological deficits (based on nerve conduction measurements, algometry test and von Frey hair test), clinical neurological examination of cutaneous sensibility, and registration of complications in the donor arm (haematoma formation, wound dehiscence, and/or infection).

The second comparison assesses two different proximal anastomotic sites, i.e. aorto-radial anastomosis versus mammario-radial anastomosis. The primary outcome is a composite of cerebrovascular events and the secondary outcome is graft patency evaluation by multi-slice computer tomography-scan. These outcomes will be assessed at 1 year postoperatively, and the results of this comparison will be exploratory only. Both comparisons will be analysed using intention-to-treat and intervention groups will be compared using linear regression, logistic regression, or Mann–Whitney U test depending on data type.

Two independent statisticians will follow the present plan and conduct the analyses which will hereafter be fused into a final analysis based on consensus.

Conclusion

This detailed analysis plan will increase the validity of the NEO trial results by predefining the statistical analysis in detail.

Trial registration

ClinicalTrials.gov identifier: NCT01848886. Registered 25 February 2013. Danish Ethics committee number: H-3–2012-116. Danish Data Protection Agency: 2007–58-0015/jr. n:30–0838.
Safety and efficacy of direct cardiac shockwave therapy in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (the CAST-HF trial): study protocol for a randomized controlled trial—an update
Authors: Nägele Felix , Pölzl Leo , Graber Michael , Hirsch Jakob , Mayr Agnes , Pamminger Mathias , Troger Felix , Theurl Markus , Schreinlechner Michael , Sappler Nikolay , Dorfmüller Christian , Mitrovic Martina , Ulmer Hanno , Grimm Michael , Gollmann-Tepeköylü Can , Holfeld Johannes
Published: December 2022

Background

Coronary artery disease (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in the progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodelling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function.

Methods

In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min walk test distance, improvement of symptoms and assessment of quality of life.

Discussion

This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure.

Trial registration

ClinicalTrials.gov NCT03859466. Registered on 1 March 2019.
A fast-convolution based space–time Chebyshev spectral method for peridynamic models
Authors: Lopez Luciano , Pellegrino Sabrina Francesca
Published: December 2022

Peridynamics is a nonlocal generalization of continuum mechanics theory which addresses discontinuous problems without using partial derivatives and replacing them by an integral operator. As a consequence, it finds applications in the framework of the development and evolution of fractures and damages in elastic materials.

In this paper we consider a one-dimensional nonlinear model of peridynamics and propose a suitable two-dimensional fast-convolution spectral method based on Chebyshev polynomials to solve the model. This choice allows us to gain the same accuracy both in space and time. We show the convergence of the method and perform several simulations to study the performance of the spectral scheme.
Parameter estimation for discretized geometric fractional Brownian motions with applications in Chinese financial markets
Authors: Sun Lin , Chen Jianxin , Lu Xianggang
Published: December 2022

It is widely accepted that financial data exhibit a long-memory property or a long-range dependence. In a continuous-time situation, the geometric fractional Brownian motion is an important model to characterize the long-memory property in finance. This paper thus considers the problem to estimate all unknown parameters in geometric fractional Brownian processes based on discrete observations. The estimation procedure is built upon the marriage between the bipower variation and the least-squares estimation. However, unlike the commonly used approximation of the likelihood and transition density methods, we do not require a small sampling interval. The strong consistency of these proposed estimators can be established as the sample size increases to infinity in a chosen sampling interval. A simulation study is also conducted to assess the performance of the derived method by comparing with two existing approaches proposed by Misiran et al. (International Conference on Optimization and Control 2010, pp. 573–586, 2010) and Xiao et al. (J. Stat. Comput. Simul. 85(2):269–283, 2015), respectively. Finally, we apply the proposed estimation approach in the analysis of Chinese financial markets to show the potential applications in realistic contexts.
Symptoms of anal incontinence and quality of life: a psychometric study of the Norwegian version of the ICIQ-B amongst hospital outpatients
Authors: Saga Susan , Vinsnes Anne Guttormsen , Norton Christine , Haugan Gørill
Published: December 2022

Background

The International Consultation on Incontinence Questionnaire-Bowel (ICIQ-B), a self-report, condition-specific questionnaire designed to assess symptoms of anal incontinence (AI), measures AI’s impact on quality of life (QoL) along with perceived bowel patterns and bowel control amongst individuals with AI. In our study, we aimed to translate the ICIQ-B to Norwegian and investigate the Norwegian version’s psychometric properties.

Methods

To establish a relevant, comprehensive, and understandable Norwegian ICIQ-B, cognitive interviews were conducted with 10 patients with AI, and six clinical experts reviewed the translated scale. The Norwegian ICIQ-B’s structural validity, scale reliability, and content validity were tested amongst patients with AI attending hospital outpatient clinics in three regions of Norway (N = 208).

Results

Assessing the Norwegian ICIQ-B’s content validity revealed that the questionnaire was relevant, comprehensive, and understandable. Missing data were infrequent (3.3%), and no floor or ceiling effects emerged. Three-factor and two-factor solution models, both with advantages and disadvantages, were found. The three-factor model offered the most parsimonious solution by covering most of the original scale, albeit with an unacceptably low reliability (α = .37) for the construct of bowel pattern. The two-factor model showed good reliability in terms of internal consistency for the constructs of bowel control (α = .80) and impact on QoL (α = .85) but was less parsimonious due to dismissing seven of the original 17 items and excluding the bowel pattern construct. Test–retest reliability demonstrates good stability for the Norwegian version, with an intra-class correlation coefficient of .90–.95 and weighted kappa of .39–.87 for single items.

Conclusions

Although the Norwegian version of ICIQ-B demonstrates good stability and content validity, the original constructs of bowel pattern and bowel control had to be adapted, whereas the construct of impact on QoL remained unchanged. Further psychometric testing of the Norwegian ICIQ-B’s factor structure is therefore recommended.
Multi-genome metabolic modeling predicts functional inter-dependencies in the Arabidopsis root microbiome
Authors: Mataigne Victor , Vannier Nathan , Vandenkoornhuyse Philippe , Hacquard Stéphane
Published: December 2022

Background

From a theoretical ecology point of view, microbiomes are far more complex than expected. Besides competition and competitive exclusion, cooperative microbe-microbe interactions have to be carefully considered. Metabolic dependencies among microbes likely explain co-existence in microbiota.

Methodology

In this in silico study, we explored genome-scale metabolic models (GEMs) of 193 bacteria isolated from Arabidopsis thaliana roots. We analyzed their predicted producible metabolites under simulated nutritional constraints including “root exudate-mimicking growth media” and assessed the potential of putative metabolic exchanges of by- and end-products to avoid those constraints.

Results

We found that the genome-encoded metabolic potential is quantitatively and qualitatively clustered by phylogeny, highlighting metabolic differentiation between taxonomic groups. Random, synthetic combinations of increasing numbers of strains (SynComs) indicated that the number of producible compounds by GEMs increased with average phylogenetic distance, but that most SynComs were centered around an optimal phylogenetic distance. Moreover, relatively small SynComs could reflect the capacity of the whole community due to metabolic redundancy. Inspection of 30 specific end-product metabolites (i.e., target metabolites: amino acids, vitamins, phytohormones) indicated that the majority of the strains had the genetic potential to produce almost all the targeted compounds. Their production was predicted (1) to depend on external nutritional constraints and (2) to be facilitated by nutritional constraints mimicking root exudates, suggesting nutrient availability and root exudates play a key role in determining the number of producible metabolites. An answer set programming solver enabled the identification of numerous combinations of strains predicted to depend on each other to produce these targeted compounds under severe nutritional constraints thus indicating a putative sub-community level of functional redundancy.

Conclusions

This study predicts metabolic restrictions caused by available nutrients in the environment. By extension, it highlights the importance of the environment for niche potential, realization, partitioning, and overlap. Our results also suggest that metabolic dependencies and cooperation among root microbiota members compensate for environmental constraints and help maintain co-existence in complex microbial communities.
Dynamics between reading and math proficiency over time in secondary education – observational evidence from continuous time models
Authors: Jindra Christoph , Sachse Karoline A. , Hecht Martin
Published: December 2022

Introduction

Reading and math proficiency are assumed to be crucial for the development of other academic skills. Further, different studies found reading and math development to be related. We contribute to the literature by looking at the relationship between reading and math using continuous time models. In contrast to previous studies, this allows us to (a) report estimates for autoregressive and cross-lagged effects for a range of possible time intervals while still only estimating one set of continuous time parameters and (b) identify peak effects for the relationship between the two. Using data from Starting Cohort 3 of the National Educational Panel Study, we find, in line with previous evidence, a larger effect of reading on math than the other way around. Furthermore, we identify peak standardized cross-lagged effects ($${a}_{reading\to math}\approx 0.30$$,$${a}_{math\to reading}\approx 0.13$$) for a time interval of approximately 6 months.
Self-assembled wide bandgap nanocoatings enabled outstanding dielectric characteristics in the sandwich-like structure polymer composites
Authors: Wang Tian-Yu , Li Xiao-Fen , Liu Shu-Ming , Liu Bai-Xin , Liang Xi-Dong , Li Shunning , Zhang Gui-Xin , Liu Jian-Bo , Dang Zhi-Min
Published: December 2022

Polymer dielectrics are insulators or energy storage materials widely used in electrical and electronic devices. Polymer dielectrics are needed with outstanding dielectric characteristics than current technologies. In this study, the self-assembly of boron nitride nanosheets (BNNSs) was applied to form an inorganic–organic nanocoating on various common polymer dielectrics. It is inexpensive and easy to fabricate this thin coating on a large scale. The coating has a wide bandgap and thus can significantly improve the breakdown strength of polymer dielectrics. The charge characteristics and trapping parameters of nano-domains on the surfaces of polymer dielectrics were measured, and the coating had shallow trap levels. This facilitated the dissipation of surface charges and thus greatly increased the flashover voltage. The coating also effectively improved the temperature stability and dielectric constant of the polymer dielectric. This nanocoating shows potential as a method to effectively improve the dielectric characteristics of polymer dielectrics and outperform existing composite polymer dielectrics, which are crucial for large-scale applications in energy storage and power and electronic devices.
Optimization of operating parameters for biogas production using two-phase bench-scale anaerobic digestion of slaughterhouse wastewater: Focus on methanogenic step
Authors: Tsegaye Dejene , Leta Seyoum
Published: December 2022

The objective of the present study was an optimization of operating parameters and the performance of the methanogenesis reactor in phased anaerobic digestion (AD) of slaughterhouse wastewater at 37.5°C. Accordingly, the feedstock of the methanogenic reactor was effluent from the hydrolytic-acidogenic reactor operating at HRT of 3-days and OLR of 1789 mg/L. The methanogenesis phase was also investigated at different hydraulic retention time (HRT) values ranging from 12 to 3 days at 3-day intervals, and organic loading rates (OLR) of 149, 199, 298, and 596 mg of COD/L. The methanogenesis reactor effluent concentrations of TN, TP, PO4− 3, SO4− 2, and S2− 2 were ranging between 424–464, 83–117, 63–86, 130–197, and 0.98–1.02 mg/L, respectively. The removal efficiencies of TN and TP were vary from 10–17% to 17–21%, respectively. The average biogas production was 125 ± 16, 150 ± 10, 185 ± 4, and 154 ± 17 mL at HRT of 12, 9, 6, and 3 days, respectively. Methane quality (%) and yield (mg/L of COD) were 55–67% and 0.02–0.03, respectively. Furthermore, the average stability indicator parameter values of (total volatile fatty acid (TVFA) = 520 ± 19 mg/L, total alkalinity (TotA) = 1424 ± 10 mg/L, TVFA:TotA. Ratio = 0.36, salinity = 1172 mg/L, pH = 6.92) and performance indicator parameters removal efficiency (RE) for (chemical oxygen demand (COD) = 81%, volatile solid (VS) RE = 95%, biogas production = 185 ± 4 mL, methane yield = 0.03 per mg COD consumed) were achieved at HRT of 6 days and OLR of 298 mg of COD/L. Low removal efficiencies of TP and TN at all HRT/OLR were observed for the methanogenic reactor signifying further treatment system.

Graphical Abstract
Functional insights from targeted imaging BACE1: the first near-infrared fluorescent probe for Alzheimer’s disease diagnosis
Authors: Bi Anyao , Wu Junyong , Huang Shuai , Li Yongjiang , Zheng Fan , Ding Jipeng , Dong Jie , Xiang Daxiong , Zeng Wenbin
Published: December 2022

Background

β-Secretase (BACE1) is the vital enzyme in the pathogenic processes of Alzheimer's disease (AD). However, the development of a powerful tool with sensitivity for BACE1 determination in vivo is a challenge.

Methods

A novel NIR fluorescent probe HBAE was synthetized from 2-hydroxy-3-methylbenzaldehyde and 2-amino-benzenethiol by 5 steps. The fluorescence mechanism in the ESIPT systems of HBAE probe was insighted with time-dependent density functional theory (TD-DFT) at the TDPBE0 level with the def2-TZVP approach. The corresponding docking between HBAE and BACE1 (PDB: 5I3Y) was performed through the ducking method by DOCK6.8. Then the BBB permeability of HBAE is verified by transwell orifice plate. 22-month-old male AD-model (5XFAD) mice and age-matched wild-type mice were employed to observe the brain kinetics by intravenous injection. Finally, Immunohistochemistry was performed on the AD brain section to reveal the levels of BACE1 in hippocampus and cortex areas and other regions in AD mice through the brain tissue slices by HBAE.

Results

The NIR fluorescent probe HBAE was successfully applied in imaging BACE1 in AD model mice. The capability of HBAE in reflecting different level of BACE1 was performed by the specific imaging of the hippocampus region.

Conclusions

We reported the first ESIPT near-infrared fluorescence probe HBAE for monitoring endogenous BACE1 in the AD live model mice, thus offering a versatile chemical tool for visualizing in the pathological processes of AD live brains. Remarkably, high resolution images showed the localization of red fluorescence stains in hippocampus of the AD brain. This study provides a promising way for functional insights from protein BACE1 in vivo.
Effective strategies against COVID-19 and the importance of infection sequelae
Authors: Khalife Jade
Published: December 2022

COVID-19 is a serious threat to human health and development. The acute burden of the pandemic includes more than 18.2 million deaths worldwide, and is unprecedented in modern times. This represents only a fraction of the total burden, as it excludes infection sequelae. An effective global strategic paradigm has been missing throughout the pandemic. The ‘flattening the curve’ approach neglected the importance of infection sequelae, and being centered on healthcare capacity was conceptually contrary to a people-centered health system. In March 2022, the World Health Organization revised its pandemic approach, importantly shifting emphasis away from managing transmission and towards prevention. Despite limitations, this now recognizes the role of infection sequelae, whose impact is becoming clearer in both variety and scale. Drawing on the foundational concepts of Sun Tzu and Carl von Clausewitz, most country approaches do not qualify as strategies, but rather as operational plans. They are also largely ineffective, neglecting infection sequelae, viral evolution dangers and other parameters. The purpose of this article is to summarize the evidence on COVID-19 infection sequelae, and alongside other contextual parameters use this to motivate that infection should be prevented. This is then used to answer the question: What is an effective strategy against COVID-19?
Peripheral facial nerve palsy in children: clinical manifestations, treatment and prognosis
Authors: Bilge Serap , Mert Gülen Gül , Hergüner M. Özlem , İncecik Faruk , Sürmelioğlu Özgür , Bilen Sevcan , Yılmaz Levent
Published: December 2022

Background

Sudden onset of unilateral weakness of the upper and lower muscles of one side of the face is defined as peripheral facial nerve palsy. Peripheral facial nerve palsy is often idiopathic and sometimes it could be due to infectious, traumatic, neoplastic, and immune causes. This study aimed to report the clinical manifestation, evaluation, and prognosis in children with peripheral facial nerve palsy.

Methods

57 children under 18 years of age diagnosed with peripheral facial nerve palsy at Çukurova University, Balcalı Hospital, between January 2018 and September 2021, were included in the study.

Results

The mean age of the children at the time of diagnosis was 9.6 ± 7, 4 years. Thirty-two (56.1%) of the patients were female and 25 (43.9%) were male. A total of 57 patients were diagnosed with peripheral facial nerve palsy and categorized into many groups by etiology: idiopathic Bell’s palsy in 27 (47.5%), infectious in 11 (19.2%), traumatic in 6 (10.5%), and others (due to congenital, immune, neoplastic, Melkersson–Rosenthal syndrome, drug toxicity, and iatrogenic causes) in 13 (22.8%). Forty-six of the children achieved full recovery under oral steroids within 1–7 months. Four patients with acute leukemia, myelodysplastic syndrome, Mobius syndrome and trauma did not recover and two patients (schwannoma, trauma) showed partial improvement. Five patients could not come to follow-up control.

Conclusion

Peripheral facial nerve palsy is a rare condition in children with different causes. It could be idiopathic, congenital, or due to infectious, traumatic, neoplastic, and immune reasons. So, when a child presents with facial palsy, a complete clinical history and a detailed clinical examination are recommended. Giving attention to the red flag is very important. Peripheral facial nerve palsy in children is considered to have a good prognosis.