bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogel-based delivery system applied in the local anti-osteoporotic bone defects
Authors: Gong Yining , Bu Yazhong , Li Yongliang , Hao Dingjun , He Baorong , Kong Lingbo , Huang Wangli , Gao Xiangcheng , Zhang Bo , Qu Zechao , Wang Dong , Yan Liang
Published: November 2022

Osteoporosis is an age-related systemic skeletal disease leading to bone mass loss and microarchitectural deterioration. It affects a large number of patients, thereby economically burdening healthcare systems worldwide. The low bioavailability and complications, associated with systemic drug consumption, limit the efficacy of anti-osteoporosis drugs currently available. Thus, a combination of therapies, including local treatment and systemic intervention, may be more beneficial over a singular pharmacological treatment. Hydrogels are attractive materials as fillers for bone injuries with irregular shapes and as carriers for local therapeutic treatments. They exhibit low cytotoxicity, excellent biocompatibility, and biodegradability, and some with excellent mechanical and swelling properties, and a controlled degradation rate. This review reports the advantages of hydrogels for adjuvants loading, including nature-based, synthetic, and composite hydrogels. In addition, we discuss functional adjuvants loaded with hydrogels, primarily focusing on drugs and cells that inhibit osteoclast and promote osteoblast. Selecting appropriate hydrogels and adjuvants is the key to successful treatment. We hope this review serves as a reference for subsequent research and clinical application of hydrogel-based delivery systems in osteoporosis therapy.
Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation
Authors: Yu Guiping , Chen Yiqi , Hu Yuwen , Zhou Yan , Ding Xiaoling , Zhou Xiaorong
Published: November 2022

Mammalian transducin-like enhancer of split family proteins (TLEs) are homologous to Drosophila Groucho (Gro) and are essential transcriptional repressors. Seven TLE family members, TLE1-7, have been identified to date. These proteins do not bind DNA directly; instead, they bind a set of transcription factors and thereby inhibit target gene expression. Loss of TLEs in mice usually leads to defective early development; however, TLE functions in developmentally mature cells are unclear. Recent studies have revealed that TLEs are dysregulated in certain human cancer types and may function as oncogenes or tumor suppressors in different contexts. TLE levels also affect the efficacy of cancer treatments and the development of drug resistance. In addition, TLEs play critical roles in the development and function of immune cells, including macrophages and lymphocytes. In this review, we provide updates on the expression, function, and mechanism of TLEs; discuss the roles played by TLEs in tumorigenesis and the inflammatory response; and elaborate on several TLE-associated signaling pathways, including the Notch, Wnt, and MAPK pathways. Finally, we discuss potential strategies for targeting TLEs in cancer therapy.
Machine learning-based identification of a novel prognosis-related long noncoding RNA signature for gastric cancer
Authors: Zhao Linli , Teng Qiong , Liu Yuan , Chen Hao , Chong Wei , Du Fengying , Xiao Kun , Sang Yaodong , Ma Chenghao , Cui Jian , Shang Liang , Zhang Ronghua
Published: November 2022

Gastric cancer (GC) is one of the most common malignancies with a poor prognosis. Immunotherapy has attracted much attention as a treatment for a wide range of cancers, including GC. However, not all patients respond to immunotherapy. New models are urgently needed to accurately predict the prognosis and the efficacy of immunotherapy in patients with GC. Long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of cancers. Recent studies have identified a variety of prognosis-related lncRNA signatures in multiple cancers. However, these studies have some limitations. In the present study, we developed an integrative analysis to screen risk prediction models using various feature selection methods, such as univariate and multivariate Cox regression, least absolute shrinkage and selection operator (LASSO), stepwise selection techniques, subset selection, and a combination of the aforementioned methods. We constructed a 9-lncRNA signature for predicting the prognosis of GC patients in The Cancer Genome Atlas (TCGA) cohort using a machine learning algorithm. After obtaining a risk model from the training cohort, we further validated the model for predicting the prognosis in the test cohort, the entire dataset and two external GEO datasets. Then we explored the roles of the risk model in predicting immune cell infiltration, immunotherapeutic responses and genomic mutations. The results revealed that this risk model held promise for predicting the prognostic outcomes and immunotherapeutic responses of GC patients. Our findings provide ideas for integrating multiple screening methods for risk modeling through machine learning algorithms.
A prospective multicenter study on varicella-zoster virus infection in children with acute lymphoblastic leukemia
Authors: Xiao Peifang , Cai Jiaoyang , Gao Ju , Gao Wei , Guan Xianmin , Leung Alex Wing Kwan , He Yiying , Zhuang Yong , Chu Jinhua , Zhai Xiaowen , Qi Benquan , Liu Aiguo , Yang Liangchun , Zhu Jiashi , Li Zheng , Tian Xin , Xue Yao , Hao Li , Wu Xuedong , Zhou Fen , Wang Lingzhen , Tang Jingyan , Shen Shuhong , Hu Shaoyan
Published: November 2022

Background and methods

The study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL) using data from the multicenter Chinese Children’s Cancer Group ALL-2015 trial.

Results

In total, 7,640 patients were recruited, and 138 cases of VZV infection were identified. The incidence of VZV infection was higher in patients aged ≥ 10 years (22.5%) and in patients with the E2A/PBX1 fusion gene (11.6%) compared to those aged < 10 years (13.25%, P = 0.003) or with other fusion genes (4.9%, P = 0.001). Of the 10 deaths in children with ALL and VZV infection, 4 resulted from VZV complications. The differences between groups in the 5-year overall survival, event-free survival, cumulative recurrence, and death in remission were not statistically significant. The proportion of complex infection was higher in children with a history of exposure to someone with VZV infection (17.9% vs. 3.6%, P = 0.022).

Conclusion

VZV exposure was associated with an increased incidence of complex VZV infection and contributed to VZV-associated death in children with ALL.
Identification of GLS as a cuproptosis-related diagnosis gene in acute myocardial infarction
Authors: Liu Zheng , Wang Lei , Xing Qichang , Liu Xiang , Hu Yixiang , Li Wencan , Yan Qingzi , Liu Renzhu , Huang Nan
Published: November 2022

Acute myocardial infarction (AMI) has the characteristics of sudden onset, rapid progression, poor prognosis, and so on. Therefore, it is urgent to identify diagnostic and prognostic biomarkers for it. Cuproptosis is a new form of mitochondrial respiratory-dependent cell death. However, studies are limited on the clinical significance of cuproptosis-related genes (CRGs) in AMI. In this study, we systematically assessed the genetic alterations of CRGs in AMI by bioinformatics approach. The results showed that six CRGs (LIAS, LIPT1, DLAT, PDHB, MTF1, and GLS) were markedly differentially expressed between stable coronary heart disease (stable_CAD) and AMI. Correlation analysis indicated that CRGs were closely correlated with N6-methyladenosine (m6A)-related genes through R language “corrplot” package, especially GLS was positively correlated with FMR1 and MTF1 was negatively correlated with HNRNPA2B1. Immune landscape analysis results revealed that CRGs were closely related to various immune cells, especially GLS was positively correlated with T cells CD4 memory resting and negatively correlated with monocytes. Kaplan–Meier analysis demonstrated that the group with high DLAT expression had a better prognosis. The area under curve (AUC) certified that GLS had good diagnostic value, in the training set (AUC = 0.87) and verification set (ACU = 0.99). Gene set enrichment analysis (GSEA) suggested that GLS was associated with immune- and hypoxia-related pathways. In addition, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, competing endogenous RNA (ceRNA) analysis, transcription factor (TF), and compound prediction were performed to reveal the regulatory mechanism of CRGs in AMI. Overall, our study can provide additional information for understanding the role of CRGs in AMI, which may provide new insights into the identification of therapeutic targets for AMI.
How to use three-dimensional optical coherence tomography effectively in coronary bifurcation stenting
Authors: Murasato Yoshinobu
Published: November 2022

Imaging-guided coronary bifurcation intervention has improved clinical outcomes due to the appropriate size selection of the devices and optimization of the procedure (sufficient stent expansion, reduction of stent malapposition, appropriate stent landing zone, and detection of vessel dissection). In particular, three-dimensional optical coherence tomography (3D OCT) facilitates clear visualization of stent configuration and guidewire position, which promotes optimal guidewire crossing to the side branch. Successive side branch dilation leads to wide ostial dilation with less strut malapposition. However, the link connection of the stent located on the bifurcated carina has been found to be an impediment to sufficient opening of the side branch, resulting in incomplete strut apposition. In such cases, the aggressive proximal optimization technique improves the jailing strut pattern, and 3D OCT navigates the guidewire crossing to the optimal cell that is most likely to be expanded sufficiently, which is not always a distal cell. In two-stent deployment, 3D OCT facilitates optimal guidewire crossing, which leads to less metallic carina, clustering, and overlapping. The present review describes a method of clear visualization and assessment with 3D OCT and discusses the efficacy of 3D OCT in coronary bifurcation stenting in clinical practice.
Microcirculation function assessment in acute myocardial infarction: A systematic review of microcirculatory resistance indices
Authors: Silva Marta , Paiva Luis , Teixeira Rogério , Ferreira Maria João , Gonçalves Lino
Published: November 2022

Background

Up to 50% of acute myocardial infarction (MI) patients present with microvascular dysfunction, after a successful percutaneous coronary intervention (PCI), which leads to worse clinical outcomes. The main purpose of this study is to provide a critical appraisal of the emerging role of invasive microvascular resistance indices in the MI setting, using the index of microcirculatory resistance (IMR), hyperemic microvascular resistance (HMR) and zero-flow pressure (Pzf).

Methods

We systematically explored relevant studies in the context of MI that correlated microcirculation resistance indices with microvascular dysfunction on cardiac magnetic resonance (CMR), microvascular dysfunction occurring in infarct related arteries (IRA) and non-IRA and its relation to clinical outcomes.

Results

The microcirculation resistance indices correlated significantly with microvascular obstruction (MVO) and infarct size (IS) on CMR. Although HMR and Pzf seem to have better diagnostic accuracy for MVO and IS, IMR has more validation data. Although, both IMR and HMR were independent predictors of adverse cardiovascular events, HMR has no validated cut-off value and data is limited to small observational studies. The presence of microvascular dysfunction in non-IRA does not impact prognosis.

Conclusion

Microvascular resistance indices are valuable means to evaluate microcirculation function following MI. Microvascular dysfunction relates to the extent of myocardial damage and clinical outcomes after MI.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228432], identifier [CRD42021228432].
Wingless-related integration site (WNT) signaling is activated during the inflammatory response upon cardiac surgery: A translational study
Authors: Krüger Bernard D. , Hofer Gilles E. , Rudiger Alain , Spahn Gabriela H. , Braun Julia , Bettex Dominique , Schoedon Gabriele , Spahn Donat R.
Published: November 2022

Objective

Cardiac surgery and the use of cardiopulmonary bypass initiate a systemic inflammatory response. Wingless-related integration site (WNT) signaling is part of the innate immunity and has been attributed a major role in the regulation of inflammation. In preclinical research, WNT-5a may sustain an inflammatory response and cause endothelial dysfunction. Our aim was to investigate WNT signaling after cardiac surgery and its association with postoperative inflammation (Clinicaltrials.gov, NCT04058496).

Methods

In this prospective, single-center, observational study, 64 consecutive patients for coronary artery bypass grafting (CABG) ± valve surgery were assigned into three groups: off-pump CABG (n = 28), on-pump CABG (n = 16) and combined valve-CABG surgery (n = 20). Blood samples were acquired before surgery, at intensive care unit (ICU) admission and 4, 8, and 48 h thereafter. Plasma concentrations of WNT-5a and its antagonists Secreted frizzled-related protein 1 (sFRP-1), Secreted frizzled-related protein 5 (sFRP-5), and WNT inhibitory factor 1 (WIF-1) were determined by enzyme-linked immunosorbent assay. In addition, plasma concentrations of six inflammatory cytokines were measured by multiplex immunoassay. Parameters were analyzed for evolution of plasma concentration over time, interactions, intergroup differences, and association with clinical outcome parameters.

Results

At baseline, WNT-5a, sFRP-1, and WIF-1 were present in a minimal concentration, while sFRP-5 was elevated. A higher baseline value of WNT-5a, sFRP-5, and WIF-1 resulted in higher subsequent values of the respective parameter. At ICU admission, WNT-5a and sFRP-5 reached their maximum and minimum value, respectively. WIF-1 decreased over time and was lowest 8 h after surgery. sFRP-1 changed minimally over time. While WNT-5a returned to the baseline within 48 h, sFRP-5 and WIF-1 did not reach their baseline value at 48 h. Of the investigated WNT system components, only WIF-1 partially reflected the severity of surgery. WNT-5a and WIF-1 had an impact on postoperative fluid balance and noradrenaline requirement.

Conclusion

WNT-5a, sFRP-5, and WIF-1 are part of the systemic inflammatory response after cardiac surgery. WNT-5a peaks immediately after cardiac surgery and returns to baseline within 48 h, presumably modulated by its antagonist sFRP-5. Based on this translational study, WNT-5a antagonism may be further investigated to assess potentially beneficial effects in patients with a dysregulated inflammation after cardiac surgery.
Real-time evaluation of the dynamic Young’s modulus for composite formations based on the drilling parameters using different machine learning algorithms
Authors: Mahmoud Ahmed Abdulhamid , Gamal Hany , Elkatatny Salaheldin , Chen Weiqing
Published: November 2022

The dynamic Young’s modulus (Edyn) is a parameter needed for optimizing different aspects related to oil well designing. Currently, Edyn is determined from the knowledge of the formation bulk density, in addition to the shear and compressional velocities, which are not always available. This study introduces three machine learning (ML) models, namely, random forest (RF), adaptive neuro-fuzzy inference system with subtractive clustering (ANFIS-SC), and support vector regression (SVR), for estimation of the Edyn from only the real-time available drilling parameters. The ML models were learned on 2054 datasets collected from Well-A and then tested and validated on 871 and 2912 datasets from Well-B and Well-C, respectively. The results showed that the three optimized ML models accurately predicted the Edyn in the three oil wells considered in this study. The optimized SVR model outperformed both the RF and ANFIS-SC models in evaluating the Edyn in all three wells. For the validation data, the Edyn was assessed accurately with low average absolute percentage errors of 3.64%, 6.74%, and 1.03% using the optimized RF, ANFIS-SC, and SVR models, respectively.
A case study of pillar extraction techniques based on strip-filling and second-mining method
Authors: Hao Jian , Chen Anfa , Li Xuelong , Bian Hua , Shi Yongkui , Wang Xin , Zhao Jiali , Liu Haojie
Published: November 2022

Strip coal pillars caused by strip mining are widely distributed in China. Over time, strip coal pillars are posing more potential hazards as their stability decreases; therefore, it becomes increasingly important to recover coal pillars without damaging the ground surface. In this paper, strip-filling and second-mining technique is adopted to probe into an optimal scheme for mine goafs. Construction waste was one type of the materials used for backfilling, which was taken to underground from the surface with a pumping system. Jisuo Coal Mine of Tengzhou, Shandong province was taken as the object of study. Through theoretical calculation and on-site survey, we set a re-mining scheme to control rock stratum stability, i.e., 8-m-wide backfilling for the first time and 4-m-wide backfilling for the second time; moreover, the ground pressure behavior and subsidence of working surface were monitored and a contour map of surface subsidence was thus mapped. In-situ practice indicated that the underground pressure from coal pillars was transmitted to the backfilling materials, the maximum normal stress of which was 5 MPa, so it was sufficient for the backfilling strip to support the weight of overlying strata; the maximum value of roof-to-floor convergence of backfilled mining face is 45 mm, the maximum surface subsidence 44mm, the maximum inclination value 0.65 mm/m, the maximum surface curvature 0.018 mm/m2, and the maximum horizontal deformation 0.16 mm/m. The filling body in the original goafs plays the role of “pier”. By the monitoring data of subsidence, its surface deformation value was less than that of buildings suffering from grade I damage, which verified the feasibility of strip-filling and second-mining scheme. The success in this technique provides reliable technical and theoretical support for mines with similar conditions.
Sensitivity of sheltered mudflats to wind events
Authors: Zhu Qin , Nie Wei , Zhu Zhenchang , Cai Yanpeng , Yang Zhifeng
Published: November 2022

The impact of waves on the morphological changes of sheltered mudflats is less well studied compared to that on open flats. To investigate the sensitivity of low-energy sheltered mudflats to hydrodynamics such as waves, we carried out in situ measurements of bed level, currents, and waves on the middle flat of a sheltered mudflat in a bay in southern China. Two 1-month measurements, March 26–26 April 2021, and July 8–8 August 2021, were performed for repetition. We found that the sheltered system was not as stable as it appeared. The maximum intratidal bed-level variation, ΔZ, was <5 mm in calm conditions. However, wind speeds slightly highly than 3.0 m/s, under which significant wave height was approximately 0.1 m, triggered significant bed-level variation patterns, with ΔZ reaching up to 2 cm. Intratidal bed-level change patterns depend on the relative dominance of waves and currents: low τc (current-induced bed shear stress) and high τw (wave-induced bed shear stress) promote the generation and migration of bed ripples; comparable τc and τw, with medium-to-high values, lead to non-cyclic bed-level change patterns; high τc and high τw result in bed accumulation/degradation superimposed by bed ripple migration. From a long-term perspective, i.e. in the time scale of month to year, sheltered mudflats are stable systems, and their high sensitivity causes short-term significant bed-level variation. The sensitivity and stability of sheltered mudflats must be further investigated to explore the effects of human intervention and global climate change.
Conservation assessment of the Drakaea livida (Orchidaceae) ecotypes and an evaluation of methods for their identification
Authors: Weinstein Alyssa M. , Bohman Björn , Linde Celeste C. , Phillips Ryan D.
Published: November 2022

Morphologically cryptic taxa must be accounted for when quantifying biodiversity and implementing effective conservation measures. Some orchids pollinated by sexual deception of male insects contain morphologically cryptic ecotypes, such as the warty hammer orchid Drakaea livida (Orchidaceae). This species is comprised of three cryptic pollination ecotypes, which can be distinguished based on differences in pollinator species and floral volatiles. The present study aims were: (a) to investigate the geographic range of the three D. livida ecotypes, enabling assessment of their conservation status; and (b) to test the efficacy of different methods of identifying the D. livida ecotypes. Three methods of ecotype identification were assessed: morphometric analysis, genome size comparison, and analysis of chemical volatile composition of labellum extracts from pollinated flowers. MaxEnt species distribution models revealed that each ecotype has a different predicted geographic range, with small areas of overlap at the range margins. One ecotype is known from just ten populations over a limited geographic area, the majority of which has been cleared for agriculture, and urban development. While there was broad overlap between the ecotypes in individual morphological traits, multivariate analysis of morphological traits provided correct assignment to ecotype in 87% of individuals. Using the labellum of pollinated flowers, screening for volatile chemical compounds associated with particular ecotypes returned an even higher correct assignment rate, of 96.5%. As such, we advocate that the use of volatiles from the labellum of recently pollinated flowers is an effective way to determine the ecotype of unknown individuals of D. livida, with minimal impact on the flowering plant.
Artificial intelligence for precision medicine in autoimmune liver disease
Authors: Gerussi Alessio , Scaravaglio Miki , Cristoferi Laura , Verda Damiano , Milani Chiara , De Bernardi Elisabetta , Ippolito Davide , Asselta Rosanna , Invernizzi Pietro , Kather Jakob Nikolas , Carbone Marco
Published: November 2022

Autoimmune liver diseases (AiLDs) are rare autoimmune conditions of the liver and the biliary tree with unknown etiology and limited treatment options. AiLDs are inherently characterized by a high degree of complexity, which poses great challenges in understanding their etiopathogenesis, developing novel biomarkers and risk-stratification tools, and, eventually, generating new drugs. Artificial intelligence (AI) is considered one of the best candidates to support researchers and clinicians in making sense of biological complexity. In this review, we offer a primer on AI and machine learning for clinicians, and discuss recent available literature on its applications in medicine and more specifically how it can help to tackle major unmet needs in AiLDs.
Importance of the choice of heat flux parameterization in regional air–sea coupled simulations: Case studies of marine heatwaves induced by atmospheric heatwaves in 1994 and 2018
Authors: Jeong Taek-Bum , Bae Hyo-Jun , Kim Baek-Min , Yang Sinil
Published: November 2022

This study investigated the marine heat wave events (MHWs) that occurred near the Korean Peninsula during the summer of 1994 and 2018, using a regional air–sea coupled model. We analyzed the fifth-generation reanalysis data, ERA5, published by the European Centre for Medium-Range Weather Forecasts for both events. We found that the North Pacific High and Tibetan High were stronger than usual and were associated with warm and moist air intrusion from the subtropical regions. Air-sea interactions play an important role in the development of MHWs. Warm and moist air combined with low-level inversion and a subsequent sinking motion induced the downward latent heat flux (LHF) toward the relatively colder sea surface, resulting in increased sea surface temperatures (SSTs). To quantify the contribution of the downward LHF and evaluate the importance of the relevant physical parameters of the MHWs, we set up two coupled model experiments, namely, CPL_down and CPL_nodown. Results show that the CPL_down experiment captured the downward LHF well in both events. The model also successfully captured the observed inversion near the surface. The cold SST bias tended to be reduced as the low-level clouds decreased in the area where the downward LHF occurred. In our simulation, permitting downward LHF improved the MHW reproducibility. Therefore, we suggest that the increased downward LHF is favorable for simulating MHWs, and surface physical parameterization must be carefully performed.
Fast vibro-acoustic response computations for finite periodic metamaterial plates using a generalized Bloch Mode Synthesis based sub-structuring approach
Authors: Van Belle Lucas , Claeys Claus , Desmet Wim , Deckers Elke
Published: November 2022

Metamaterials have recently emerged and shown great potential for noise and vibration reduction in specific frequency ranges, called stop bands. To predict stop bands, their often periodic nature is exploited and dispersion curves are calculated based on a single representative unit cell, typically modeled using the finite element method. Since their sub-wavelength nature and often intricate design can lead to large unit cell models, model reduction methods such as the Generalized Bloch Mode Synthesis have been proposed to greatly accelerate dispersion curve calculations. In order to calculate forced vibro-acoustic responses of finite periodic elastic metamaterial plates composed of an assembly of unit cells, however, full order finite element models rapidly become computationally unaffordable. Therefore, in this work the Generalized Bloch Mode Synthesis is incorporated in a sub-structuring approach, which enables fast forced vibration response calculations of finite elastic metamaterial plates based on a single reduced order unit cell model. The main advantage as compared to a regular Craig-Bampton approach is the additional local reduction of unit cell boundary degrees of freedom, whereby a compatible basis for the identical neighboring unit cells is incorporated. In addition, by combining this Generalized Bloch Mode Synthesis based sub-structuring approach with the Elementary Radiator Approach, efficient sound transmission loss computations of finite periodic metamaterial plates are enabled. The performance of the proposed approach for fast vibro-acoustic response predictions is demonstrated for different cases.
The biodiversity dose-response curve translates theory and practice from ecological restoration into research and clinical priorities for fecal microbiota transplantation
Authors: Orr Matthew R.
Published: November 2022

Discoveries of the beneficial effects of gut microbiota have led to efforts to cultivate healthy gut flora to treat disease. The field of ecological restoration specializes on reestablishment of desired species in disturbed ecosystems, which suggests that it may be applicable to microbe restoration in the gut. Common language can lower barriers to interdisciplinary insights. Here I introduce the concept of a “biodiversity dose-response curve” to translate ideas from ecological restoration into research and clinical priorities for fecal microbiota transplantation (FMT). The curve is based on a relationship between ecosystem structure, measured as species diversity found in both nature and gut ecosystems, and ecosystem function, which are the measurable parameters that contribute to ecosystem and human health. I explain why the biodiversity dose-response curve may follow the ecological model of a “rivet-redundancy” relationship, in which the overlap of multiple organisms’ functional contributions to a system mask the impact of initial losses of diversity, but, at a certain level of loss, function declines sharply. (Imagine an airplane that flies with a few rivets missing, until it loses enough to fail.) The biodiversity dose-response curve indicates that seemingly healthy individuals may be suboptimal donors; it highlights the importance of recipient diet in FMT success; and it introduces the concept of “passive restoration” into the field of gut medicine. These insights, which may help to explain low success rates of FMT in the treatment of non-Clostridium dificile conditions, are less apparent in the absence of interdisciplinary integration.
Rehabilitation among individuals experiencing homelessness and traumatic brain injury: A scoping review
Authors: Chan Vincy , Estrella Maria Jennifer , Baddeliyanage Richelle , Shah Riya , Babineau Jessica , Colantonio Angela
Published: November 2022

Traumatic brain injury (TBI) is disproportionately prevalent among individuals experiencing homelessness. While rehabilitation is critical to facilitating recovery after TBI, there is currently limited information on the extent to which rehabilitation is provided to individuals experiencing homelessness and TBI. If unaddressed, this knowledge gap can perpetuate TBI-related challenges and contribute to a repetitive cycle of TBI and homelessness. This scoping review explored the extent to which rehabilitation, including the types of rehabilitation interventions, are available to, or used by, individuals experiencing homelessness and TBI. A systematic search of electronic databases (MEDLINE, Embase, Cochrane CENTRAL Register of Clinical Trials, CINAHL, APA PsycINFO, Applied Social Sciences Index and Abstracts, and Proquest Nursing and Allied Health) was conducted to identify peer-reviewed articles that met predetermined eligibility criteria. Gray literature and reference lists of eligible articles were also searched for relevant content. A descriptive numerical summary of extracted data was conducted, and qualitative analytic techniques were applied to analyze the data. Fifteen peer-reviewed articles and three gray literature reports were included, describing interventions for individuals experiencing homelessness and TBI (N = 4), rehabilitation for individuals experiencing homelessness without specific inclusion criteria for TBI (N = 11), and rehabilitation interventions that included individuals experiencing homelessness and TBI, without specific inclusion criteria for experiences of homelessness or TBI (N = 3). This review demonstrates that rehabilitation programs or interventions for this population already exist, and those that are focused on individuals experiencing homelessness are already serving individuals with TBI. Findings highlight opportunities to adapt existing rehabilitation for individuals who experience homelessness and TBI through screening for TBI, conducting cognitive and functional assessments, and tailoring interventions with multidisciplinary teams. Education and training for healthcare professionals working with individuals experiencing homelessness and TBI should be explored, including structured education and training, collaboration with a multidisciplinary team, and co-development of educational materials with service users. Research that considers the rehabilitation needs of diverse individuals experiencing homelessness and TBI is urgently needed.
Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
Authors: Zhou Ning , Tang Quanying , Yu Haochuan , Li Tong , Ren Fan , Zu Lingling , Chen Gang , Chen Jun , Xu Song
Published: November 2022

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is a global public health concern. One-carbon (1C) metabolism plays a crucial role in the occurrence and development of multiple cancer types. However, there are limited studies investigating 1C metabolism in LUAD. This study aims to evaluate the prognostic value of 1C metabolism-related genes in LUAD and to explore the potential correlation of these genes with gene methylation, the tumor microenvironment, and immunotherapy.

Methods: We identified 26 1C metabolism-related genes and performed a Kaplan-Meier and Cox regression analysis to evaluate the prognostic value of these genes. Consensus clustering was further performed to determine the 1C metabolism-related gene patterns in LUAD. The clinical and molecular characteristics of subgroups were investigated based on consensus clustering. CIBERSORT and ssGSEA algorithms were used to calculate the relative infiltration levels of multiple immune cell subsets. The relationship between 1C metabolism-related genes and drug sensitivity to immunotherapy was evaluated using the CellMiner database and IMvigor210 cohort, respectively.

Results: The expression levels of 23 1C metabolism-related genes were significantly different between LUAD tumor tissues and normal tissues. Seventeen of these genes were related to prognosis. Two clusters (cluster 1 and cluster 2) were identified among 497 LUAD samples based on the expression of 7 prognosis-related genes. Distinct expression patterns were observed between the two clusters. Compared to cluster 2, cluster 1 was characterized by inferior overall survival (OS) (median OS = 41 vs. 60 months, p = 0.00031), increased tumor mutation burden (15.8 vs. 7.5 mut/Mb, p < 0.001), high expression of PD-1 (p < 0.001) and PD-L1 (p < 0.001), as well as enhanced immune infiltration. 1C metabolism-related genes were positively correlated with the expression of methylation enzymes, and a lower methylation level was observed in cluster 1 (p = 0.0062). Patients in cluster 1 were resistant to chemotherapy drugs including pemetrexed, gemcitabine, paclitaxel, etoposide, oxaliplatin, and carboplatin. The specific expression pattern of 1C metabolism-related genes was correlated with a better OS in patients treated with immunotherapy (median OS: 11.2 vs. 7.8 months, p = 0.0034).

Conclusion: This study highlights that 1C metabolism is correlated with the prognosis of LUAD patients and immunotherapy efficacy. Our findings provide novel insights into the role of 1C metabolism in the occurrence, development, and treatment of LUAD, and can assist in guiding immunotherapy for LUAD patients.
The implication of a diversity of non-neuronal cells in disorders affecting brain networks
Authors: Carrier Micaël , Dolhan Kira , Bobotis Bianca Caroline , Desjardins Michèle , Tremblay Marie-Ève
Published: November 2022

In the central nervous system (CNS) neurons are classically considered the functional unit of the brain. Analysis of the physical connections and co-activation of neurons, referred to as structural and functional connectivity, respectively, is a metric used to understand their interplay at a higher level. A myriad of glial cell types throughout the brain composed of microglia, astrocytes and oligodendrocytes are key players in the maintenance and regulation of neuronal network dynamics. Microglia are the central immune cells of the CNS, able to affect neuronal populations in number and connectivity, allowing for maturation and plasticity of the CNS. Microglia and astrocytes are part of the neurovascular unit, and together they are essential to protect and supply nutrients to the CNS. Oligodendrocytes are known for their canonical role in axonal myelination, but also contribute, with microglia and astrocytes, to CNS energy metabolism. Glial cells can achieve this variety of roles because of their heterogeneous populations comprised of different states. The neuroglial relationship can be compromised in various manners in case of pathologies affecting development and plasticity of the CNS, but also consciousness and mood. This review covers structural and functional connectivity alterations in schizophrenia, major depressive disorder, and disorder of consciousness, as well as their correlation with vascular connectivity. These networks are further explored at the cellular scale by integrating the role of glial cell diversity across the CNS to explain how these networks are affected in pathology.
On the representation of hierarchical structure: Revisiting Darwin’s musical protolanguage
Authors: Miyagawa Shigeru , Arévalo Analía , Nóbrega Vitor A.
Published: November 2022

In this article, we address the tenability of Darwin’s musical protolanguage, arguing that a more compelling evolutionary scenario is one where a prosodic protolanguage is taken to be the preliminary step to represent the hierarchy involved in linguistic structures within a linear auditory signal. We hypothesize that the establishment of a prosodic protolanguage results from an enhancement of a rhythmic system that transformed linear signals into speech prosody, which in turn can mark syntactic hierarchical relations. To develop this claim, we explore the role of prosodic cues on the parsing of syntactic structures, as well as neuroscientific evidence connecting the evolutionary development of music and linguistic capacities. Finally, we entertain the assumption that the capacity to generate hierarchical structure might have developed as part of tool-making in human prehistory, and hence was established prior to the enhancement of a prosodic protolinguistic system.
Fatigue performance in patients with chronic insomnia
Authors: Xu Lin , Zhang Qianran , Dong Hongming , Qiao Dandan , Liu Yanyan , Tian Junfang , Xue Rong
Published: November 2022

Insomnia is associated with fatigue and poor driving performance, thus increasing the risk of traffic accidents. This study aimed to evaluate the effect of fatigue on driving in patients with chronic insomnia in a free-flow traffic scenario and car-following scenario, and to investigate the relationships between driving performance, cognitive function, and insomnia. The Trail Making Test (TMT), Stroop Color and Word Test (SCWT), Symbol Digit Modalities Test (SDMT), and Digit Span Test (DST) of 15 participants with mild-to-moderate chronic insomnia and 16 healthy participants were assessed. During the fatigue driving task, drivers completed simulated driving tasks under free-flow traffic and car-following scenarios. The mean speed (MS), mean acceleration (MA), mean lateral position (MLP), and standard deviation of lateral position (SDLP) were measured to assess driving performance. During fatigued tasks, the MA and MLP in the free-driving scenario were higher than those in the car-following scenario (P < 0.01), the SDLP was higher in the insomnia group than in the healthy group (P = 0.02), and the interaction effect was significantly different for MLP between the groups (P = 0.03). MS was negatively correlated with TMT score, SDMT score, and DST score, and positively correlated with time to complete TMT, errors in SCWT, and time to complete SCWT. SDLP was negatively correlated with DST score and positively correlated with time to complete SCWT. Furthermore, the insomnia group had poorer lateral vehicle control ability than the healthy group. The insomnia group had a more impaired driving performance in the free-driving scenario than in the car-following scenario. Drivers with impaired cognitive function exhibited impaired driving performance.
To shift or to rotate? Comparison of acquisition strategies for multi-slice super-resolution magnetic resonance imaging
Authors: Nicastro Michele , Jeurissen Ben , Beirinckx Quinten , Smekens Céline , Poot Dirk H. J. , Sijbers Jan , den Dekker Arnold J.
Published: November 2022

Multi-slice (MS) super-resolution reconstruction (SRR) methods have been proposed to improve the trade-off between resolution, signal-to-noise ratio and scan time in magnetic resonance imaging. MS-SRR consists in the estimation of an isotropic high-resolution image from a series of anisotropic MS images with a low through-plane resolution, where the anisotropic low-resolution images can be acquired according to different acquisition schemes. However, it is yet unclear how these schemes compare in terms of statistical performance criteria, especially for regularized MS-SRR. In this work, the estimation performance of two commonly adopted MS-SRR acquisition schemes based on shifted and rotated MS images respectively are evaluated in a Bayesian framework. The maximum a posteriori estimator, which introduces regularization by incorporating prior knowledge in a statistically well-defined way, is put forward as the estimator of choice and its accuracy, precision, and Bayesian mean squared error (BMSE) are used as performance criteria. Analytic calculations as well as Monte Carlo simulation experiments show that the rotated scheme outperforms the shifted scheme in terms of precision, accuracy, and BMSE. Furthermore, the superior performance of the rotated scheme is confirmed in real data experiments and in retrospective simulation experiments with and without inter-image motion. Results show that the rotated scheme allows regularized MS-SRR with a higher accuracy and precision than the shifted scheme, besides being more resilient to motion.
Peak width of skeletonized mean diffusivity in cerebral amyloid angiopathy: Spatial signature, cognitive, and neuroimaging associations
Authors: Zanon Zotin Maria Clara , Schoemaker Dorothee , Raposo Nicolas , Perosa Valentina , Bretzner Martin , Sveikata Lukas , Li Qi , van Veluw Susanne J. , Horn Mitchell J. , Etherton Mark R. , Charidimou Andreas , Gurol M. Edip , Greenberg Steven M. , Duering Marco , Santos Antonio Carlos dos , Pontes-Neto Octavio M. , Viswanathan Anand
Published: November 2022

Background

Peak width of skeletonized mean diffusivity (PSMD) is a promising diffusion tensor imaging (DTI) marker that shows consistent and strong cognitive associations in the context of different cerebral small vessel diseases (cSVD).

Purpose

Investigate whether PSMD (1) is higher in patients with Cerebral Amyloid Angiopathy (CAA) than those with arteriolosclerosis; (2) can capture the anteroposterior distribution of CAA-related abnormalities; (3) shows similar neuroimaging and cognitive associations in comparison to other classical DTI markers, such as average mean diffusivity (MD) and fractional anisotropy (FA).

Materials and methods

We analyzed cross-sectional neuroimaging and neuropsychological data from 90 non-demented memory-clinic subjects from a single center. Based on MRI findings, we classified them into probable-CAA (those that fulfilled the modified Boston criteria), subjects with MRI markers of cSVD not attributable to CAA (presumed arteriolosclerosis; cSVD), and subjects without evidence of cSVD on MRI (non-cSVD). We compared total and lobe-specific (frontal and occipital) DTI metrics values across the groups. We used linear regression models to investigate how PSMD, MD, and FA correlate with conventional neuroimaging markers of cSVD and cognitive scores in CAA.

Results

PSMD was comparable in probable-CAA (median 4.06 × 10–4 mm2/s) and cSVD (4.07 × 10–4 mm2/s) patients, but higher than in non-cSVD (3.30 × 10–4 mm2/s; p < 0.001) subjects. Occipital-frontal PSMD gradients were higher in probable-CAA patients, and we observed a significant interaction between diagnosis and region on PSMD values [F(2, 87) = 3.887, p = 0.024]. PSMD was mainly associated with white matter hyperintensity volume, whereas MD and FA were also associated with other markers, especially with the burden of perivascular spaces. PSMD correlated with worse executive function (β = −0.581, p < 0.001) and processing speed (β = −0.463, p = 0.003), explaining more variance than other MRI markers. MD and FA were not associated with performance in any cognitive domain.

Conclusion

PSMD is a promising biomarker of cognitive impairment in CAA that outperforms other conventional and DTI-based neuroimaging markers. Although global PSMD is similarly increased in different forms of cSVD, PSMD’s spatial variations could potentially provide insights into the predominant type of underlying microvascular pathology.
Alterations of RNA-binding protein found in neurons in Drosophila neurons and glia influence synaptic transmission and lifespan
Authors: Lin Wei-Yong , Liu Chuan-Hsiu , Cheng Jack , Liu Hsin-Ping
Published: November 2022

The found in neurons (fne), a paralog of the RNA-binding protein ELAV gene family in Drosophila, is required for post-transcriptional regulation of neuronal development and differentiation. Previous explorations into the functions of the FNE protein have been limited to neurons. The function of fne in Drosophila glia remains unclear. We induced the knockdown or overexpression of fne in Drosophila neurons and glia to determine how fne affects different types of behaviors, neuronal transmission and the lifespan. Our data indicate that changes in fne expression impair associative learning, thermal nociception, and phototransduction. Examination of synaptic transmission at presynaptic and postsynaptic terminals of the larval neuromuscular junction (NMJ) revealed that loss of fne in motor neurons and glia significantly decreased excitatory junction currents (EJCs) and quantal content, while flies with glial fne knockdown facilitated short-term synaptic plasticity. In muscle cells, overexpression of fne reduced both EJC and quantal content and increased short-term synaptic facilitation. In both genders, the lifespan could be extended by the knockdown of fne in neurons and glia; the overexpression of fne shortened the lifespan. Our results demonstrate that disturbances of fne in neurons and glia influence the function of the Drosophila nervous system. Further explorations into the physiological and molecular mechanisms underlying neuronal and glial fne and elucidation of how fne affects neuronal activity may clarify certain brain functions.
Association between dietary sodium, potassium, and the sodium-to-potassium ratio and mortality: A 10-year analysis
Authors: Kwon Yu-Jin , Lee Hye Sun , Park Goeun , Lee Ji-Won
Published: November 2022

There is inconclusive evidence of the association between dietary sodium, potassium, and the sodium-to-potassium ratio and all-cause and cardiovascular disease mortality. To investigate the association between dietary sodium, potassium, and the sodium-to-potassium ratio and all-cause and cardiovascular disease mortality risks. Data from 143,050 adult participants were analyzed from prospective 10-year community-based cohort analysis. Dietary sodium, potassium, and the sodium-to-potassium ratio at baseline were assessed by a food frequency questionnaire. In Cox proportional hazards regression models, the association between dietary sodium, potassium, and their ratio and all-cause and cardiovascular disease mortality was estimated using hazard ratios and 95% confidence intervals, and their predictive ability as mortality predictors was evaluated using Harrell’s c-index. During the mean (range) 10.1 (0.2–15.9) years of follow-up, 5,436 participants died, of whom 985 died of cardiovascular causes. After adjustment for age, sex, body mass index, alcohol intake, smoking, regular exercise, total calorie intake, dyslipidemia, hypertension, diabetes, chronic kidney diseases (CKDs), and potassium or sodium intake, respectively, sodium intake was unassociated with all-cause mortality whereas potassium intake was significantly associated inversely with all-cause (Quintile-5 vs. Quintile-1, hazard ratio, 95% confidence interval, 1.09, 0.97–1.22, and 0.79, 0.69–0.91, respectively). The sodium-to-potassium ratio was not significantly associated with all-cause mortality in the adjusted model, and similar trends were observed for cardiovascular disease mortality.