bluuebunny/crossref_metadata_2025 huggingface dataset:
Burden of musculoskeletal disorders in the gulf cooperation council countries, 1990–2019: Findings from the global burden of disease study 2019
Authors: Alzahrani Hosam , Alshehri Mansour A. , Alotaibi Mazyad , Alhowimel Ahmed , Alodaibi Faris , Alamam Dalyah , Zheng Yan , Tyrovolas Stefanos
Published: October 2022

Objective

The purpose of this study was to investigate the burden of musculoskeletal (MSK) health conditions in Gulf Cooperation Council (GCC) countries based on the Global Burden of Disease (GBD) data.

Methods

The data for GCC countries were obtained from the 2019 GBD study to evaluate the burden of MSK disorders which include the following countries: Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates (UAE). The main outcome measures were age-standardized prevalence and years of life lived with disability (YLDs) associated with MSK disorders. The burden of MSK disorders attributable to the category of behavioral, metabolic, or environmental/occupational was reported to estimate the risk-attributable fractions of disease.

Results

MSK disorders prevalence ranked fifth in Kuwait, sixth in Bahrain, Oman, Qatar, and UAE, and seventh in Saudi Arabia among all the diseases in 2019. For all GCC countries, MSK disorders were ranked the second leading cause of disability as measured by YLDs for the years 1990 and 2019. The age-standardized prevalence of MSK disorders in 2019 for Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and UAE was 18.56% (95% UI: 17.51–19.66), 19.35% (18.25–20.52), 18.23% (17.14–19.36), 18.93% (17.81–20.06), 19.05% (17.96–20.22), and 18.26% (17.18–19.38), respectively. The age-standardized YLDs per 100,000 individuals of MSK disorders in 2019 for Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and UAE were 1,734 (1,250–2,285), 1,764 (1,272–2,322), 1,710 (1,224–2,256), 1,721 (1,246–2,274), 1,715 (1,230–2,274), and 1,681 (1,207–2,235), respectively. For risk factors, high body mass index (BMI) had the highest contribution to MSK disorders YLDs in most GCC countries (Bahrain, Kuwait, Oman, and Saudi Arabia), followed by the exposure to occupational ergonomic factors which had the highest contribution to MSK disorders YLDs in Qatar and UAE.

Conclusion

There was an increase in both age-standardized prevalence of MSK disorders and YLDs between 1990 and 2019 that was observed for all GCC countries. Some risk factors such as higher BMI and exposure to occupational ergonomic factors were highly associated with YLDs due to MSK disorders. The results of this study provide guidance for the potential nature of preventative and management programs to optimize the individual’s health.
mRNA vaccines: A novel weapon to control infectious diseases
Authors: Tian Yuying , Deng Zhuoya , Yang Penghui
Published: October 2022

Infectious diseases have always threatened human life, but with the development of vaccines, effective strategies for preventing and controlling these diseases have become available. The global outbreak of COVID-19 ushered in the advent of mRNA vaccine technologies, which quickly led to the introduction of mRNA vaccines effective against SARS-CoV-2. The success of this approach has stimulated research into the use of mRNA vaccines in the fight against other emerging as well as remerging infectious diseases. This review examines the constructive strategies and delivery systems used in mRNA vaccines and provides an overview of current clinical trials of those vaccines in the prevention of infectious diseases. The underlying mechanisms of mRNA vaccines are also discussed, including the double-edged sword of the innate immune response. Finally, the challenges but also the potential of mRNA vaccines are considered.
Heterologous prime-boost BCG with DNA vaccine expressing fusion antigens Rv2299c and Ag85A improves protective efficacy against Mycobacterium tuberculosis in mice
Authors: Wu Juan , Hu Zhidong , Lu Shui-Hua , Fan Xiao-Yong
Published: October 2022

The development of heterologous prime-boost regimens utilizing Bacille Calmette–Guerin (BCG) as the priming vaccine is a promising approach to improve the efficacy of vaccination against tuberculosis (TB). In this study, we examined the ability of a DNA vaccine that expressed a fusion of antigens Rv2299c and Ag85A to boost BCG immunity and protection against Mycobacterium tuberculosis (Mtb) in Balb/c mice. The fusion DNA vaccine was moderately immunogenic and afforded some protection when used on its own. After a priming BCG vaccination, the DNA boost significantly amplified Th1-type cell-mediated immunity compared to that resulting from either BCG or DNA immunization. In the DNA-boosted mice, Ag-specific CD4+ and CD8+ T cells that were mono-positive for IFN-γ alone were the most prominently expanded in infected lungs. The protective efficacy afforded by BCG against challenge infection was greatly improved by the DNA boost; bacterial loads were significantly reduced in both spleen and lung and histological damage in the lung was less. The use of a DNA vaccine containing the fusion antigens Rv2299c and Ag85A to boost BCG may be a good choice for the rational design of an efficient vaccination strategy against TB.
Broad-spectrum resistance mechanism of serine protease Sp1 in Bacillus licheniformis W10 via dual comparative transcriptome analysis
Authors: Yang Lina , Yan Chun , Peng Shuai , Chen Lili , Guo Junjie , Lu Yihe , Li Lianwei , Ji Zhaolin
Published: October 2022

Antagonistic microorganisms are considered to be the most promising biological controls for plant disease. However, they are still not as popular as chemical pesticides due to complex environmental factors in the field. It is urgent to exploit their potential genetic characteristics and excellent properties to develop biopesticides with antimicrobial substances as the main components. Here, the serine protease Sp1 isolated from the Bacillus licheniformis W10 strain was confirmed to have a broad antifungal and antibacterial spectrum. Sp1 treatment significantly inhibited fungal vegetative growth and damaged the structure of hyphae, in accordance with that caused by W10 strain. Furthermore, Sp1 could activate the systemic resistance of peach twigs, fruits and tobacco. Dual comparative transcriptome analysis uncovered how Sp1 resisted the plant pathogenic fungus Phomopsis amygdali and the potential molecular resistance mechanisms of tobacco. In PSp1 vs. P. amygdali, RNA-seq identified 150 differentially expressed genes (DEGs) that were upregulated and 209 DEGs that were downregulated. Further analysis found that Sp1 might act on the energy supply and cell wall structure to inhibit the development of P. amygdali. In TSp1 vs. Xanthi tobacco, RNA-seq identified that 5937 DEGs were upregulated and 2929 DEGs were downregulated. DEGs were enriched in the metabolic biosynthesis pathways of secondary metabolites, plant hormone signal transduction, plant–pathogen interactions, and MAPK signaling pathway–plant and further found that the genes of salicylic acid (SA) and jasmonic acid (JA) signaling pathways were highly expressed and the contents of SA and JA increased significantly, suggesting that systemic resistance induced by Sp1 shares features of SAR and ISR. In addition, Sp1 might induce the plant defense responses of tobacco. This study provides insights into the broad-spectrum resistance molecular mechanism of Sp1, which could be used as a potential biocontrol product.
Dynamic change of bacterial diversity, metabolic pathways, and flavor during ripening of the Chinese fermented sausage
Authors: Wang Ji , Aziz Tariq , Bai Ruxue , Zhang Xin , Shahzad Muhammad , Sameeh Manal Y. , Khan Ayaz Ali , Dablool Anas S. , Zhu Yingchun
Published: October 2022

Chinese fermented sausage is a famous fermented meat product with a complex microbiota that has a potential impact on flavor and quality. In this study, Lactobacillus plantarum MSZ2 and Staphylococcus xylosus YCC3 were used as starter cultures to investigate the change in bacterial diversity, metabolic pathways, and flavor compounds during the ripening process of fermented sausages. High-throughput sequencing technology and headspace solid-phase microextraction-gas chromatography–mass spectrometry (HS-SPME-GC/MS) were applied for characterizing the profiles of bacterial diversity, metabolic pathways, and flavor compounds in sausage samples on days 0, 6, and 12 during ripening. Results showed that Lactobacillus, Staphylococcus, Lactococcus, Leuconostoc, and Weissella were the most abundant bacterial genera found in the sausage samples during all stages of fermentation. Functional prediction reveals the abundance of 12 different metabolic pathways, the most important pathways are carbohydrate metabolism, nucleotide metabolism, lipid metabolism, and amino acid metabolism. A total of 63 volatile compounds were successfully identified in fermented sausage samples. Correlational analysis demonstrated that Staphylococcus and Leuconostoc were closely related to the formation of flavor compounds. Therefore, the present study may provide guidance for future use of microbiota to improve flavor, quality, and preservation of fermented sausages.
Mild cognitive impairment is associated with poor gait performance in patients with Parkinson’s disease
Authors: Kang Sung Hoon , Kim Jinhee , Lee Jungyeun , Koh Seong-Beom
Published: October 2022

Cognitive impairment may be commonly accompanied by gait disturbance in patients with Parkinson’s disease (PD). However, it is still controversial whether gait disturbance is associated with mild cognitive impairment (MCI) and which cognitive function has a more important effect on specific gait parameter. Our objective was to investigate the association of gait parameters with MCI and the correlation between performance on comprehensive neuropsychological tests and gait parameters in PD patients. We enrolled 257 patients with de novo PD (111 PD-normal cognition and 146 PD-MCI). All patients underwent comprehensive neuropsychological tests and gait evaluation using the GAITRite system. We used logistic regression analysis and partial correlation to identify the association between gait parameters and MCI and correlations between neuropsychological performance and gait parameters. Gait velocity (odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.97−0.99) and stride length (OR = 0.98; 95% CI = 0.97−0.99) were associated with MCI in patients with PD. Specifically, gait velocity, stride length, and double support ratio were only associated with attention and frontal-executive function performance in patients with PD. Our findings provide insight into the relationship between gait disturbance and MCI in patients with PD. Furthermore, the evaluation of gait disturbance is necessary for PD patients with cognitive impairment.
Cognitive dysfunction associated with COVID-19: Prognostic role of circulating biomarkers and microRNAs
Authors: Alvarez Marissa , Trent Erick , Goncalves Bruno De Souza , Pereira Duane G. , Puri Raghav , Frazier Nicolas Anthony , Sodhi Komal , Pillai Sneha S.
Published: October 2022

COVID-19 is renowned as a multi-organ disease having subacute and long-term effects with a broad spectrum of clinical manifestations. The evolving scientific and clinical evidence demonstrates that the frequency of cognitive impairment after COVID-19 is high and it is crucial to explore more clinical research and implement proper diagnostic and treatment strategies. Several central nervous system complications have been reported as comorbidities of COVID-19. The changes in cognitive function associated with neurodegenerative diseases develop slowly over time and are only diagnosed at an already advanced stage of molecular pathology. Hence, understanding the common links between COVID-19 and neurodegenerative diseases will broaden our knowledge and help in strategizing prognostic and therapeutic approaches. The present review focuses on the diverse neurodegenerative changes associated with COVID-19 and will highlight the importance of major circulating biomarkers and microRNAs (miRNAs) associated with the disease progression and severity. The literature analysis showed that major proteins associated with central nervous system function, such as Glial fibrillary acidic protein, neurofilament light chain, p-tau 181, Ubiquitin C-terminal hydrolase L1, S100 calcium-binding protein B, Neuron-specific enolase and various inflammatory cytokines, were significantly altered in COVID-19 patients. Furthermore, among various miRNAs that are having pivotal roles in various neurodegenerative diseases, miR-146a, miR-155, Let-7b, miR-31, miR-16 and miR-21 have shown significant dysregulation in COVID-19 patients. Thus the review consolidates the important findings from the numerous studies to unravel the underlying mechanism of neurological sequelae in COVID-19 and the possible association of circulatory biomarkers, which may serve as prognostic predictors and therapeutic targets in future research.
Deconstructing delirium in the post anaesthesia care unit
Authors: Banerji Antara , Sleigh Jamie W. , Voss Logan J. , Garcia Paul S. , Gaskell Amy L.
Published: October 2022

The course of neuro-cognitive recovery following anaesthesia and surgery is distinctive and poorly understood. Our objective was to identify patterns of neuro-cognitive recovery of the domains routinely assessed for delirium diagnosis in the post anaesthesia care unit (PACU) and to compare them to the cognitive recovery patterns observed in other studies; thereby aiding in the identification of pathological (high risk) patterns of recovery in the PACU. We also compared which of the currently available tests (3D-CAM, CAM-ICU, and NuDESC) is the best to use in PACU. This was a post hoc secondary analysis of data from the Alpha Max study which involved 200 patients aged over 60 years, scheduled for elective surgery under general anaesthesia lasting more than 2 h. These patients were assessed for delirium at 30 min following arrival in the PACU, if they were adequately arousable (Richmond Agitation Sedation Score ≥ −2). All tests for delirium diagnosis (3D-CAM, CAM-ICU, and NuDESC) and the sub-domains assessed were compared to understand temporal recovery of neurocognitive domains. These data were also analysed to determine the best predictor of PACU delirium. We found the incidence of PACU delirium was 35% (3D-CAM). Individual cognitive domains were affected differently. Few individuals had vigilance deficits (6.5%, n = 10 CAM-ICU) or disorganized thinking (19% CAM-ICU, 27.5% 3D-CAM), in contrast attention deficits were common (72%, n = 144) and most of these patients (89.5%, n = 129) were not sedated (RASS ≥ −2). CAM-ICU (27%) and NuDESC (52.8%) detected fewer cases of PACU delirium compared to 3D-CAM. In conclusion, return of neurocognitive function is a stepwise process; Vigilance and Disorganized Thinking are the earliest cognitive functions to return to baseline and lingering deficits in these domains could indicate an abnormal cognitive recovery. Attention deficits are relatively common at 30 min in the PACU even in individuals who appear to be awake. The 3D CAM is a robust test to check for delirium in the PACU.
Targeting the cannabinoid system to counteract the deleterious effects of stress in Alzheimer’s disease
Authors: Shade Ronnie D. , Ross Jennifer A. , Van Bockstaele Elisabeth J.
Published: October 2022

Alzheimer’s diseaseis a progressive neurodegenerative disorder characterized histologically in postmortem human brains by the presence of dense protein accumulations known as amyloid plaques and tau tangles. Plaques and tangles develop over decades of aberrant protein processing, post-translational modification, and misfolding throughout an individual’s lifetime. We present a foundation of evidence from the literature that suggests chronic stress is associated with increased disease severity in Alzheimer’s patient populations. Taken together with preclinical evidence that chronic stress signaling can precipitate cellular distress, we argue that chronic psychological stress renders select circuits more vulnerable to amyloid- and tau- related abnormalities. We discuss the ongoing investigation of systemic and cellular processes that maintain the integrity of protein homeostasis in health and in degenerative conditions such as Alzheimer’s disease that have revealed multiple potential therapeutic avenues. For example, the endogenous cannabinoid system traverses the central and peripheral neural systems while simultaneously exerting anti-inflammatory influence over the immune response in the brain and throughout the body. Moreover, the cannabinoid system converges on several stress-integrative neuronal circuits and critical regions of the hypothalamic-pituitary-adrenal axis, with the capacity to dampen responses to psychological and cellular stress. Targeting the cannabinoid system by influencing endogenous processes or exogenously stimulating cannabinoid receptors with natural or synthetic cannabis compounds has been identified as a promising route for Alzheimer’s Disease intervention. We build on our foundational framework focusing on the significance of chronic psychological and cellular stress on the development of Alzheimer’s neuropathology by integrating literature on cannabinoid function and dysfunction within Alzheimer’s Disease and conclude with remarks on optimal strategies for treatment potential.
Effects of motor-cognitive interaction based on dual-task gait analysis recognition in middle age to aging people with normal cognition and mild cognitive impairment
Authors: Zheng Yuxin , Lang Shijuan , Liang Junjie , Jiang Yongchun , Zhao Biyi , Chen Hongxin , Huang Dongqing , Li Qinyi , Liu Huijin , Chen Shudi , Yilifate Anniwaer , Xu Fangqiu , Ou Haining , Lin Qiang
Published: October 2022

Background

Mild cognitive impairment (MCI) is considered a transitional stage between cognitive normality and dementia among the elderly, and its associated risk of developing Alzheimer’s disease (AD) is 10–15 times higher than that of the general population. MCI is an important threshold for the prevention and control of AD, and intervention in the MCI stage may be the most effective strategy to delay the occurrence of AD.

Materials and methods

In this study, 68 subjects who met the inclusion criteria were divided into an MCI group (38 subjects) and normal elderly (NE) group (30 subjects). Both groups underwent clinical function assessments (cognitive function, walking function, and activities of daily living) and dual-task three-dimensional gait analysis (walking motor task and walking calculation task). Spatial-temporal parameters were obtained and reduced by principal component analysis, and the key biomechanical indexes were selected. The dual-task cost (DTC) was calculated for intra-group (task factor) and inter-group (group factor) comparisons.

Results

The results of the principal component analysis showed that the cadence parameter had the highest weight in all three walking tasks. In addition, there were significant differences in the cadence both walking motor task (WMT) vs. walking task (WT) and walking calculation task (WCT) vs. WT in the MCI group. The cadence in the NE group only showed a significant difference between WMT and WT. The only differences between the MCI group and NE group was DTC cadence in WCT, and no differences were found for cadence in any of the three walking tasks.

Conclusion

The results show that dual tasks based on cognitive-motor gait analysis of DTCcadence in MCI have potential value for application in early identification and provide theoretical support to improve the clinical diagnosis of MCI.
Inorganic nanoparticle empowered biomaterial hybrids: Engineered payload release
Authors: Morillas-Becerill Lucía , De Cola Luisa , Zuidema Jonathan M.
Published: October 2022

There are many challenges in delivering active pharmaceutical ingredients from biomaterials, including retention of payload activity, accurate temporal release, and precise spatial administration, to name only a few. With our constantly increasing knowledge of biology and physiology, pathologies that require therapeutic interventions are becoming more understood. While the desired temporal and spatial administration of a therapy might be theorized, the ability to deliver an active therapeutic in a precise location during a specific time frame is often challenging. This has led researchers to develop hybrid biomaterials containing inorganic nanoparticles in order to combine the advantages of both inorganics and organics in payload delivery applications. Organic materials have many beneficial properties, including the ability to form networks and matrices to create three-dimensional structures from the nanometer to centimeter scale, biodegradability, the versatility to use both synthetic and natural precursors, and ease of chemical modifications, while inorganic materials offer highly controllable nanoscale features, can entrap and protect therapeutics, and have degradation properties that can be tightly regulated. Here in, we discuss the current state-of-the-art in active pharmaceutical ingredient delivery from biomaterial hybrids, demonstrate the added levels of control that these hybrid biomaterials offer, and give our perspective on future innovations in the field.
Preferential consolidation of emotional reactivity during sleep: A systematic review and meta-analysis
Authors: Lipinska Gosia , Austin Holly , Moonsamy Jasmin R. , Henry Michelle , Lewis Raphaella , Baldwin David S. , Thomas Kevin G. F. , Stuart Beth
Published: October 2022

Many studies have investigated whether sleep affects cognitively unmodulated reactivity to emotional stimuli. These studies operationalize emotion regulation by using subjective and/or objective measures to compare pre- and post-sleep reactivity to the same emotional stimuli. Findings have been inconsistent: some show that sleep attenuates emotional reactivity, whereas others report enhanced or maintained reactivity. Across-study methodological differences may account for discrepant findings. To resolve the questions of whether sleep leads to the attenuation, enhancement, or maintenance of emotional reactivity, and under which experimental conditions particular effects are observed, we undertook a synthesized narrative and meta-analytic approach. We searched PubMed, PsycINFO, PsycARTICLES, Web of Science, and Cochrane Library databases for relevant articles, using search terms determined a priori and search limits of language = English, participants = human, and dates = January 2006–June 2021. Our final sample included 24 studies that investigated changes in emotional reactivity in response to negatively and/or positively valenced material compared to neutral material over a period of sleep compared to a matched period of waking. Primary analyses used random effects modeling to investigate whether sleep preferentially modulates reactivity in response to emotional stimuli; secondary analyses examined potential moderators of the effect. Results showed that sleep (or equivalent periods of wakefulness) did not significantly affect psychophysiological measures of reactivity to negative or neutral stimuli. However, self-reported arousal ratings of negative stimuli were significantly increased post-sleep but not post-waking. Sub-group analyses indicated that (a) sleep-deprived participants, compared to those who slept or who experienced daytime waking, reacted more strongly and negatively in response to positive stimuli; (b) nap-exposed participants, compared to those who remained awake or who slept a full night, rated negative pictures less negatively; and (c) participants who did not obtain substantial REM sleep, compared to those who did and those exposed to waking conditions, had attenuated reactivity to neutral stimuli. We conclude that sleep may affect emotional reactivity, but that studies need more consistency in methodology, commitment to collecting both psychophysiological and self-report measures, and should report REM sleep parameters. Using these methodological principles would promote a better understanding of under which conditions particular effects are observed.
The relationship between vertebrobasilar artery calcification and intracranial atherosclerosis-related occlusion in thrombectomy
Authors: Han Nannan , Zhang Gejuan , Yang Shiyao , Ma Haojun , Ge Hanming , Zhang Xiao , Li Shilin , Wang Yanfei , Fan Xiaonan , Yin Yanling , Gao Yanjun , Shi Wenzhen , Zhang Xiaobo , Chang Mingze , Tian Ye
Published: October 2022

Background and purpose

Distinguishing between intracranial atherosclerosis-related occlusion (ICAS-O) and non-ICAS-O can benefit strategies of identifying the need for surgical plans prior to thrombectomy. We investigated the association between vertebrobasilar artery calcification (VBAC) and ICAS-O in acute ischemic stroke patients undergoing thrombectomy.

Methods

Patients were recruited from a prospective single-center registration study who had undergone thrombectomy between October 2017 and October 2021. The enrolled patients were divided into ICAS-O and non-ICAS-O, as determined by the intraarterial therapy process. The occurrences of VBAC were recorded on intracranial non-contrast computed tomography (NCCT) scans before thrombectomy. The association between VBAC and ICAS-O was assessed using binary logistic regression.

Results

A total of 2732 patients who had undergone digital subtraction angiography were reviewed, and 314 thrombectomy patients (mean age: 65.4 years, 36.6% female) with NCCT were enrolled in this study. VBAC was detected before thrombectomy in 113 (36%) out of 314 patients. Age, hypertension, and diabetes were associated with VBAC, and a higher frequency of VBAC was identified in patients presenting posterior circulation. ICAS-O accounts for 43% (135/314) in eligible patients. From multivariable analyses, VBAC was identified as an independent predictor of ICAS-O (adjusted odds ratio, 6.16 [95% CI, 2.673–14.217], P < 0.001). Meanwhile, the (VBAC[+] atrial fibrillation[-]) group displayed higher rates of ICAS-O than the (VBAC[-] atrial fibrillation [-]) group (P < 0.001).

Conclusions

We demonstrated that VBAC is an independent risk factor for ICAS-O in patients who underwent thrombectomy. Patients free of atrial fibrillation with VBAC have more trend to be ICAS-O.
Abnormal cortical morphology in children and adolescents with intermittent exotropia
Authors: Wang Xi , Lu Lu , Liao Meng , Wei Hong , Chen Xiaohang , Huang Xiaoqi , Liu Longqian , Gong Qiyong
Published: October 2022

Purpose

To investigate cortical differences, age-related cortical differences, and structural covariance differences between children with intermittent exotropia (IXT) and healthy controls (HCs) using high-resolution magnetic resonance imaging (MRI).

Methods

Sixteen IXT patients and 16 HCs underwent MRI using a 3-T MR scanner. FreeSurfer software was used to obtain measures of cortical volume, thickness, and surface area. Group differences in cortical thickness, volume and surface area were examined using a general linear model with intracranial volume (ICV), age and sex as covariates. Then, the age-related cortical differences between the two groups and structural covariance in abnormal morphometric changes were examined.

Results

Compared to HCs, IXT patients demonstrated significantly decreased surface area in the left primary visual cortex (PVC), and increased surface area in the left inferior temporal cortex (ITC). We also found increased cortical thickness in the left orbitofrontal cortex (OFC), right middle temporal cortex (MT), and right inferior frontal cortex (IFC). No significant differences were found in cortical volume between the two groups. There were several negative correlations between neuroanatomic measurements and age in the HC group that were not observed in the IXT group. In addition, we identified altered patterns of structural correlations across brain regions in patients with IXT.

Conclusion

To our knowledge, this study is the first to characterize the cortical morphometry of the children and adolescents with IXT. Based on our results, children and adolescents with IXT exhibited significant alterations in the PVC and association cortices, different cortical morphometric development patterns, and disrupted structural covariance across brain regions.
WNT signaling at the intersection between neurogenesis and brain tumorigenesis
Authors: Alkailani Maisa I. , Aittaleb Mohamed , Tissir Fadel
Published: October 2022

Neurogenesis and tumorigenesis share signaling molecules/pathways involved in cell proliferation, differentiation, migration, and death. Self-renewal of neural stem cells is a tightly regulated process that secures the accuracy of cell division and eliminates cells that undergo mitotic errors. Abnormalities in the molecular mechanisms controlling this process can trigger aneuploidy and genome instability, leading to neoplastic transformation. Mutations that affect cell adhesion, polarity, or migration enhance the invasive potential and favor the progression of tumors. Here, we review recent evidence of the WNT pathway’s involvement in both neurogenesis and tumorigenesis and discuss the experimental progress on therapeutic opportunities targeting components of this pathway.
C-type natriuretic peptide preserves central neurological function by maintaining blood-brain barrier integrity
Authors: Perez-Ternero Cristina , Pallier Patrick N. , Tremoleda Jordi L. , Delogu Alessio , Fernandes Cathy , Michael-Titus Adina T. , Hobbs Adrian J.
Published: October 2022

C-type natriuretic peptide (CNP) is highly expressed in the central nervous system (CNS) and key to neuronal development; however, a broader role for CNP in the CNS remains unclear. To address this deficit, we investigated behavioral, sensory and motor abnormalities and blood-brain barrier (BBB) integrity in a unique mouse model with inducible, global deletion of CNP (gbCNP–/–). gbCNP–/– mice and wild-type littermates at 12 (young adult) and 65 (aged) weeks of age were investigated for changes in gait and motor coordination (CatWalk™ and rotarod tests), anxiety-like behavior (open field and elevated zero maze tests), and motor and sensory function (modified neurological severity score [mNSS] and primary SHIRPA screen). Vascular permeability was assessed in vivo (Miles assay) with complementary in vitro studies conducted in primary murine brain endothelial cells. Young adult gbCNP–/– mice had normal gait but reduced motor coordination, increased locomotor activity in the open field and elevated zero maze, and had a higher mNSS score. Aged gbCNP–/– animals developed recurrent spontaneous seizures and had impaired gait and wide-ranging motor and sensory dysfunction. Young adult and aged gbCNP–/– mice exhibited increased BBB permeability, which was partially restored in vitro by CNP administration. Cultured brain endothelial cells from gbCNP–/– mice had an abnormal ZO-1 protein distribution. These data suggest that lack of CNP in the CNS impairs tight junction protein arrangement and increases BBB permeability, which is associated with changes in locomotor activity, motor coordination and late-onset seizures.
Automatic autism spectrum disorder detection using artificial intelligence methods with MRI neuroimaging: A review
Authors: Moridian Parisa , Ghassemi Navid , Jafari Mahboobeh , Salloum-Asfar Salam , Sadeghi Delaram , Khodatars Marjane , Shoeibi Afshin , Khosravi Abbas , Ling Sai Ho , Subasi Abdulhamit , Alizadehsani Roohallah , Gorriz Juan M. , Abdulla Sara A. , Acharya U. Rajendra
Published: October 2022

Autism spectrum disorder (ASD) is a brain condition characterized by diverse signs and symptoms that appear in early childhood. ASD is also associated with communication deficits and repetitive behavior in affected individuals. Various ASD detection methods have been developed, including neuroimaging modalities and psychological tests. Among these methods, magnetic resonance imaging (MRI) imaging modalities are of paramount importance to physicians. Clinicians rely on MRI modalities to diagnose ASD accurately. The MRI modalities are non-invasive methods that include functional (fMRI) and structural (sMRI) neuroimaging methods. However, diagnosing ASD with fMRI and sMRI for specialists is often laborious and time-consuming; therefore, several computer-aided design systems (CADS) based on artificial intelligence (AI) have been developed to assist specialist physicians. Conventional machine learning (ML) and deep learning (DL) are the most popular schemes of AI used for diagnosing ASD. This study aims to review the automated detection of ASD using AI. We review several CADS that have been developed using ML techniques for the automated diagnosis of ASD using MRI modalities. There has been very limited work on the use of DL techniques to develop automated diagnostic models for ASD. A summary of the studies developed using DL is provided in the Supplementary Appendix. Then, the challenges encountered during the automated diagnosis of ASD using MRI and AI techniques are described in detail. Additionally, a graphical comparison of studies using ML and DL to diagnose ASD automatically is discussed. We suggest future approaches to detecting ASDs using AI techniques and MRI neuroimaging.
Gut microbiota changes and biological mechanism in hepatocellular carcinoma after transarterial chemoembolization treatment
Authors: Bian Chao-fan , Wang Ying , Yu Ao , Fu Lulan , Zhang Ding , Zhu Wenzhi , Lv Weifu
Published: October 2022

Background and aims

Intestinal flora is closely associated with the occurrence and development of hepatocellular carcinoma (HCC). However, gut microbial changes and biological mechanisms in HCC after transarterial chemoembolization (TACE) treatment are rarely reported.

Methods

We evaluated changes in intestinal flora after TACE in rabbit HCC models and assessed the impact of these changes on the disease. Twenty-four rabbit VX2 HCC models were established and intestinal flora structures, intestinal barrier function, changes in blood lipopolysaccharide (LPS) levels, Toll-like receptor 4 (TLR4), Cyclooxygenase-2 (COX-2), and p-signal transducer and activator of transcription 3(p-STAT3) protein expression levels were studied after TACE treatment.

Results

Compared with healthy rabbits, the intestinal flora in HCC models exhibited structural changes; intestinal barrier function was decreased, and increased LPS levels entered the circulation. A short-term follow-up after TACE showed the procedure partially reversed the intestinal microflora disorder caused by the tumor: intestinal barrier and liver functions were improved, intestinal LPS levels in the blood were reduced, and liver metabolism toward LPS was enhanced. Correlation analyses of the first 75 significantly changed bacteria with clinical factors showed that harmful bacteria had decreased and beneficial bacteria increased. Blood LPS levels and downstream signaling molecule TLR4, COX-2, and p-STAT3 protein expression levels were reduced, which correlated with tumor drug resistance and invasion capabilities.

Conclusions

We first characterized gut microbiota changes and biological mechanisms in HCC after TACE treatment. Our data provide a theoretical research basis for TACE combined with an intestinal flora intervention and systemic chemotherapy.
COL10A1 allows stratification of invasiveness of colon cancer and associates to extracellular matrix and immune cell enrichment in the tumor parenchyma
Authors: Kahlert Ulf D. , Shi Wenjie , Strecker Marco , Scherpinski Lorenz A. , Wartmann Thomas , Dölling Maximilian , Perrakis Aristotelis , Relja Borna , Mengoni Miriam , Braun Andreas , Croner Roland S.
Published: October 2022

Background

Treatment options for metastatic colorectal cancer (CRC) are mostly ineffective. We present new evidence that tumor tissue collagen type X alpha 1 (COL10A1) is a relevant candidate biomarker to improve this dilemma.

Methods

Several public databases had been screened to observe COL10A1 expression in transcriptome levels with cell lines and tissues. Protein interactions and alignment to changes in clinical parameters and immune cell invasion were performed, too. We also used algorithms to build a novel COL10A1-related immunomodulator signature. Various wet-lab experiments were conducted to quantify COL10A1 protein and transcript expression levels in disease and control cell models.

Results

COL10A1 mRNA levels in tumor material is clinical and molecular prognostic, featuring upregulation compared to non-cancer tissue, increase with histomorphological malignancy grading of the tumor, elevation in tumors that invade perineural areas, or lymph node invasion. Transcriptomic alignment noted a strong positive correlation of COL10A1 with transcriptomic signature of cancer-associated fibroblasts (CAFs) and populations of the immune compartment, namely, B cells and macrophages. We verified those findings in functional assays showing that COL10A1 are decreased in CRC cells compared to fibroblasts, with strongest signal in the cell supernatant of the cells.

Conclusion

COL10A1 abundance in CRC tissue predicts metastatic and immunogenic properties of the disease. COL10A1 transcription may mediate tumor cell interaction with its stromal microenvironment.
Patient-associated risk factors for severe anemia in patients with advanced ovarian or breast cancer receiving olaparib monotherapy: A multicenter retrospective study
Authors: Tashiro Ryota , Kawazoe Hitoshi , Mamishin Kanako , Seto Keisuke , Udagawa Ryoko , Saito Yoshimasa , Hashimoto Hironobu , Shimoi Tatsunori , Yonemori Kan , Yonemura Masahito , Terakado Hiroyuki , Kawasaki Toshikatsu , Furukawa Tetsuya , Nakamura Tomonori
Published: October 2022

Background

Olaparib-induced anemia is a frequently occurring complication in patients with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and is associated with a marked deterioration in patients’ health-related quality of life. This study aimed to clarify patient-specific risk factors for severe anemia in patients with advanced ovarian or breast cancer receiving olaparib monotherapy in a real-world setting.

Methods

This multicenter, retrospective, observational study enrolled consecutively presenting patients with advanced ovarian or breast cancer who received olaparib monotherapy as maintenance or palliative treatment between April 2018 and December 2020 at three participating medical institutions in Japan. The primary endpoint was patient-associated risk factors underlying the onset of grade ≥3 anemia from olaparib treatment initiation to 90 days after treatment. Receiver operating characteristic curves were constructed and univariable and multivariable logistic regression analyses were performed to evaluate the association between patient-associated risk factors and grade ≥3 anemia.

Results

Of 113 patients evaluated in this study, 32.7% (n= 37) had grade ≥3 anemia. Multivariable logistic regression analysis revealed that low baseline red blood cell (RBC) count (<3.3 × 106cells/μL), low baseline hematocrit level (<35%), low baseline hemoglobin level (<11.6 g/dL), and breast cancer susceptibility (BRCA1/2) mutation were significantly associated with the onset of grade ≥3 anemia (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 1.28–9.62;P= 0.017, adjusted OR, 3.63; 95% CI, 1.28–11.64;P= 0.021, adjusted OR, 3.89; 95% CI, 1.39–12.21;P= 0.014, and adjusted OR, 4.09; 95% CI, 1.55–11.67;P= 0.006, respectively).

Conclusions

Our findings suggest that low baseline RBC count, low baseline hematocrit level, and low baseline hemoglobin level might be the patient-associated risk factors for severe anemia induced by olaparib monotherapy. Additionally,BRCA1/2mutation was suggested to be a patient-related risk factor for anemia regardless of severity. Therefore, applying these patient-associated risk factors would help classify and screen patients at risk of severe anemia.
Childhood cancer survivorship care: A qualitative study of healthcare providers’ professional preferences
Authors: McLoone Jordana K. , Chen Weihan , Wakefield Claire E. , Johnston Karen , Bell Rachael , Thornton-Benko Elysia , Cohn Richard J. , Signorelli Christina
Published: October 2022

Purpose

Childhood cancer survivorship care is a complex specialty, though it is increasingly being integrated into the general practitioner’s (GP) remit. Establishing the essential components of tertiary- and primary-led care, to maximize the benefits and overcome the challenges inherent to each, is essential to inform the development of survivor-centered, sustainable care models.

Methods

We used the qualitative principles of semi-structured interviewing, verbatim transcription, coding (supported by NVivo12) and thematic analysis, to collect and evaluate the views and preferences of pediatric oncologists, survivorship nurse coordinators, and GPs currently caring for childhood cancer survivors.

Results

Seventy healthcare providers (19 oncology staff and 51 GPs) from 11 tertiary hospitals and 51 primary practices across Australia and New Zealand participated. Participants reported specialist expertise and holistic family-centered care as the key benefits of tertiary and primary care respectively. Participants reported that tertiary-led survivorship care was significantly challenged by a lack of dedicated funding and costs/travel burden incurred by the survivor, whereas primary-led survivorship care was challenged by insufficient GP training and GPs’ reliance on oncologist-developed action plans to deliver guideline-based care. GPs also reported a need for ongoing access to survivorship expertise/consultants to support care decisions at critical times. The discharge of survivors into primary care limited late-effects data collection and the rapid implementation of novel research findings.

Conclusions

Healthcare professionals report that while a risk-stratified, collaborative model of survivor-centered care is optimal, to be implemented successfully, greater provisions for the ongoing engagement of GPs and further access to GP education/training are needed.
Real-time optical imaging of the hypoxic status in hemangioma endothelial cells during propranolol therapy
Authors: Wu Yue , Yang Xiaojuan , Zhai Mingrui , Chen Yi , Lu Xiaoya , Ju Jiandong , Zhang Huanqing , Wang Guanduo , Zhang Zhe , Zhu Baocun , Wang Xuan , Chen Zhanwei , Huang Shengyun
Published: October 2022

Infantile hemangioma (IH) is the most common microvascular tumor of infancy involving the area of head and neck. One of the most important independent risk factors of IH is the hypoxia microenvironment. Fluorescent chemosensor provides a noninvasive intervention, high spatiotemporal resolution, ultrasensitive response, and real-time feedback approach to reveal the hypoxic status of cells. Our research group developed an ultrasensitive fluorescent chemosensor, HNT-NTR, and investigated the potential ability of imaging the hypoxic status of hemangioma-derived endothelial cells (HemECs). In this study, we successfully visualized the propranolol (PRN) treatment in HemECs using NHT-NTR with “Turn-off” sensing method. This chemosensor exhibited high sensitivity and selectivity for optical imaging of hypoxic status with fast responsiveness, real-time feedback and durable photostability of the fluorescent signal. It was also confirmed that HNT-NTR could monitor nitroreductase in vivo. Paramountly, we expected this chemosensor to offer an available optical method for imaging of the hypoxic status and visualizing the therapeutic status of PRN therapy in IH with the hypoxia-imaging capability.
Impact on clinical outcomes from transcatheter closure of the Fontan fenestration: A systematic review and meta-analysis
Authors: Greenleaf Christopher E. , Lim Zhia Ning , Li Wen , LaPar Damien J. , Salazar Jorge D. , Corno Antonio F.
Published: October 2022

Background

Meta-analysis of the impact on clinical outcome from transcatheter closure of Fontan fenestration.

Methods

Cochrane, Embase, MEDLINE, and Open-Gray were searched. Parameters such as changes in oxygen saturation, cavo-pulmonary pressure, maximum heart rate during exercise, exercise duration, and oxygen saturation after fenestration closure were pooled and statistical analysis performed.

Results

Among 922 publications, 12 retrospective observational studies were included. The included studies involved 610 patients, of which 552 patients (90.5%) had a fenestration. Of those patients, 505 patients (91.5%) underwent attempt at trans-catheter closure. When it could be estimated, the pooled overall mean age at trans-catheter fenestration closure was 6.6 ± 7.4 years, and the mean follow-up time was 34.4 ± 10.7 months. There were 32 minor (6.3%) and 20 major (4.0%) complications during or after trans-catheter Fontan fenestration closure. The forest plots demonstrate that following fenestration closure, there was a significant increase in the mean arterial oxygen saturation of 7.9% (95% CI 6.4–9.4%, p < 0.01). There was also a significant increase in the mean cavo-pulmonary pressure of 1.4 mmHg (95% CI 1.0–1.8 mmHg, p < 0.01) following fenestration closure. The exercise parameters reported in 3 studies also favored closing the fenestration as well, yet the exercise duration increase of 1.7 min (95% CI 0.7–2.8 min, p < 0.01) after fenestration closure is probably clinically insignificant.

Conclusion

Late closure of a Fontan fenestration has the impact of improving resting oxygen saturation, exercise oxygen saturation, and a modest improvement of exercise duration. These clinical benefits, however, may be at the expense of tolerating slightly higher cavo-pulmonary mean pressures.
Rotation of both X- and Y-axes is a predictive confounder of ulnar nerve injury and open reduction in pediatric lateral flexion supracondylar humeral fractures: A retrospective cohort study
Authors: Sun Jun , Shan Jing , Meng Lian , Liu Tianjing , Wang Enbo , Jia Guoqiang
Published: October 2022

Background

Rotation of the distal fragment often occurs in flexion-type supracondylar humerus fractures (SCHFs), potentially leading to ulnar nerve injury (UNI) and open reduction. We analyzed the correlation between the rotations and UNI or open reduction and then assessed the risk factors associated with these rotations.

Methods

Data of Wilkins type III lateral flexion SCHFs were collected over a 10-year time period (1 January 2012 to 31 December 2021) in Children's Hospital of Fudan University Anhui Hospital. We defined the rotation of the distal fragment on the coordinate axis as two types, IIIA (X-axis rotation) and IIIB (the rotation of bothX- andY-axes) on X-ray radiography. Demographic data, the incidence of the two-type rotation, odds ratios (ORs) of UNI and open reduction, and risk factors of the rotation of bothX- andY-axes were analyzed.

Results

Totally, 152 patients were found (50 with IIIA vs. 102 IIIB). The UNI rate was 13%, and the open reduction rate was 22%. The UNI rate of the IIIB was five-fold higher than that of the IIIA [OR, 5.143; 95% confidence interval (CI), 1.414–23.125;p= 0.019], and the open reduction rate of the IIIB was nearly five-fold higher than that of the IIIA (OR, 4.729, 95%CI, 1.584–14.495;p= 0.003). In these two types, patients with UNI had a higher risk of open reduction than those without UNI (OR, 9.816; 95%CI, 3.503–27.508;p= 0.001). In the multiple regression analysis, a high level of fracture was identified as a risk factor for the rotation of bothX- andY-axes.

Conclusion

Type IIIB lateral flexion-type SCHFs have higher rates of UNI and open reduction, and a high level of fracture is a risk factor associated with this type.