bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Life Experience of the Effects of Cladribine Tablets on Lymphocyte Subsets and Serum Neurofilament Light Chain Levels in Relapsing Multiple Sclerosis Patients
Authors: Paolicelli Damiano , Ruggieri Maddalena , Manni Alessia , Gargano Concetta D. , Carleo Graziana , Palazzo Claudia , Iaffaldano Antonio , Bollo Luca , Guerra Tommaso , Saracino Annalisa , Frigeri Antonio , Iaffaldano Pietro , Trojano Maria
Published: November 2022

Although cladribine induces sustained reductions in peripheral T and B lymphocytes, little is known about its effect on axonal damage reduction in multiple sclerosis (MS), which could be demonstrated by assessing the serum neurofilament light chain (sNfL) levels. We investigated the reduction/reconstitution of different lymphocyte subsets (LS) by verifying the correlation with no evidence of disease activity (NEDA) and the variation in sNfL levels during cladribine treatment. We analysed 33 highly active relapsing MS patients and followed them up for 12 ± 3.3 months; blood samples were collected at treatment start (W0) and after 8, 24 and 48 weeks. Seventeen patients (60.7%) showed NEDA during the first treatment. At week 8, we observed a significant decrease in B memory cells, B regulatory 1 CD19+/CD38+ and B regulatory 2 CD19+/CD25+, a significant increase in T regulatory CD4+/CD25+, a slight increase in T cytotoxic CD3+/CD8+ and a non-significant decrease in T helper CD3+/CD4+. Starting from week 24, the B subsets recovered; however, at week 48, CD19+/CD38+ and CD19+/CD25+ reached values near the baseline, while the Bmem were significantly lower. The T cell subsets remained unchanged except for CD4+/CD25+, which increased compared to W0. The LS changes were not predictive of NEDA achievement. The sNfL levels were significantly lower at week 24 (p = 0.046) vs. baseline. These results could demonstrate how cladribine, by inflammatory activity depletion, can also reduce axonal damage, according to the sNfL levels.
Cannabinoids in Late Life Parkinson’s Disease and Dementia: Biological Pathways and Clinical Challenges
Authors: Costa Alana C. , Joaquim Helena P. G. , Pedrazzi João F. C. , Pain Andreia de O. , Duque Gustavo , Aprahamian Ivan
Published: November 2022

The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and neuroprotective effects. These findings suggest a potential therapeutic role of cannabinoids to neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer. Emerging evidence suggests that CBD and tetrahydrocannabinol have neuroprotective therapeutic-like effects on dementias. In clinical practice, cannabinoids are being used off-label to relieve symptoms of PD and AD. In fact, patients are using cannabis compounds for the treatment of tremor, non-motor symptoms, anxiety, and sleep assistance in PD, and managing responsive behaviors of dementia such as agitation. However, strong evidence from clinical trials is scarce for most indications. Some clinicians consider cannabinoids an alternative for older adults bearing Parkinson’s disease and Alzheimer’s dementia with a poor response to first-line treatments. In our concept and experience, cannabinoids should never be considered a first-line treatment but could be regarded as an adjuvant therapy in specific situations commonly seen in clinical practice. To mitigate the risk of adverse events, the traditional dogma of geriatric medicine, starting with a low dose and proceeding with a slow titration regime, should also be employed with cannabinoids. In this review, we aimed to address preclinical evidence of cannabinoids in neurodegenerative disorders such as PD and AD and discuss potential off-label use of cannabinoids in clinical practice of these disorders.
Anxiety in Autism Spectrum Disorder: Clinical Characteristics and the Role of the Family
Authors: Guerrera Silvia , Pontillo Maria , Tata Maria Cristina , Di Vincenzo Cristina , Bellantoni Domenica , Napoli Eleonora , Valeri Giovanni , Vicari Stefano
Published: November 2022

Background: Anxiety Disorder (AD) is among the most common psychiatric comorbidity in children and adolescents with Autism Spectrum Disorder (ASD). Likewise, parental psychological distress (PPD) was linked to anxiety symptoms in children and adolescents with ASD. The aim of this study was to characterise, in a sample of children and adolescents with ASD, anxiety symptoms, the functional impairment associated and the presence of PPD. Methods: Participants were divided into three groups based on their diagnosis: children and adolescents with a diagnosis of ASD + AD, others with a diagnosis of AD but without a diagnosis of ASD, and others with a diagnosis of ASD but without a diagnosis of AD. Results: Group ASD + AD showed lower global functioning than Group ASD and Group AD. Generalised Anxiety Disorder, Separation Anxiety Disorder and Specific Phobias were more frequent in Group ASD + AD. Our findings also showed higher depressive symptoms in Group ASD + AD, both in the child and parent reports. Finally, parents of the Group ASD + AD revealed higher levels of PPD. Conclusions: Our findings suggest that early assessment of AD with functional impairment associated with the role of PPD could define individualised treatments and consequently mean a better prognosis in children and adolescents with ASD and AD.
Predictors of Carotid Atherosclerosis Progression: Evidence from an Ultrasonography Laboratory
Authors: Caproni Stefano , Riva Alice , Barresi Giada , Costanti Danilo , Costantini Franco , Galletti Francesca , Di Schino Chiara , Appolloni Elisa , Muti Marco , Colosimo Carlo
Published: November 2022

Background and purpose: The purpose of this study was to investigate the role of risk factors in predicting the variation in carotid atherosclerosis at ultrasonographic follow-up and, therefore, its role in the progression of large-vessel disease. Methods: This retrospective population study included all the outpatients that underwent at least two carotid ultrasonographies at our laboratory from 2001 to 2017. Demographic data, vascular risk factors, and the results at follow-up were analysed to determine if correlations exist between these risk factors and variation in carotid atherosclerosis. Results: Data from 600 patients (327 males and 273 females with a mean age of 67 years) were collected. The mean follow-up period was 49 months (range: 1–195). We analysed each demographic variable and risk factor to assess its correlation with a worsening of carotid atherosclerosis; previous myocardial infarction (2.594), previous carotid surgical treatment (2.368), and hypertension (1.85) were found to have the highest odds ratios, respectively. Furthermore, the sample was divided into specific subpopulations (diabetes, hypertension, and smoking), and an association was found between age and worsening stenosis. Discussion and conclusions: Our results confirm the importance of carotid ultrasonographic follow-up in the monitoring and managing of large-vessel disease. Myocardial infarction, previous stroke, and previous surgical treatment were the strongest predictors of a worsening of carotid atherosclerosis. These findings suggest a strict follow-up is needed, even in the absence of significant carotid atherosclerosis at baseline.
Classification of Alzheimer’s Disease Based on Weakly Supervised Learning and Attention Mechanism
Authors: Wu Xiaosheng , Gao Shuangshuang , Sun Junding , Zhang Yudong , Wang Shuihua
Published: November 2022

The brain lesions images of Alzheimer’s disease (AD) patients are slightly different from the Magnetic Resonance Imaging of normal people, and the classification effect of general image recognition technology is not ideal. Alzheimer’s datasets are small, making it difficult to train large-scale neural networks. In this paper, we propose a network model (WS-AMN) that fuses weak supervision and an attention mechanism. The weakly supervised data augmentation network is used as the basic model, the attention map generated by weakly supervised learning is used to guide the data augmentation, and an attention module with channel domain and spatial domain is embedded in the residual network to focus on the distinctive channels and spaces of images respectively. The location information enhances the corresponding features of related features and suppresses the influence of irrelevant features.The results show that the F1-score is 99.63%, the accuracy is 99.61%. Our model provides a high-performance solution for accurate classification of AD.
Association between Asthma and Suicidality in 9–12-Year-Old Youths
Authors: Hoffman Kevin W. , Visoki Elina , Argabright Stirling T. , Schultz Laura M. , Didomenico Grace E. , Tran Kate T. , Gordon Joshua H. , Chaiyachati Barbara H. , Moore Tyler M. , Almasy Laura , Barzilay Ran
Published: November 2022

Purpose: Suicidal ideation and attempts in youth are a growing health concern, and more data are needed regarding their biological underpinnings. Asthma is a common chronic inflammatory disorder in youth and has been associated with suicidal ideation and attempts in adolescent and adult populations, but data in younger children and early adolescents are lacking. We wished to study associations of asthma with childhood suicidality considering asthma’s potential as a clinically relevant model for childhood chronic immune dysregulation. Methods: Using data from the Adolescent Brain Cognitive Development (ABCD) Study (n = 11,876, 47.8% female, mean age 9.9 years at baseline assessment and 12.0 years at two-year follow-up), we assessed associations between asthma and suicidal ideation and attempts through baseline to two-year follow-up. Results: Asthma history as defined by parent report (n = 2282, 19.2% of study population) was associated with suicide attempts (SA) (odds ratio (OR) = 1.44, p = 0.01), and this association remained significant even when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.46, p = 0.028). History of asthma attacks was associated with both suicidal ideation (SI) and SA when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.27, p = 0.042; OR = 1.83, p = 0.004, respectively). The association of asthma attack with SA remained significant when controlling for self-reported psychopathology (OR = 1.92, p = 0.004). The total number of asthma attacks was associated with both SI and SA (OR = 1.03, p = 0.043; OR = 1.06, p = 0.05, respectively). Conclusions: Findings suggest an association between asthma and suicidality in early adolescence. Further research is needed to investigate mechanisms underlying this relationship.
Characterization of Resting-State Striatal Differences in First-Episode Depression and Recurrent Depression
Authors: Sun Jifei , Du Zhongming , Ma Yue , Guo Chunlei , Gao Shanshan , Luo Yi , Chen Qingyan , Hong Yang , Xiao Xue , Yu Xue , Fang Jiliang
Published: November 2022

The presence of reward deficits in major depressive disorder is associated with abnormal striatal function. However, differences in striatal whole-brain functional between recurrent depressive episode (RDE) and first-episode depression (FDE) have not been elucidated. Thirty-three patients with RDE, 27 with FDE, and 35 healthy controls (HCs) were recruited for this study. A seed-based functional connectivity (FC) method was used to analyze abnormalities in six predefined striatal subregion circuits among the three groups of subjects and to further explore the correlation between abnormal FC and clinical symptoms. The results revealed that compared with the FDE group, the RDE group showed higher FC of the striatal subregion with the left middle occipital gyrus, left orbital area of the middle frontal gyrus, and bilateral posterior cerebellar gyrus, while showing lower FC of the striatal subregion with the right thalamus, left inferior parietal lobule, left middle cingulate gyrus, right angular gyrus, right cerebellum anterior lobe, and right caudate nucleus. In the RDE group, the HAMD-17 scores were positively correlated with the FC between the left dorsal rostral putamen and the left cerebellum posterior lobe. This study provides new insights into understanding the specificity of striatal circuits in the RDE group.
Sex Differences of the Functional Brain Activity in Treatment-Resistant Depression: A Resting-State Functional Magnetic Resonance Study
Authors: Sun Jifei , Luo Yi , Ma Yue , Guo Chunlei , Du Zhongming , Gao Shanshan , Chen Limei , Wang Zhi , Li Xiaojiao , Xu Ke , Hong Yang , Yu Xue , Xiao Xue , Fang Jiliang
Published: November 2022

The presence of different clinical symptoms in patients with treatment-resistant depression (TRD) of different sexes may be related to different neuropathological mechanisms. A total of 16 male patients with TRD, 18 female patients with TRD, 18 male healthy controls (HCs) and 19 female HCs completed this study. We used the amplitude of low frequency fluctuations (ALFF) method to analyze the results. Moreover, the correlation between abnormal brain areas and clinical symptoms in different sexes of the TRD groups was also analyzed. The effects of the sex-by-group interaction difference in ALFF among the four groups was located in the left middle frontal gyrus, left precentral gyrus and left precuneus. Post hoc comparisons revealed that the male TRD group had lower ALFF in the left middle frontal gyrus and left precentral gyrus compared with the female TRD group. There was a positive correlation between the left middle frontal gyrus, the left precuneus and the 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores, and a negative correlation between the left precentral gyrus and the HAMD-17 scores in the female TRD group. This study will provide some clinical reference value for the sex differences in neuropathological mechanisms of TRD.
BIM Style Restoration Based on Image Retrieval and Object Location Using Convolutional Neural Network
Authors: Yang Yalong , Wang Yuanhang , Zhou Xiaoping , Su Liangliang , Hu Qizhi
Published: November 2022

BIM is one of the main technical ways to realize building informatization, and the model’s texture is essential to its style design during BIM construction. However, the texture maps provided by mainstream BIM software are not realistic enough and monotonous to meet the actual needs of users for the model style. Therefore, an interior furniture BIM style restoration method was proposed based on image retrieval and object location using convolutional neural network. First, two types of furniture images, namely grayscale contour images from BIM software and real images from the Internet, were collected to train the following network model. Second, a multi-feature weighted fusion neural network model based on an attention mechanism (AM-rVGG) was proposed, which focused on the structural information of furniture images to retrieve the most similar real image, and then some furniture image patches from the retrieved one were generated with object location and random cropping techniques as the candidate texture maps of the furniture BIM. Finally, the candidate ones were fed back into the BIM software to realize the restoration of the furniture BIM style. The experimental results showed that the average retrieval accuracy of the proposed network model was 83.1%, and the obtained texture maps could effectively restore the real style of the furniture BIM. This work provides a new idea for restoring the realism in other BIM.
Investigation of the Deterioration of Medium-Rise-Wall Type Reinforced Concrete Buildings with External Insulation in Snowy Cold Districts
Authors: Adachi Yusuke , Hirakawa Hideki , Fukushima Akira , Uematsu Takeyoshi , Kikuta Koki , Taniguchi Madoka
Published: November 2022

We have clarified that external insulation reduces the probability of reinforcement corrosion in reinforced concrete buildings in cold snowy districts by 45–78%. Renovation of external insulation is one of the effective methods for improving the insulation performance and durability of reinforced concrete buildings, but there are almost no data that demonstrate durability. Therefore, the carbonation depth and the cover depth were investigated for six medium-rise-wall type reinforced concrete buildings in Hokkaido, Japan, which had been refurbished for external insulation. As a result, it was clarified that the external insulation suppressed the carbonation depth by 30% or more, even when the bonding method of the external insulation was different. In addition, it was clarified that the external insulation further suppressed carbonation in walls where the carbonation depth tended to increase in snowy cold districts. Specifically, external insulation reduced carbonation by up to 35% on surfaces that tend to dry out due to sunlight, and by 49% on surfaces that are affected by water that deteriorates the concrete surface layer.
Contractor Recommendation Model Using Credit Networking and Collaborative Filtering
Authors: Zhang Yao , Tai Shuangliang , Ye Kunhui
Published: November 2022

The credit of contractors in the construction market directly affects the cooperative intentions of owners. Although previous scholars have attempted to use credit to select appropriate contractors, they have rarely considered the trust relationship between decision-making and former owners. This work introduces and verifies a credit network recommendation model based on a collaborative filtering algorithm. The contractor’s credit established based on this model serves as a viable method for owners to select efficient contractors. The application of the model includes relevant information collection, neighbor set formation, contractor’s credit evaluation, and recommendation list formation, among which the neighbor set of the owner is used to calculate the comprehensive trust degree of the decision-making owner to the former owner. A time decay function is adopted to correct the difference in the trust relationship between an owner and a contractor introduced over time. To verify the feasibility of this model, an actual scenario was simulated, and the results obtained via simulations were compared and found to be consistent. Thus, a contractor with a high credit can be recommended to the decision-making owner. This approach is crucial for promoting contractors’ credit and conducive to the healthy development of the construction market.
Early Postoperative Low Compliance to Enhanced Recovery Pathway in Rectal Cancer Patients
Authors: Ceresoli Marco , Pedrazzani Corrado , Pellegrino Luca , Muratore Andrea , Ficari Ferdinando , Polastri Roberto , Scatizzi Marco , Totis Mauro , Tamini Nicolò , Ripamonti Lorenzo , Braga Marco
Published: November 2022

Early postoperative low compliance to enhanced recovery protocols has been associated with morbidity following colon surgery. The purpose of this study is to evaluate the possible causes of early postoperative low compliance to the enhanced recovery pathway and its relationship with morbidity following rectal surgery for cancer. A total of 439 consecutive patients who underwent elective surgery for rectal cancer have been included in the study. Compliance to enhanced recovery protocol on postoperative day (POD) 2 was evaluated in all patients. Indicators of compliance were naso-gastric tube and urinary catheter removal, recovery of both oral feeding and mobilization, and the stopping of intravenous fluids. Low compliance on POD 2 was defined as non- adherence to two or more items. One-third of patients had low compliance on POD 2. Removal of urinary catheter, intravenous fluids stop, and mobilization were the items with lowest adherence. Advanced age, duration of surgery, open surgery and diverting stoma were predictive factors of low compliance at multivariate analysis. Overall morbidity and major complications were significantly higher (p < 0.001) in patients with low compliance on POD 2. At multivariate analysis, failure to remove urinary catheter on POD 2 (OR = 1.83) was significantly correlated with postoperative complications. Low compliance to enhanced recovery protocol on POD 2 was significantly associated with morbidity. Failure to remove the urinary catheter was the most predictive indicator. Advanced age, long procedure, open surgery and diverting stoma were independent predictive factors of low compliance.
The microRNA Lifecycle in Health and Cancer
Authors: de Rooij Laura Adriana , Mastebroek Dirk Jan , ten Voorde Nicky , van der Wall Elsken , van Diest Paul Joannes , Moelans Cathy Beatrice
Published: November 2022

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that regulate gene expression at the post-transcriptional level. They can bind to around 60% of all protein-coding genes with an average of 200 targets per miRNA, indicating their important function within physiological and pathological cellular processes. miRNAs can be quickly produced in high amounts through canonical and non-canonical pathways that involve a multitude of steps and proteins. In cancer, miRNA biogenesis, availability and regulation of target expression can be altered to promote tumour progression. This can be due to genetic causes, such as single nucleotide polymorphisms, epigenetic changes, differences in host gene expression, or chromosomal remodelling. Alternatively, post-transcriptional changes in miRNA stability, and defective or absent components and mediators of the miRNA-induced silencing complex can lead to altered miRNA function. This review provides an overview of the current knowledge on the lifecycle of miRNAs in health and cancer. Understanding miRNA function and regulation is fundamental prior to potential future application of miRNAs as cancer biomarkers.
Patterns of Hearing Loss in Irradiated Survivors of Head and Neck Rhabdomyosarcoma
Authors: Diepstraten Franciscus A. , Wiersma Jan , Schoot Reineke A. , Knops Rutger R. G. , Zuur Charlotte L. , Meijer Annelot J. M. , Dávila Fajardo Raquel , Pieters Bradley R. , Balgobind Brian V. , Westerveld Henrike , Freling Nicole , van Tinteren Harm , Smeele Ludwig E. , Bel Arjan , van den Heuvel-Eibrink Marry M. , Stokroos Robert J. , Merks Johannes H. M. , Hoetink Alexander E. , Hol Marinka L. F.
Published: November 2022

Purpose: The frequency and patterns of HL in a HNRMS survivor cohort were investigated. A dose–effect relationship between the dose to the cochlea and HL was explored. Methods: Dutch survivors treated for HNRMS between 1993 and 2017 with no relapse and at least two years after the end of treatment were eligible for inclusion. The survivors were evaluated for HL with pure-tone audiometry. HL was graded according to the Muenster, Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and International Society for Paediatric Oncology (SIOP) classification. We defined deleterious HL as Muenster ≥ 2b, CTCAE ≥ 2, and SIOP ≥ 2. Mixed-effects logistic regression was used to search for the dose–effect relationship between the irradiation dose to the cochlea and the occurrence of HL. Results: Forty-two HNRMS survivors underwent pure-tone audiometry. The Muenster, CTCAE and SIOP classification showed that 19.0% (n = 8), 14.2% (n = 6) and 11.9% (n = 5) of survivors suffered from HL, respectively. A low-frequency HL pattern with normal hearing or milder hearing loss in the higher frequencies was seen in four survivors. The maximum cochlear irradiation dose was significantly associated with HL (≥Muenster 2b) (p = 0.047). In our series, HL (≥Muenster 2b) was especially observed when the maximum dose to the cochlea exceeded 19 Gy. Conclusion: HL occurred in up to 19% of survivors of HNRMS. More research is needed on HL patterns in HNRMS survivors and on radiotherapy dose–effect relationships.
Adenosine 2A Receptor Activation Amplifies Ibrutinib Antiplatelet Effect; Implications in Chronic Lymphocytic Leukemia
Authors: Elaskalani Omar , Gilmore Grace , Hagger Madison , Baker Ross I. , Metharom Pat
Published: November 2022

Chronic lymphocytic leukemia patients have an increased bleeding risk with the introduction of Bruton tyrosine kinase (BTK) inhibitors. BTK is a signaling effector downstream of the platelet GPVI receptor. Innate platelet dysfunction in CLL patients and the contribution of the leukemia microenvironment to the anti-platelet effect of BTK inhibitors are still not well defined. Herein, we investigated platelet function in stable, untreated CLL patients in comparison to age-matched healthy subjects as control. Secondly, we proposed a novel mechanism of platelet dysfunction via the adenosinergic pathway during BTK inhibitor therapy. Our data indicate that the nucleotidase that produces adenosine, CD73, was expressed on one-third of B-cells in CLL patients. Inhibition of CD73 improved platelet response to ADP in the blood of CLL patients ex vivo. Using healthy platelets, we show that adenosine 2A (A2A) receptor activation amplifies the anti-platelet effect of ibrutinib (10 nM). Ibrutinib plus an A2A agonist—but not ibrutinib as a single agent—significantly inhibited collagen (10 µg/mL)-induced platelet aggregation. Mechanistically, A2A activation attenuated collagen-mediated inhibition of p-VASP and synergized with ibrutinib to inhibit the phosphorylation of AKT, ERK and SYK kinases. This manuscript highlights the potential role of adenosine generated by the microenvironment in ibrutinib-associated bleeding in CLL patients.
Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients
Authors: Marx Sascha , Wilken Fabian , Miebach Lea , Ispirjan Mikael , Kinnen Frederik , Paul Sebastian , Bien-Möller Sandra , Freund Eric , Baldauf Jörg , Fleck Steffen , Siebert Nikolai , Lode Holger , Stahl Andreas , Rauch Bernhard H. , Singer Stephan , Ritter Christoph , Schroeder Henry W. S. , Bekeschus Sander
Published: November 2022

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future.
The Role of Extracellular Vesicles in Optic Nerve Injury: Neuroprotection and Mitochondrial Homeostasis
Authors: Park Mira , Shin Hyun Ah , Duong Van-An , Lee Hookeun , Lew Helen
Published: November 2022

Stem cell therapies hold great promise as alternative treatments for incurable optic nerve disorders. Although mesenchymal stem cells exhibit various tissue regeneration and recovery capabilities that may serve as valuable therapies, the clinical applications remain limited. Thus, we investigated the utility of extracellular vesicles (EVs) from human placenta-derived mesenchymal stem cells (hPSCs) in this context. Hypoxically preconditioned hPSCs (HPPSCs) were prepared via short-term incubation under 2.2% O2 and 5.5% CO2. The EVs were then isolated. R28 cells (retinal precursor cells) were exposed to CoCl2 and treated with EVs for 24 h. Cell proliferation and regeneration were measured using a BrdU assay and immunoblotting; ATP quantification revealed the extent of the mitochondrial function. The proteome was determined via liquid chromatography-tandem mass spectroscopy. Differentially expressed proteins (DEPs) were detected and their interactions identified. HPPSC_EVs functions were explored using animal models of optic nerve compression. HPPSC_EVs restored cell proliferation and mitochondrial quality control in R28 cells damaged by CoCl2. We identified DEPs (p < 0.05) that aided recovery. The mitochondrial DEPs included LONP1; PARK7; VDAC1, 2, and 3; HSPD1; and HSPA9. EVs regulated the levels of mitophagic proteins in R28 cells injured by hypoxia; the protein levels did not increase in LONP1 knockdown cells. LONP1 is a key mediator of the mitophagy that restores mitochondrial function after hypoxia-induced optic nerve injury.
Molecular Mechanisms of Chronic Intestinal Diseases in Response to Microbiota
Authors: Grasa Laura
Published: November 2022

Chronic disorders of the intestine, such as inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS), involve complex interactions between host and microbiota [...]
Mechanical Force Modulates Alveolar Bone Marrow Mesenchymal Cells Characteristics for Bone Remodeling during Orthodontic Tooth Movement through Lactate Production
Authors: Zhai Mingrui , Cui Shuyue , Li Lan , Cheng Chen , Zhang Zijie , Liu Jiani , Wei Fulan
Published: November 2022

Orthodontic tooth movement (OTM) relies on mechanical force-induced bone remodeling. As a metabolic intermediate of glycolysis, lactate has recently been discovered to participate in bone remodeling by serving as a signaling molecule. However, whether lactate could respond to mechanical stimulus during OTM, as well as whether lactate has an impact on the alveolar bone remodeling during orthodontics, remain to be further elucidated. In the current study, we observed physiologically elevated production of lactate along with increased osteogenic differentiation, proliferation, and migration of alveolar bone marrow mesenchymal cells (ABMMCs) under mechanical force. Inhibition of lactate, induced by cyclic mechanical stretch by GNE-140, remarkably suppressed the osteogenic differentiation, proliferation, and migration, yet enhanced apoptosis of ABMMCs. Mechanistically, these regulatory effects of lactate were mediated by histone lactylation. Taken together, our results suggest that force-induced lactate is involved in controlling bone remodeling-related cellular activities in ABMMCs and plays a vital role in the alveolar bone remodeling during OTM. Our findings indicate that lactate might be a critical modulator for alveolar bone remodeling during OTM, providing a novel therapeutic target for the purpose of more effectively controlling tooth movement and improving the stability of orthodontic results.
The Drosophila simulans Genome Lacks the crystal-Stellate System
Authors: De Grassi Anna , Tritto Patrizia , Palumbo Valeria , Bozzetti Maria Pia , Berloco Maria Francesca
Published: November 2022

The cry-Ste system is a genetic interaction system between heterochromatin and euchromatin in Drosophila melanogaster, regulated via the piRNA pathway. Deregulation of this system leads to meiotic defects and male sterility. Although the cry-Ste system is peculiar to D. melanogaster, ancestors of Ste and Su(Ste) elements are present in the three closely related species, D. simulans, D. sechellia, and D. mauritiana. The birth, evolution, and maintenance of this genetic system in Drosophila melanogaster are of interest. We investigate the presence of sequences homologous to cry and Ste elements in the simulans complex and describe their chromosomal distribution. The organization and expression of cry- and Ste-like sequences were further characterized in the D. simulans genome. Our results allow us to conclude that the cry-Ste genetic interaction system is absent in the D. simulans genome.
Hydroxysafflor Yellow A Exerts Neuroprotective Effects via HIF-1α/BNIP3 Pathway to Activate Neuronal Autophagy after OGD/R
Authors: Wei Ruheng , Song Lijuan , Miao Zhuyue , Liu Kexin , Han Guangyuan , Zhang Haifei , Ma Dong , Huang Jianjun , Tian Hao , Xiao Baoguo , Ma Cungen
Published: November 2022

In the process of ischemic stroke (IS), cellular macroautophagy/autophagy and apoptosis play a vital role in neuroprotection against it. Therefore, regulating their balance is a potential therapeutic strategy. It has been proved that hydroxysafflor yellow A (HSYA) has anti-inflammatory and antioxidant effects, which can both protect neurons. By exploring bioinformatics combined with network pharmacology, we found that HIF1A and CASP3, key factors regulating autophagy and apoptosis, may be important targets of HSYA for neuroprotection in an oxygen glucose deprivation and reperfusion (OGD/R) model. In this study, we explored a possible new mechanism of HSYA neuroprotection in the OGD/R model. The results showed that OGD/R increased the expression of HIF1A and CASP3 in SH-SY5Y cells and induced autophagy and apoptosis, while HSYA intervention further promoted the expression of HIF1A and inhibited the level of CASP3, accompanied by an increase in autophagy and a decrease in apoptosis in SH-SY5Y cells. The inhibition of HIF1A diminished the activation of autophagy induced with HSYA, while the inhibition of autophagy increased cell apoptosis and blocked the neuroprotective effect of HSYA, suggesting that the neuroprotective effect of HSYA should be mediated by activating the HIF1A/BNIP3 signaling pathway to induce autophagy. These results demonstrate that HSYA may be a promising agent for treating IS.
Identification and Validation of Glycosyltransferases Correlated with Cuproptosis as a Prognostic Model for Colon Adenocarcinoma
Authors: Ma Wei , Zhu Lingyuan , Song Shushu , Liu Bo , Gu Jianxin
Published: November 2022

Cuproptosis is a newly defined programmed cell death pattern and is believed to play an important role in tumorigenesis and progression. In addition, many studies have shown that glycosylation modification is of vital importance in tumor progression. However, it remains unclear whether glycosyltransferases, the most critical enzymes involved in glycosylation modification, are associated with cuproptosis. In this study, we used bioinformatic methods to construct a signature of cuproptosis-related glycosyltransferases to predict the prognosis of colon adenocarcinoma patients. We found that cuproptosis was highly correlated with four glycosyltransferases in COAD, and our model predicted the prognosis of COAD patients. Further analysis of related functions revealed the possibility that cuproptosis-related glycosyltransferase Exostosin-like 2 (EXTL2) participated in tumor immunity.
Hypoxia as a Double-Edged Sword to Combat Obesity and Comorbidities
Authors: Wang Ruwen , Sun Qin , Wu Xianmin , Zhang Yiyin , Xing Xiaorui , Lin Kaiqing , Feng Yue , Wang Mingqi , Wang Yibing , Wang Ru
Published: November 2022

The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.
Reducing Birth Defects by Decreasing the Prevalence of Maternal Chronic Diseases—Evaluated by Linked National Registration Dataset
Authors: Chen Lih-Ju , Chen Ping-Ju , Huang Jing-Yang , Yang Shun-Fa , Chen Jia-Yuh
Published: November 2022

Birth defects (BDs) are an important cause of abortion, stillbirth, and infant mortality that may cause lifelong disability. The defects can be caused by genetics, environmental exposure, or maternal chronic diseases. We conducted a study to analyze the association between maternal chronic diseases and BDs and to evaluate the effect of decreasing the prevalence of maternal chronic diseases on reducing BDs. The data of newborns and their mothers were concatenated and analyzed from three national population databases: the National Health Insurance Research Database, the Birth Certificate Application, and the Birth Registration Database in Taiwan during the period of 2005 to 2014. Codes 740-759 of the International Classification of Diseases 9th Revision—Clinical Modification (ICD-9-CM) were used as the diagnosis of BDs. The prevalence of BDs was 2.72%. Mothers with cardiovascular diseases, hypertension, anemia, genitourinary tract infections, renal diseases, neurotic or psychotic disorders, gestational diabetes mellitus (DM), and pregestational type 1 or type 2 DM had a significantly higher prevalence of BDs. The population attributable risk percent (PAR%) of BDs was 1.63%, 0.55%, 0.18%, 1.06%, 0.45%, 0.22%, 0.48%, and 0.24% for maternal hypertension, cardiovascular disease, renal disease, genitourinary infection, anemia, neurotic and psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, respectively. The percentage change (−1%, −5%, and −10% of prevalence in 2034 compared with the prevalence in 2005–2014) of maternal disease and the predicted number of live births was used to estimate the decrease in the number of newly diagnosed BDs in 2034. By using the middle-estimated number of live births in 2034, we predicted that the number of BDs would decrease by 302, 102, 33, 196, 83, 41, 89, and 44 with a −5% prevalence of maternal hypertension, cardiovascular disease, renal disease, genitourinary infection, anemia, neurotic and psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, respectively. We conclude that mothers with chronic diseases, including cardiovascular diseases, hypertension, anemia, genitourinary tract infections, renal diseases, neurotic or psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, have a significantly higher (p < 0.01) prevalence of having offspring with BDs. Mothers with chronic diseases are associated with BDs. It is very important to set up a policy to decrease the prevalence of these maternal chronic diseases; then, we can reduce the incidence of BDs.
A Qualitative Study of the Pain Experiences of Children and Their Parents at a Canadian Children’s Hospital
Authors: Kammerer Elise , Eszczuk Joshua , Caldwell Katie , Dunn Jacob , Appelman-Eszczuk Sharon , Dunn Jennifer , MacNeil Megan , Ali Samina
Published: November 2022

Current literature is lacking in describing families’ experiences in being involved in children’s pain management. This study sought to understand children and their parents’ experiences with pain management at a tertiary care children’s hospital. Twelve child–parent dyads were recruited to participate in the study from January to August 2022. Children and their parents chose whether to be interviewed together or separately. Transcripts were analyzed using inductive, data-driven codes. Codes and themes were developed using a codebook and member-checking. Three main themes were identified: a. Painful experiences can have a significant positive or negative effect on families’ lives and healthcare trajectories; b. There can be a mismatch between families’ expectations of pain management and how they perceive the pain was managed; c. Families feel that they must advocate for better pain care, but often feel too intimidated to do so, or worry that their concerns will be dismissed by healthcare professionals. Families want healthcare professionals to proactively manage their children’s pain, supporting the shaping of early positive memories of the child’s healthcare interactions. Healthcare providers must further recognize that poorly treated pain can significantly impact families’ lives and should both seek and be receptive to child and parent input for better pain care.
Mechanical, Corrosion, and Wear Properties of TiZrTaNbSn Biomedical High-Entropy Alloys
Authors: Wang Xiaohong , Hu Tingjun , Ma Tengfei , Yang Xing , Zhu Dongdong , Dong Duo , Xiao Junjian , Yang Xiaohong
Published: November 2022

The phase composition, microstructure, mechanical, corrosion, and wear behaviors of the Ti15Zr35Ta10Nb10Sn30 (Sn30) and Ti15Zr30Ta10Nb10Sn35 (Sn35) biomedical high-entropy alloys (BHEAs) were studied. We found that the Ti–Zr–Ta–Nb–Sn BHEAs showed hyper-eutectic and eutectic structures with body-centered cubic (BCC) and face-centered cubic (FCC) solid-solution phases. The Sn30 BHEA exhibited a high Vickers hardness of approximately 501.2 HV, a compressive strength approaching 684.5 MPa, and plastic strain of over 46.6%. Furthermore, the Vickers hardness and compressive strength of Sn35 BHEA are 488.7 HV and 999.2 MPa, respectively, with a large plastic strain of over 49.9%. Moreover, the Sn30 and Sn 35 BHEA friction coefficients are 0.152 and 0.264, respectively. Sn30 BHEA has the smallest and shallowest furrow-groove width, and its wear rate is 0.86 (km/mm3); at the same time, we observed the delamination phenomenon. Sn35 BHEA has a wear rate value of 0.78 (km/mm3), and it displays wear debris and the largest–deepest furrow groove. Sn30 BHEA has the highest impedance value, and its corrosion current density Icorr is 1.261 × 10−7 (A/cm2), which is lower than that of Sn35 BHEA (1.265 × 10−6 (A/cm2)) by 88%, and the passivation current density Ipass of Sn30 BHEA and Sn35 BHEA is 4.44 × 10−4 (A/cm2) and 3.71 × 10−3 (A/cm2), respectively. Therefore, Sn30 BHEA preferentially produces passive film and has a small corrosion tendency, and its corrosion resistance is considerably better than that of the Sn35 BHEA alloy.
Comparative Corrosion Characterization of Hybrid Zinc Coatings in Cl−-Containing Medium and Artificial Sea Water
Authors: Boshkova Nelly , Kamburova Kamelia , Radeva Tsetska , Simeonova Silviya , Grozev Nikolay , Shipochka Maria , Boshkov Nikolai
Published: November 2022

The presented investigations demonstrate the corrosion behavior and protective ability of hybrid zinc coatings specially designed for combined protection of low-carbon steel from localized corrosion and biofouling. Polymer-modified copper oxide (CuO) nanoparticles as widely used classic biocide are applied for this purpose, being simultaneously electrodeposited with zinc from electrolytic bath. The corrosion behavior of the hybrid coatings is evaluated in a model corrosive medium of 5% NaCl solution and in artificial sea water (ASW). Scanning electron microscopy (SEM) and atomic force microscopy (AFM) are used to characterize the surface morphology of pure and hybrid zinc coatings. Contact angle measurements are realized with an aim to determine the hydrophobicity of the surface. X-ray photoelectron spectroscopy (XPS) is applied for evaluation of the chemical composition of the surface products appearing as a result of the corrosion treatment. Potentiodynamic polarization (PDP) curves and polarization resistance (Rp) measurements are used to estimate the protective characteristics in both model corrosive media. The results obtained for the hybrid coatings are compared with the corrosion characteristics of ordinary zinc coating with the same thickness. It was found that the hybrid coating improves the anticorrosion behavior of low-carbon steel during the time interval of 35 days and at conditions of external polarization. The tests demonstrate much larger corrosion resistance of the hybrid coating in ASW compared to 5% NaCl solution. The obtained results indicated that the proposed hybrid zinc coating has a potential for antifouling application in marine environment.
Co0.6Ni0.4S2/rGO Photocatalyst for One-Pot Synthesis of Imines from Nitroaromatics and Aromatic Alcohols by Transfer Hydrogenation
Authors: Zhang Hongming , Zhuang Jiahe , Feng Xiangrui , Ma Ben
Published: November 2022

Co0.6Ni0.4S2/rGO catalysts exhibit excellent photocatalytic performance for one-step synthesis of N-benzylideneaniline from nitrobenzene and benzyl alcohol by transfer hydrogenation, and the selectivity and yield of N-benzylideneaniline can reach as high as 93% and 77.2%, respectively. The reaction process for the synthesis of imines can be divided into two steps: benzyl alcohol is oxidized to benzaldehyde, while nitrobenzene is reduced to aniline; benzaldehyde and aniline are condensed to form imines. Under visible light irradiation, photo-induced electrons in Co0.6Ni0.4S2/rGO photocatalyst play an important role in activating nitrobenzene and benzaldehyde. Photo-induced holes are mainly responsible for the partial dehydrogenation of benzyl alcohol to benzaldehyde. Next, aniline molecules condense with benzaldehyde molecules to synthesize imine. The photocatalytic system provides an environmentally friendly for the synthesis of imines and supplies an alternative approach for hydrogen auto-transfer reactions.
Reevaluating Graph-Neural-Network-Based Runtime Prediction of SAT-Based Circuit Deobfuscation
Authors: Zhao Guangwei , Shamsi Kaveh
Published: November 2022

Logic locking is a technique that can help hinder reverse-engineering-based attacks in the IC supply chain from untrusted foundries or end-users. In 2015, the Boolean Satisfiability (SAT) attack was introduced. Although the SAT attack is effective in deobfuscating a wide range of logic locking schemes, its execution time varies widely from a few seconds to months. Previous research has shown that Graph Convolutional Networks (GCN) may be used to estimate this deobfuscation time for locked circuits with varied key sizes. In this paper, we explore whether GCN models truly understand/capture the structural/functional sources of deobfuscation hardness. In order to tackle this, we generate different curated training datasets: traditional ISCAS benchmark circuits locked with varying key sizes, as well as an important novel class of synthetic benchmarks: Substitution-Permutation Networks (SPN), which are circuit structures used to produce the most secure and efficient keyed-functions used today: block-ciphers. We then test whether a GCN trained on a traditional benchmark can predict the simple fact that a deeper SPN is superior to a wide SPN of the same size. We find that surprisingly the GCN model fails at this. We propose to overcome this limitation by proposing a set of circuit features motivated by block-cipher design principles. These features can be used as stand-alone or combined with GCN models to provide deeper topological cues than what GCNs can access.