bluuebunny/crossref_metadata_2025 huggingface dataset:
The phenotypic and genetic features of arrhythmogenic cardiomyopathy in the pediatric population
Authors: Kofeynikova Olga , Alekseeva Daria , Vershinina Tatiana , Fetisova Svetlana , Peregudina Olga , Kovalchuk Tatiana , Yakovleva Elena , Sokolnikova Polina , Klyushina Alexandra , Chueva Kseniia , Kostareva Anna , Pervunina Tatiana , Vasichkina Elena
Published: September 2023

Introduction

The present study aimed to describe the phenotypic features and genetic spectrum of arrhythmogenic cardiomyopathy (ACM) presented in childhood and test the validity of different diagnostic approaches using Task Force Criteria 2010 (TFC) and recently proposed Padua criteria.

Patients and methods

Thirteen patients (mean age at diagnosis 13.6 ± 3.7 years) were enrolled using “definite” or “borderline” diagnostic criteria of ACM according to the TFC 2010 and the Padua criteria in patients <18 years old. Clinical data, including family history, 12-lead electrocardiogram (ECG), signal-averaged ECG, 24-h Holter monitoring, imaging techniques, genetic testing, and other relevant information, were collected.

Results

All patients were classified into three variants: ACM of right ventricle (ACM-RV; n = 6, 46.1%), biventricular ACM (ACM-BV; n = 3, 23.1%), and ACM of left ventricle (ACM-LV; n = 4, 30.8%). The most common symptoms at presentations were syncope (n = 6; 46.1%) and palpitations (n = 5; 38.5%). All patients had more than 500 premature ventricular contractions per day. Ventricular tachycardia was reported in 10 patients (76.9%), and right ventricular dilatation was registered in 8 patients (61.5%). An implantable cardiac defibrillator was implanted in 61.5% of cases, and three patients with biventricular involvement underwent heart transplantation. Desmosomal mutations were identified in 8 children (53.8%), including four patients with PKP2 variants, two with DSP variants, one with DSG2 variant, and one with JUP. Four patients carried compound heterozygous variants in desmosomal genes associated with left ventricular involvement.

Conclusion

Arrhythmias and structural heart disease, such as chamber dilatation, should raise suspicion of different ACM phenotypes. Diagnosis of ACM might be difficult in pediatric patients, especially for ACM-LV and ACM-BV forms. Our study confirmed that using “Padua criteria” in combination with genetic testing improves the diagnostic accuracy of ACM in children.
Do metabolic factors increase the risk of thyroid cancer? a Mendelian randomization study
Authors: Liang Weiwei , Sun FangFang
Published: September 2023

Background

Epidemiological studies emphasize the link between metabolic factors and thyroid cancer. Using Mendelian randomization (MR), we assessed the possible causal impact of metabolic factors on thyroid cancer for the first time.

Methods

Summary statistics for metabolic factors and thyroid cancer were obtained from published Genome-wide association studies. The causal relationships were assessed using the inverse-variance weighted (IVW) method as the primary method through a two-sample Mendelian Randomization (MR) analysis. To account for the potential existence of horizontal pleiotropy, four additional methods were employed, including Mendelian Randomization–Egger (MR-Egger), weighted median method (WM), simple mode, and weighted mode method. Given the presence of interactions between metabolic factors, a multivariable MR analysis was subsequently conducted.

Results

The results showed there was a genetic link between HDL level and protection effect of thyroid cancer using IVW (OR= 0.75, 95% confidence intervals [CIs] 0.60-0.93, p=0.01) and MR-Egger method (OR= 0.70, 95% confidence intervals [CIs] 0.50- 0.97, p=0.03). The results remained robust in multivariable MR analysis for the genetic link between HDL level and protection effect of thyroid cancer (OR= 0.74, 95% confidence intervals [CIs] 0.55-0.99, p=0.04).

Conclusions

This study suggests a protection role for HDL on thyroid cancer. The study findings provide evidence for the public health suggestion for thyroid cancer prevention. HDL’s potential as a pharmacological target needs further validation.
Suitability of photovoltaic development and emission reduction benefits based on geographic information sensing and multi-criteria decision making method—an example from Inner Mongolia Autonomous Region
Authors: Xu Wei , Liu Zhenling , Liu Susu
Published: September 2023

With the rapid development of the photovoltaic (PV) industry, the problem of the blind construction of PV power plants is becoming increasingly prominent. Thus, the scientific evaluation of the suitability of regional PV products, power generation potential, and emission reduction benefits is of great significance to the sustainable development of the PV industry. In this study, geographic information sensing and multi-criteria decision making methods are to be combined to calculate a PV development suitability index based on meteorology, topography, location, and vegetation to characterize the spatial patterns of the PV development in the Inner Mongolia Autonomous Region. Subsequently, the power generation potential and emission reduction benefits under different development scenarios were quantitatively assessed. The particularly suitable, and more suitable areas for the PV development in the Inner Mongolia Autonomous Region are 23.66% of the total area. Among these, the more suitable areas are the most extensive. The suitability of PV development in the western part of the Inner Mongolia Autonomous Region is more than that in the central and eastern parts. The suitable areas are mainly distributed in the Alashan League and Bayannur City in the west. Thus, the Inner Mongolia Autonomous Region has enormous potential for electricity generation. The development of 12.57% of the particularly suitable areas can meet the electricity consumption of the Inner Mongolia Autonomous Region in 2021. Moreover, sensitivity analysis is conducted to investigate the impacts of system efficiency variation on energy output. The distribution of the power generation potential and electricity demand in the Inner Mongolia Autonomous Region has robust spatial heterogeneity. PV power generation can achieve remarkable energy saving and emission reduction. If all particularly suitable areas are developed, the annual carbon emission reduction of the Inner Mongolia Autonomous Region will be approximately 2,446,621,000 t, which is 4.46 times the total carbon emission of the Autonomous Region and 21.2% of the total carbon emission of China in 2021. Therefore, this study provides a scientific reference and guide for selecting suitable sites for PV power plants and their sustainable development in the Inner Mongolia Autonomous Region.
Current approaches and potential challenges in the delivery of gene editing cargos into hematopoietic stem and progenitor cells
Authors: Murugesan Ramya , Karuppusamy Karthik V. , Marepally Srujan , Thangavel Saravanabhavan
Published: September 2023

Advancements in gene delivery and editing have expanded the applications of autologous hematopoietic stem and progenitor cells (HSPCs) for the treatment of monogenic and acquired diseases. The gene editing toolbox is growing, and the ability to achieve gene editing with mRNA or protein delivered intracellularly by vehicles, such as electroporation and nanoparticles, has highlighted the potential of gene editing in HSPCs. Ongoing phase I/II clinical trials with gene-edited HSPCs for β-hemoglobinopathies provide hope for treating monogenic diseases. The development of safe and efficient gene editing reagents and their delivery into hard-to-transfect HSPCs have been critical drivers in the rapid translation of HSPC gene editing into clinical studies. This review article summarizes the available payloads and delivery vehicles for gene editing HSPCs and their potential impact on therapeutic applications.
Pregnancy outcomes and genetic analysis for fetal ventriculomegaly
Authors: Tao Huimin , Zhang Lin , Tan Fangfang , Han Yu , Wang Xuezhen , Wu Jiebin , Zhai Jingfang
Published: September 2023

Introduction: Fetal ventriculomegaly (VM) is associated with neurodevelopmental disorders, partly caused by genetic factor.

Methods: To systematically investigate the genetic etiology of fetal VM and related pregnancy outcomes in different subgroups: IVM (isolated VM) and NIVM (non-isolated VM); unilateral and bilateral VM; mild, moderate, and severe VM, a retrospective study including 131 fetuses with VM was carried out from April 2017 to August 2022.

Results: 82 cases underwent amniocentesis or cordocentesis, of whom 8 cases (9.8%) were found chromosomal abnormalities by karyotyping. Meanwhile, additional 8 cases (15.7%) with copy number variations (CNVs) were detected by copy number variation sequencing (CNV-seq). The detection rate (DR) of chromosomal abnormalities was higher in NIVM, bilateral VM and severe VM groups. And CNVs frequently occurred in NIVM, bilateral VM and moderate VM groups. In the NIVM group, the incidence of chromosomal aberrations and CNVs in multiple system anomalies (19.0%, 35.7%) was higher than that in single system anomalies (10.0%, 21.1%). After dynamic ultrasound follow-up, 124 cases were available in our cohort. 12 cases were further found other structural abnormalities, and lateral ventricular width was found increased in 8 cases and decreased in 15 cases. Meanwhile, 82 cases underwent fetal brain MRI, 10 cases of brain lesions and 11 cases of progression were additionally identified. With the involvement of a multidisciplinary team, 45 cases opted for termination of pregnancy (TOP) and 79 cases were delivered with live births. One infant death and one with developmental retardation were finally found during postnatal follow-ups.

Discussion: CNV-seq combined with karyotyping could effectively improve the diagnostic rate in fetuses with VM. Meanwhile, dynamic ultrasound screening and multidisciplinary evaluation are also essential for assessing the possible outcomes of fetuses with VM.
Association study of WNK1 genetic variants and essential hypertension risk in the Northern Han Chinese in Beijing
Authors: Liu Kuo , Liu Jielin , Liu Ya , Wang Hao , Wang Zuoguang , Liu Jinghua , Wen Shaojun
Published: September 2023

Background: Essential hypertension (EH) is a complex disorder resulting from interaction of genetic and environmental factors. Lysine deficient protein kinase 1 (WNK1) plays a very important role in maintaining renal potassium, sodium and chlorine ions balance as well as the regulation of blood pressure, so the WNK1 gene is considered a key gene for EH. This study thus sought to evaluate possible genetic associations between the WNK1 genetic variants and EH risk in the Northern Han Chinese population in Beijing.

Methods: This study included 476 hypertensive subjects and 491 normotensive subjects. A total of 12 tag SNVs of WNK1 gene were genotyped successfully by TaqMan assay. Comparisons of the genotypic and allelic frequency between cases and controls were made by using the chi-square test. Logistic regression analyses were performed under different genetic models, and haplotype analysis was also conducted.

Results: A total of 12 SNVs were identified as the tag SNVs for WNK1 gene. Significant associations were observed between WNK1 gene rs7305099 variant and EH risk, and T allele influenced hypertension risk in a protective manner. After correcting for multiple testing using Bonferroni, the significance remained for the SNV of rs7305099 in three genetic models [allele comparison, p < 0.0002, OR = 0.627, 95%CI (0.491–0.801); homozygote comparison, p < 0.0003, OR = 0.278, 95%CI (0.140–0.552); additive model, p < 0.0003, OR = 0.279, 95%CI (0.140–0.553)]. In the haplotype analyses, we found that the haplotype A-A-A-C-G-G-G was significantly associated with increased risk for EH (p = 0.043, OR = 1.23).

Conclusion: Our data suggested that the rs7305099 genetic variant and the haplotype A-A-A-C-G-G-G on WNK1 gene might be associated with the susceptibility of EH in the Northern Han Chinese population. These could provide evidences to the risk assessment, early prevention and individualized therapy of EH to some extent.
Metabolic control from the endolysosome: lysosome-resident amino acid transporters open novel therapeutic possibilities
Authors: Kobayashi Toshihiko , Toyama-Sorimachi Noriko
Published: September 2023

Amino acid transporters are generally recognized as machinery that transport amino acids from the extracellular environment into the cytoplasm. Although their primary function is the uptake of amino acids to supply the cell with nutrients and energy, endolysosome-resident amino acid (EL-aa) transporters possess several unique functions in accordance with their localization in intracellular vesicular membranes. They play pivotal roles in the maintenance of metabolic homeostasis via direct involvement in the amino acid sensing pathway, which regulates the activity of mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cellular metabolism. Additionally, some EL-aa transporters contribute to the maintenance of dynamic homeostasis of endolysosomes, including the regulation of endolysosomal acidity, by carrying amino acids out of endolysosomes. In addition, EL-aa transporters act as a scaffold to gather signaling molecules and multiple enzymes to control cellular metabolism on the endolysosomal membrane. Among EL-aa transporters, solute carrier family 15 member 4 (SLC15A4) is preferentially expressed in immune cells, including macrophages, dendritic cells, and B cells, and plays a key role in the integration of metabolic and inflammatory signals. In this review, we summarize our recent findings on EL-aa transporter contributions to inflammatory and metabolic signaling in the endolysosomes of immune cells by focusing on the SLC15 family, including SLC15A4 and SLC15A3, and discuss their uniqueness and universality. We also discuss the potential of targeting these EL-aa transporters in immune cells for the development of novel therapeutic strategies for inflammatory diseases. Because these transporters are highly expressed in immune cells and significantly alter the functions of immune cells, targeting them would provide a great advantage in ensuring a wide safety margin.
Mechanism study on the soil mechanical behavior of the mixed soil based on energy multi-scale method
Authors: Chen Jian , Yuan Jie , Tong Huawei , Fang Yingguang , Gu Renguo
Published: September 2023

The presence of mixed soil is widespread in nature, rendering it susceptible to geological hazards such as landslides, liquefaction, and debris flows. This soil type displays pronounced structural anisotropy due to its diverse mineral composition and the broad range of particle sizes it encompasses across multiple geometric scales. However, there exists an array of conflicting research outcomes concerning the impact of particle composition, size, and content on the mechanical properties of mixed soil. This study delves into the mechanical behavior of mixed soil across varying particle contents and sizes using direct shear testing. Subsequently, the distinctive mechanical responses are dissected by scrutinizing the interplay of particle contact interfaces. Concurrently, the underlying mechanism behind this behavior is explored by examining particle surface adsorption energy through a multi-energy scale approach. In conclusion, the following findings are established: 1) The influence of fine particle content (FC) on mixed soil strength varies according to distinct filling conditions; 2) The contribution to mixed soil strength differs among particles with distinct mineral components; 3) Sand particle size within mixed soil holds no sway over its strength under equivalent mass conditions; 4) The particle surface energy equation derived from the multi-energy scale technique comprehensively elucidates the interplay between particle composition, content, and mechanical behavior in mixed soil.
Direct oral anti-Xa anticoagulants versus warfarin in newly diagnosed atrial fibrillation and CKD: the Korean National Health Insurance Data
Authors: Kee Youn Kyung , Jeon Hee Jung , Oh Jieun , Yoo Tae-Hyun , Kang Dongwoo , Lee Jungkuk , Shin Dong Ho
Published: September 2023

Introduction

Despite the benefits of direct oral anti-Xa anticoagulants (DOACs), the risk–benefit profile of DOAC therapy compared to warfarin therapy in patients with non-valvular atrial fibrillation (AF) and chronic kidney disease (CKD), including end-stage renal disease (ESRD), is uncertain.

Methods

We conducted a retrospective study using the Korea National Health Insurance Database from 2013 to 2018. We evaluated patients with incident non-valvular AF and CKD. The primary and secondary effectiveness outcomes were ischemic stroke and all-cause mortality. The primary safety outcomes included intracranial hemorrhage, gastrointestinal bleeding, and extracranial or unclassified major bleeding.

Results

Among the 1,885 patients evaluated, 970 (51.5%) initiated warfarin therapy, and 915 (48.5%) initiated DOAC therapy. During a mean follow-up period of 23.8 months, there were 293 and 214 cases of ischemic stroke and all-cause death, respectively. Kaplan–Meier survival analysis showed significantly lower all-cause mortality in DOAC users than in warfarin users. In multivariate Cox regression analyses, DOAC therapy had a hazard ratio for all-cause mortality of 0.41 (95% CI, 0.30–0.56; p < 0.001) compared to warfarin therapy. Additionally, DOAC therapy significantly reduced intracranial hemorrhage and gastrointestinal bleeding.

Discussion

Our study demonstrates that DOAC therapy has a better risk–benefit profile than warfarin therapy in patients with AF and CKD. Further well-designed clinical trials are needed to clarify the benefits of DOACs in this patient population.
A rehabilitative approach beyond the acute stroke event: a scoping review about functional recovery perspectives in the chronic hemiplegic patient
Authors: Paolucci Teresa , Agostini Francesco , Mussomeli Elena , Cazzolla Sara , Conti Marco , Sarno Francescapia , Bernetti Andrea , Paoloni Marco , Mangone Massimiliano
Published: September 2023

Background

Stroke is a main cause of disability worldwide and its neuro-rehabilitative management is not limited to the acute phase but requires continuity in the rehabilitation approach especially in the chronic phase. The aim of this scoping review was to highlight the different treatment opportunities available in neurorehabilitation, effective for patients with chronic stroke sequelae, not only in terms of maintaining motor function but also improving it.

Methods

The literature search was conducted using the following databases: MEDLINE (PubMed), PEDro, Scopus, Web of Science (WOS), Cochrane from 2012 to February 2023. We selected Randomized Clinical Trials in English dealing with neurorehabilitation strategies in chronic hemiplegic patients after stroke focusing on motor function, muscular strength, gait, postural balance, spasticity, and quality of life.

Results

According to the inclusion criteria, 47 articles were selected for our review. All of them were analyzed following the primary outcome and the rehabilitation technique used. Despite the different protocols used within the same technique and despite the chronicity of the disease, all studies report an improvement after the rehabilitation treatment of motor function and quality of life.

Conclusion

The literature analyzed invites us to reflect respect to neurorehabilitation approach to the patient with chronic stroke sequelae often considered to have as its objective the maintenance of the present motor function and contain disability: instead, the review reports how, even in chronicity, the patient always reports margins of statistically and clinically significant improvement. The chronic stroke rehabilitation over 6 months has been proved effective in obtaining recovery in different settings.
Epidemiology of myelin oligodendrocyte glycoprotein antibody-associated disease: a review of prevalence and incidence worldwide
Authors: Hor Jyh Yung , Fujihara Kazuo
Published: September 2023

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) with the presence of conformation-sensitive antibodies against MOG. The spectrum of MOGAD includes monophasic/relapsing optic neuritis, myelitis, neuromyelitis optica spectrum disorder (NMOSD) phenotype without aquaporin 4 (AQP4) antibodies, acute/multiphasic demyelinating encephalomyelitis (ADEM/MDEM)-like presentation, and brainstem and cerebral cortical encephalitis. There is no apparent female preponderance in MOGAD, and MOGAD can onset in all age groups (age at onset is approximately 30 years on average, and approximately 30% of cases are in the pediatric age group). While prevalence and incidence data have been available for AQP4+ NMOSD globally, such data are only beginning to accumulate for MOGAD. We reviewed the currently available data from population-based MOGAD studies conducted around the world: three studies in Europe, three in Asia, and one joint study in the Americas. The prevalence of MOGAD is approximately 1.3–2.5/100,000, and the annual incidence is approximately 3.4–4.8 per million. Among White people, the prevalence of MOGAD appears to be slightly higher than that of AQP4+ NMOSD. No obvious latitude gradient was observed in the Japanese nationwide survey. The data available so far showed no obvious racial preponderance or strong HLA associations in MOGAD. However, precedent infection was reported in approximately 20–40% of MOGAD cases, and this is worthy of further investigation. Co-existing autoimmune disorders are less common in MOGAD than in AQP4+ NMOSD, but NMDAR antibodies may occasionally be positive in patients with MOGAD. More population-based studies in different populations and regions are useful to further inform the epidemiology of this disease.
Mitochondrial apoptosis-related gene polymorphisms are associated with responses to anthracycline-based chemotherapy in acute myeloid leukaemia
Authors: Meng Guangqiang , Li Mingying , Xia Yuan , Wu Yuyan , Ma Yuechan , Ji Min , Zhang Jingru , Ye Jingjing , Sun Tao , Ji Chunyan
Published: September 2023

Background

Although anthracyclines are the first-line chemotherapy drugs for treating non-M3 acute myeloid leukaemia (AML), their efficacy remains limited. It is important to identify factors that influence the efficacy of anthracyclines against AML. Mitochondrial apoptosis-related genes play significant roles in the pathogenesis, treatment, and prognosis of AML.

Methods

We utilized the CRISPR/Cas9 screening system to find AML anthracyclines resistance related genes and several mitochondrial apoptosis-related genes, such as BCL2L11, CASP8, TP63, TP53BP2, PLAUR, SOD2, BNIP3L, and MMP9, were screened out. Then, DNA from 279 patients with AML and 321 healthy individuals were extracted and the contributions of single nucleotide polymorphisms (SNPs) within these genes to the patient’s chemotherapy response, susceptibility to AML, and overall survival were investigated.

Results

Our findings indicated that SNP rs4251864 in the PLAUR gene was associated with an increase in complete remission after anthracycline-based induction chemotherapy. rs4880 in SOD2 was associated with the response to the second course of chemotherapy, whereas rs3789068 in BCL2L11 was associated with susceptibility to AML.

Conclusions

Our results about the association of SNPs in mitochondrial apoptosis-related genes with the response to anthracycline-based chemotherapy in AML provide an important reference for predicting the treatment outcomes in patients with this disease.
Restriction spectrum imaging with elastic image registration for automated evaluation of response to neoadjuvant therapy in breast cancer
Authors: Andreassen Maren M. Sjaastad , Loubrie Stephane , Tong Michelle W. , Fang Lauren , Seibert Tyler M. , Wallace Anne M. , Zare Somaye , Ojeda-Fournier Haydee , Kuperman Joshua , Hahn Michael , Jerome Neil P. , Bathen Tone F. , Rodríguez-Soto Ana E. , Dale Anders M. , Rakow-Penner Rebecca
Published: September 2023

Purpose

Dynamic contrast-enhanced MRI (DCE) and apparent diffusion coefficient (ADC) are currently used to evaluate treatment response of breast cancer. The purpose of the current study was to evaluate the three-component Restriction Spectrum Imaging model (RSI3C), a recent diffusion-weighted MRI (DWI)-based tumor classification method, combined with elastic image registration, to automatically monitor breast tumor size throughout neoadjuvant therapy.

Experimental design

Breast cancer patients (n=27) underwent multi-parametric 3T MRI at four time points during treatment. Elastically-registered DWI images were used to generate an automatic RSI3C response classifier, assessed against manual DCE tumor size measurements and mean ADC values. Predictions of therapy response during treatment and residual tumor post-treatment were assessed using non-pathological complete response (non-pCR) as an endpoint.

Results

Ten patients experienced pCR. Prediction of non-pCR using ROC AUC (95% CI) for change in measured tumor size from pre-treatment time point to early-treatment time point was 0.65 (0.38-0.92) for the RSI3C classifier, 0.64 (0.36-0.91) for DCE, and 0.45 (0.16-0.75) for change in mean ADC. Sensitivity for detection of residual disease post-treatment was 0.71 (0.44-0.90) for the RSI3C classifier, compared to 0.88 (0.64-0.99) for DCE and 0.76 (0.50-0.93) for ADC. Specificity was 0.90 (0.56-1.00) for the RSI3C classifier, 0.70 (0.35-0.93) for DCE, and 0.50 (0.19-0.81) for ADC.

Conclusion

The automatic RSI3C classifier with elastic image registration suggested prediction of response to treatment after only three weeks, and showed performance comparable to DCE for assessment of residual tumor post-therapy. RSI3C may guide clinical decision-making and enable tailored treatment regimens and cost-efficient evaluation of neoadjuvant therapy of breast cancer.
Ammonia nitrogen stress damages the intestinal mucosal barrier of yellow catfish (Pelteobagrus fulvidraco) and induces intestinal inflammation
Authors: Liu Senyue , Luo Lin , Zuo Fengyuan , Huang Xiaoli , Zhong Liang , Liu Sha , Geng Yi , Ou Yangping , Chen Defang , Cai Wenlong , Deng Yongqiang
Published: September 2023

Nitrogen from ammonia is one of the most common pollutants toxics to aquatic species in aquatic environment. The intestinal mucosa is one of the key mucosal defenses of aquatic species, and the accumulation of ammonia nitrogen in water environment will cause irreversible damage to intestinal function. In this study, histology, immunohistochemistry, ultrastructural pathology, enzyme activity analysis and qRT-PCR were performed to reveal the toxic effect of ammonia nitrogen stress on the intestine of Pelteobagrus fulvidraco. According to histological findings, ammonia nitrogen stress caused structural damage to the intestine and reduced the number of mucous cells. Enzyme activity analysis revealed that the activity of bactericidal substances (Lysozyme, alkaline phosphatase, and ACP) had decreased. The ultrastructure revealed sparse and shortened microvilli as well as badly degraded tight junctions. Immunohistochemistry for ZO-1 demonstrated an impaired intestinal mucosal barrier. Furthermore, qRT-PCR revealed that tight junction related genes (ZO-1, Occludin, Claudin-1) were downregulated, while the pore-forming protein Claudin-2 was upregulated. Furthermore, as ammonia nitrogen concentration grew, so did the positive signal of Zap-70 (T/NK cell) and the expression of inflammation-related genes (TNF, IL-1β, IL-8, IL-10). In light of the above findings, we conclude that ammonia nitrogen stress damages intestinal mucosal barrier of Pelteobagrus fulvidraco and induces intestinal inflammation.
Group-based psychoeducational workshop for parents in Kenya: findings from a pilot study
Authors: Alemu Rediet Emebet Getnet , Nyatete Hilda , Baseke Rosine , Ngatia Veronicah , Osborn Tom L. , Wasanga Christine M.
Published: September 2023

Introduction

Low levels of mental health literacy amongst parents can have negative effects on youth mental wellbeing and help-seeking behaviors. Here, we explored the impact of a brief psychoeducational workshop on improving parent mental health literacy and family relationships in Kibera, a low-resource high-risk setting in Nairobi, Kenya.

Methods

The workshop was designed to address this issue, and it was delivered by trained facilitators to small groups of parents (N = 72). Data was collected at baseline, post-workshop, two-week follow-up, and one-month follow-up.

Results

Statistical and thematic analysis of the data revealed significant improvements in parent mental health literacy scores and family relationships, indicating the acceptability and effectiveness of this workshop.

Discussion

The findings suggest that brief, group-based psychoeducational workshops can be effective in improving parent mental health literacy and family relationships, thereby addressing challenges faced by parents and youth in the Kenyan context. Future studies are needed to conclusively determine if such workshops can improve participants’ own mental health or their perception of child behavior.
Nadofaragene firadenovec: a breakthrough in the field of bladder oncology
Authors: Nadeem Abdullah , Qamar Khulud , Bilal Wajeeha , Vohra Laiba Imran , Ahsan Areeba , Tariq Rabeea
Published: September 2023

Muscle-invasive bladder tumors pose a grave mortality risk due to their propensity for distant metastases. The therapeutic spectrum for such tumors encompasses surgery, chemotherapy, and radiation, tailored to the cancer’s severity. In the context of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC), a novel treatment has emerged as a beacon of hope. Nadofaragene firadenovec, a pioneering gene therapy, has gained worldwide approval for combating this condition, marking a watershed moment in bladder cancer therapy. Nadofaragene firadenovec is ingeniously designed to address high-risk BCG-unresponsive NMIBC, particularly carcinoma in situ (CIS) with or without papillary tumors, in adult patients. Rooted in a vector DNA, this therapy encodes interferon (IFN)-2b, which imparts urothelial cells with the ability to generate IFN-2b. The resulting cascade of events triggers a multifaceted assault on cancer, characterized by its immunostimulatory, antiangiogenic, and apoptotic effects. The therapeutic efficacy of nadofaragene firadenovec rests on its capacity to exploit the transformed urothelial cells to deliver these targeted anticancer activities. The evolutionary trajectory of nadofaragene firadenovec culminated in its monumental approval in December 2022 by the United States, signifying a pivotal juncture in the field. Notably, a segment of patients, approximately 30%, prove refractory to BCG treatment. For these individuals, alternative therapeutic avenues are imperative. Presently, the landscape for patients with non-muscle invasive bladder cancer lacks a definitive, enduring solution. Against this backdrop, the introduction of nadofaragene firadenovec heralds a momentous stride toward the global availability of an authorized therapeutic intervention.
Image-guidance in endoscopic pituitary surgery: an in-silico study of errors involved in tracker-based techniques
Authors: Enkaoua Aure , Islam Mobarakol , Ramalhinho João , Dowrick Thomas , Booker James , Khan Danyal Z. , Marcus Hani J. , Clarkson Matthew J.
Published: September 2023

Background

Endoscopic endonasal surgery is an established minimally invasive technique for resecting pituitary adenomas. However, understanding orientation and identifying critical neurovascular structures in this anatomically dense region can be challenging. In clinical practice, commercial navigation systems use a tracked pointer for guidance. Augmented Reality (AR) is an emerging technology used for surgical guidance. It can be tracker based or vision based, but neither is widely used in pituitary surgery.

Methods

This pre-clinical study aims to assess the accuracy of tracker-based navigation systems, including those that allow for AR. Two setups were used to conduct simulations: (1) the standard pointer setup, tracked by an infrared camera; and (2) the endoscope setup that allows for AR, using reflective markers on the end of the endoscope, tracked by infrared cameras. The error sources were estimated by calculating the Euclidean distance between a point’s true location and the point’s location after passing it through the noisy system. A phantom study was then conducted to verify the in-silico simulation results and show a working example of image-based navigation errors in current methodologies.

Results

The errors of the tracked pointer and tracked endoscope simulations were 1.7 and 2.5 mm respectively. The phantom study showed errors of 2.14 and 3.21 mm for the tracked pointer and tracked endoscope setups respectively.

Discussion

In pituitary surgery, precise neighboring structure identification is crucial for success. However, our simulations reveal that the errors of tracked approaches were too large to meet the fine error margins required for pituitary surgery. In order to achieve the required accuracy, we would need much more accurate tracking, better calibration and improved registration techniques.
Identification of Anaplasma marginale, Babesia bovis and Babesia bigemina resistance alleles in Crioulo Lageano cattle using PCR-SBT and BoLA-DRB3 gene sequencing
Authors: Casa Mariana da Silva , Giovambattista Guillermo , Fonteque Graziela Vieira , Miguel Ellen Lara , Vogel Carla Ivane Ganz , Miletti Luiz Claudio , Takeshima Shin-Nosuke , Fonteque Joandes Henrique
Published: September 2023

Introduction

The BoLA-DRB3 gene in cattle is associated with tolerance to several infectious diseases, such as neosporosis, dermatophilosis, leukosis, and mastitis.

Methods

This study used PCR-SBT and BoLA-DRB3 gene sequencing to determine the association between the presence or absence of Anaplasma marginale, Babesia bovis, and Babesia bigemina infections in 208 Crioulo Lageano cattle and alleles present in the population. The chi-square test and odds ratio analysis were employed to establish the association.

Results

Of the BoLA-DRB3 gene alleles present in the population, two alleles were significantly associated with resistance to A. marginale infections: BoLA-DRB3001:01 (p < 0.001; OR = 0.224), which had a frequency of 7.93%, and BoLA-DRB3024:06 (p = 0.007; OR < 0.00001), which had a frequency of 0.72%. Regarding B. bovis infection, the BoLA-DRB3*011:01 allele (p = 0.002; OR = 0.271) had a frequency of 6% in the population and was associated with resistance to the infection. None of the alleles was associated with resistance to infection by B. bigemina.

Discussion

The Crioulo Lageano breed has alleles that may confer resistance against infection by A. marginale and B. bovis.
On the Aeroelasticity of a Cantilever Wing Equipped with the Spanwise Morphing Trailing Edge Concept
Authors: Pilakkadan Jafar S. , Ajaj Rafic M. , Haider Zawar , Amoozgar Mohammadreza
Published: September 2023

This paper studies the aeroelastic behavior of a rectangular, cantilever wing equipped with the spanwise morphing trailing edge (SMTE) concept. The SMTE consists of multiple trailing edge flaps that allow controlling the spanwise camber distribution of a wing. The flaps are attached at the wing’s trailing edge using torsional springs. The Rayleigh–Ritz method is used to develop the equations of motion of the wing-flap system. The use of shape functions allows for representing the wing as an equivalent 2D airfoil with generalized coordinates that are defined at the wingtip. Strip theory, based on Theodorsen’s unsteady aerodynamic model, is used to compute the aerodynamic loads acting on the wing. A representative Padé approximation for Theodorsen’s function is utilized to model the aerodynamic behaviors in a state-space form allowing time-domain simulation and analysis. The model is validated using a rectangular cantilever wing and the data are available in the literature. A comprehensive parametric comparison study is conducted to assess the impact of flap stiffness on the aeroelastic boundary. In addition, the potential of the SMTE to provide load alleviation and flutter suppression is assessed for a wide range of flight conditions, using a discrete (1-cosine) gust. Finally, the implementation and validation of a controller for a wing with SMTE for gust load alleviation are studied and controller parameters are tuned for a specific gust model.
Electric Aerospace Actuator Manufactured by Laser Powder Bed Fusion
Authors: Lizarribar Borja , Prieto Borja , Aristizabal Miren , Martín Jose Manuel , Martínez-Iturralde Miguel , San José Ekain , Golvano Ione , Montes Sergio
Published: September 2023

Recent advances in manufacturing methods have accelerated the exploration of new materials and advantageous shapes that could not be produced by traditional methods. In this context, additive manufacturing is gaining strength among manufacturing methods for its versatility and freedom in the geometries that can be produced. Taking advantage of these possibilities, this research presents a case study involving an electric aerospace actuator manufactured using additive manufacturing. The main objectives of this research work are to assess the feasibility of additively manufacturing electric actuators and to evaluate potential gains in terms of weight, volume, power consumption and cost over conventional manufacturing technologies. To do so and in order to optimise the actuator design, a thorough material study is conducted in which three different magnetic materials are gas-atomised (silicon iron, permendur and supermalloy) and test samples of the most promising materials (silicon iron and permendur) are processed by laser powder bed fusion. The final actuator design is additively manufactured in permendur for the stator and rotor iron parts and in 316L stainless steel for the housing. The electric actuator prototype is tested, showing compliance with design requirements in terms of torque production, power consumption and heating. Finally, a design intended to be manufactured via traditional methods (i.e., punching and stacking for the stator laminations and machining for the housing) is presented and compared to the additively manufactured design. The comparison shows that additive manufacturing is a viable alternative to traditional manufacturing for the application presented, as it highly reduces the weight of the actuator and facilitates the assembly, while the cost difference between the two designs is minimal.
Using the Impulse Method to Determine High-Pressure Dynamic Burning Rate of Solid Propellants
Authors: Liu Jiahao , Wang Yinghong , Li Xinyang , Cong Junhao
Published: September 2023

A new method for determining the burning rate of a solid propellant, called the Impulse Method, is proposed in this paper. It is based on the proportional relationship between the impulse generated and the mass of the burned propellant. The pressure–time and thrust–time curves are obtained from a tubular propellant grain burning in the chamber, whose inner surface serves as the initial burning surface. Consequently, the mass of the propellant that was burned off at different pressures can be determined, and the burning rates at different pressures are derived according to the geometric parameters of the propellant grain. The Impulse Method was applied to test the burning rate of two types of propellants twice. The results show that the burning rates were consistent for the same propellant at corresponding pressures, demonstrating the feasibility and reliability of the Impulse Method. The burning rate of a GAP-based composite propellant at 20 MPa measured using the Standard Motor Method was 22.6 mm/s, and that measured using the Impulse Method was 22.2 mm/s and 22.7 mm/s, respectively. These findings indicate that the two methods have comparable accuracy. However, the Impulse Method has the advantage of obtaining the burning rate of the solid propellant at any pressure through a single test. In addition, the nozzle erosion only affected the pressure and not the burning rate. Finally, the rationality of the approach for determining the actual specific impulse was proven by comparing the results with those from another testing method.
Deep Learning of Speech Data for Early Detection of Alzheimer’s Disease in the Elderly
Authors: Ahn Kichan , Cho Minwoo , Kim Suk Wha , Lee Kyu Eun , Song Yoojin , Yoo Seok , Jeon So Yeon , Kim Jeong Lan , Yoon Dae Hyun , Kong Hyoun-Joong
Published: September 2023

Background: Alzheimer’s disease (AD) is the most common form of dementia, which makes the lives of patients and their families difficult for various reasons. Therefore, early detection of AD is crucial to alleviating the symptoms through medication and treatment. Objective: Given that AD strongly induces language disorders, this study aims to detect AD rapidly by analyzing the language characteristics. Materials and Methods: The mini-mental state examination for dementia screening (MMSE-DS), which is most commonly used in South Korean public health centers, is used to obtain negative answers based on the questionnaire. Among the acquired voices, significant questionnaires and answers are selected and converted into mel-frequency cepstral coefficient (MFCC)-based spectrogram images. After accumulating the significant answers, validated data augmentation was achieved using the Densenet121 model. Five deep learning models, Inception v3, VGG19, Xception, Resnet50, and Densenet121, were used to train and confirm the results. Results: Considering the amount of data, the results of the five-fold cross-validation are more significant than those of the hold-out method. Densenet121 exhibits a sensitivity of 0.9550, a specificity of 0.8333, and an accuracy of 0.9000 in a five-fold cross-validation to separate AD patients from the control group. Conclusions: The potential for remote health care can be increased by simplifying the AD screening process. Furthermore, by facilitating remote health care, the proposed method can enhance the accessibility of AD screening and increase the rate of early AD detection.
A Bionic Venus Flytrap Soft Microrobot Driven by Multiphysics for Intelligent Transportation
Authors: Wang Xiaowen , Gao Yingnan , Ma Xiaoyang , Li Weiqiang , Yang Wenguang
Published: September 2023

With the continuous integration of material science and bionic technology, as well as increasing requirements for the operation of robots in complex environments, researchers continue to develop bionic intelligent microrobots, the development of which will cause a great revolution in daily life and productivity. In this study, we propose a bionic flower based on the PNIPAM–PEGDA bilayer structure. PNIPAM is temperature-responsive and solvent-responsive, thus acting as an active layer, while PEGDA does not change significantly in response to a change in temperature and solvent, thus acting as a rigid layer. The bilayer flower is closed in cold water and gradually opens under laser illumination. In addition, the flower gradually opens after injecting ethanol into the water. When the volume of ethanol exceeds the volume of water, the flower opens completely. In addition, we propose a bionic Venus flytrap soft microrobot with a bilayer structure. The robot is temperature-responsive and can reversibly transform from a 2D sheet to a 3D tubular structure. It is normally in a closed state in both cold (T < 32 °C) and hot water (T > 32 °C), and can be used to load and transport objects to the target position (magnetic field strength < 1 T).
Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update
Authors: Alsajjan Roa , Mason Warren P.
Published: September 2023

Glioblastoma is the most common malignant primary brain tumor in adults. The prognosis is extremely poor even with standard treatment of maximal safe resection, radiotherapy, and chemotherapy. Recurrence is inevitable within months, and treatment options are very limited. Chimeric antigen receptor T-cell therapy (CART) and bispecific T-cell engagers (TCEs) are two emerging immunotherapies that can redirect T-cells for tumor-specific killing and have shown remarkable success in hematological malignancies and been under extensive study for application in glioblastoma. While there have been multiple clinical trials showing preliminary evidence of safety and efficacy for CART, bispecific TCEs are still in the early stages of clinical testing, with preclinical studies showing very promising results. However, there are multiple shared challenges that need to be addressed in the future, including the route of delivery, antigen escape, the immunosuppressive tumor microenvironment, and toxicity resulting from the limited choice of tumor-specific antigens. Efforts are underway to optimize the design of both these treatments and find the ideal combination therapy to overcome these challenges. In this review, we describe the work that has been performed as well as novel approaches in glioblastoma and in other solid tumors that may be applicable in the future.
Study on the Coupling Effect of Stress Field and Gas Field in Surrounding Rock of Stope and Gas Migration Law
Authors: Li Shizhe , Wang Zhaofeng
Published: September 2023

In the process of working face mining, the permeability of the coal seam and the crack evolution characteristics of overlying strata are very important for efficient gas drainage. In this study, the distribution characteristics of the stress field and crack field in the working face and their relations are analyzed mainly by 3DEC numerical simulation. Furthermore, combined with the on-site measurement of coal seam stress, gas pressure, and gas seepage in front of the working face and the gas seepage in overlying strata before and after mining, the coupling effect of stress field and gas field and the law of gas migration and distribution in the working face are deeply explored. The results show that the changing trend of gas seepage and gas pressure is controlled by the stress change of the working face, and with the increase of stress, gas pressure and gas seepage also increase. The peak position of gas pressure is the farthest from the coal wall, about 22.5~25 m, followed by the peak of stress and gas seepage. When the permeability of coal and rock mass increases, the gas seepage increases and the gas pressure decreases. The coal seam stress and gas seepage in the working face and gas seepage in the overlying strata fracture zone along the tailgate side are generally greater than those on the headgate side, but the gas pressure is the opposite. Mining cracks and strata separation provide a good channel and space for gas migration and accumulation. Along the strike and tendency of the working face, gas is mainly concentrated in the overlying strata crack space above the separation zone and the roof and overlying strata crack space on the side of the tailgate, respectively. Based on this, the directional borehole gas drainage technology and borehole layout scheme in the fractured zone are put forward, which effectively reduce the gas concentration in the working face by 30~36%.