bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and delivery of national housing in the UAE: an alternative approach
Authors: Mohamed Basem Eid , Elkaftangui Mohamed , Zureikat Rana , Hiyasat Rund
Published: July 2023

The provision of national housing to citizens in the United Arab Emirates (UAE) is considered a crucial topic. Over the past four decades, the process of developing national housing has emerged into multiple housing programs and schemes, all with the same aim of offering affordable and high-quality housing to citizens, in addition to meeting the needs of local families regarding spatial configurations while maintaining cultural values. However, despite all these efforts, the question has always remained: are the offered housing practices suited for family needs, socioeconomic trends, and environmental challenges? This study aims to offer an alternative approach for the design and delivery of national housing practices in the UAE. The proposed process is structured based on the following ethos: first, a conceptual approach for design flexibility toward offering customization while maintaining contextual and cultural qualities for inhabitants; second, a computational design strategy for facade optimization that illustrates the significance of incorporating environmentally conscious design strategies in response to local climatic conditions toward enhancing overall building performance; and third, a hybrid production model that relies on a prefabricated building approach that combines precast concrete systems with 3D printing technology. The efforts described in this article represent a significant phase of an ongoing research endeavor that explores how technological capacities could help rethink national housing in the UAE.
Alterations in the gut microbiota and the efficacy of adjuvant probiotic therapy in liver cirrhosis
Authors: Wu Zengrong , Zhou Hejun , Liu Deliang , Deng Feihong
Published: July 2023

Background

Liver cirrhosis is the end stage of various chronic liver diseases (CLDs). The gut microbiota can impact the liver environment and trigger chronic liver inflammation through the gut-liver axis. Alteration of the gut microbiota has become an effective strategy in the biological treatment of cirrhosis.

Methods

Twenty-eight patients with liver cirrhosis and 16 healthy individuals were included, and fresh stool samples were collected. We analyzed changes in the gut microbiota between groups by 16S rRNA sequencing and evaluated the association between microbiota alterations and hepatic function. Additionally, 102 cirrhotic patients were retrospectively enrolled and divided into a probiotic group (n=44) and a nonprobiotic group (n=58) in addition to standard treatment for cirrhosis. Patients were monitored for hematological parameters and hepatic function during the six-month follow-up.

Results

The gut microbiota profile of patients with cirrhosis was greatly different from that of healthy individuals, presenting with significantly reduced α diversity and decreased abundance of representative SCFA-producing bacteria including Firmicutes, Coprococcus and Clostridium IV. The pathogenic bacteria Gammaproteobacteria, Veillonella, and Bacilli were greatly enriched in cirrhotic patients. Additionally, patients with decompensated cirrhosis (DCPC) had a significantly reduced abundance of Oscillibacter compared to compensated cirrhosis (CPC), which is also a SCFA-producing bacteria, and the lower Firmicutes to Bacteroidetes ratio and enhanced MDR values were also shown in DCPC patients compared to CPC patients. In addition, the abundance of Firmicutes was negatively related to hepatic function in cirrhotic patients, including the levels of ALT, AST, and DBIL. From the retrospective study, we found that biochemical improvements in alanine transaminase (ALT) and total bilirubin (TBIL) were obtained in DCPC patients who received oral probiotic therapy compared with the nonprobiotic group.

Conclusion

Severe microbial dysbiosis existed in patients with liver cirrhosis, especially patients who reached the decompensatory stage. SCFA-producing bacteria were significantly reduced in cirrhosis. Altered gut microbiota cause changes in functional modules, which may contribute to cirrhosis progression and are associated with clinical prognosis. Adjuvant probiotic supplementation to enhance SCFA-producing bacteria can be a prospective therapy for patients with cirrhosis.
Case report: Surgery combined with extracorporeal membrane oxygenation for a patient with type A aortic dissection complicated with myocardial infarction after percutaneous coronary intervention
Authors: Yu Junjian , Yu Wenbo , Zeng Hui , Gao Jianfeng , Xiong Jianxian
Published: July 2023

Background

Aortic dissection (AD) is a severe cardiovascular disease characterized by aortic rupture, aortic valve insufficiency, aortic branch lumen stenosis, and occlusion. Acute ST-segment elevation myocardial infarction may be the primary manifestation when aortic dissection affects the coronary artery, leading to delayed or missed diagnosis of aortic dissection, and preventing patients from receiving timely and comprehensive treatment. Simultaneous aortic repair and coronary artery bypass grafting surgery are controversial because of their high mortality rates. Personalized and optimal treatment plans for patients should be taken seriously based on their different conditions and treatment options.

Case presentation

A 42-year-old man who experienced 1 h of persistent precordialgia was admitted to a local second-level hospital for emergency treatment. Electrocardiogram (ECG) showed evidence of ST-segment elevation, and myocardial enzyme levels were CK-MB 18.35 ng/ml and troponin 0.42 ng/ml. The patient was treated for acute myocardial infarction (AMI) and urgently sent to the interventional catheter room. Coronary angiography showed stenosis of the starting part of the right coronary artery trunk. Thus, stent implantation was performed, and the stenosis section recovered patency; however, postoperative precordialgia was not alleviated. Computed tomography angiography (CTA) revealed a type A AD. The patient was immediately transferred to a higher-level hospital, underwent emergency surgery with cardiopulmonary bypass (CPB) ascending aorta replacement, SUN's procedure (total arch replacement and stented elephant trunk implantation), and simultaneous implantation of extracorporeal membrane oxygenation (ECMO), and regained consciousness within intensive care unit care. ECMO was discontinued when hemodynamics stabilized. The patient ultimately recovered well and was discharged.

Conclusion

This case demonstrated that precordialgia is not limited to myocardial infarction but may also be accompanied by aortic dissection. Percutaneous coronary intervention (PCI) can timely and effectively restore coronary artery perfusion, strive for the opportunity of aortic repair surgery, and can overcome pump failure caused by myocardial infarction, cardiopulmonary bypass, heart block time, and myocardial ischemia-reperfusion injury. Personalized treatment is crucial for patients with complex type A aortic dissection.
Well log prediction while drilling using seismic impedance with an improved LSTM artificial neural networks
Authors: Wang Heng , Xu Yungui , Tang Shuhang , Wu Lei , Cao Weiping , Huang Xuri
Published: July 2023

Well log prediction while drilling estimates the rock properties ahead of drilling bits. A reliable well log prediction is able to assist reservoir engineers in updating the geological models and adjusting the drilling strategy if necessary. This is of great significance in reducing the drilling risk and saving costs. Conventional interactive integration of geophysical data and geological understanding is the primary approach to realize well log prediction while drilling. In this paper, we propose a new artificial intelligence approach to make the well log prediction while drilling by integrating seismic impedance with three neural networks: LSTM, Bidirectional LSTM (Bi-LSTM), and Double Chain LSTM (DC-LSTM). The DC-LSTM is a new LSTM network proposed in this study while the other two are existing ones. These three networks are thoroughly adapted, compared, and tested to fit the artificial intelligent prediction process. The prediction approach can integrate not only seismic information of the sedimentary formation around the drilling bit but also the rock property changing trend through the upper and lower formations. The Bi-LSTM and the DC-LSTM networks achieve higher prediction accuracy than the LSTM network. Additionally, the DC-LSTM approach significantly promotes prediction efficiency by reducing the number of training parameters and saving computational time without compromising prediction accuracy. The field data application of the three networks, LSTM, Bi-LSTM, and DC-LSTM, demonstrates that prediction accuracy based on the Bi-LSTM and DC-LSTM is higher than that of the LSTM, and DC-LSTM has the highest efficiency overall.
How digital tools support the validation of outdoor modelling results
Authors: Jablonski Simone , Barlovits Simon , Ludwig Matthias
Published: July 2023

Mathematical modelling addresses numerous demands of modern mathematics education: The learning of mathematics is directly linked to reality and hence to real objects. At the same time, these tasks are very challenging for students, especially when their own solution process needs to be validated and refined. Studies even show that some students do not validate their results at all. Recent research has shown that digital tools can enhance the support of modelling activities in different ways. In this paper, we take the modelling step of validation into a deeper account and explore the potential of MathCityMap, a digital tool for outdoor mathematics education. Hereby, its automatic solution validation by means of a predefined interval and assessment of the result’s quality are taken into consideration. The modelling activities of secondary school students are compared on a quantitative and qualitative level – half of the students working with the MathCityMap app and half of them solving the tasks without any digital support. Based on the quantitative results, we can see that the app functionalities for elaborative feedback are used to varying degrees: While student groups frequently access the hints, the sample solution is hardly accessed. Moreover, our analysis can show the value of corrective app feedback. Student groups that used the app solved a comparable number of problems, but failed significantly less often than student groups that worked on math trails without the app. The qualitative results show that in particular the solution validation forces the students to proceed with a second run in the modelling cycle if a result is valued as wrong in the app. In addition, it helps the students to assess their own result in terms of its correctness. Based on the combined results, we draw conclusions about the app usage in mathematical modelling tasks.
CFD simulations to study bed characteristics in gas–solid fluidized beds with binary mixtures of Geldart B particles: II quantitative analysis
Authors: Ganguli Arijit , Bhatt Viraj
Published: July 2023

Hydrodynamics of fluidized beds with binary mixtures of particles is important in many industrial applications. The binary particles are generally in the Geldart particle range. In our earlier work, (Part I) of this work simulations were carried out and qualitative analysis was presented. Quantitative predictions of gas velocity and particle velocity profiles have been presented in the present work, which is Part II of the two-part work on computational fluid dynamics (CFD) simulations of binary fluidized beds. It was observed that the dynamics of the bed vary for different binary mixtures and are a strong function of superficial velocity and bed height. Mixing and segregation in beds for two different initial bed heights and six different binary mixtures and superficial velocities have been identified. Segregation is prominent for binary mixtures with 20 wt.% and 80 wt.% of large particles, whereas mixing is observed in 40 wt.% and 60 wt.% large particle mixtures. Bypassing of gas near the walls is prominently seen for 60 wt.% large particles with gas velocities as high as 5 m/s. Time-averaged axial particle volume fractions have been observed to be lower in the dilute phase with large undulations in the middle whenever the bed is well mixed for central axial profiles. The axial volume fraction profiles also confirm the mixing and segregation for the 40 wt.% and 20 wt.% composition of large particles for the operating conditions considered for the study. Bed height expansion is linear until a certain superficial velocity with the increase or decrease depending on the superficial velocity or bed height of operation. Furthermore, correlations for minimum fluidization velocity and pressure drops from the literature have been compared with experimental results. The simulated data have been considered for the development of a correlation for minimum fluidization velocity. The predicted results match experimental data with a 10%–15% deviation.
The traceability of sudden water pollution in river canals based on the pollutant diffusion quantification formula
Authors: Lin Fei , Ren Honglei , Tao Yuezan , Zhang Naifeng , Li Yucheng , Wang Rujing , Hu Yimin
Published: July 2023

For the problem that the traceability parameters of sudden water pollution are difficult to determine, a fast traceability model based on a simplified mechanistic model coupled with an optimization algorithm is proposed to improve the accuracy of sudden water pollution traceability. In this paper, according to the diffusion law of pollutants, a quantitative formula of pollutant diffusion is proposed, and the differential calculation process of the pollutant convection equation is optimized. The Dynamic Programming and Beetle Antennae Search algorithm (DP-BAS) with dynamic step size is used in the reverse optimization process, which can avoid the problem of entering the local optimal solution in the calculation process. The DP-BAS is used to inverse solve the quantization equation to realize the decoupling of pollutant traceability parameters, transforming the multi-parameter coupled solution into a single-parameter solution, reducing the solution dimension, and optimizing the difficulty and solution complexity of pollutant traceability. The proposed traceability model is applied to the simulation case, the results show that the mean square errors of pollutant placement mass, location, and time are 2.39, 1.16, and 1.19 percent, respectively. To further verify the model reliability, the Differential Evolution and Markov Chain Monte Carlo simulation method (DE-MCMC) as well as Genetic Algorithms (GA) were introduced to compare with the proposed model to prove that the model has certain reliability and accuracy.
Event-scaled hydrological response of a headwater catchment in Hong Kong
Authors: Zhang Li , Xu Qian , Wang Keyi , Chen Guoxin , Luo Zhuoran , Li Xiang , Guo Biyun
Published: July 2023

To improve understanding of rainfall-runoff processes and the fundamental hydrological mechanisms, rainfall and runoff data during six hydrological years (2007/06–2012/06) were collected in a small headwater catchment at the Kadoorie Agricultural Research Centre (KARC) in Shek Kong, Yuen Long District, New Territories, Hong Kong. Totally, 28 storms were selected; using the one parameter filter method, the direct and baseflow hydrographs were obtained. Their runoff coefficients (which are the ratios of direct runoff volumes to the total rainfall volumes) were computed and the values were very low (mean value is less than 2%). At the event scale, the results revealed that the runoff coefficient which represents the catchment response was highly correlated with rainfall depth, maximum 15-min rainfall intensity and initial discharge. Linear relationships were found and two variables (rainfall depth and initial discharge) gave a better result to predict runoff coefficient indicating that hydrological response depended both on rainfall depth and initial discharge. The principal component analysis and cluster method were used to discriminate types of hydrological responses. Three types of characteristics of hydrological behavior were identified. The different types of hydrological responses show similar characteristics such as the quick rise and the prolonged recession. This study highlights the importance of interflow in the rainfall-runoff process and provides insight into the relationship between rainfall and runoff. The findings have significant implications for water resources management and will help inform decision-making processes.
Molecular evolution in introduced insect species—a mitochondrial perspective
Authors: D’Ercole Jacopo , Vila Roger , Dapporto Leonardo , Pentinsaari Mikko , Talavera Gerard , Dincă Vlad , Hebert Paul D. N.
Published: July 2023

Introduced species provide the opportunity to study evolutionary change on short time scales—a key first step to understand and manage the ecosystem-level impact of invasions. This study examined mitochondrial DNA sequence variation in cytochrome c oxidase subunit 1 (COI) for 26 insect species—Coleoptera (9), Hymenoptera (9), and Lepidoptera (8)—introduced to the Nearctic from the Palearctic. A total of 6,302 barcode records were retrieved from BOLD (boldsystems.org) to compare sequence diversity between the native and introduced range. As expected, genetic variation averaged nearly an order of magnitude lower in introduced populations (2.19 × 10−5 substitutions per nucleotide) than in the native range (1.48 ×10−4 substitutions per nucleotide). Nonsynonymous and synonymous changes had a similar incidence in the introduced populations (p-value = 0.83, averaging respectively 1.08 × 10−5 and 1.11 × 10−5 substitutions). By contrast, nonsynonymous changes were ten-fold less frequent than synonymous changes in the native populations (p-value < 0.001, averaging 1.74 × 10−5 and 1.3 × 10−4 substitutions, respectively). Patterns of sequence variation in the introduced range were largely congruent across the three insect orders which suggests that they are produced by general processes. This study explores the molecular evolution of introduced species, a fundamental aspect to improve understanding of their biology and manage their impact on ecosystems.
Primary oxidative phosphorylation defects lead to perturbations in the human B cell repertoire
Authors: Gordon-Lipkin Eliza M. , Banerjee Payal , Franco Jose Luis Marin , Tarasenko Tatiana , Kruk Shannon , Thompson Elizabeth , Gildea Derek E. , Zhang Suiyuan , Wolfsberg Tyra G. ,   NISC Comparative Sequencing Program, Flegel Willy A. , McGuire Peter J.
Published: July 2023

Introduction

The majority of studies on oxidative phosphorylation in immune cells have been performed in mouse models, necessitating human translation. To understand the impact of oxidative phosphorylation (OXPHOS) deficiency on human immunity, we studied children with primary mitochondrial disease (MtD).

Methods

scRNAseq analysis of peripheral blood mononuclear cells was performed on matched children with MtD (N = 4) and controls (N = 4). To define B cell function we performed phage display immunoprecipitation sequencing on a cohort of children with MtD (N = 19) and controls (N = 16).

Results

Via scRNAseq, we found marked reductions in select populations involved in the humoral immune response, especially antigen presenting cells, B cell and plasma populations, with sparing of T cell populations. MTRNR2L8, a marker of bioenergetic stress, was significantly elevated in populations that were most depleted. mir4485, a miRNA contained in the intron of MTRNR2L8, was co-expressed. Knockdown studies of mir4485 demonstrated its role in promoting survival by modulating apoptosis. To determine the functional consequences of our findings on humoral immunity, we studied the antiviral antibody repertoire in children with MtD and controls using phage display and immunoprecipitation sequencing. Despite similar viral exposomes, MtD displayed antiviral antibodies with less robust fold changes and limited polyclonality.

Discussion

Overall, we show that children with MtD display perturbations in the B cell repertoire which may impact humoral immunity and the ability to clear viral infections.
Real-world treatment patterns, discontinuation and clinical outcomes in patients with B-cell lymphoproliferative diseases treated with BTK inhibitors in China
Authors: Yan Yuting , Lv Rui , Wang Tingyu , Yu Ying , Huang Yanshan , Xiong Wenjie , Li Yuxi , Sui Weiwei , Wang Qi , Huang Wenyang , An Gang , Zou Dehui , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: July 2023

Introduction

Bruton tyrosine kinase inhibitor (BTKi) has demonstrated substantial efficacy in treating B-cell lymphoproliferative diseases (BLPD). Nonetheless, the significant discontinuation rates due to toxicity or financial reasons cannot be overlooked. In China, empirical evidence on the usage of BTKi remains scarce.

Methods

To address this, a retrospective cohort study was conducted focused on 673 Chinese patients with BLPD who underwent at least one month of BTKi therapy.

Results

Median age at BTKi initiation was 60 years. The median duration on BTKi treatment of the whole cohort was 36.4 months. The median post-BTK survival was not reach. BTKi-based treatment was permanently discontinued in 288 (43.8%) patients during follow-up, mostly attributed to progressive disease. Within the first 6 months of BTKi treatment, 76 patients (26.3%) had early treatment discontinuation. Patients with early discontinuation had extreme worse outcome with a median post-discontinuation survival of only 6.9 months. On multivariate analysis, withdrawal BTKi by toxicity and withdrawal BTKi within 6 months retained to be independent predictors of post-BTK survival, after taking account of the response depth, lines of therapy and baseline cytogenetics including 17p deletion. The decision between BTKi monotherapy and combination therapy, along with the preference for first or second-generation BTKi, exerted no significant impact on survival.

Discussions

These observations contribute valuable real-world insights into the utilization of BTKi in China. We concluded that BTKi is an effective and well-tolerated treatment for long-term use in Chinese patient population. However, it is imperative to stress that a proportion of patients discontinue BTKi early, leading to suboptimal outcomes. This study underscores the importance of adherence to BTKi therapy for improved clinical outcomes in real-world patients.
Real-time GAN-based image enhancement for robust underwater monocular SLAM
Authors: Zheng Ziqiang , Xin Zhichao , Yu Zhibin , Yeung Sai-Kit
Published: July 2023

Underwater monocular visual simultaneous localization and mapping (SLAM) plays a vital role in underwater computer vision and robotic perception fields. Unlike the autonomous driving or aerial environment, performing robust and accurate underwater monocular SLAM is tough and challenging due to the complex aquatic environment and the collected critically degraded image quality. The underwater images’ poor visibility, low contrast, and color distortion result in ineffective and insufficient feature matching, leading to the poor or even failure of the existing SLAM algorithms. To address this issue, we propose introducing the generative adversarial network (GAN) to perform effective underwater image enhancement before conducting SLAM. Considering the inherent real-time requirement of SLAM, we conduct knowledge distillation to achieve GAN compression to reduce the inference cost, while achieving high-fidelity underwater image enhancement and real-time inference. The real-time underwater image enhancement acts as the image pre-processing to build a robust and accurate underwater monocular SLAM system. With the introduction of real-time underwater image enhancement, we can significantly promote underwater SLAM performance. The proposed method is a generic framework, which could be extended to various SLAM systems and achieve various scales of performance gain.
Impact of conventional and advanced cleaning techniques on the durability of firefighter turnout ensembles
Authors: Girase Arjunsing , Thompson Donald B. , Ormond R. Bryan
Published: July 2023

The concern for firefighters’ occupational exposure to harmful contaminants is growing due to the increase in health issues in the firefighting community. At such times, effective decontamination of personnel and equipment is an essential component of a hazard mitigation strategy. The current decontamination practices used for firefighter protective clothing have been shown to not be very effective. Hence, the scientific community is looking for several alternatives to conventional washing procedures. Liquid carbon dioxide (CO2) has been used in laundering and has distinct advantages over conventional dry-cleaning solvents such as perchloroethylene. The following study is aimed to assess how different washing procedures affect the durability of the turnout material. The study includes using three washing procedures on different samples: 1) conventional washing procedure, 2) liquid CO2 washing procedure, and 3) a high-temperature washing procedure. Samples for durability testing were constructed from a common aramid fabric used in firefighter turnout ensembles. These swatches were subjected to different washing techniques. The durability assessment was performed for physical testing of the samples, visual inspection, water repellency, and quantifying color changes using spectrophotometric analysis. The conventional wash and high-temperature washing affected the durability of the outer shell material in a significant manner. The liquid CO2 process did not affect the samples’ water repellency or physical strength. In contrast, conventional and high-temperature washing significantly affected the durability of the outer shell material. However, all samples met the criteria for tearing strength outlined in the NFPA 1971 standard subsection 7.1.11.
Cancer-testis antigen CEP55 serves as a prognostic biomarker and is correlated with immune infiltration and immunotherapy efficacy in pan-cancer
Authors: Xie Xiaodong , Liang Hongyin , Jiangting Wushuang , Wang Yu , Ma Xiao , Tan Zhen , Cheng Long , Luo Zhulin , Wang Tao
Published: July 2023

Background: Centrosomal Protein 55 (CEP55) was initially described as a main participant in the final stage of cytokinesis. Further research identified CEP55 as a cancer-testis antigen (CTA) that is aberrantly expressed in different malignancies and a cancer vaccination candidate. The current study aimed to disclose the complete expression of CEP55, its effect on various malignancy prognoses, and its role in the tumor microenvironment.

Methods: Transcriptional information regarding tumor and normal tissues, as well as externally validated and protein expression data were gathered from the Cancer Genome Atlas, Genotype-Tissue Expression project, Gene Expression Omnibus, and Human Protein Atlas. We examined the effect of CEP55 on tumor prognosis using Kaplan-Meier (KM) and univariate Cox regression analyses. In addition, we investigated the connections between CEP55 expression and hallmark cancer pathways, immune cell infiltration, and immune regulator expression across malignancies. We constructed and validated a CEP55-related risk model for hepatocellular carcinoma (HCC) and explored the correlations between CEP55 expression and HCC molecular subtypes. Finally, we investigated putative small-molecule drugs targeting CEP55 using a connectivity map (CMap) database and validated them using molecular docking analysis.

Findings: CEP55 was aberrantly expressed in most cancers and revealed a prognostic value for several malignancies. Cancers with high CEP55 expression showed significantly enhanced cell cycle, proliferation, and immune-related pathways. For most malignancies, elevated CEP55 expression was associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 cells. In addition, CEP55 expression was linked to immunomodulators and the potential prediction of immune checkpoint inhibitor (ICI) responses, and strongly associated with distinct molecular HCC subtypes, whereby the CEP55-based nomogram performed well in predicting short- and long-term HCC survival. Finally, we used connectivity map (CMap) and molecular docking analyses to discover three candidate small-molecule drugs that could directly bind to CEP55.

Conclusion: CEP55 affected the occurrence and development of various cancers and possibly the regulation of the tumor immune microenvironment. Our findings suggest that CEP55 is a potential biomarker for prognosis and a powerful biomarker for ICI efficacy prediction.
Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification
Authors: Zhang Lin-ming , Chen Ling , Zhao Yi-fei , Duan Wei-mei , Zhong Lian-mei , Liu Ming-wei
Published: July 2023

One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member (KCNA) 1, KCNA2, potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11), and KCNS1. A protein–protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target KCNA1, KCNA2, and KCNS1. Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for KCNJ11. Compared to normal mice, the expression of KCNA1, KCNA2, KCNJ11, and KCNS1 was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.
Development, delivery, and evaluation of a training program for the early identification of autism: Monitoring of Social Attention, Interaction, and Communication
Authors: Gilbert Melissa , Gore Katherine , Hawke Marguerite , Barbaro Josephine
Published: July 2023

Introduction

Early identification of Autistic children is an important precursor to diagnosis, and access to supports and services. Here we describe the training of the maternal and child health (MCH) workforce in the state of Victoria, Australia in the early identification of infants and toddlers with a high likelihood of autism.

Methods

In 2019, 1,428 MCH nurses completed early autism training held at venues across the state, with an additional 82 nurses completing online-only training. A training needs analysis enabled the research team to determine the workforce’s current skill and knowledge levels, and to identify knowledge gaps, training needs and workplace barriers. The professional development program, known as Monitoring of Social Attention, Interaction, and Communication (MoSAIC), comprised: online pre-workshop modules; a face-to-face instructor-led workshop, which included the use of the Social Attention and Communication-Revised (SACS-R) tool; and online post-workshop modules, which included a recording of a face-to-face workshop with all accompanying resources. This was the first time that the MCH workforce received this training package. Attendees were asked to complete a training satisfaction survey immediately following the face-to-face instructor-led workshop and a follow-up survey regarding their autism knowledge and SACS-R implementation 4–6 weeks after the workshop.

Results

Over 90% (n = 325) of MCH nurses who completed the training satisfaction survey agreed or strongly agreed with statements that the training was clear and of high quality. Most nurses also reported that the training was well-presented and that they would recommend it to a colleague. In the 6 months following the training, a total of 82,581 SACS-R assessments were conducted by the MCH workforce, reflecting that MCH nurses had successfully integrated SACS-R assessments into their work practice after receiving the early autism identification training.

Discussion

This study demonstrated that training on the early identification of autism can be successfully designed, customized, and delivered to a large primary healthcare workforce for universal developmental surveillance of autism.
Microsurgical revascularization of a symptomatic proximal vertebral artery: pilot experiences from a single center
Authors: Zhang Tongfu , Zhou Donglin , Xu Yangyang , Li Maogui , Zhuang Jianfeng , Wang Hai , Zhong Weiying , Chen Chao , Kuang Hong , Wang Donghai , Wang Yunyan
Published: July 2023

Background

Vertebral artery stenosis and occlusion (VASO) is a high-risk factor for posterior circulation stroke. Post-stent restenosis and drug tolerance have facilitated the exploration of microsurgical vascular reconstruction. This study aims to evaluate the safety and efficacy of microsurgical reconstruction of the proximal VA.

Methods

Twenty-nine patients (25 men, aged 63.2 years) who had symptoms of posterior circulation ischemia underwent microsurgical revascularization for proximal VASO were retrospectively included in this study. Procedural complications and clinical and angiographic outcomes were reviewed.

Results

Twelve, three, and five patients underwent VA endarterectomy, artery transposition, or both, respectively; seven patients underwent vertebral endarterectomy plus stent implantation; and two patients failed surgery because of the difficult exposure of the VA and the occurrence of vascular dissection. The perioperative period-related complications included seven cases of Horner’s syndrome, five cases of hoarseness, and one case of chylothorax. No cases of perioperative stroke or death were reported. The mean follow-up period was 28.4 (8–62 months). Most patients improved clinically; however, the vertebrobasilar ischemia symptoms did not decrease significantly in two patients during the follow-up. Moreover, follow-up imaging was performed in all the patients, and no signs of anastomotic stenosis were reported.

Conclusion

Microsurgical reconstruction is an alternative option that can effectively treat refractory proximal VASO disease and in-stent stenosis, with a high rate of postoperative vascular recirculation. Prospective cohort studies with larger sample sizes must be conducted to validate the above conclusions.
A computer-aided diagnosis system for brain tumors based on artificial intelligence algorithms
Authors: Chen Tao , Hu Lianting , Lu Quan , Xiao Feng , Xu Haibo , Li Hongjun , Lu Long
Published: July 2023

The choice of treatment and prognosis evaluation depend on the accurate early diagnosis of brain tumors. Many brain tumors go undiagnosed or are overlooked by clinicians as a result of the challenges associated with manually evaluating magnetic resonance imaging (MRI) images in clinical practice. In this study, we built a computer-aided diagnosis (CAD) system for glioma detection, grading, segmentation, and knowledge discovery based on artificial intelligence algorithms. Neuroimages are specifically represented using a type of visual feature known as the histogram of gradients (HOG). Then, through a two-level classification framework, the HOG features are employed to distinguish between healthy controls and patients, or between different glioma grades. This CAD system also offers tumor visualization using a semi-automatic segmentation tool for better patient management and treatment monitoring. Finally, a knowledge base is created to offer additional advice for the diagnosis of brain tumors. Based on our proposed two-level classification framework, we train models for glioma detection and grading, achieving area under curve (AUC) of 0.921 and 0.806, respectively. Different from other systems, we integrate these diagnostic tools with a web-based interface, which provides the flexibility for system deployment.
Methylphenidate is more effective to improve inhibitory control and working memory compared to tDCS in children and adolescents with attention deficit/hyperactivity disorder: a proof-of-concept study
Authors: D’Aiello Barbara , Lazzaro Giulia , Battisti Andrea , Pani Pierpaolo , Di Vara Silvia , De Rossi Pietro , Pretelli Italo , Costanzo Floriana , Vicari Stefano , Menghini Deny
Published: July 2023

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD.

Methods

After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH.

Results

Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual–spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS.

Discussion

In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.
Sensory and emotional responses to deep pressure stimulation at myofascial trigger points: a pilot study
Authors: Lee Seoyoung , Moon Heeyoung , Ryu Yeonhee , Lee In-Seon , Chae Younbyoung
Published: July 2023

Objective

Although manual pressure, such as that used during a massage, is often associated with pain, it can simultaneously be perceived as pleasant when applied to certain body areas. We hypothesized that stimulation of myofascial trigger points (TPs) leads to simultaneous pain and pleasure. TPs are hyperirritable points located in the taut band of the skeletal muscle.

Method

In this study, we measured the muscle tone, muscle stiffness, and pressure pain threshold of TPs and control points in the left brachioradialis muscle of 48 healthy participants. We also applied deep compression to the two points and collected subjective data on pain, pleasantness, unpleasantness, and relief.

Result

Greater muscle stiffness was observed in the TPs versus control points (t = 6.55, p < 0.001), and the pain threshold was significantly lower in the TPs (t = −6.21, p < 0.001). Unpleasantness ratings after deep compression were significantly lower in the TPs compared with control points (t = −2.68, p < 0.05). Participants experienced greater relief at the TPs compared with control points (t = 2.01, p < 0.05), although the perceived pain did not differ between the two types of points.

Conclusion

We compared the properties of TPs and control points, and found that deep compression at TPs was associated with higher muscle tone and stiffness, lower unpleasantness ratings, and higher relief ratings compared with the control points. These findings suggest that, at least for some TPs, pain and pleasantness are simultaneously elicited by deep pressure stimulation.
Targeted transcutaneous spinal cord stimulation promotes persistent recovery of upper limb strength and tactile sensation in spinal cord injury: a pilot study
Authors: Chandrasekaran Santosh , Bhagat Nikunj A. , Ramdeo Richard , Ebrahimi Sadegh , Sharma Pawan D. , Griffin Doug G. , Stein Adam , Harkema Susan J. , Bouton Chad E.
Published: July 2023

Long-term recovery of limb function is a significant unmet need in people with paralysis. Neuromodulation of the spinal cord through epidural stimulation, when paired with intense activity-based training, has shown promising results toward restoring volitional limb control in people with spinal cord injury. Non-invasive neuromodulation of the cervical spinal cord using transcutaneous spinal cord stimulation (tSCS) has shown similar improvements in upper-limb motor control rehabilitation. However, the motor and sensory rehabilitative effects of activating specific cervical spinal segments using tSCS have largely remained unexplored. We show in two individuals with motor-complete SCI that targeted stimulation of the cervical spinal cord resulted in up to a 1,136% increase in exerted force, with weekly activity-based training. Furthermore, this is the first study to document up to a 2-point improvement in clinical assessment of tactile sensation in SCI after receiving tSCS. Lastly, participant gains persisted after a one-month period void of stimulation, suggesting that targeted tSCS may lead to persistent recovery of motor and sensory function.
HER2-low metastases of HER2-negative primary tumors: a single institution analysis of intertumoral and internodal heterogeneity in node-positive breast cancer
Authors: Pellas Ulrika , Bauer Annette , Baroš Ilija Vladimir , Fattorini Caterina , Tot Tibor
Published: July 2023

Objective

HER2 status in breast cancer is an essential parameter in individual therapeutic decision-making and is routinely assessed in primary tumors in accordance with international recommendations. Reports of HER2 heterogeneity raise the question of basing treatment decisions on HER2 status in metastases, if present. We investigated the degree and clinical implications of HER2 heterogeneity in lymph node–positive breast cancer. Because of recent recognition of therapeutic opportunities in this group of tumors, we especially focused on cases involving low-level HER2 expression.

Methods

The HER2 status of primary tumors and of corresponding lymph node metastases was determined in archived material at the protein and gene levels using the gene– protein assay and interpreted in accordance with 2018 ASCO/CAP criteria. HER2-low status was defined as protein expression levels 1+ or 2+ with negative amplification status.

Results

We analyzed a series of 43 cases of primary infiltrating breast cancer, each with at least two axillary nodes harboring macrometastases (>2 mm), in total 206 such nodes. In 7% of cases, we detected intertumoral HER2 heterogeneity. Three of nine HER2-positive primary tumors were associated with HER2-negative metastases. No cases with HER2-negative primary tumors had HER2-positive metastases, but 55% (6/11) of HER2 0 primary tumors had HER2 1+ and/or 2+ metastases, and 19% (3/16) HER2 1+ cases had exclusively HER2 0 metastases. All metastases in HER2 2+ cases showed HER2-low protein expression levels. Internodal HER2 heterogeneity at low protein expression levels (presence of HER2 0, HER2 1+, and/or HER2 2+ metastatic deposits within the same axilla) was seen in 40% (17/43) of cases. We found no statistically significant association between HER2 heterogeneity and other tumor-related parameters. Survival data indicated worse outcomes in the HER2-low group compared with the rest of the cohort.

Conclusion

Our results indicate a substantial instability of HER2 protein expression, leading to considerable intertumoral and internodal HER2 heterogeneity in lymph node–positive breast carcinomas. This heterogeneity is particularly relevant in HER2-low tumors in which the corrective effects of HER2 gene copy number analysis definitionally is absent. Our findings suggest that determining HER2 status in metastatic lymph nodes may generate relevant information for therapeutic decision-making.
B7-H3-targeted CAR T cell activity is enhanced by radiotherapy in solid cancers
Authors: Ventin Marco , Cattaneo Giulia , Maggs Luke , Jia Jingyu , Arya Shahrzad , Ferrone Soldano , Wang Xinhui , Ferrone Cristina R.
Published: July 2023

Adoptive cell therapy utilizing T cells genetically modified to express a chimeric antigen receptor (CAR) has demonstrated promising clinical results in hematological malignancies. However, solid cancers have not seen a similar success due to multiple obstacles. Investigating these escape mechanisms and designing strategies to counteract such limitations is crucial and timely. Growing evidence in the literature supports the hypothesis that radiotherapy has the potential to enhance the susceptibility of solid tumors to CAR T cell therapy, by overcoming mechanisms of resistance. Radiation treatment can increase the susceptibility of different types of solid cancers (TNBC, HNSCC, PDAC) to B7-H3 CAR T cell-mediated eradication. Multiple mechanisms, including reduced cancer cell proliferation, upregulation of the targeted antigen, modulation of apoptotic molecules may contribute to this signal. The information in the literature and the results we describesupport the ability of radiotherapy to improve the efficacy of CAR T cell therapy in solid tumors.
Mitigation of paclitaxel-induced peripheral neuropathy in breast cancer patients using limb-cooling apparatus: a study protocol for a randomized controlled trial
Authors: Funasaka Chikako , Hanai Akiko , Zenda Sadamoto , Mori Keita , Fukui Makoto , Hirano Nami , Shinohara Rie , Fuse Nozomu , Wakabayashi Masashi , Itagaki Mai , Tomioka Yutaka , Nishina Michihiko , Arai Yasuaki , Kogawa Takahiro , Ozaki Yukinori , Nishimura Meiko , Kobayashi Takayuki , Hara Fumikata , Takano Toshimi , Mukohara Toru
Published: July 2023

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment.

Methods

This study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation.

Discussion

The results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic.

Clinical trial registration

https://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.