bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, Efficacy, and Immunogenicity of a Novel IgG Degrading Enzyme (KJ103): Results from Two Randomised, Blinded, Phase 1 Clinical Trials
Authors: Liu Yanjun , Cao Mengdie , Katial Rohit , Wang Zheng , Lu Xiaoyu , Gu Qin , Chen Chen , Liu Katie , Zhu Zhen , Marshall Mark , Yu Yanxia 
Published: May 2024

Abstract

The approved recombinant adeno-associated virus (AAV) intravenous drugs are limited by the high prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients’ ability to receive gene therapy and limit transfection efficacy in vivo. Based on that, we developed a novel and low immunogenicity recombinant human immunoglobulin G degrading enzyme (KJ103), which has clinical value in removing anti- AAV antibodies in vivo gene transfer. Herein, we performed two randomized, blinded, placebo-controlled, single ascending dose phase I studies in China and New Zealand, to evaluate pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy participants. The results comfirmed that KJ103 rapidly reduced IgG and maintained low levels for 1 week. The 0.01 to 0.40 mg/kg dose range of KJ103 had a favorable safety and tolerability profile in healthy participants of different ethnic and gender groups. KJ103 has low percentage of pre-existing ADAs compared to currently licensed human IgG degrading enzyme (i.e. IdeS), and the induced ADAs mostly return to baseline six months after administration. These characteristics are well suited for the treatment of immune disorders, immune rejection, and immunotherapy where pre-existing antibodies reduce efficacy (e.g. AAV-mediated gene therapy in individuals positive for pre-existing anti-AAV antibodies). The potential of KJ103 warrants further exploration.
Comparison of D3 lymphadenectomy with conventional D2 dissection in patients that underwent right hemicolectomy at a district general hospital
Authors: Butnari Valentin , Jones Timothy , Mansuri Ahmer , Patel Maitreyi , Kung Victor , Banerjee Saswata , Rajendran Nirooshun , Huang Joseph , Boulton Richard , Kaul Sandeep 
Published: May 2024

Abstract

Background and Objectives
: Observational studies suggest a link between D3 lymphadenectomy and improved disease-free survival in some colon cancer patients. However, high-quality randomized controlled trials are needed to confirm its advantage over D2 lymphadenectomy. Concerns about potential complications with D3 have limited its use outside of Japan. This study examines short-term outcomes following D3 lymphadenectomy for right-sided colon cancer compared to the established D2 procedure. Materials and Methods: This retrospective study analyzed data on patients with right-sided colon cancer who underwent curative surgery within our healthcare trust between January 2019 and November 2022. Only patients treated by surgeons who routinely perform D3 lymphadenectomy were included for a homogenous study population. The decision to perform D3 was at the discretion of the operating surgeon. Data were collected from both paper charts and electronic medical records. Non-parametric statistical tests were used for data analysis. Results: A total of 214 patients met the criteria, with 170 undergoing D2 lymphadenectomy and 44 undergoing D3 lymphadenectomy. There were no significant differences between the groups in terms of surgery duration, blood loss, postoperative hemoglobin levels, or transfusion needs. Interestingly, the D3 group had a lower complication rate (25%) compared to the D2 group (41.2%). However, the D3 group also had a higher rate of lymph node spread (45.5% vs. 30.6% for D2) and more lymph nodes removed (23 vs. 19). Importantly, both groups achieved similar complete tumour removal rates. Conclusions: This study suggests D3 lymphadenectomy for right-sided colon cancer might be safe with potential benefits, especially for younger patients with suspected lymph node involvement. However, the limited sample size necessitates larger, randomized trials to confirm these findings and potentially establish D3 lymphadenectomy as standard care.
Fabrication of micro holes with high surface quality and mechanical properties by high-speed laser trepanning and electrochemical post-treatment
Authors: Liu Xiaolong , Wang Yufeng , Yang Yong , Bao Lin , Liu Yunfeng , Zhang Wenwu , Li Lin 
Published: May 2024

Abstract

Laser processing could drill micro holes with very high efficiency, but the micro holes suffer from recast layers, microcracks and heat-affected zones, which has limited its wide application in engineering. In this paper, the high-speed laser drilling and electrochemical post-treatment has been combined to improve the machining efficiency and surface quality. To reduce the surface sputtering and redeposit in laser drilling, avoid the stray current induced corrosion and improve the machining precision in electrochemical post-treatment, the double-side coating has been applied to the workpiece before processing. Influences of laser power ratio, frequency, duty cycle and defocus amount on the diameter and taper of the laser drilled micro holes were explored experimentally. Results showed that the micro hole diameter increased with the increase of laser power ratio, duty cycle and defocus amount and decreased with the increase of pulse frequency. The micro hole taper increased with the increase of frequency, duty cycle and defocus amount. A laser power ratio of larger than 70% was recommended to reduce the taper of the laser drilled micro holes. Additionally, orthogonal experiments were employed to study the effects of laser power ratio, frequency, duty cycle and defocus on laser drilled micro hole diameter, taper, and recast layer thickness. Results show that duty cycle has the greatest impact on aperture, and power ratio has the greatest impact on taper, and frequency has the greatest impact on the thickness of the recast layer. Micro holes with an average diameter of 0.58 mm, a taper angle of 1.77°, and an average recast layer thickness of 25 µm have been obtained by laser drilling utilizing the optimal parameters. Finally, electrochemical post-processing was adopted to improve the surface quality and mechanical properties of the laser drilled micro holes. Results had shown that micro holes without recast layer and micro cracks were obtained by electrochemical posttreatment with a processing time of 20 s. Moreover, the inner hole surface roughness has been reduced by 68.16% and the micro hardness was reduced by 63.40%. A surface roughness of Ra 0.71 μm has been achieved. The proposed laser and electrochemical machining could be applied to the fabrication of micro holes with high surface quality and high efficiency.
Improving physical activity in older patients with atrial fibrillation combined with frailty: development of an intervention using the behaviour change wheel framework
Authors: Liu Jingzhe , Xi Guangdi , Chen Dexin , Xu Jianan , Liu Meng , Yang Fuguo 
Published: May 2024

Abstract

Background：Physical activity is inadequate in older adults with AF and frailty. Being physically active improves health outcomes and reduces the healthcare burden. Theory-based behaviour change interventions are necessary to enhance physical activity. The aim of this study was to develop an intervention guided by the Behaviour Change Wheel theory to improve physical activity in older patients with AF and frailty.
Objective：Our aim was to develop a behaviour change intervention for older patients with AF and frailty to increase their physical activity, improve physical health and reduce the national healthcare burden.
Methods：Our study used a framework based on the Behaviour Change Wheel theory to develop a behaviour change intervention through eight steps. Using semi-structured interviews, we identified the determinants of physical activity in older patients with AF and frailty using the COM-B and TDF. Appropriate intervention functions and various policies addressing the determinants of physical functioning in elderly patients with AF and frailty were then selected based on APEASE criteria. Finally, appropriate behaviour change techniques were screened after the APEASE criteria to help achieve translation of the intervention function into intervention content.
Results：Our study identified 12 factors that promote and 12 factors that hinder physical activity. We selected seven intervention functions and 15 behavior change techniques based on these factors. These 7 intervention functions and 15 behavior change techniques are eligible for APEASE criteria. We then determined to use an app as a delivery model. Finally, behavioral change interventions were provided for elderly patients with AF combined with frailty to increase the physical activity level and compliance.
Conclusions：The Behavior Change Wheel provides a systematic approach to designing behavior change interventions, which can enhance physical activity and delay frailty in elderly patients with AF and frailty and reduce healthcare burden. Findings suggest that potential interventions should focus on enhancing disease knowledge, teaching physical activity skills, providing social support, and using appropriate behavior change techniques in older adults with AF and frailty. Our next step will be to conduct a feasibility study to assess the acceptability and effectiveness of intervention programs.
Smad7 ameliorate small airway remodeling in COPD by modulating epithelial-mesenchymal transition
Authors: Liu Xianyang , Sun Shenghua , He Shengyang , Xie Lihua 
Published: May 2024

Abstract

Small airway remodeling is widely recognized as one of the major pathological changes 11 in chronic obstructive pulmonary disease (COPD), yet the underlying mechanisms remain 12 unclear. In the present study, we observed higher levels of epithelial-mesenchymal transition 13 (EMT) and increased collagen deposition in the lungs of both COPD patients and mice 14 models compared to the control group. Additionally, exposure to cigarette smoke extract 15 (CSE) led to an upregulation of TGF-β1 secretion in bronchial epithelial cells BEAS-2B. Further 16 analyses revealed that TGF-β1 upregulated E-Cadherin and downregulated N-cadherin and 17 Vimentin, as confirmed by rt-qPCR, Western Blot, and Immunofluorescence staining. 18 Morphological changes were also observed as a result of TGF-β1 induction. Interestingly, 19 these TGF-β1-induced changes could be reversed by overexpression of Smad7, while they 20 were enhanced by gene interference. In conclusion, smoking may contribute to TGF-β1–21 induced small airway remodeling, which can be reversed by modulating the EMT process 22 through Smad7.
The intraspecific trade-off between photosynthesis and phenolics in selected crop species: A meta-analysis study
Authors: Kostidis George , Karabourniotis George 
Published: May 2024

Abstract

Phenolics are multifunctional secondary metabolites taking part in both the defence against biotic and the protection against abiotic stress factors. At the interspecific level the concentration of leaf phenolics is negatively correlated with net photosynthesis: Plant species with inherently high photosynthetic rates (mainly annuals) are characterized by low phenolic pool, whereas slow growing species (mainly perennials) show the opposite trend. Crop plants represent a special case of the first group because they have been bred to maximize photosynthesis at the expense of defence and protection. We conducted meta-analyses in four selected crop plants (tomato, pepper, cucumber and olive) in order to test if the trade-off between photosynthesis and phenolics is valid at the intraspecific level as well. We observed that all plants are able to accumulate phenolics under conditions that reduce photosynthesis. However this negative correlation shows different characteristics, pending on the individual species. Moreover, both the basic and maximum level of phenolics in olive leaves is higher than the corresponding ones of the other species. The present investigation indicates that the trade-off between photosynthesis and phenolics at the intraspecific level reflects the answer given by each plant species against the growth–defense/protection dilemma.
Multiplex one-step RT‒qPCR assays for simultaneous detection of AMDV, MEV and CDV
Authors: Cao Zhi , Xu Hang , Zhao Xinru , Zhang Ke , Yin Dehua , Ma Shuai , Li Wenling , Li Siyu , Ren Jianwei , Wen Jianxin 
Published: May 2024

Abstract

Background: Aleutian mink disease, mink viral enteritis and canine distemper are known as the three most serious diseases that cause great economic loss in the mink industry. In clinical practice, aleutian mink disease virus (AMDV), mink enteritis virus (MEV) and canine distemper virus (CDV) are common mixed infections, and they have similar clinical symptoms, such as diarrhoea. Therefore, a rapid and accurate differential diagnosis method for use on mink ranches is essential for the control of these three pathogens. Here, we developed multiplex one-step real-time quantitative PCR (RT‒qPCR) assays for the simultaneous detection and quantification of AMDV, MEV and CDV by using three primers and probes based on the conserved NS1, VP2 and N genes, respectively.
Results: The results showed that the established method was less likely to cross-react with other mink pathogens, with a detection sensitivity of 25 copies/μL and a coefficient of variation less than 3.51%. Moreover, the interference experiment showed that the presence of AMDV, MEV and CDV templates at different concentrations would not interfere with the detection results. Furthermore, two hundred clinical samples of mink with diarrhoea were simultaneously analysed using multiplex RT‒qPCR and single RT‒qPCR, the Kappa values were all greater than 0.921, indicating that there was a high degree of coincidence between the two detection methods.
Conclusions: In conclusion, multiplex RT‒qPCR exhibited high speciﬁcity, sensitivity, and reproducibility, indicating that this method can be used as a reliable and speciﬁc tool for the differential detection and quantiﬁcation of AMDV, MEV and CDV.
In-silico identification of extended-spectrum beta-lactamase potential inhibitors in edible millipedes
Authors: Nkaiwuatei Jimmy 
Published: May 2024

Abstract

Antimicrobial resistance is currently one of the leading causes of death globally, and one of the heaviest health burdens in the African region. Despite this challenge, research and development of novel antimicrobial drugs is still quite slow due to the long process and cost involved. Some of the serious pathogens attributable to antimicrobial-resistant infections are the Extended-spectrum beta-lactamase (ESBL) producing pathogens which mainly include the gram-negative bacteria. The goal of this study was to identify potential ESBL inhibitors from edible millipedes. Millipedes contain a variety of bioactive compounds including alkaloids (p-benzoquinone) and phenols (p-cresol), and they have been used as sources of food for humans. Studies have shown that the Bobo people of Burkina Faso consume three types of millipede species, namely;Tymbodesmus falcatus,Sphenodesmus sheribongensisandSpirostreptidaeas food sources. Based on the literature, these edible millipede species contain a variety of compounds in their grandular defensive secretions which include; p-cresol, p-benzoquinone, hydrogen cyanide, toluquinone, 2, 3-dimethoxybenzoquinone, 2-methoxy-3-methylbenzoquinone, toluhydroquinone and mandelonitrile. The aim of this study was therefore to investigate the activity of these compounds secreted by the edible millipede species on ESBL in comparison with 2 positive and 2 negative controls. This work was entirely performed computationally using various bioinformatics tools and softwares and was achieved by performing molecular docking of the ligands (the millipede compounds) against the target protein (ESBL) which served as the receptor. First, the 3D structures of all the ligands were downloaded from the PubChem chemical structures database while that of the target protein (ESBL) was obtained from the RCS Protein Databank (PDB). The structures of both the ligands and the target protein were prepared using UCSF Chimera tool as well as Autodock4 tool and subsequently converted into executable files. Then molecular docking was performed using Autodock vina and the scripts were run on the Windows Command Prompt to determine the binding affinities of the ligands on the target protein, the binding residues, and the physicochemical properties of the ligands as well as the best beta-lactamase enzyme inhibitor. The drug-likeness of the ligands, ADME properties and toxicity were tested using Lipinski’s rule of five, the Swiss Institute of Bioinformatics (Swiss-ADME) software and admetSAR web server, respectively. Out of the eight ligands tested, it was found that 2, 3-dimethoxybenzoquinone with a binding energy of -7.2 is a potential ESBL inhibitor.
Early stopping strategies in Deep Image Prior
Authors: Benfenati Alessandro , Catozzi Ambra , Franchini Giorgia , Porta Federica 
Published: May 2024

Abstract

The so-called Deep Image Prior approach is an unsupervised deep learning methodology which has gained great interest in recent years due to its effectiveness in tackling imaging problems.
However, a well known drawback of Deep Image Prior is the need for a proper early stopping technique to prevent undesired corruptions in the reconstructed images. Determining the optimal number of iterations depends on both the specific application and the features of the images being processed. As a consequence, several numerical trials are typically required to decide when to stop the Deep Image Prior procedure, resulting in significant computational costs and time requirements.
This paper aims to introduce two early stopping techniques for Deep Image Prior, based on different approaches and different perspectives. The first one relies on the Neural Architecture Search strategy by generating hyperparameters configurations for the neural network employed in Deep Image Prior, configurations that shall be able to provide clean images comparable to those obtained by the standard configuration, optimally stopped, but with significantly fewer iterations. The second proposed early stopping strategy is based on a modified version of the BRISQUE metric, a no-reference image quality measure, and it aims to track the behaviour of the PSNR curve, obtained by applying Deep Image Prior, without knowing the ground truth image. While the NAS-based early stopping technique is particularly suited in those situations where the computational time is limited, this latter one is also relevant when a larger number of iterations is allowed. Several numerical experiments on different denoising applications show a promising performance of Deep Image Prior combined with the suggested early stopping procedures.
Challenges of Primary, Secondary, and Tertiary Education in Bangladesh During COVID-19 Pandemic: Students’ Perspectives
Authors: Hannan Md. Abdul 
Published: May 2024

Abstract

Coronavirus disease 2019 (COVID-19) is a deadly disease affecting almost all the countries of the world. The education system of Bangladesh has been highly affected by it. For around 18 months, education was being delivered online which was not adequate for all the students of Bangladesh due to some systemic constraints. Most of the primary students were not at all prepared to receive their education online. Although the secondary level students somehow managed to continue online education by preparing and submitting their assignments, the tertiary level students had to wait a long time for their online final examinations. This study aimed at identifying the major challenges of primary, secondary, and tertiary level education in Bangladesh during Covid-19 pandemic, from students' perspectives. The approach was mixed, non-experimental and descriptive in nature. Surveying a total of 60 students through semi-structured interviews and focus group discussions, it was found that major challenges of the students include educational difficulties, socio-psychological abnormalities, pedagogical limitations, infrastructural shortcomings, economic disorders, technological barriers, mental health issues, and so on. Level-specific challenges of the students were also observed as the tertiary level students were found to be the worst affected due to this pandemic.
Cutting Path Planning Using Reinforcement Learning with Adaptive Sequence Adjustment and Attention Mechanisms
Authors: Wang Kaiqi , Zhang Shijin , Wu Yuqiang , Jiang Fengyang 
Published: May 2024

Abstract

In industrial manufacturing, cutting path planning is very important since it directly affects cutting quality and efficiency. However, traditional methods are no longer suitable for large-scale and real-time cutting path planning due to the long computation time needed. Currently, though the deep learning method can be used for cutting path planning, the node number has to be fixed, and a large amount of labeled data is required. Another method is deep reinforcement learning, which can be used for cutting path planning. The node number also has to be fixed. As a result, these two potential methods are unsuitable for practical industrial cutting problems. To solve the above problem, this study provides a new reinforcement learning approach that integrates adaptive sequence adjustment and attention mechanisms. Compared to traditional methods, which took hours or days to finish a complicated cutting path plan, this approach significantly improves processing efficiency, completing tasks in seconds, and also minimizes non-cutting travel paths. And compared to deep learning and deep reinforcement learning provided by others, a variable number of nodes can be processed with this method. Therefore, it is more suitable for practical industrial cutting problems.