bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative molecule self-attention transformer
Authors: Maziarka Łukasz , Majchrowski Dawid , Danel Tomasz , Gaiński Piotr , Tabor Jacek , Podolak Igor , Morkisz Paweł , Jastrzębski Stanisław
Published: January 2024

The prediction of molecular properties is a crucial aspect in drug discovery that can save a lot of money and time during the drug design process. The use of machine learning methods to predict molecular properties has become increasingly popular in recent years. Despite advancements in the field, several challenges remain that need to be addressed, like finding an optimal pre-training procedure to improve performance on small datasets, which are common in drug discovery. In our paper, we tackle these problems by introducing Relative Molecule Self-Attention Transformer for molecular representation learning. It is a novel architecture that uses relative self-attention and 3D molecular representation to capture the interactions between atoms and bonds that enrich the backbone model with domain-specific inductive biases. Furthermore, our two-step pretraining procedure allows us to tune only a few hyperparameter values to achieve good performance comparable with state-of-the-art models on a wide selection of downstream tasks.
Structure-based, deep-learning models for protein-ligand binding affinity prediction
Authors: Wang Debby D. , Wu Wenhui , Wang Ran
Published: January 2024

The launch of AlphaFold series has brought deep-learning techniques into the molecular structural science. As another crucial problem, structure-based prediction of protein-ligand binding affinity urgently calls for advanced computational techniques. Is deep learning ready to decode this problem? Here we review mainstream structure-based, deep-learning approaches for this problem, focusing on molecular representations, learning architectures and model interpretability. A model taxonomy has been generated. To compensate for the lack of valid comparisons among those models, we realized and evaluated representatives from a uniform basis, with the advantages and shortcomings discussed. This review will potentially benefit structure-based drug discovery and related areas.

Graphical Abstract
InterDILI: interpretable prediction of drug-induced liver injury through permutation feature importance and attention mechanism
Authors: Lee Soyeon , Yoo Sunyong
Published: January 2024

Safety is one of the important factors constraining the distribution of clinical drugs on the market. Drug-induced liver injury (DILI) is the leading cause of safety problems produced by drug side effects. Therefore, the DILI risk of approved drugs and potential drug candidates should be assessed. Currently, in vivo and in vitro methods are used to test DILI risk, but both methods are labor-intensive, time-consuming, and expensive. To overcome these problems, many in silico methods for DILI prediction have been suggested. Previous studies have shown that DILI prediction models can be utilized as prescreening tools, and they achieved a good performance. However, there are still limitations in interpreting the prediction results. Therefore, this study focused on interpreting the model prediction to analyze which features could potentially cause DILI. For this, five publicly available datasets were collected to train and test the model. Then, various machine learning methods were applied using substructure and physicochemical descriptors as inputs and the DILI label as the output. The interpretation of feature importance was analyzed by recognizing the following general-to-specific patterns: (i) identifying general important features of the overall DILI predictions, and (ii) highlighting specific molecular substructures which were highly related to the DILI prediction for each compound. The results indicated that the model not only captured the previously known properties to be related to DILI but also proposed a new DILI potential substructural of physicochemical properties. The models for the DILI prediction achieved an area under the receiver operating characteristic (AUROC) of 0.88–0.97 and an area under the Precision-Recall curve (AUPRC) of 0.81–0.95. From this, we hope the proposed models can help identify the potential DILI risk of drug candidates at an early stage and offer valuable insights for drug development.
Association of health behaviors with function and health-related quality of life among patients with Parkinson’s disease
Authors: Duvdevani Michal , Yogev-Seligmann Galit , Schlesinger Ilana , Nassar Maria , Erich Ilana , Hadad Rafi , Kafri Michal
Published: January 2024

Background

Current evidence on chronic conditions favors promotion of health behaviors as a mean to positively impact health outcomes. In Parkinson’s disease, performing health behaviors is indicated as a means to fight the long-lasting burden of the disease. Understanding actual engagement in health behaviors and patient activation and their association to function and health-related quality of life is therefore important. Our objectives were, among people with Parkinson’s disease: (1) to characterize health behaviors including utilization of rehabilitative treatments, physical activity, and patient activation levels, and (2) to test the associations between these health behaviors and health outcomes.

Methods

A cross-sectional study of 88 people with Parkinson’s disease (age 66.84 ± 8.8) was conducted. Participants answered questionnaires measuring health behaviors including utilization of health professions treatments, physical activity, patient activation, and health outcomes consisting of function and health-related quality of life. Linear regression models were conducted to test associations between measured health behaviors, function and health-related quality of life.

Results

Participants rarely engage in rehabilitative treatments, but showed high levels of patient activation. Controlled by demographics and disease severity, physical activity and patient activation were associated with function (b = 0.41, p < .001; b = 0.2, p = .02, respectively) and physical activity but not patient activation, which was associated with health-related quality of life (b = 0.19, p = .03). There was also interaction effects of physical activity and non-motor symptoms, and physical activity and motor symptoms on health-related quality of life (b = 0.19, p = .02 and b = − 0.22, p = .01, respectively).

Conclusions

In respect to their potential health-related benefits for people with Parkinson’s disease, health professionals’ treatments are underutilized. Findings supported the importance of health behaviors for maintaining function and health-related quality of life among people with Parkinson’s disease. They also show a differential contribution of motor and non-motor symptoms to the association between physical activity and quality of life. It is suggested that policy makers encourage opportunities for physical activity tailored for people with Parkinson’s disease and adopt a proactive stance towards enhancing awareness and use of rehabilitation services.

Trial registration NCT05211700, ClinicalTrials.gov ID: NCT05211700 first release 12/30/2021, https://classic.clinicaltrials.gov/ct2/show/NCT05211700
Time decay of solutions for compressible isentropic non-Newtonian fluids
Authors: Wang Jialiang , Jiang Han
Published: January 2024

In this paper, we consider the Cauchy problem of a compressible Navier–Stokes system of Eills-type non-Newtonian fluids. We investigate the time decay properties of classical solutions for the compressible non-Newtonian fluid equations. More specifically, we construct a new linearized system in terms of a combination of the solutions, and then we investigate the long-time behavior of the Cauchy problem for the three-dimensional isentropic compressible Eills-type non-Newtonian fluids with an initial perturbation.
Context-aware environment online monitoring for safety autonomous vehicle systems: an automata-theoretic approach
Authors: Zhang Yu , Xu Sijie , Chen Hongyi , Aslam Bhatt Uzair , Huang Mengxing
Published: January 2024

Intelligent Transport System (ITS) is a typical class of Cyber-Physical Systems (CPS), and due to the special characteristics of such systems, higher requirements are placed on system security. Runtime verification is a lightweight verification technique which is used to improve the security of such systems. However, current runtime verification methods often ignore the effects of the physical environment (e.g., the effects of rain, snow, and other weather changes on road conditions), which results in the inability of the monitor to effectively monitor the system according to the changes in the environment. To address this problem, this paper proposes a method for constructing a runtime monitor with environmental context-awareness capability. First, the physical environment factors affecting the system are formally described and constructed into an environment model, then the system statute is transformed into a Büchi automaton, and then a synthesis algorithm combining the environment model and the Büchi automaton is designed based on the network of automatons, and the corresponding monitor is generated. Finally, the proposed method is applied and verified on simulation and real objects. The experimental results show that the monitors generated based on the method of this paper can effectively monitor unsafe events in different environments, thus improving the safety of intelligent driving systems.
Non-thermal plasma enhances rice seed germination, seedling development, and root growth under low-temperature stress
Authors: Bian Jing-Yang , Guo Xiao-Yu , Lee Dong Hun , Sun Xing-Rong , Liu Lin-Shuai , Shao Kai , Liu Kai , Sun Hu-Nan , Kwon Taeho
Published: January 2024

Recently, non-thermal plasma (NTP) technologies have found widespread application across diverse fields, including plant growth, medical science, and biological and environmental research. Rice (Oryza sativa L.) is exceptionally sensitive to temperature changes. Notably, low-temperature stress primarily affects the germination and reproductive stages of rice, often leading to reduced crop yield. This study aimed to identify optimal conditions for enhancing rice seed germination and seedling growth under low temperatures using NTP technology. Our research indicated that NTP treatment at 15.0 kV for 30 s optimally promotes rice seed germination and growth under low-temperature stress. Furthermore, NTP treatment increases the activity and expression of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), under low-temperature conditions. Moreover, it downregulates the expression of β-ketoacyl-[acyl carrier protein] synthase I (KASI) and cis-epoxy carotenoid dioxygenase 3 (NCED3) and upregulates the expression of alternative oxidase (AOX1B), BREVIS RADIX-like homologous gene (BRXL2), WRKY transcription factor 29 (WRKY29), and EREBP transcription factor 2 (EREBP2) in roots after tandem 7 days low-temperature (16 ℃) and 7 days room-temperature (28 ℃) treatments. Transcriptomic analysis revealed the involvement of various key genes in phosphotransferase activity, phosphate-containing compound metabolic processes, and defense responses. These analyses provide comprehensive information on gene expression at the transcriptional level, offering new insights for a deeper understanding of candidate genes required for root growth in rice.
WD repeat domain 76 predicts poor prognosis in lower grade glioma and provides an original target for immunotherapy
Authors: Cheng Xingbo , Liu Zhendong , Chang Haigang , Liang Wenjia , Li Pengxu , Gao Yanzheng
Published: January 2024

Background

The WD40 repeat (WDR) domain provides scaffolds for numerous protein–protein interactions in multiple biological processes. WDR domain 76 (WDR76) has complex functionality owing to its diversified interactions; however, its mechanism in LGG has not yet been reported.

Methods

Transcriptomic data from public databases were multifariously analyzed to explore the role of WDR76 in LGG pathology and tumor immunity. Laboratory experiments were conducted to confirm these results.

Results

The results first confirmed that high expression of WDR76 in LGG was not only positively associated with clinical and molecular features of malignant LGG, but also served as an independent prognostic factor that predicted shorter survival in patients with LGG. Furthermore, high expression of WDR76 resulted in the upregulation of oncogenes, such as PRC1 and NUSAP1, and the activation of oncogenic mechanisms, such as the cell cycle and Notch signaling pathway. Finally, WDR76 was shown to be involved in LGG tumor immunity by promoting the infiltration of immune cells, such as M2 macrophages, and the expression of immune checkpoints, such as PDCD1 (encoding PD-1).

Conclusions

This study shows for the first time the diagnostic and prognostic value of WDR76 in LGG and provides a novel personalized biomarker for future targeted therapy and immunotherapy. Thus, WDR76 may significantly improve the prognosis of patients with LGG.
Circulating inflammatory biomarkers and risk of intracranial aneurysm: a Mendelian randomization study
Authors: Fang Jianxun , Cao Yuze , Ni Jun
Published: January 2024

Background

Intracranial aneurysm (IA) accounts for a substantial source of non-traumatic subarachnoid hemorrhage, with inflammation postulated as a potential factor in its pathogenesis. The present study aims at evaluating the association between circulating inflammatory cytokines and risk of IA under a bidirectional two-sample Mendelian randomization (MR) design.

Methods

For primary analysis, summary statistics of inflammatory regulators was obtained from a genome-wide association study (GWAS) comprising 8293 Finnish participants. Summary data of IA were extracted from a GWAS which comprised 7495 cases and 71,934 controls in European descent. For targeted analysis, summary statistics were extracted from two proteomic studies, which recruit 3301 and 5368 European participants, respectively. Summary data of IA were acquired from FinnGen study with 5342 cases and 342,673 controls. We employed inverse variance weighted (IVW) method as main approach, with sensitivity analyses using weighted median, MR-Egger, and MR-PRESSO methods. Reverse MR analyses were conducted to minimize bias from reverse causality.

Results

No causation of cytokines with IA subtypes was identified in both primary and targeted analysis after Bonferroni correction. In primary analysis, vascular endothelial growth factor (VEGF) and fibroblast growth factor basic (bFGF) levels were suggestively associated with aneurysmal subarachnoid hemorrhage (aSAH) [VEGF → aSAH: OR = 1.15, 95%CI  1.04–1.26, P = 0.005; bFGF → aSAH: OR = 0.62, 95% CI 0.42–0.92, P = 0.02]. Statistical significance failed to replicate in targeted analysis. Instead, suggestive protective effects for aSAH were identified in FGF-9 (FGF-9 → aSAH: OR = 0.74, 95% CI 0.62–0.89, P = 0.001) and FGF-16 (FGF-16 → aSAH: OR = 0.84, 95% CI 0.72–0.97, P = 0.017). Furthermore, reverse analyses identified suggestive effect of unruptured IA on RANTES, MIF, GRO-alpha, FGF-16, and FGF-19. Result remained robust after applying sensitivity tests.

Conclusions

No causality of inflammatory biomarkers on the risk of IA subtypes was identified. Future large-scale studies are in need to evaluate the temporal dynamics of cytokines in conjunction with IA.
Exploring the prognostic potential of m6A methylation regulators in low-grade glioma: implications for tumor microenvironment modulation
Authors: Wu Honggang , Chen Siqi , Hu Ziliang , Ge Rong , Ma Lu , You Chao , Huang Yi
Published: January 2024

Background

The biological behavior of low-grade glioma (LGG) is significantly affected by N6-methyladenosine (m6A) methylation, an essential epigenetic alteration. Therefore, it is crucial to create a prognostic model for LGG by utilizing genes that regulate m6A methylation.

Methods

Using TCGA and GTEx databases. We examined m6A modulator levels in LGG and normal tissues, and investigated PD-L1 and PD-1 expression, immune scores, immune cell infiltration, tumor immune microenvironment (TIME) and potential underlying mechanisms in different LGG clusters. We also performed immunohistochemistry and RT-qPCR to identify essential m6A adjustment factor.

Results

The results showed that m6A regulatory element expression was significantly increased in LGG tissues and was significantly associated with TMIE. A substantial increase in PD-L1 and PD-1 levels in LGG tissues and high-risk cohorts was observed. PD-L1 expression was positively correlated with FTO, ZCCHC4, and HNRNPD, whereas PD-1 expression was negatively correlated with FTO, ZC3H7B, and HNRNPD. The prognostic signature created using regulators of m6A RNA methylation was shown to be strongly associated with the overall survival of LGG patients, and FTO and ZCCHC4 were confirmed as independent prognostic markers by clinical samples. Furthermore, the results revealed different TIME characteristics between the two groups of patients, indicating disrupted signaling pathways associated with LGG.

Conclusion

Our results present that the m6A regulators play vital role in regulating PD-L1/PD-1 expression and the infiltration of immune cells, thereby exerting a sizable impact on the TIME of LGG. Therefore, m6A regulators have precise predictive value in the prognosis of LGG.
Blockage of VEGF function by bevacizumab alleviates early-stage cerebrovascular dysfunction and improves cognitive function in a mouse model of Alzheimer’s disease
Authors: Zhang Min , Zhang Zhan , Li Honghong , Xia Yuting , Xing Mengdan , Xiao Chuan , Cai Wenbao , Bu Lulu , Li Yi , Park Tae-Eun , Tang Yamei , Ye Xiaojing , Lin Wei-Jye
Published: January 2024

Background

Alzheimer's disease (AD) is a neurodegenerative disorder and the predominant type of dementia worldwide. It is characterized by the progressive and irreversible decline of cognitive functions. In addition to the pathological beta-amyloid (Aβ) deposition, glial activation, and neuronal injury in the postmortem brains of AD patients, increasing evidence suggests that the often overlooked vascular dysfunction is an important early event in AD pathophysiology. Vascular endothelial growth factor (VEGF) plays a critical role in regulating physiological functions and pathological changes in blood vessels, but whether VEGF is involved in the early stage of vascular pathology in AD remains unclear.

Methods

We used an antiangiogenic agent for clinical cancer treatment, the humanized monoclonal anti-VEGF antibody bevacizumab, to block VEGF binding to its receptors in the 5×FAD mouse model at an early age. After treatment, memory performance was evaluated by a novel object recognition test, and cerebral vascular permeability and perfusion were examined by an Evans blue assay and blood flow scanning imaging analysis. Immunofluorescence staining was used to measure glial activation and Aβ deposits. VEGF and its receptors were analyzed by enzyme-linked immunosorbent assay and immunoblotting. RNA sequencing was performed to elucidate bevacizumab-associated transcriptional signatures in the hippocampus of 5×FAD mice.

Results

Bevacizumab treatment administered from 4 months of age dramatically improved cerebrovascular functions, reduced glial activation, and restored long-term memory in both sexes of 5×FAD mice. Notably, a sex-specific change in different VEGF receptors was identified in the cortex and hippocampus of 5×FAD mice. Soluble VEGFR1 was decreased in female mice, while full-length VEGFR2 was increased in male mice. Bevacizumab treatment reversed the altered expression of receptors to be comparable to the level in the wild-type mice. Gene Set Enrichment Analysis of transcriptomic changes revealed that bevacizumab effectively reversed the changes in the gene sets associated with blood–brain barrier integrity and vascular smooth muscle contraction in 5×FAD mice.

Conclusions

Our study demonstrated the mechanistic roles of VEGF at the early stage of amyloidopathy and the protective effects of bevacizumab on cerebrovascular function and memory performance in 5×FAD mice. These findings also suggest the therapeutic potential of bevacizumab for the early intervention of AD.
Deciphering the gut microbiome of grass carp through multi-omics approach
Authors: Li Ming , Liang Hui , Yang Hongwei , Ding Qianwen , Xia Rui , Chen Jie , Zhou Wenhao , Yang Yalin , Zhang Zhen , Yao Yuanyuan , Ran Chao , Zhou Zhigang
Published: January 2024

Background

Aquaculture plays an important role in global protein supplies and food security. The ban on antibiotics as feed additive proposes urgent need to develop alternatives. Gut microbiota plays important roles in the metabolism and immunity of fish and has the potential to give rise to novel solutions for challenges confronted by fish culture. However, our understanding of fish gut microbiome is still lacking.

Results

We identified 575,856 non-redundant genes by metagenomic sequencing of the intestinal content samples of grass carp. Taxonomic and functional annotation of the gene catalogue revealed specificity of the gut microbiome of grass carp compared with mammals. Co-occurrence analysis indicated exclusive relations between the genera belonging to Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes, suggesting two independent ecological groups of the microbiota. The association pattern of Proteobacteria with the gene expression modules of fish gut and the liver was consistently opposite to that of Fusobacteria, Firmicutes, and Bacteroidetes, implying differential functionality of Proteobacteria and Fusobacteria/Firmicutes/Bacteroidetes. Therefore, the two ecological groups were considered as two functional groups, i.e., Functional Group 1: Proteobacteria and Functional Group 2: Fusobacteria/Firmicutes/Bacteroidetes. Further analysis revealed that the two functional groups differ in genetic capacity for carbohydrate utilization, virulence factors, and antibiotic resistance. Finally, we proposed that the ratio of “Functional Group 2/Functional Group 1” can be used as a biomarker that efficiently reflects the structural and functional characteristics of the microbiota of grass carp.

Conclusions

The gene catalogue is an important resource for investigating the gut microbiome of grass carp. Multi-omics analysis provides insights into functional implications of the main phyla that comprise the fish microbiota and shed lights on targets for microbiota regulation.
Methanolobus use unspecific methyltransferases to produce methane from dimethylsulphide in Baltic Sea sediments
Authors: Tsola S. L. , Zhu Y. , Chen Y. , Sanders I. A. , Economou C. K. , Brüchert V. , Eyice Ö.
Published: January 2024

Background

In anoxic coastal and marine sediments, degradation of methylated compounds is the major route to the production of methane, a powerful greenhouse gas. Dimethylsulphide (DMS) is the most abundant biogenic organic sulphur compound in the environment and an abundant methylated compound leading to methane production in anoxic sediments. However, understanding of the microbial diversity driving DMS-dependent methanogenesis is limited, and the metabolic pathways underlying this process in the environment remain unexplored. To address this, we used anoxic incubations, amplicon sequencing, genome-centric metagenomics and metatranscriptomics of brackish sediments collected along the depth profile of the Baltic Sea with varying sulphate concentrations.

Results

We identified Methanolobus as the dominant methylotrophic methanogens in all our DMS-amended sediment incubations (61–99%) regardless of their sulphate concentrations. We also showed that the mtt and mta genes (trimethylamine- and methanol-methyltransferases) from Methanolobus were highly expressed when the sediment samples were incubated with DMS. Furthermore, we did not find mtsA and mtsB (methylsulphide-methyltransferases) in metatranscriptomes, metagenomes or in the Methanolobus MAGs, whilst mtsD and mtsF were found 2–3 orders of magnitude lower in selected samples.

Conclusions

Our study demonstrated that the Methanolobus genus is likely the key player in anaerobic DMS degradation in brackish Baltic Sea sediments. This is also the first study analysing the metabolic pathways of anaerobic DMS degradation in the environment and showing that methylotrophic methane production from DMS may not require a substrate-specific methyltransferase as was previously accepted. This highlights the versatility of the key enzymes in methane production in anoxic sediments, which would have significant implications for the global greenhouse gas budget and the methane cycle.
Emotion regulation from a virtue perspective
Authors: Kim Jeong Han , Chun Jina , Kim Jaeyoung , Ju Hyun-Ju , Kim Byung Jin , Jeong Jeongwoon , Lee Dong Hun
Published: January 2024

Background

The ability to regulate one’s emotional state is an important predictor of several behaviors such as reframing a challenging situation to reduce anger or anxiety, concealing visible signs of sadness or fear, or focusing on reasons to feel happy or calm. This capacity is referred to as emotion regulation. Deficits in this ability can adversely affect one’s adaptive coping, thus are associated with a variety of other psychopathological symptoms, including but not limited to depression, borderline personality disorder, substance use disorders, eating disorders, and somatoform disorders.

Methods

The present study examined emotion regulation in relation to the virtue-based psychosocial adaptation model (V-PAM). 595 participants were clustered based on their Difficulties in Emotion Regulation Scale (DERS) score, producing two clusters (i.e., high functioning vs. low functioning). Then, emotion regulation group membership was discriminated by using five V-PAM virtue constructs, including courage, integrity, practical wisdom, committed action, and emotional transcendence.

Results

Results show that five virtues contribute to differentiating group membership. Practical wisdom was the strongest contributor, followed by integrity, emotional transcendence, committed action, and courage. Predictive discriminant analysis was conducted and 71% of cases were correctly classified. A discussion of the relationship between emotion regulation and virtues was elaborated.

Conclusion

The concept of virtue holds significant importance in the comprehension of an individual’s capacity to regulate their emotions, meriting future study.
Inhibition of miR-542-3p augments autophagy to promote diabetic corneal wound healing
Authors: Liao Danling , Wei Shijia , Hu Jianzhang
Published: January 2024

Background

Autophagy has recently been shown to be critical for protecting peripheral nerve regeneration. This study explored the impact of miR-542-3p on diabetic corneal nerve regeneration and epithelial healing through the regulation of autophagy.

Methods

A type 1 diabetes model was established in male mice through streptozotocin administration. Immunofluorescence staining of β-Tubulin III and sodium fluorescein staining were performed to observe corneal nerve fiber density and corneal epithelial healing, respectively. Western blotting, immunofluorescence and transmission electron microscopy were used to determine autophagy levels. Subconjunctival injection of RAPA and 3-MA altered autophagy levels; with them, we evaluated the role of autophagy in diabetic keratopathy. miRNA sequencing and bioinformatics analysis were performed to identify miRNA-mRNA networks with potential autophagy-regulating roles, and miR-542-3p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). miR-542-3p antagomir was injected subconjunctivally to assess the role in diabetic corneal neuropathy.

Results

Our data suggest that autophagy is suppressed in the diabetic corneal nerve and that activation of autophagy promotes diabetic corneal wound healing. We identified a potential autophagy-regulating miRNA-mRNA network in the diabetic trigeminal ganglion, in which miR-542-3p expression was significantly upregulated. Inhibition of miR-542-3p significantly enhanced the level of autophagy in trigeminal ganglion by upregulating ATG4D expression, thereby accelerating diabetic corneal nerve regeneration and epithelial healing.

Conclusions

Dysregulated autophagy is an important contributor to delayed diabetic corneal injury healing. Inhibiting miR-542-3p promotes diabetic corneal nerve regeneration and epithelial healing through autophagy activation by ATG4D.
NCAPD2 is a favorable predictor of prognostic and immunotherapeutic biomarker for multiple cancer types including lung cancer
Authors: Feng Linyuan , Yang Yang , Lin Zhenhua , Cui Minghua , Jin Aihua , Cui Aili
Published: January 2024

Background

Non-SMC condensin I complex subunit D2 (NCAPD2) belongs to the chromosomal structural maintenance family. While the different contribution of NCAPD2 to chromosome in mitosis have been thoroughly investigated, much less is known about the expression of NCAPD2 in pan-cancer. Thus, we used a bioinformatics dataset to conduct a pan-cancer analysis of NCAPD2 to determine its regulatory role in tumors.

Methods

Multiple online databases were analyzed NCAPD2 gene expression, protein level, patient survival and functional enrichment in pan-cancer. Genetic alteration and tumor stemness of NCAPD2 were analyzed using cBioPortal and SangerBox. The GSCA and CellMiner were used to explore the relationship between NCAPD2 and drug sensitivity. The diagnostic value of prognosis was evaluated by ROC curve. Subsequently, the immune infiltration level and immune subtype of NCAPD2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were analyzed using TIMER1 and TISIDB.

Results

NCAPD2 gene expression was significantly higher in most cancers and associated with clinical stage and poor prognosis. Genomic heterogeneity of NCAPD2 promoted the occurrence and development of tumors. GO enrichment analysis suggested NCAPD2 might be involved in DNA repair and immune response. NCAPD2 was involved in immune infiltration of LUAD and LUSC. ROC curves showed that NCAPD2 has important prognosis diagnostic value in LUAD and LUSC. Moreover, NCAPD2 was drug sensitive to topotecan, which may be an optimize immunotherapy.

Conclusions

It was found that NCAPD2 was overexpressed in pan-cancers, which was associated with poor outcomes. Importantly, NCAPD2 could be a diagnostic marker and an immune related biomarker for LUAD and LUSC.
A scoping review on efficacy and safety of medicinal plants used for the treatment of diarrhea in sub-Saharan Africa
Authors: Plaatjie Moitshepi T. A. , Onyiche ThankGod E. , Ramatla Tsepo , Bezuidenhout Johannes J. , Legoabe Lesetja , Nyembe Nthatisi I. , Thekisoe Oriel
Published: January 2024

Background

In sub-Saharan Africa (SSA), significant morbidity and mortality have been linked to diarrhea, which is frequently caused by microorganisms. A rise in antimicrobial-resistant pathogens has reignited the search for alternative therapies. This scoping review aims to map the literature on medicinal plants in relation to their anti-diarrheal potential from SSA.

Methods

Studies published from 1990 until April 2022 on medicinal plants used for the treatment of diarrhea from each country in SSA were searched on Scopus, Web of Science, Science Direct and PubMed. The selection of articles was based on the availability of data on the in vitro and/or in vivo, ethnobotanical, and cross-sectional studies on the efficacy of medicinal plants against diarrhea. A total of 67 articles (ethnobotanical (n = 40); in vitro (n = 11), in vivo (n = 7), cross-sectional (n = 3), in vitro and in vivo (n = 2) and ethnobotanical and in vitro (n = 2), were considered for the descriptive analysis, which addressed study characteristics, herbal intervention information, phytochemistry, outcome measures, and toxicity findings.

Results

A total of 587 different plant species (from 123 families) used for diarrhea treatment were identified. Most studies were conducted on plants from the Fabaceae family. The plants with the strongest antimicrobial activity were Indigoferadaleoides and Punicagranatum. Chromatographic methods were used to isolate six pure compounds from ethyl acetate extract of Hydnorajohannis, and spectroscopic methods were used to determine their structures. The majority of anti-diarrheal plants were from South Africa (23.9%), Ethiopia (16.4%), and Uganda (9%). This study highlights the value of traditional remedies in treating common human diseases such as diarrhea in SSA.

Conclusion

Baseline knowledge gaps were identified in various parts of SSA. It is therefore recommended that future ethnobotanical studies document the knowledge held by other countries in SSA that have so far received less attention. Additionally, we recommend that future studies conduct phytochemical investigations, particularly on the widely used medicinal plants for the treatment of diarrheal illnesses, which can serve as a foundation for future research into the development of contemporary drugs.
Novel MTR compound-heterozygous mutations in a Chinese girl with HHcy due to methionine synthase deficiency, cblG: a case report
Authors: Luo Juan , Chen Xiaohong , Guo Hongxi , Zhao Peiwei , Yao Hui , Feng Lifang , Yang Luhong
Published: January 2024

Background

The methylcobalamin deficiency G (cblG) disorder, a rare autosomal recessive disease, is attributed to mutations in the MTR gene, resulting in heightened homocysteine levels and reduced methionine and megaloblastic anemia levels. This disease is predominantly diagnosed using MTR gene variation analysis.

Case presentation

Herein, we report the case of a 2.1-month-old Chinese girl with the cblG disorder with poor feeding, failure to thrive, and pancytopenia, esotropia, ocular nystagmus, and hypotonia. However, in order to determine the possible genetic cause of the disease, whole-exome sequencing was adopted and detected compound-heterozygous mutations in MTR gene. One was splicing site mutation c.1812 + 3A > G and the other was missense mutation c.2405G > A (p.A802G), which were likely disease-causing mutations (DM). Variant c.1812 + 3A > G has not been reported before in the literature.

Conclusion

Our data elucidated the genetic etiology of the patient and enriched the known spectrum of mutations in the MTR gene worldwide, offering exhaustive and invaluable insights for early diagnosis and appropriate medication of the cblG disorder.
A 5-kW unidirectional wireless power transfer EV charger with a novel multi-level PFC boost converter on front-end side
Authors: Dakka Obulesu , Patthi Sridhar , Rao J. V. G. Rama , Kumar Parveen
Published: January 2024

The greatest advantages of wireless power transfer (WPT) are its absence of severe environmental hazards, its portability, and its independence from other factors. The wireless charging system for electric vehicles has a serious problem with the amount of misalignment it can tolerate. This study explores the usage of a novel multi-level boost power factor correction (PFC) rectifier with less switch count to improve the efficiency of power conversion of a 5-kW wireless electric vehicle (EV) charger. Especially in the context of wireless charging, which provides convenience and flexibility, there is a pressing need for efficient and dependable charging infrastructure to keep up with the rising demand for electric vehicles. In contrast to wired EV chargers, wireless chargers often have poorer power conversion efficiency because of losses in power semiconductor devices. An innovative multi-level boost PFC rectifier design is offered as a solution to this problem since it uses fewer switches while retaining high-performance levels. The suggested rectifier achieves much higher power conversion efficiency. In addition, power factor correction capabilities are improved, making it comply with global rules. Simpler, cheaper, and more dependable rectifiers improve the whole system.
Anonymous and robust biometric authentication scheme for secure social IoT healthcare applications
Authors: Arpitha T. , Chouhan Dharamendra , Shreyas J.
Published: January 2024

In the era of rapid technological advancement, the Internet of Things (IoT) has revolutionised healthcare through systems like the Telecare Medicine Information System (TMIS), designed to streamline patient-doctor interactions and enhance medical treatment. However, the transmission of sensitive patient data over inherently insecure Internet channels exposes it to a spectrum of security risks. Protecting patient medical privacy and ensuring system reliability necessitate mutual authentication between both patients and medical servers. TMIS relies on robust authentication mechanisms, and combining passwords and smart cards has been a recognised approach for mutual authentication. This research introduces an innovative three-factor authentication technique with perfect forward secrecy by leveraging the power of Elliptic Curve Cryptography (ECC) in tandem with smart cards. Additionally, we have incorporated biometric authentication with a Fuzzy Extractor technology to enhance the security and reliability of the system, setting a new standard for user authentication within the realm of Social IoT healthcare. The use of ECC in the method is justified due to its compact key size and robust security measures, making the solution both efficient and secure. The proposed method safeguards user privacy by permitting registered users to change their passwords without divulging their identity to the server. The Burrows–Abadi–Needham logic (also known as the BAN logic) serves as a proof-of-concept for the proposed scheme’s security. Our system provides privacy protection along with mutual authentication and session key negotiation at a considerably low computation cost and communication cost of up to 71.03% compared to the other four relevant techniques, making it more useful in real-world scenarios.
Finite element solutions of Double diffusion effects on three-dimensional MHD Nano-Powell-Erying fluid flow in presence of thermal and mass Biot numbers
Authors: Gundagani Murali , Mamidi Lakshmi Prasanna , Tanuku Poorna Kantha
Published: January 2024

This work uses a numerical method to investigate the effects of diffusion on the flow of three-dimensional magnetohydrodynamic (MHD) nanofluids. The applicable equations for this problem are derived from the Nano-Powell-Erying fluid model. The result of the differential equation is calculated by solving the problem using the finite element method. The numerical solutions are used to study the three-dimensional structures with the flow of nanofluid to investigate the influence of well-known fluid parameters. The study found that the Hartmann number and buoyancy ratio parameter have a significant impact on the velocity profile, while the Brownian motion and thermophoresis parameters, as well as the thermal and mass Biot numbers, are the main factors influencing the temperature and concentration fields. This study aims to analyse the effect of two different parameters on the flow of MHD nanofluids to improve our basic understanding of this phenomenon. The findings that were produced are compared to the previous work and incipiently, the present numerical results are veritably in good agreement with the previous results. The results of this study can be useful for the optimization and design of various engineering applications.
Integrated analysis of cyclic steam stimulation in a heavy oil reservoir: Microseismicity, brittleness, and landing height
Authors: Feroz Amna , van der Baan Mirko
Published: January 2024

We compare microseismic observations against pumping information, landing heights, and various well logs. The data were acquired during cyclic-steam injection between September 2002 and December 2005. Ninety-five percent of the microseismicity occurred during injection and in the overburden; 70% of the events happened during the first cycle. Microseismicity in the overburden is likely caused by a greater brittleness than in the reservoir and a cluster of microseismic events in regions with a smaller landing height, thereby facilitating dry cracking due to the volumetric expansion of the reservoir. Yet, other areas with equally shallow landing heights displayed little to no microseismicity, pointing to an inhomogeneous steam front. Furthermore, recorded microseismicity is subject to the Kaiser effect in that event rates are low in subsequent cycles until the current injection pressure exceeds the previous maximum, explaining why 70% of the events occurred during the first cycle and possibly why microseismicity during production accounted for only 5%. Microseismicity in brittle formations can be caused by pore-pressure variations (wet cracking) and/or changes in the total stresses (dry cracking). Identification of pore-pressure variations in the overburden is important because it may indicate containment challenges. Analysis of the growth rate of the microseismic cloud combined with the shallow landing height indicated dry cracking to be more likely than wet cracking but analysis of additional data is required to strengthen this conclusion.
Waiting for the Cool Moon
Authors: Matsumura Wendy
Published: January 2024

In Waiting for the Cool Moon Wendy Matsumura interrogates the erasure of colonial violence at the heart of Japanese nation-state formation. She critiques Japan studies’ role in this effacement and contends that the field must engage with anti-Blackness and anti-Indigeneity as the grounds on which to understand imperialism, colonialism, fascism, and other forces that shape national consciousness. Drawing on Black radical thinkers’ critique of the erasure of the Middle Passage in universalizing theories of modernity’s imbrication with fascism, Matsumura traces the consequences of the Japanese empire’s categorization of people as human and less-than-human as manifested in the 1920s and 1930s, and the struggles of racialized and colonized people against imperialist violence. She treats the archives safeguarded by racialized, colonized women throughout the empire as traces of these struggles, including the work they performed to keep certain stories out of view. Matsumura demonstrates that tracing colonial sensibility and struggle is central to grappling with their enduring consequences for the present.
Just War Determination through Human Acts Valuation: An Igbo-African Experience
Authors: Ezebuiro Anthony Udoka , Ejim Emeka Simon , Uke Innocent Anthony
Published: January 2024

This paper analytically reflects and x-rays the African perspective of just war using human act valuation as the basis of argument. In the wake of time, philosophers, psychologists and ethicists have differentiated between two kinds of actions, namely human action and action of man. Accordingly, man is convinced that he is different from the rest of the animal family; hence he acts at a level which dogs, for example, cannot attain. In any case, man does not always act as a man; his activity is not always stamped by what distinguishes him from other beings, namely rationality. Sometimes, he acts at the level he shares with other living beings; in other words, his activity at this level is ruled by a natural necessity or determined in the sense that doings at this sphere are not called actions, for they are ‘instinctive, thoughtless movement, mannerisms, reflex actions, or what is done under the influence of psychic constraints, hypnotic suggestions or demented frenzy etc.’ Such actions are rightly called actions of a human being, since their source is that bodily and spiritual individual who is called Peter, Paul, etc., but they are not human actions per se. They do not express the individual being; they do not proceed from him precisely as a human being. The only genuinely human action is the one which a human being performs in virtue of what distinguishes him from other beings. Since this is nothing other than reason, or rather, rationality, human actions are the actions which are performed when he acts as a rational being. Therefore, human acts are those actions of man that have their source in man’s rationality or spirituality, understood in terms of human’s interiority from which his activities flow. Beyond this, the African has got another sense of human act valuation, which is community-based or community-centered. In line with this, an attempt is made here to demonstrate how just war can be determined through human act valuation using the Igbo-African perspective as a case study.
The Problem of the Legitimacy of War in the Context of Ethical Concepts: The Example of the 44-day War
Authors: Sargsyan Armen
Published: January 2024

The article analyzes the issues of the legitimacy of war, the relationship between war and morality in the context of different ethical concepts. It is shown that the somewhat ‘fashionable’ notion of the ethics of war is actually problematic and does not clearly express the peculiarities of the relationship between war and morality. Analyzing the main conceptual discourses about war, it is argued that in some of them the acceptance of the legitimacy of war does not make sense with the logic of the watershed between war and morality. Analyzing the 44-day War separately for the first time in the context of the principles of the conception of just wars, it is argued that Azerbaijan’s military aggression against Artsakh was actually accompanied by a gross violation of many of these principles, despite the propaganda efforts of the Azerbaijani side to claim the opposite.
Killer Robots and Inauthenticity: A Heideggerian Response to the Ethical Challenge Posed by Lethal Autonomous Weapons Systems
Authors: Roden-Bow Ashley
Published: January 2024

This paper addresses the ethical challenges raised by the use of lethal autonomous weapons systems. Using aspects of the philosophy of Martin Heidegger, the paper demonstrates that lethal autonomous weapons systems create ethical problems because of the lack of moral agency in an autonomous system, and the inauthentic nature of the deaths caused by such a system. The paper considers potential solutions for these issues before arguing that from a Heideggerian standpoint they cannot be overcome, and thus the development and use of lethal autonomous weapons systems should be resisted and prohibited.
The Ethics of Military Influence Operations
Authors: Skerker Michael
Published: January 2024

This article articulates a framework for normatively assessing influence operations, undertaken by national security institutions. Section I categorizes the vast field of possible types of influence operations according to the communication’s content, its attribution, the rights of the target audience, the communication’s purpose, and its secondary effects. Section II populates these categories with historical examples and section III evaluates these cases with a moral framework. I argue that deceptive or manipulative communications directed at non-liable audiences are presumptively immoral and illegitimate for liberal states, as are deceptive operations aimed at an unjust end, or even operations aimed at a just end where secondary effects are forecast to be disproportionate to the proximate end.