bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on deformation characteristics of toppling failure of anti-dip rock slopes under different soft and hard rock conditions
Authors: Cai Junchao , Wang Junping , Li Zhen , Kong Yanli , Zhang Liang , Qi Guoqing
Published: June 2024

For the widespread exposure of toppling deformation phenomena in anti-dip engineering slopes such as hydropower, transportation, and mining, especially deep-seated toppling, these large-scale deep-seated toppling deformations reaching depths of hundreds of meters have become significant geotechnical engineering problems that restrict large-scale engineering construction and require urgent solutions. There are significant differences in the failure characteristics and mechanisms of anti-dip rock slopes under different soft and hard rock conditions. This study, starting from the failure characteristics and mechanisms under different soft and hard conditions of rocks, summarizes two types of toppling deformation: ductile bending deep toppling (DBDT) and brittle fracture shallow toppling (BFST). The UDEC method is used to preliminarily explore the threshold of rock mechanical parameters for these two types of toppling, with 80 MPa (UCS, uniaxial compressive strength) mechanical parameters serving as the preliminary threshold. The results indicate that hard rock undergoes BFST, whereas soft rock undergoes DBDT. The rock mechanical parameters of 100 MPa (UCS) and 20 MPa (UCS) were selected to study the evolution process and mechanism of DBDT and BFST deformations, respectively. Numerical simulation results have innovatively revealed the mechanical behavior characteristics between rock layers during the process of toppling deformation. Because toppling deformation mainly originates from interlayer displacement deformation and intra-layer tensile deformation of rock layers, the interlayer mechanical characteristics are of great significance for understanding the mechanism of toppling deformation. This research can provide a theoretical basis for the stability assessment and development utilization of anti-dip rock slopes and toppled slopes.
Research on the minimum network loss optimization control strategy of the active distribution network based on the distributed power flow controller
Authors: Liu Zhu , Wang Jinfeng , Guo Guowei , Feng KangHeng , Zhan Ximei , Peng Fadong , Gong Dehuang , Tang Aihong , Lulu Ma , Xiang Caili
Published: June 2024

With large-scale access to distributed new energy, the power flow form of the distribution network tends to be complex. The distribution loop network rate increases, resulting in serious circulation of the distribution network, which places significant pressure on the loss of the distribution network. The problem of network loss change caused by distributed new energy grid connection, coupled with the inconsistency between load fluctuation and output power change of distributed new energy, will have a significant impact on the safety, reliability, and economic operation of the distribution network. Therefore, it is urgent to have good economic and technical means of power flow control. This paper proposes a minimum network loss optimization control strategy for active distribution networks based on a distributed power flow controller. First, according to the characteristics of the distribution network load and the new energy power supply along the distribution line, the multiple sub-modules of the distributed power flow controller are arranged in sections in the distribution loop network line. The regulation effect of the distributed power flow controller on the voltage and power flow of the distribution loop network is analyzed. The loop network current equation and power loss equation after the distributed power flow controller are constructed, and the power equation with the minimum active loss of the active distribution loop network is derived. Second, the control strategy for minimum network loss of the active distribution network based on the distributed power flow controller is proposed. Finally, the simulation model of the active distribution loop network is constructed by PSCAD/EMTDC. The loss of the loop network before and after the distributed power flow controller is simulated and analyzed, and the effectiveness of the proposed strategy is verified.
Exploring energy management integration into upstream supply chains: a systematic literature review
Authors: Xavier Bruna Maria , Thollander Patrik , Hilletofth Per , Johansson Maria
Published: June 2024

In the effort to limit global warming to 1.5°C above the pre-industrial level, decarbonization of supply chains is crucial. Companies will need to reduce not only their direct and indirect emissions (scope 1 and 2) but also their indirect emissions (scope 3). In some sectors, the upstream scope 3 emissions can actually be larger than the companies’ direct emissions. Therefore, a systematic literature review was carried out to understand how previous research in the field of supply chain management (SCM) approached energy efficiency and energy management in the upstream supply chain. The results indicate that only a few studies have addressed energy efficiency within SCM, and the majority assess energy solely as total energy use, without exploring opportunities to reduce final energy use among upstream suppliers. Moreover, results show that there is a lack of standards and methods to assess suppliers’ energy use, making it difficult for suppliers, particularly small and medium-sized enterprises, to overcome barriers to implementing energy management. In conclusion, even though energy efficiency is a cost-effective means to reduce CO2 emissions, only a limited number of studies in the field of SCM have integrated energy efficiency, revealing a vast knowledge gap in this field.
Neutrophil in the suppressed immune microenvironment: Critical prognostic factor for lung adenocarcinoma patients with KEAP1 mutation
Authors: Wang Zhongzhao , Wang Haojue , Liu Mingjia , Ning Xinhang , Chen Yang , Tang Hao
Published: June 2024

Purpose

It is still unclear whether KEAP1 mutation is detrimental to immunotherapy of lung adenocarcinoma (LUAD) patients, we try to analyse the exact changes in the TME in LUAD patients with KEAP1 mutations and to identify key factors influencing prognosis.

Experimental design

A total of 1,029 patients with lung squamous carcinoma (LUSC) or LUAD with data obtained from The Cancer Genome Atlas were included in this study. The TME and OS of patients with LUAD stratified by mutant versus wild-type KEAP1 status were comprehensively measured. Moreover, we classified LUAD patients with KEAP1 mutations into three subtypes, by unsupervised consensus clustering. We further analysed the TME, OS, commutated genes and metabolic pathways of different subgroups. A total of 40 LUAD patients underwent immunotherapy were collected and classified into mutant KEAP1 group and wild-type KEAP1 group. We also conducted immunohistochemical staining in KEAP1-MT groups.

Result

Suppressed TME was observed not only in LUAD patients but also in LUSC patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than wild-type KEAP1. Unsupervised consensus clustering analysis suggested that the three subtypes of patients exhibited different densities of neutrophil infiltration and had different OS results: cluster 2 patients had significantly higher levels of neutrophils had significantly worse prognoses than those of patients in clusters 1 and 3 and patients with wild-type KEAP1. Univariate and multivariate Cox analyses proved that a high density of neutrophils was significantly associated with worse OS and immunohistochemical staining proved that shorter PFS showed high density of neutrophils.

Conclusion

KEAP1 mutation significantly suppresses the tumour immune microenvironment in LUAD patients. LUAD patients with mutant KEAP1 underwent immunotherapy had worse PFS than with wild-type KEAP1. Neutrophils may play an important role in the prognosis of LUAD patients with KEAP1 mutations and may provide a promising therapeutic target.
Succinic semialdehyde dehydrogenase deficiency: a metabolic and genomic approach to diagnosis
Authors: Glinton Kevin E. , Gijavanekar Charul , Rajagopal Abbhirami , Mackay Laura P. , Martin Kirt A. , Pearl Phillip L. , Gibson K. Michael , Wilson Theresa A. , Sutton V. Reid , Elsea Sarah H.
Published: June 2024

Genomic sequencing offers an untargeted, data-driven approach to genetic diagnosis; however, variants of uncertain significance often hinder the diagnostic process. The discovery of rare genomic variants without previously known functional evidence of pathogenicity often results in variants being overlooked as potentially causative, particularly in individuals with undifferentiated phenotypes. Consequently, many neurometabolic conditions, including those in the GABA (gamma-aminobutyric acid) catabolism pathway, are underdiagnosed. Succinic semialdehyde dehydrogenase deficiency (SSADHD, OMIM #271980) is a neurometabolic disorder in the GABA catabolism pathway. The disorder is due to bi-allelic pathogenic variants in ALDH5A1 and is usually characterized by moderate-to-severe developmental delays, hypotonia, intellectual disability, ataxia, seizures, hyperkinetic behavior, aggression, psychiatric disorders, and sleep disturbances. In this study, we utilized an integrated approach to diagnosis of SSADHD by examining molecular, clinical, and metabolomic data from a single large commercial laboratory. Our analysis led to the identification of 16 patients with likely SSADHD along with three novel variants. We also showed that patients with this disorder have a clear metabolomic signature that, along with molecular and clinical findings, may allow for more rapid and efficient diagnosis. We further surveyed all available pathogenic/likely pathogenic variants and used this information to estimate the global prevalence of this disease. Taken together, our comprehensive analysis allows for a global approach to the diagnosis of SSADHD and provides a pathway to improved diagnosis and potential incorporation into newborn screening programs. Furthermore, early diagnosis facilitates referral to genetic counseling, family support, and access to targeted treatments–taken together, these provide the best outcomes for individuals living with either GABA-TD or SSADHD, as well as other rare conditions.
Engineering strategies to safely drive CAR T-cells into the future
Authors: Rossi Matteo , Breman Eytan
Published: June 2024

Chimeric antigen receptor (CAR) T-cell therapy has proven a breakthrough in cancer treatment in the last decade, giving unprecedented results against hematological malignancies. All approved CAR T-cell products, as well as many being assessed in clinical trials, are generated using viral vectors to deploy the exogenous genetic material into T-cells. Viral vectors have a long-standing clinical history in gene delivery, and thus underwent iterations of optimization to improve their efficiency and safety. Nonetheless, their capacity to integrate semi-randomly into the host genome makes them potentially oncogenic via insertional mutagenesis and dysregulation of key cellular genes. Secondary cancers following CAR T-cell administration appear to be a rare adverse event. However several cases documented in the last few years put the spotlight on this issue, which might have been underestimated so far, given the relatively recent deployment of CAR T-cell therapies. Furthermore, the initial successes obtained in hematological malignancies have not yet been replicated in solid tumors. It is now clear that further enhancements are needed to allow CAR T-cells to increase long-term persistence, overcome exhaustion and cope with the immunosuppressive tumor microenvironment. To this aim, a variety of genomic engineering strategies are under evaluation, most relying on CRISPR/Cas9 or other gene editing technologies. These approaches are liable to introduce unintended, irreversible genomic alterations in the product cells. In the first part of this review, we will discuss the viral and non-viral approaches used for the generation of CAR T-cells, whereas in the second part we will focus on gene editing and non-gene editing T-cell engineering, with particular regard to advantages, limitations, and safety. Finally, we will critically analyze the different gene deployment and genomic engineering combinations, delineating strategies with a superior safety profile for the production of next-generation CAR T-cell.
Prediction of significant wave height using a VMD-LSTM-rolling model in the South Sea of China
Authors: Ding Tong , Wu De’an , Shen Liangshuai , Liu Qiang , Zhang Xiaogang , Li Yuming
Published: June 2024

Accurate prediction of significant wave height is crucial for ocean engineering. Traditional time series prediction models fail to achieve satisfactory results due to the non-stationarity of significant wave height. Decomposition algorithms are adopted to address the problem of non-stationarity, but the traditional direct decomposition method exists information leakage. In this study, a hybrid VMD-LSTM-rolling model is proposed for non-stationary wave height prediction. In this model, time series are generated by a rolling method, after which each time series is decomposed, trained and predicted, then the predictions of each time series are combined to generate the final prediction of significant wave height. The performance of the LSTM model, the VMD-LSTM-direct model and the VMD-LSTM-rolling model are compared in terms of multi-step prediction. It is found that the error of the VMD-LSTM-direct model and the VMD-LSTM-rolling model is lower than that of the LSTM model. Due to the decomposition of the testing set, the VMD-LSTM-direct model has a slightly higher accuracy than the VMD-LSTM-rolling model. However, given the issue of information leakage, the accuracy of the VMD-LSTM-direct model is considered false. Thus, it has been proved that the VMD-LSTM-rolling model exhibits superiority in predicting significant wave height and can be applied in practice.
Rock-like material under large diameter SHPB dynamic splitting tension: meso-damage mechanical behavior and stress wave propagation model
Authors: Yang Rongzhou , Xu Ying , Yu Meilu , Ge Jinjin , An Qi , Ma Pengying
Published: June 2024

The mechanical behavior of splitting tensile damage and the law of stress wave propagation of rock-like materials (RLM) are of great significance to further reveal the dynamic disaster mechanism of the deep rock mass. The meso-damage mechanical behavior and stress wave propagation characteristics of RLM disks under impact splitting were studied by using a large diameter split Hopkinson pressure bar (SHPB). In terms of dynamic damage, the splitting tensile stress-compression strain curves of RLM disks obviously showed three stages of mechanical behavior evolution: initial elastic-plastic deformation, pre-peak plastic damage, and post-peak brittle fracture failure. The macro-damage of RLM disks increased with the increase of strain rate. The meso-tensile fracture was the result of both the initial meso-damage and the impact splitting meso-damage. The dynamic splitting damage variable defined based on the damage fracture energy can accurately describe the damage evolution characteristics of impact splitting on RLM disks. In the aspect of stress wave propagation, the peak value of transmission stress showed an advanced effect with the increase of incident stress wave. In the early stage (0–50 μs), the transmission stress wave ratio (σT/σI) increased with the increase of strain rate, while in the later stage (82–200 μs), the transmission stress wave ratio (σT/σI) decreased with the increase of strain rate. The stress wave propagation law in the process of impact splitting on RLM disks was clearly revealed based on the stress wave propagation model established by the one-dimensional elastic stress wave theory. Finally, the dynamic mechanical mechanism of splitting damage and fracture of RLM disks under different strain rates was discussed deeply.
Case report: Management of liver cancer complicated by gastric varices rupture and bleeding: transjugular intrahepatic portosystemic shunt utilizing the mesenteric venous pathway
Authors: Sun Guoliang , Wang Jiangye , Zhang Beining , Zheng Ninggang
Published: June 2024

To avoid recurrent variceal bleeding, transjugular intrahepatic portosystemic shunt (TIPS) in conjunction with variceal embolization is considered to be an effective strategy. However, due to changes in conditions and variations in the patient's state, individuals undergoing TIPS may face challenges and limitations during procedures. The transjugular technique and combined transsplenic portal venous recanalization (PVR) with TIPS were not effective in this case due to a blocked portal vein and a previous splenectomy. With an abdominal incision, we successfully punctured the mesenteric venous system and navigated the occluded segment of the portal vein through the mesenteric approach. TIPS was then performed under balloon guidance. This study aims to explore the management of risks and complications during surgical operations and propose multiple preoperative surgical techniques to improve the success rate of the procedure.
An optimal combined slow-release nitrogen fertilizer and urea can enhance the decomposition rate of straw and the yield of maize by improving soil bacterial community and structure under full straw returning system
Authors: Yu Lihong , Li Duo , Zhang Yifei , Wang Yufeng , Yao Qin , Yang Kejun
Published: June 2024

Under a full straw returning system, the relationship between soil bacterial community diversity and straw decomposition, yield, and the combined application of slow-release nitrogen and urea remains unclear. To evaluate these effects and provide an effective strategy for sustainable agricultural production, a 2-year field positioning trial was conducted using maize as the research object. Six experimental treatments were set up: straw returning + no nitrogen fertilizer (S1N0), straw returning + slow-release nitrogen fertilizer:urea = 0:100% (S1N1), straw returning + slow-release nitrogen fertilizer:urea = 30%:70% (S1N2), straw returning + slow-release nitrogen fertilizer:urea = 60%:40% (S1N3), straw returning + slow-release nitrogen fertilizer:urea = 90%:10% (S1N4), and straw removal + slow-release nitrogen fertilizer:urea = 30%:70% (S0N2). Significant differences (p < 0.05) were observed between treatments for Proteobacteria, Acidobacteriota, Myxococcota, and Actinobacteriota at the jointing stage; Proteobacteria, Acidobacteriota, Myxococcota, Bacteroidota, and Gemmatimonadota at the tasseling stage; and Bacteroidota, Firmicutes, Myxococcota, Methylomirabilota, and Proteobacteria at the maturity stage. The alpha diversity analysis of the soil bacterial community showed that the number of operational taxonomic units (OTUs) and the Chao1 index were higher in S1N2, S1N3, and S1N4 compared with S0N2 at each growth stage. Additionally, the alpha diversity measures were higher in S1N3 and S1N4 compared with S1N2. The beta diversity analysis of the soil bacterial community showed that the bacterial communities in S1N3 and S1N4 were more similar or closely clustered together, while S0N2 was further from all treatments across the three growth stages. The cumulative straw decomposition rate was tested for each treatment, and data showed that S1N3 (90.58%) had the highest decomposition rate. At the phylum level, straw decomposition was positively correlated with Proteobacteria, Actinobacteriota, Myxococcota, and Bacteroidota but significantly negatively correlated with Acidobacteriota. PICRUSt2 function prediction results show that the relative abundance of bacteria in soil samples from each treatment differed significantly. The maize yield of S1N3 was 15597.85 ± 1477.17 kg/hm2, which was 12.80 and 4.18% higher than that of S1N1 and S0N2, respectively. In conclusion, a combination of slow-release nitrogen fertilizer and urea can enhance the straw decomposition rate and maize yield by improving the soil bacterial community and structure within a full straw returning system.
Microbiome modeling: a beginner's guide
Authors: Lange Emanuel , Kranert Lena , Krüger Jacob , Benndorf Dirk , Heyer Robert
Published: June 2024

Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with each other, their environment, and hosts via ecological interactions. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding between microbiologists and modelers/bioinformaticians, stemming from a lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored for microbiologists, researchers new to microbiome modeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metaomics methods, common modeling formalisms, and how models facilitate microbiome control. It concludes with guidelines and repositories for modeling. Each section provides entry-level information, example applications, and important references, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling.
Heat acclimation with probiotics-based ORS supplementation alleviates heat stroke-induced multiple organ dysfunction via improving intestinal thermotolerance and modulating gut microbiota in rats
Authors: Li Lei , Chen Juelin , Wang Yawei , Pei Yankun , Ren Lijun , Dai Xiaoyu , Li Jinfeng , Ma Jun , Wang Man , Chang Wenjun , Chen Jikuai , Song Qing , Xu Shuogui
Published: June 2024

Heat stroke (HS) is a critical condition with extremely high mortality. Heat acclimation (HA) is widely recognized as the best measure to prevent and protect against HS. Preventive administration of oral rehydration salts III (ORSIII) and probiotics have been reported to sustain intestinal function in cases of HS. This study established a rat model of HA that was treated with probiotics-based ORS (ORSP) during consecutive 21-day HA training. The results showed that HA with ORSP could attenuate HS-induced hyperthermia by regulating thermoregulatory response. We also found that HA with ORSP could significantly alleviate HS-induced multiple organ injuries. The expression levels of a series of heat-shock proteins (HSPs), including HSP90, HSP70, HSP60, and HSP40, were significantly up-regulated from the HA training. The increases in intestinal fatty acid binding protein (I-FABP) and D-Lactate typically seen during HS were decreased through HA. The representative TJ proteins including ZO-1, E-cadherin, and JAM-1 were found to be significantly down-regulated by HS, but sustained following HA. The ultrastructure of TJ was examined by TEM, which confirmed its protective effect on the intestinal barrier protection following HA. We also demonstrated that HA raised the intestinal levels of beneficial bacteria Lactobacillus and lowered those of the harmful bacteria Streptococcus through 16S rRNA gene sequencing. These findings suggest that HA with ORSP was proven to improve intestinal thermotolerance and the levels of protective gut microbiota against HS.
Isolation and identification of specific Enterococcus faecalis phage C-3 and G21-7 against Avian pathogenic Escherichia coli and its application to one-day-old geese
Authors: Wang Tianli , Zhang Ling , Zhang Yi , Tong Panpan , Ma Wanpeng , Wang Yan , Liu Yifan , Su Zhanqiang
Published: June 2024

Colibacillosis caused by Avian pathogenic Escherichia coli (APEC), including peritonitis, respiratory tract inflammation and ovaritis, is recognized as one of the most common and economically destructive bacterial diseases in poultry worldwide. In this study, the characteristics and inhibitory potential of phages were investigated by double-layer plate method, transmission electron microscopy, whole genome sequencing, bioinformatics analysis and animal experiments. The results showed that phages C-3 and G21-7 isolated from sewage around goose farms infected multiple O serogroups (O1, O2, O18, O78, O157, O26, O145, O178, O103 and O104) Escherichia coli (E.coli) with a multiplicity of infection (MOI) of 10 and 1, respectively. According to the one-step growth curve, the incubation time of both bacteriophage C-3 and G21-7 was 10 min. Sensitivity tests confirmed that C-3 and G21-6 are stable at 4 to 50 °C and pH in the range of 4 to 11. Based on morphological and phylogenetic analysis, phages C-3 and G21-7 belong to Enterococcus faecalis (E. faecalis) phage species of the genus Saphexavirus of Herelleviridae family. According to genomic analysis, phage C-3 and G21-7 were 58,097 bp and 57,339 bp in size, respectively, with G+C content of 39.91% and 39.99%, encoding proteins of 97 CDS (105 to 3,993 bp) and 96 CDS (105 to 3,993 bp), and both contained 2 tRNAs. Both phages contained two tail proteins and holin-endolysin system coding genes, and neither carried resistance genes nor virulence factors. Phage mixture has a good safety profile and has shown good survival probability and feed efficiency in both treatment and prophylaxis experiments with one-day-old goslings. These results suggest that phage C-3 and G21-7 can be used as potential antimicrobials for the prevention and treatment of APEC.
Tobacco crop rotation enhances the stability and complexity of microbial networks
Authors: Yan Huilin , Wu Shaolong , Li Ping , Jin Xin , Shi Dejun , Tu Danjia , Zeng Wei-ai , Tan Lin
Published: June 2024

Introduction

The effects of continuous cropping and rotation cropping, two important tobacco cultivation practices, on soil microbial communities at different stages remain unclear. Different planting patterns have been shown to influence soil physical and chemical properties, which in turn can affect the composition and diversity of soil microbial communities.

Methods

In order to investigate the impact of different planting methods on soil microbial community structure, we selected two representative planting methods: continuous cropping (tobacco) and rotational cropping (tobacco-maize). These methods were chosen as the focal points of our research to explore the potential effects on soil microbial communities. High-throughput sequencing technology was employed to investigate the structure of soil microbial communities, as well as their relationships with soil environmental factors, by utilizing the 16S rRNA, ITS, and 18S genes. Furthermore, the interaction among microorganisms was explored through the application of the Random Matrix Theory (RMT) molecular ecological network approach.

Results

There was no significant difference in α diversity, but significant difference in β diversity based on Jaccard distance test. Compared to continuous cropping, crop rotation significantly increased the abundance of beneficial prokaryotes Verrucomicrobia and Rhodanobacter. These findings indicate that crop rotation promotes the enrichment of Verrucomicrobia and Rhodanobacter in the soil microbial community. AP and NH4-N had a greater effect on the community structure of prokaryotes and fungi in tobacco soil, while only AP had a greater effect on the community structure of protist. Molecular ecological network analysis showed that the network robustness and Cohesion of rotation were significantly higher than that of continuous cropping, indicating that the complexity and stability of molecular ecological networks were higher in the rotational, and the microbial communities cooperated more effectively, and the community structure was more stable.

Discussion

From this point of view, rotational cropping is more conducive to changing the composition of soil microbial community, enhancing the stability of microbial network structure, and enhancing the potential ecological functions in soil.
Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome
Authors: Tan Zhen , Shen Pan , Wen Yi , Sun Hong-yu , Liang Hong-yin , Qie Hua-ji , Dai Rui-wu , Gao Yue , Huang Zhu , Zhou Wei , Tang Li-jun
Published: June 2024

Background

High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA.

Methods

We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites.

Result

Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5).

Conclusion

We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.
The effectiveness and predictors influencing the outcome of onabotulinumtoxinA treatment in chronic migraine: understanding from diverse patient profiles in a single session
Authors: Ilgaz Aydinlar Elif , Erdogan Soyukibar Tuba , Yalinay Dikmen Pinar
Published: June 2024

Objective

This real-world study aimed to investigate how onabotulinumtoxinA affects the outcome of migraine, along with accompanying anxiety, depression, and bruxism among a group of patients with chronic migraine (CM) and define predictors of good response.

Methods

Patients diagnosed with CM who received onabotulinumtoxinA were included in this single-center, real-world retrospective cohort study. Monthly headache days (MHDs), monthly migraine days (MMDs), headache intensity (numeric rating scale-NRS) and headache characteristics were evaluated at baseline and 12 weeks post-treatment. Patient-reported outcome measures (PROMs) included Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6) scores, 12-item Allodynia Symptom Checklist (ASC-12), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Response to onabotulinumtoxinA (% reduction in MHDs) and treatment-related adverse events (TRAEs) were also evaluated. OnabotulinumA was applied to the masseter muscles in patients complaining of bruxism.

Results

A total of 72 patients (mean ± SD age: 36.3 ± 8.5 years; 91.7% were female) diagnosed with CM were included. OnabotulinumtoxinA revealed significant decrease in median (IQR) MHDs [from 20(15–25) at baseline to 6(4–10), p < 0.001], MMDs [from 9(6–12) to 3(1–6), p < 0.001] and NRS [from 9(8–10) to 7(6–8), p < 0.001], and the MIDAS [from 54(30–81) to 16(7–24), p < 0.001], HIT-6 [from 67(65–69) to 58(54–64), p < 0.001], ASC-12 [from 6(1.5–9) to 2(0–9), p = 0.002], BAI [from 12(6.5–19) to 9(3–17), p < 0.001] and BDI [from 11(6.5–17) to 3(2–7) p < 0.001] scores at 12 weeks post-treatment. Patients complaining of bruxism received onabotulinumtoxinA injections in the first n = 27 (37.5%) and 12. week post-treatment n = 19 (70.4%) periods. Overall, 70.8% of patients responded (≥50% reduction in MHDs), while 29.2% did not (<50% reduction). Both groups showed similar characteristics in demographics, migraine history, baseline PROMs scores, comorbidities, and prior treatments.

Conclusion

OnabotulinumtoxinA is an effective treatment option that rapidly improves migraine outcomes, disability, and impact while also alleviating comorbid depression and/or anxiety. This study’s noteworthy finding is that onabotulinumtoxinA is effective in a majority of CM patients, irrespective of their prior treatment history, migraine characteristics, or concurrent comorbidities. Furthermore, we identified no specific predictors for a favorable response to onabotulinumtoxinA. Applying onabotulinumtoxinA to the masseter muscles can relieve discomfort associated with concurrent bruxism; however, it does not impact migraine outcomes.
The comparison of DBS and RNS for adult drug-resistant epilepsy: a systematic review and meta-analysis
Authors: Li Qinghua , Shan Yongzhi , Wei Penghu , Zhao Guoguang
Published: June 2024

Objective

Neuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE.

Methods

PubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis.

Results

A total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50–62%, p > 0.05) and 61% (95% CI 54–68%, p > 0.05). The responder rate of DBS and RNS were 67% (95% CI 58–76%, p > 0.05) and 71% (95% CI 64–78%, p > 0.05). Different targets of DBS did not show significant effect on seizure reduction (p > 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, p < 0.01). The mean follow-up time was 47.3 months for DBS and 39.5 months for RNS (p > 0.05).

Conclusion

Both DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.
Effectiveness of dairy products to protect against cognitive decline in later life: a narrative review
Authors: Anderson Rachel C. , Alpass Fiona M.
Published: June 2024

As the world's population ages the prevalence of age-related health concerns is increasing, including neurodegeneration disorders such as mild cognitive impairment, vascular dementia and Alzheimer's disease. Diet is a key modifiable risk factor for the development of neurodegeneration, likely due to gut-brain axis interactions related to neuroinflammation. Analyses of dietary patterns identified dairy as being part of a cognitively healthy diet; however, its contribution to cognitive outcomes is difficult to discern. This narrative review evaluates the literature to determine whether there is sufficient evidence that the consumption of dairy products helps to maintain cognitive function in later life. A search using the terms (dairy OR milk OR cheese OR yogurt OR yogurt) AND (“mild cognitive impairment” OR dementia OR “Alzheimer's disease”) identified 796 articles. After screening and sorting, 23 observational studies and 6 intervention studies were identified. The results of the observational studies implied that the relationship between total dairy consumption and cognitive outcomes is inverse U-shaped, with moderate consumption (1–2 servings per day) being the most beneficial. The analysis of the intake of different types of dairy products indicated that fermented products, particularly cheese, were most likely responsible for the observed benefits. The experimental studies all used dairy-derived peptides produced during fermentation as the dietary intervention, and the results indicated that these could be an effective treatment for early-stage cognitive impairment. Further experimental studies with whole dairy products, particularly fermented dairy, are needed to determine whether the regular consumption of these foods should be recommended to maximize the likelihood of healthy cognitive aging.
Association of oxidative balance score with hearing loss and tinnitus: NHANES 1999–2018
Authors: Lai Haohong , Yin Jiyuan , Yang Haidi
Published: June 2024

Background

Oxidative stress is associated with the occurrence of hearing loss and tinnitus. The oxidative balance score (OBS), a composite indicator evaluating the balance between antioxidant and pro-oxidative components across various dietary and lifestyle factors, indicates the overall oxidative balance status. However, the association of OBS with hearing loss and tinnitus has not been reported previously.

Methods

Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were analyzed. Weighted multivariable logistic regression, weighted multivariable linear regression, and restricted cubic spline curve (RCS) regression were employed to explore the relationship between OBS and hearing loss at speech, low, and high frequencies, along with tinnitus. Subgroup analysis and sensitivity analysis were used to ascertain the consistency across subgroups and stability of the results.

Results

We included 13,715 and 21,644 individuals to investigate the association between OBS and hearing loss, as well as between OBS and tinnitus, respectively. The second, third, and fourth quartiles of OBS were significantly associated with a lower risk of hearing loss at speech, low, and high frequencies, as well as tinnitus, compared to the lowest quartile. The RCS regression analysis indicated a negative linear association of OBS with hearing loss and tinnitus. Most associations were maintained in subgroup analysis and sensitivity analysis. Additionally, the dietary and lifestyle OBS independently contribute to the protection against hearing loss and tinnitus.

Conclusion

OBS is negatively correlated with the risk of hearing loss and tinnitus. The findings suggest that combined antioxidant diet and lifestyle hold promise as potential strategies for reducing the prevalence of hearing loss and tinnitus.
Improving skin cancer detection by Raman spectroscopy using convolutional neural networks and data augmentation
Authors: Zhao Jianhua , Lui Harvey , Kalia Sunil , Lee Tim K. , Zeng Haishan
Published: June 2024

Background

Our previous studies have demonstrated that Raman spectroscopy could be used for skin cancer detection with good sensitivity and specificity. The objective of this study is to determine if skin cancer detection can be further improved by combining deep neural networks and Raman spectroscopy.

Patients and methods

Raman spectra of 731 skin lesions were included in this study, containing 340 cancerous and precancerous lesions (melanoma, basal cell carcinoma, squamous cell carcinoma and actinic keratosis) and 391 benign lesions (melanocytic nevus and seborrheic keratosis). One-dimensional convolutional neural networks (1D-CNN) were developed for Raman spectral classification. The stratified samples were divided randomly into training (70%), validation (10%) and test set (20%), and were repeated 56 times using parallel computing. Different data augmentation strategies were implemented for the training dataset, including added random noise, spectral shift, spectral combination and artificially synthesized Raman spectra using one-dimensional generative adversarial networks (1D-GAN). The area under the receiver operating characteristic curve (ROC AUC) was used as a measure of the diagnostic performance. Conventional machine learning approaches, including partial least squares for discriminant analysis (PLS-DA), principal component and linear discriminant analysis (PC-LDA), support vector machine (SVM), and logistic regression (LR) were evaluated for comparison with the same data splitting scheme as the 1D-CNN.

Results

The ROC AUC of the test dataset based on the original training spectra were 0.886±0.022 (1D-CNN), 0.870±0.028 (PLS-DA), 0.875±0.033 (PC-LDA), 0.864±0.027 (SVM), and 0.525±0.045 (LR), which were improved to 0.909±0.021 (1D-CNN), 0.899±0.022 (PLS-DA), 0.895±0.022 (PC-LDA), 0.901±0.020 (SVM), and 0.897±0.021 (LR) respectively after augmentation of the training dataset (p<0.0001, Wilcoxon test). Paired analyses of 1D-CNN with conventional machine learning approaches showed that 1D-CNN had a 1–3% improvement (p<0.001, Wilcoxon test).

Conclusions

Data augmentation not only improved the performance of both deep neural networks and conventional machine learning techniques by 2–4%, but also improved the performance of the models on spectra with higher noise or spectral shifting. Convolutional neural networks slightly outperformed conventional machine learning approaches for skin cancer detection by Raman spectroscopy.
Activation of non-classical Wnt signaling pathway effectively enhances HLA-A presentation in acute myeloid leukemia
Authors: Ma YuHan , Yue JunShuai , Gao Ling , Zhou JingXin , Chen Wei , Su Jing , Yao JinRong , Shi QiaoMei , Zhao XiaoDong , Hu Na
Published: June 2024

Objective

The escape from T cell-mediated immune surveillance is an important cause of death for patients with acute myeloid leukemia (AML). This study aims to identify clonal heterogeneity in leukemia progenitor cells and explore molecular or signaling pathways associated with AML immune escape.

Methods

Single-cell RNA sequencing (scRNA-seq) was performed to identified AML-related cellular subsets, and intercellular communication was analyzed to investigate molecular mechanisms associated with AML immune escape. Bulk RNA sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs) related to hematopoietic stem cell progenitors (HSC-Prog) in AML, and critical ore signaling pathways and hub genes were found by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The mRNA level of the hub gene was verified using quantitative real-time PCR (qRT-PCR) and the protein level of human leukocyte antigen A (HLA-A) using enzyme-linked immuno sorbent assay (ELISA).

Results

scRNA-seq analysis revealed a large heterogeneity of HSC-Prog across samples, and the intercellular communication analysis indicated a strong association between HSC-Prog and CD8+-T cells, and HSC-Prog also had an association with HLA-A. Transcriptome analysis identified 1748 DEGs, enrichment analysis results showed that non-classical wnt signaling pathway was associated with AML, and 4 pathway-related genes (RHOA, RYK, CSNK1D, NLK) were obtained. After qRT-PCR and ELISA validation, hub genes and HLA-A were found to be down-regulated in AML and up-regulated after activation of the non-classical Wnt signaling pathway.

Conclusion

In this study, clonal heterogeneity of HSC-Prog cells in AML was identified, non-classical wnt signaling pathways associated with AML were identified, and it was verified that HLA-A could be upregulated by activation of non-classical wnt signaling, thereby increasing antigen presentation.
Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy
Authors: Piñana José Luis , Vazquez Lourdes , Heras Inmaculada , Aiello Tommaso Francesco , López-Corral Lucia , Arroyo Ignacio , Soler-Espejo Eva , García-Cadenas Irene , Garcia-Gutierrez Valentín , Aroca Cristina , Chorao Pedro , Olave María T. , Lopez-Jimenez Javier , Gómez Marina Acera , Arellano Elena , Cuesta-Casas Marian , Avendaño-Pita Alejandro , González-Santillana Clara , Hernández-Rivas José Ángel , Roldán-Pérez Alicia , Mico-Cerdá Mireia , Guerreiro Manuel , Morell Julia , Rodriguez-Galvez Paula , Labrador Jorge , Campos Diana , Cedillo Ángel , Vidal Carolina Garcia , Martino Rodrigo , Solano Carlos
Published: June 2024

Introduction

Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era.

Purpose

To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting.

Methods

A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed.

Results

Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality.

Conclusions

The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.