bluuebunny/crossref_metadata_2025 huggingface dataset:
RESEARCH METHODOLOGY AND CHARACTERISTICS OF NORMAL NONLINEAR RESONANT OSCILLATIONS OF THE SYSTEM ” SPRUNG AND UNSPRUNG PARTS OF WHEELED VEHICLES”
Authors: Romanchuk Yaroslav , Sokil Mariia
Published: November 2024

The authors have discussed the method applicable for the system of sprung-unsprung parts of the vehicle, carrying out vertical oscillations under nonlinear elastic force interactions, which allow evaluating the influence of the elastic characteristics of tires, the suspension system, and road irregularities on the determining parameters of the oscilla-tions of the sprung-unsprung parts. What’s obtained: a) the analytical dependence of natural oscillation frequencies on the system amplitudes and parameters; b) the relationship between the levels of amplitude of the sprung and unsprung parts oscillations, at which an internal resonance occurs; c) the condition for occurrence of the resonance in case of the motor vehicle movement along the road, which is described by the ordered system of inequalities; d) the ratios that set the main parameters of vibrations of the sprung and unsprung parts in case of the resonant and non-resonant vibrations. It is shown that a larger value of the oscillation amplitude of the sprung part corresponds to a larger value of the natural frequency in a suspension system with a progressive law of changes in the elasticity of shock absorbers, and the opposite is true when a regressive law; speaking of shock absorbers and elastic tires with their progressive or regressive power characteristics, a larger value of the oscillation amplitude of the unsprung part corresponds to a larger value of the oscil-lation amplitude of the sprung part, when an internal resonance is possible; for regressive power characteristics of tires and progressive power characteristics of shock absorbers – vice versa; the resonance value of the oscillation amplitude of the unsprung part is higher for the lower speeds of movement with regressive power characteristics of the tires and, on the contrary, – for the progressive power characteristics of tires; the amplitude of the transition through the resonance of the unsprung part takes a larger value for elastic tires with a smaller value of their static deformation and a slower transition to resonance.
Keywords: sprung and unsprung parts of the wheeled vehicle, natural frequencies of oscillations, resonant oscillations, internal resonance of the unsprung and sprung parts of the wheeled vehicle.
ON THE CONVERGENCE OF QUALITY INDICATORS OF ROAD BITUMEN FOR PENETRATION AND SUPERPAVE SYSTEMS
Authors: Zolotaryov Viktor
Published: November 2024

Currently, there are two systems for assessing the quality of road bitumen: European – penetration and American SHRP-SUPERPAVE. The first is based on empirical, the second on rheological indicators. They are considered to be incompatible. The present work proposes a convergent system. This is based on the following postulates: penetration characterizes the resistance of bitumen to shear; at softening point temperature penetration is 800 0.1 mm, and at breaking one is 1.25 0.1 mm; the penetration dependence on temperature in this range is logarithmic. It is shown that the convergent (generalized) system can be supplemented by the median temperature of the plasticity interval and equal shear temperature. The values of these indicators are interconnected within all 37 PG zones.
Keywords: indicators, modifications, road bitumen, penetration, polymers, SHRP-SUPERPAVE systems.
Climatic factors, but not geographic distance, promote genetic structure and differentiation of Cleistogenes squarrosa (Trin.) Keng populations
Authors: Song Ruyan , Zhang Xueli , Zhang Zhuo , Zhou Chan
Published: November 2024

Climate can shape plant genetic diversity and genetic structure, and genetic diversity and genetic structure can reflect the adaptation of plants to climate change. We used rbcl and trnL-trnF sequences to analyze the genetic diversity and genetic structure of C. squarrosa under the influence of different environmental factors in Inner Mongolia grassland. The results showed that the genetic diversity of this species was low. (The trnL-trnF sequences have higher genetic diversity than rbcl sequences.) C. squarrosa had low genetic diversity compared to other prairie plants, but had a more pronounced genetic structure. The haplotype network diagram of the combined sequences could be divided into two categories, and the results of the NJ, MP, and ML trees also showed that the haplotypes were divided into two branches. The results of genetic structure analysis showed that that the populations located in the desert steppe fall into exactly one cluster, and the populations located in the typical steppe fall into exactly another cluster. The neutrality tests were all negative and the mismatch distribution also showed a single peak across the population, suggesting that C. squarrosa had undergone population expansion and was well adapted to the local environment. The results of the mantel test showed that climate had a greater influence on the genetic distance of C. squarrosa, with annual precipitation having a higher influence than mean annual temperature. This study provided basic genetic information on the genetic structure of C. squarrosa and contributes to the study of genetic adaptation mechanisms in grassland plants.
Prospective and challenges of locally applied repurposed pharmaceuticals for periodontal tissue regeneration
Authors: El-Nablaway Mohammad , Rashed Fatema , Taher Ehab S. , Abdeen Ahmed , Taymour Noha , Soliman Magdalen M. , Shalaby Hany K. , Fericean Liana , Ioan Bănățean-Dunea , El-Sherbiny Mohamed , Ebrahim Elturabi , Abdelkader Afaf , Abdo Mohamed , Alexandru Cucui-Cozma , Atia Gamal A.
Published: November 2024

Periodontitis is a persistent inflammatory condition that causes periodontal ligament degradation, periodontal pocket development, and alveolar bone destruction, all of which lead to the breakdown of the teeth’s supporting system. Periodontitis is triggered by the accumulation of various microflora (especially anaerobes) in the pockets, which release toxic substances and digestive enzymes and stimulate the immune system. Periodontitis can be efficiently treated using a variety of techniques, both regional and systemic. Effective therapy is dependent on lowering microbial biofilm, minimizing or eradicating pockets. Nowadays, using local drug delivery systems (LDDSs) as an adjuvant therapy to phase I periodontal therapy is an attractive option since it controls drug release, resulting in improved efficacy and lesser adverse reactions. Choosing the right bioactive agent and mode of delivery is the foundation of an efficient periodontal disease management approach. The objective of this paper is to shed light on the issue of successful periodontal regeneration, the drawbacks of currently implemented interventions, and describe the potential of locally delivered repurposed drugs in periodontal tissue regeneration. Because of the multiple etiology of periodontitis, patients must get customized treatment with the primary goal of infection control. Yet, it is not always successful to replace the lost tissues, and it becomes more challenging as the defect gets worse. Pharmaceutical repurposing offers a viable, economical, and safe alternative for non-invasive, and predictable periodontal regeneration. This article clears the way in front of researchers, decision-makers, and pharmaceutical companies to explore the potential, effectiveness, and efficiency of the repurposed pharmaceuticals to generate more economical, effective, and safe topical pharmaceutical preparations for periodontal tissue regeneration.
Magnetically driven hydrogel microrobots for enhancing the therapeutic effect of anlotinib on osteosarcoma
Authors: Wang Haoyu , Jiang Haitian , Tao Yining , Yang Binghui , Shen Jiakang , Mu Haoran , Wang Chongren , Yang Xiyu , Cai Zhengdong , Li Mu , Sun Wei , Yang Liu , Sun Mengxiong
Published: November 2024

Introduction

Osteosarcoma, characterized by high mortality and disability rates, poses a significant challenge due to its complex genetic background and the absence of specific membrane receptors, which hinder effective targeted therapy. Active targeting has emerged as a promising approach to address this issue.

Methods

In this study, magnetically driven hydrogel robots (MMHR) were utilized to load and deliver drugs precisely to target sites. The drugs included SCR1481B16, a specific MET inhibitor proven to inhibit MET-driven tumor growth, and Anlotinib. The microrobots were designed to navigate under magnetic guidance, enhancing drug efficacy while minimizing damage to normal tissues.

Results

The study explored the potential of MMHR loaded with SCR1481B16 and Anlotinib in the treatment of Anlotinib-resistant osteosarcoma. The microrobots were successfully designed and produced, demonstrating the ability to deliver drugs precisely to tumor sites. Evaluation of the microrobots showed an enhanced sensitivity of tumors to Anlotinib, providing new insights into the treatment of drug-resistant osteosarcoma.

Discussion

Tumors overexpressing MET often develop resistance to VEGFR-targeted drugs. The use of SCR1481B16 as a MET inhibitor in combination with Anlotinib, delivered by magnetically driven hydrogel microrobots, offers a novel strategy to overcome this resistance. However, further in-depth research and validation are required before the clinical application of this method can be considered.

Conclusion

In conclusion, magnetically driven hydrogel microrobots loaded with SCR1481B16 provide a promising new strategy for enhancing the sensitivity of Anlotinib-resistant osteosarcoma, bringing hope for future clinical applications in the treatment of this challenging disease.
Enhanced T-cell activation and chemokine-associated function in CD14-positive cells from venous sinus blood in sub-acute cerebral venous sinus thrombosis
Authors: Chang Yu-Zhou , Song Yu-Qi , Zhu Hao-Yu , Zhang Jia-Rui , Fu Xi-Guang , Wang Yi-Long , Dong Ke-Hui , Jiang Chu-Han , Mo Da-Peng , Zhang Yu-Peng
Published: November 2024

Background

Patients with sub-acute cerebral venous sinus thrombosis experience (SA.CVST) severe symptoms compared to two other venous sinus-related diseases, including chronic cerebral venous sinus thrombosis (C.CVST) and idiopathic intracranial hypertension (IIH).

Objective

This study aimed to determine whether the different immune reactions in different venous sinuses are related.

Methods

Stagnant blood in the cerebral venous sinuses was extracted by passing a microcatheter and CD14-positive cells were sorted by magnetic beads and subjected to RNA-seq sequencing.

Results

Compared to patients with IIH, 128 genes were significantly down-regulated and 373 genes were significantly up-regulated in the sub-acute CVST samples. The functions of these genes were mainly focused on “immune response”, “T cell activation” and “plasma membrane”. Gene Set Enrichment Analysis (GSEA) showed T cell survival and activation-related function significantly unregulated in sub-acute CVST. On the other hand, there were 366 genes down-regulated in chronic CVST and 75 genes up-regulated in chronic CVST. In functional annotation, these differently expressed genes were enriched in the “extracellular region”, “chemokine-mediated signaling pathway” and “immune response”. GSEA analysis confirmed that chemokine-related functions were all up-regulated in sub-acute CVST and monocyte-macrophage adhesion functions were also significantly up-regulated.

Conclusion

This study suggested the CD14-positive created an activated immune response in sub-acute CVST.
Chemical characterization of wheat-based waste derived from a pharmaceutical process for its potential valorization
Authors: Ciriaco Lidia , Izzo Luana , Graziani Giulia , Ferraro Maria Grazia , Piccolo Marialuisa , Ciampaglia Roberto , Maglione Barbara , Palladino Roberta , Albarella Simone , Romano Eugenia , Ritieni Alberto , Irace Carlo , Grieco Paolo
Published: November 2024

Introduction

We report the analysis and characterization and the preliminary biological evaluation, of both liquid and solid wastes obtained from the processing of wheat (Triticum vulgare) to produce the most iconic phytostimulin-based pharmaceutical products. The study aims to verify whether the waste can be reused in another process and not destined to its simple destructive disposal.

Methods

In this perspective, we first carried out an in-depth chemical-physical analysis of the waste together with a biocompatibility evaluation to plan the feasible final choice of waste destination. The liquid and solid waste derived from the processing of wheat extract were analyzed and characterized through ultra-high-performance liquid chromatography coupled with high-resolution Orbitrap mass spectrometry (UHPLC-Q-Orbitrap HRMS).

Results

Results highlight that ferulic acid represent the most abundant phenolic compound for solid waste with a content of 89.782 mg/kg and dihydroferulic acid is the predominant for liquid waste (6.24 mg/L). These concentrations represent 55.87% and 84.39% of the total concentration of bioactive compounds for liquid and solid waste, respectively. The antioxidant activity registered for the solid extract was 8.598 and 7.262 mmol trolox/kg, respectively for ABTS and FRAP assays. The total phenolic content (TPC) in the liquid extract undergoes a significant percentage reduction compared to the solid waste. As regards toxicity, both liquid and solid wastes were investigated in vitro preclinical models of human skin (HaCaT cells and HDFa) after 24, 48, and 72 h of exposure. No cytotoxic effect was noted even at the highest tested concentration (100 μg/mL) at 72 h.

Discussion

Overall, considering its chemo-physical features and active ingredients, we believe that this waste is highly reusable as a starting material for the development of cosmeceutical products. Thus, this study allows us to motivate the destination of the waste of the production in a recyclable raw material for additional industrial processes, thereby promoting an eco-friendly circular economy operation.
Pathogenicity and identification of host adaptation genes of the avian pathogenic Escherichia coli O145 in duck
Authors: Tan Mei-Fang , Tan Jia , Fang Shao-Pei , Kang Zhao-Feng , Li Hai-Qin , Zhang Fan-Fan , Wu Cheng-Cheng , Li Na , Zeng Yan-Bin , Lin Cui , Huang Jiang-Nan
Published: November 2024

Introduction

Avian pathogenic Escherichia coli (APEC) is a critical bacterial pathogen that causes severe infections in poultry. Diverse serotypes increase the complexity of treatment and controlling APEC infections. Recent epidemiological investigations indicate O145 is emerging as a predominant serogroup of APEC in China. However, limited information is known about this newly emerged serogroup.

Methods

A virulent strain, NC22, was selected to elucidate the mechanisms underlying APEC O145-related pathogenicity and host adaptation. Whole-genome sequencing and pathogenicity assays was conducted on this strain. We further performed a transcriptional analysis of the bacteria during the early colonization stage in the duck liver and compared them with those in liquid cultures in vitro.

Results

Subcutaneous inoculation of NC22 induced typical symptoms in ducks. The bacterial loads in the blood and various tissues peaked at 2 and 3 days post infection, respectively. The affected tissues included the heart, liver, spleen, lung, kidney, bursa of Fabricius, duodenum, jejunum, and cecum. We then analyzed the transcriptome profiles of NC22 during growth in duck liver versus lysogeny broth and identified 87 genes with differential expression levels.These included key metabolic enzymes and recognized host adaptation factors. Analysis of the metabolic pathways revealed an inhibition of the metabolic shift from glycolysis towards pentose phosphate pathway and an interference of the citrate cycle. Moreover, significantly differentially expressed small regulatory RNAs were examined, such as SroC, CsrC, and GadY.

Discussion

These findings enhance our understanding of the pathogenicity of APEC O145 and the molecular mechanisms underlying APEC-related pathogen−host interactions.
Heterogeneous effects of climate change on displacement-inducing disasters
Authors: Beyer Robert , Miranda Espinosa Maria Teresa , Ponserre Sylvain , Mengel Matthias , Milan Andrea
Published: November 2024

With an estimated 357.7 million internal displacements caused since 2008, weather-related disasters are a major driver of human mobility worldwide. As climate change is projected to increase the frequency and intensity of extreme weather events in many parts of the world, it is important to better understand how trends in weather patterns related to global warming have affected the intensity of disasters that have caused displacements. Here we combined observational and counterfactual climate data with global internal displacement records to estimate how climate change has affected precipitation and wind speeds at the time and location of floods and storms that led to internal displacements. We estimate that, on average, climate change increased precipitation and decreased wind speeds during such events by +3.7% and − 1.4%, respectively. However, the variability across events is considerable (±28.6 and ± 6.6%, respectively), highlighting the large signal of natural variability of the weather system as compared to the global warming signal. Our results caution against overstating the role of climate change in displacement-inducing disasters in the past, especially compared to socio-economic and development factors of vulnerability and adaptive capacity that determine whether weather-related hazards turn into disasters.’
How do emoticons affect youth social interaction? The impact of emoticon use on youths online interpersonal interactions
Authors: Ju Gaofei , Zhao Ru
Published: November 2024

Emoticons are non-verbal symbols that are employed during online interactions, and they constitute an integral component of online interpersonal communication. The influence of emoticons on the online interpersonal interactions of young people was investigated through in-depth interviews with 25 young people who utilize emoticons to a moderate or significant extent. The study identified three key aspects through which the impact of emoticons on youth’s online social interactions is manifested. Firstly, this is reflected in the level of emotion and meaning conveyed. The utilization of emoticons by young people has, to a certain extent, rectified the contextual limitation of “embodied absence” in online virtual social interaction. Secondly, this is reflected in young people’s recognition of emoticons. The use of emoticons by young people in online social interactions has led to the formation of a distinct “emoticon community.” This phenomenon not only facilitates the development of a more profound social identity among young people in online social interactions but also contributes to the expansion of the adolescent network, resulting in the emergence of a novel “social divide.” Thirdly, the use of emoticons by young people can be seen to contribute to a sense of alienation. As young people become increasingly reliant on emoticons, their influence is gradually extending from the digital realm to the physical world, impacting the normal social interactions of young people in real life. Emoticons have gradually become a means of facilitating young people’s online socialization, but they have also had the unintended consequence of limiting their normal social interaction. The deterioration of online interpersonal communication among young people is a key factor in the symbolic generalization and alienation of expression in the use of emoticons by this demographic.
Genetically predicted smoking and body mass index mediate the relationship between insomnia and myocardial infarction
Authors: Deng Limei , Gao Yuan , Wan Dongmei , Dong Zheng , Shao Yuming , Gao Jing , Zhai Wenji , Xu Qian
Published: November 2024

Objective

This study aimed to investigate the causal relationship between insomnia and the risk of myocardial infarction (MI) and explore potential mediators such as smoking initiation, alcohol consumption and body mass index (BMI) using mendelian randomization (MR) analysis.

Methods

Data from 1,207,228 individuals of European ancestry were obtained from the UK Biobank and 23andMe for insomnia-related genetic associations. Genetic instruments for MI, smoking initiation, alcohol consumption, and BMI were derived from large-scale genome-wide association studies. Univariate MR analysis mainly utilized the inverse variance weighting method, and multivariable MR analysis assessed the mediation effects of smoking initiation and BMI.

Results

The univariate MR analysis revealed a 96% increased risk of MI in individuals with insomnia [odds ratio (OR) = 1.96; 95% CI: 1.67, 2.31]. Smoking initiation and BMI were identified as potential mediators. The multivariable MR analysis indicated smoking initiation accounted for 29% of the total effect (95% CI: 13%, 61%), while BMI accounted for 15% (95% CI: 7%, 27%), with a combined mediation proportion of 54% (95% CI: 31%, 91%).

Conclusions

The results of this MR analysis demonstrate that insomnia increases the risk of MI. Quitting smoking and losing weight may reduce this risk; however, there is still a portion of the impact of insomnia on MI that cannot be explained. Therefore, further investigation into other potentially modifiable intermediate factors is necessary.
Effect of low-dose rivaroxaban on bleeding events in low-weight patients with nonvalvular atrial fibrillation: a retrospective propensity score-matched cohort study
Authors: Liu Yuan , Lai Hengli , Chen Zhenhuan , Xiong Ganwei
Published: November 2024

Objective

To investigate the effect of low-dose rivaroxaban on bleeding events in low-weight patients with nonvalvular atrial fibrillation.

Methods

A retrospective study was conducted in patients with nonvalvular atrial fibrillation (weight ≤ 60 kg) who were admitted to the Department of Cardiology of Jiangxi Provincial People's Hospital from June 1, 2022, to December 12, 2022 and received anticoagulant therapy with rivaroxaban. The patients were divided into standard-dose group (15–20 mg) and low-dose group (10–15 mg). The patients were followed up for an average of 15 months by outpatient examination, telephone follow-up, or medical record inquiry of readmission patients. The bleeding events of the two groups were recorded during the follow-up period, and the two groups were balanced by propensity score weighting.

Results

A total of 198 patients with NVAF and body weight ≤60 kg receiving rivaroxaban anticoagulation therapy were enrolled, including 65 patients in the standard-dose group (15–20 mg) and 133 patients in the low-dose group (10–15 mg). In this study, only 24.1% (65/241) of the patients followed the standard dose of rivaroxaban. There was no significant difference in the incidence of bleeding events between the two groups after the balance of baseline characteristics (age) (P > 0.05). This was also consistent in patients weighing less than 50 kg.

Conclusions

In the real world, in lower-weight patients with nonvalvular atrial fibrillation, a reduced dose of rivaroxaban did not reduce the risk of bleeding, and this was consistent in patients weighing less than 50 kg.
Do professors favor liberal students? Examining political orientation appearance cues and professor bias
Authors: Woodzicka Julie A. , Boudreau Grace H. , Hayne Sarah L.
Published: November 2024

The perception of political bias in higher education persists even in the face of scarce evidence that liberal professors penalize conservative students or favor liberal ones. We investigated the degree to which college professors used student appearance to ascertain political orientation, and whether liberal-looking students were rated more favorably. Ninety-eight (98) professors rated a student on logic, likeability, and political leaning. The hypothetical student’s dress (bohemian vs. business casual) and hairstyle (brown hair vs. pink hair) were manipulated to cue political orientation. Results indicated that professors used student appearance to ascertain liberal political leaning but did not rate the students significantly different on logic and likeability. These results suggest that while professors use appearance cues, they do not favor students who appear liberal leaning or punish those who look less liberal.
Robust reference gene selection in Norway spruce: essential for real-time quantitative PCR across different tissue, stress and developmental conditions
Authors: Singh Vivek Vikram , Naseer Aisha , Sellamuthu Gothandapani , Mogilicherla Kanakachari , Gebauer Roman , Roy Amit , Jakuš Rastislav
Published: November 2024

Accurate gene expression analysis in Norway spruce (Picea abies) under diverse stress conditions requires the identification of stable reference genes for normalization. Notably, the literature lacks reports on suitable reference genes in Norway spruce. Here, we aimed to address this gap by identifying suitable reference genes for quantitative real-time PCR in Norway spruce across various stress conditions (drought, heat, pathogen infection) in seedlings, tissues (needle, phloem, root), and developmental stages (seedlings, mature trees). We evaluated the stability of 15 candidate reference genes and assessed their expression stability using five statistical algorithms (ΔCt, geNorm, NormFinder, BestKeeper, and RefFinder). Our results highlight ubiquitin-protein ligase (SP1), conserved oligomeric Golgi complex (COG7), and tubby-like F-box protein (TULP6) as the most stable reference genes, while succinate dehydrogenase (SDH5) and heat shock protein 90 (HSP90) were the least stable under various experimental conditions. COG7 and TULP6 are novel candidate reference genes reported for the first time. The expression stability of the identified reference genes was further validated using dehydrin-like protein 5 (PaDhn5) under drought conditions in Norway spruce. Pairwise variation analysis suggests that two reference genes were sufficient to normalize gene expression across all sample sets. This study provides a comprehensive analysis of reference gene stability under different experimental conditions and a catalog of genes for each condition, facilitating future functional genomic research in Norway spruce and related conifers.
SOX combined with tislelizumab and low-dose radiation therapy for the neoadjuvant treatment of locally advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, multicenter, single-arm, phase Ib/II clinical trial
Authors: Zhang Peng-Fei , Chen Ye , Li Wen-Ke , Luo Zhu-Mei , Chen Ji , Qian Kun , Chen Xiao-Dong , Wang Mo-Jin , Liu Ming
Published: November 2024

Background

Recently, the clinical benefits of neoadjuvant chemotherapy combined with immunotherapy have been observed in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer; however, the pathological complete response (pCR) and long-term survival rates are still unsatisfactory. The aim of this study is to investigate the efficacy and safety of chemotherapy combined with tislelizumab and low-dose radiation therapy (LDRT) for the neoadjuvant treatment of locally advanced G/GEJ cancer.

Methods

This is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib study, 5 patients will be enrolled in each treatment group with different radiation doses. In the phase II study, a total of 44 patients will be enrolled. Eligible patients will be registered and receive three cycles of SOX regimen chemotherapy (S-1: 40-60 mg Bid, d1-14, q3w; oxaliplatin: 130 mg/m2, iv drip, d1, q3w) plus tislelizumab (200 mg, iv drip, d1, q3w). Simultaneously, LDRT will be planned and administered after the first cycle of systemic therapy. Radical D2 gastrectomy will be performed 4-6 weeks after the last administration of chemotherapy plus tislelizumab. The primary endpoint of phase Ib study is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pCR rate. The secondary endpoints include R0 resection rate, major pathological response (MPR) rate, 2-year event-free survival (EFS) rate, 2-year overall survival (OS) rate and safety profile. Moreover, we will also explore potential molecular markers for predicting the benefit and safety of this neoadjuvant regimen. Written informed consent should be provided by all patients enrolled in the study. The study protocol was approved by the independent ethics committee at each institution.

Discussion

This is the first study to explore the efficacy and safety of neoadjuvant chemotherapy combined with tislelizumab and LDRT in G/GEJ cancer patients, the results of which may provide novel treatment strategy for patients with locally advanced G/GEJ adenocarcinoma.

Clinical trial registration

ClinicalTrials.Gov, identifier NCT06266871.
Nutrient transporter pattern in CD56dim NK cells: CD16 (FcγRIIIA)-dependent modulation and association with memory NK cell functional profile
Authors: De Federicis Davide , Capuano Cristina , Ciuti Daniel , Molfetta Rosa , Galandrini Ricciarda , Palmieri Gabriella
Published: November 2024

Background

Human memory NK cells represent a heterogeneous CD56dim population that expands and persists in human cytomegalovirus (HCMV)-seropositive healthy individuals. They are characterized by the preferential, not fully overlapping, expression of NKG2C (activating receptor for HLA-E) and CD57 maturation marker, and by the lack of FcεRIγ adaptor chain. Hyperresponsiveness to Fcγ receptor IIIA (CD16) engagement represents the distinctive functional signature of memory NK cells. Although CD16 engagement was shown to acutely enhance glycolytic and oxidative pathways, its capability to induce a persisting metabolic reprogramming of human NK cells is poorly understood yet.

Results

Here, we describe the peculiar nutrient transporter expression pattern of FcεRIγ- memory NK cells, characterized by higher levels of CD98 neutral amino acid antiporter and CD71 transferrin receptor, and lower expression of GLUT1 glucose transporter, with respect to FcεRIγ+ conventional NK cells. Although CD16 engagement acutely enhances glycolytic and oxidative pathways, its capability to induce a persisting metabolic reprogramming of human NK cells is poorly understood yet. Our results firstly show that sustained CD16 engagement by contact with IgG-opsonized target cells induces the mTORC1-dependent upregulation of CD98 and CD71 nutrient receptors on CD56dim NK cells, in a transporter-specific fashion, that is finely tuned by cell-dependent (grade of functional maturation, and memory or conventional lineage) and stimulus-dependent (time length and cooperation with cytokines) factors. We also demonstrate that CD98 antiporter function is required for CD16-dependent IFN-γ production, and that enhanced CD98-mediated neutral amino acid uptake associates with heightened memory NK cell functional response.

Conclusion

Collectively, our work documents that CD16 engagement leads to a metabolic rewiring of human NK cells and suggests that a distinct nutrient transporter expression pattern may contribute to memory NK cell peculiar functional features.
Fostering the international interoperability of clinical research networks to tackle undiagnosed and under-researched rare diseases
Authors: Zanello Galliano , Chan Chun-Hung , Parker Samantha , Julkowska Daria , Pearce David A.
Published: November 2024

Clinical research is an essential component to advance diagnosis and therapeutic development. In 2022, the International Rare Diseases Research Consortium (IRDiRC) and the European Joint Programme on Rare Diseases (EJP RD) brought together key stakeholders from across the globe to discuss common themes in clinical research networks (CRNs) for rare diseases. Various topics were raised during discussions including current state of CRNs, the need for new CRNs, multi-stakeholder perspectives on value of CRNs, and ways to collaborate on a global scale. Communication and coordination between various groups, taking advantage of existing experiences, can expedite establishment and execution of complex collaborations that will be necessary for CRNs. In this perspective, we discuss opportunities and highlight key considerations for developing successful collaborative CRNs across the globe.
The thromboelastogram is confounded by hematocrit in clinical samples tested on both mechanical and acoustic platforms
Authors: Hess Aaron S.
Published: November 2024

Red blood cells are critical participants in normal hemostasis, but in vitro experiments have shown that the thromboelastogram (TEG) maximum amplitude has a paradoxical inverse relationship with hematocrit. This study reviewed all samples at a single academic institution where any mechanical (TEG 5000) or acoustic (TEG 6s) TEG was drawn within 5 min of hematocrit measurement. A total of 7,176 samples were identified using complete TEG and conventional coagulation test data (6,384 mechanical, 744 acoustic, and 48 both). In the primary analysis, hematocrit was negatively associated with the maximum amplitude on both mechanical and acoustic platforms after adjusting for relevant confounders. This suggests that the thromboelastogram may misrepresent the contribution of red blood cells in normal hemostasis.
Correlation between the diameter of esophageal varices measured using a virtual ruler under endoscopy and portal pressure gradient
Authors: Mao Yudi , Fang Zhongliang , He Yingying , Jin Jing , Ding Xiping , Kong Derun
Published: November 2024

Background

Esophageal variceal diameter (EVD) is a crucial factor in determining the risk of esophageal variceal bleeding, which is associated with an increased portal pressure gradient (PPG). However, research into the relationship between EVD and PPG has been limited, primarily because the assessment of EVD depends on visual estimation during endoscopy. Recently, we developed an artificial intelligence (AI)-based method to accurately detect EVD. In this study, we aim to investigate the correlation between EVD and PPG, with the goal of evaluating EVD as a potential non-invasive indicator of PPG.

Methods

This study included both retrospective and prospective data from 128 patients diagnosed with portal hypertension and gastroesophageal varices, gathered from two medical institutions. Clinical data including PPG, biochemical markers, and routine blood tests were collected. In the retrospective phase, EVD was evaluated using an AI-based virtual ruler. In the prospective phase, PPG was measured using radiological intervention methods, and EVD was measured during endoscopy with the aid of AI.

Results

A positive correlation between PPG and EVD was identified (r = 0.521, P < 0.001), which was further supported by multivariate linear regression analysis (b = 6.521, t = 6.872, P < 0.001). When patients were stratified into two groups based on PPG levels (27 patients with PPG < 20 mmHg and 101 patients with PPG ≥ 20 mmHg), a significant difference in EVD was observed between the groups (OR = 29.275, 95% CI 5.590–153.304, P < 0.001), with larger EVD in the higher PPG group. These findings suggest that EVD may serve as a predictor of adverse events associated with elevated PPG levels. In addition, receiver operating characteristic (ROC) curve analysis showed that EVD had an accuracy of 0.814 in diagnosing PPG function (standard error 0.048, 95% CI 0.720-0.908; P < 0.001), indicating that PPG levels are likely to exceed 20 mmHg when the variceal diameter is greater than 1.1 cm.

Conclusion

EVD demonstrated a positive correlation with PPG and could potentially be used as a predictive marker for assessing PPG levels. These findings provide novel insights for the non-invasive evaluation of PPG in clinical practice.
Effective automatic classification methods via deep learning for myopic maculopathy
Authors: Zhang Zheming , Gao Qi , Fang Dong , Mijit Alfira , Chen Lu , Li Wangting , Wei Yantao
Published: November 2024

Background

Pathologic myopia (PM) associated with myopic maculopathy (MM) is a significant cause of visual impairment, especially in East Asia, where its prevalence has surged. Early detection and accurate classification of myopia-related fundus lesions are critical for managing PM. Traditional clinical analysis of fundus images is time-consuming and dependent on specialist expertise, driving the need for automated, accurate diagnostic tools.

Methods

This study developed a deep learning-based system for classifying five types of MM using color fundus photographs. Five architectures—ResNet50, EfficientNet-B0, Vision Transformer (ViT), Contrastive Language-Image Pre-Training (CLIP), and RETFound—were utilized. An ensemble learning approach with weighted voting was employed to enhance model performance. The models were trained on a dataset of 2,159 annotated images from Shenzhen Eye Hospital, with performance evaluated using accuracy, sensitivity, specificity, F1-Score, Cohen’s Kappa, and area under the receiver operating characteristic curve (AUC).

Results

The ensemble model achieved superior performance across all metrics, with an accuracy of 95.4% (95% CI: 93.0–97.0%), sensitivity of 95.4% (95% CI: 86.8–97.5%), specificity of 98.9% (95% CI: 97.1–99.5%), F1-Score of 95.3% (95% CI: 93.2–97.2%), Kappa value of 0.976 (95% CI: 0.957–0.989), and AUC of 0.995 (95% CI: 0.992–0.998). The voting ensemble method demonstrated robustness and high generalization ability in classifying complex lesions, outperforming individual models.

Conclusion

The ensemble deep learning system significantly enhances the accuracy and reliability of MM classification. This system holds potential for assisting ophthalmologists in early detection and precise diagnosis, thereby improving patient outcomes. Future work could focus on expanding the dataset, incorporating image quality assessment, and optimizing the ensemble algorithm for better efficiency and broader applicability.
Enhanced skin cancer diagnosis: a deep feature extraction-based framework for the multi-classification of skin cancer utilizing dermoscopy images
Authors: Alharbi Hadeel , Sampedro Gabriel Avelino , Juanatas Roben A. , Lim Se-jung
Published: November 2024

Skin cancer is one of the most common, deadly, and widespread cancers worldwide. Early detection of skin cancer can lead to reduced death rates. A dermatologist or primary care physician can use a dermatoscope to inspect a patient to diagnose skin disorders visually. Early detection of skin cancer is essential, and in order to confirm the diagnosis and determine the most appropriate course of therapy, patients should undergo a biopsy and a histological evaluation. Significant advancements have been made recently as the accuracy of skin cancer categorization by automated deep learning systems matches that of dermatologists. Though progress has been made, there is still a lack of a widely accepted, clinically reliable method for diagnosing skin cancer. This article presented four variants of the Convolutional Neural Network (CNN) model (i.e., original CNN, no batch normalization CNN, few filters CNN, and strided CNN) for the classification and prediction of skin cancer in lesion images with the aim of helping physicians in their diagnosis. Further, it presents the hybrid models CNN-Support Vector Machine (CNNSVM), CNN-Random Forest (CNNRF), and CNN-Logistic Regression (CNNLR), using a grid search for the best parameters. Exploratory Data Analysis (EDA) and random oversampling are performed to normalize and balance the data. The CNN models (original CNN, strided, and CNNSVM) obtained an accuracy rate of 98%. In contrast, CNNRF and CNNLR obtained an accuracy rate of 99% for skin cancer prediction on a HAM10000 dataset of 10,015 dermoscopic images. The encouraging outcomes demonstrate the effectiveness of the proposed method and show that improving the performance of skin cancer diagnosis requires including the patient's metadata with the lesion image.
Clinical characteristics associated with peripartum maternal bloodstream infection
Authors: Gao Xiao-Li , Li Yang , Hou Su-Juan , Fan Wen-Jun , Fang Ling-Yi , Ni Shi-Jun , Yan Ye , Li Jie , Han Cha
Published: November 2024

Objective

Bloodstream infection (BSI) during the peripartum period is a major cause of maternal morbidity and mortality. However, data on maternal BSI during hospitalization for delivery are limited. This study aimed to investigate the incidence, clinical characteristics, risk factors, microbiological features, and antibiotic resistance patterns of maternal peripartum BSI, with a focus on understanding the role of premature rupture of membranes (PROM), fever, and other risk factors in its development.

Methods

We investigated the clinical characteristics associated with maternal BSI during the peripartum period. This study included febrile women with blood cultures obtained during hospitalization for delivery. We analyzed the clinical characteristics, pathogenic microorganisms, antibiotic resistance, and maternal and neonatal outcomes of these patients. Participants were divided into BSI (n = 85) and non-BSI (n = 361) groups.

Results

Spontaneous rupture of membranes, PROM, PROM >24 h before labor, vaginal examinations >5 times, and cesarean sections during labor were more common in the BSI group. Escherichia coli (51.8%; 44/85) was the predominant causative pathogen, followed by Enterococcus faecalis (7.1%, 6/85). Approximately 31.2% of E. coli were resistant to levofloxacin, and 38.6% were extended-spectrum β-lactamase-producing bacteria. The BSI group had higher rates of maternal sepsis and Apgar scores ≤ 7 at 1 min than the non-BSI group. Furthermore, PROM, fever ≥38.9°C (102°F), and fever within 24 h after delivery were risk factors for postpartum BSI in the adjusted analysis.

Conclusion

Maternal BSI is a potentially life-threatening disease associated with PROM and the timing and severity of fever. Early identification and surveillance of pathogen composition and antimicrobial resistance can help prevent adverse outcomes.
Lingguizhugan decoction alleviates obesity in rats on a high-fat diet through the regulation of lipid metabolism and intestinal microbiota
Authors: Huang Wenjing , Wang Jiuyuan , Xiao Zixuan , Lin Jiayi , Tan Zhoujin , Sun Guixiang
Published: November 2024

Background

Individuals with obesity often experience elevated blood lipid levels, leading to a chronic low-grade inflammatory state, exacerbating liver oxidative stress, and increasing the risk of various metabolic diseases. Recent evidence suggests that intestinal microbiota and short-chain fatty acids (SCFAs) play crucial roles in the development and progression of obesity. While the mechanisms by which Lingguizhugan decoction (LGZGD) intervenes in obesity by improving lipid metabolism, enhancing insulin sensitivity, and reducing inflammatory responses are well-documented, its potential in intestinal microbiota and SCFAs remains unclear. This study aims to explore the impact of LGZGD on high-fat diet (HFD) induced obesity in rats and its regulatory effects on intestinal microbiota and SCFAs, providing new insights for obesity prevention and treatment.

Methods

Fifty-one male SD rats were randomly divided into groups, with six in the normal control group (NC) receiving a ddH2O treatment and a standard diet. The remaining 45 rats were fed a high-fat diet (HFD) using D12451 feed. After 10 weeks, the rats on the HFD gained 20% more weight than the NC group, confirming the successful modeling of obesity. These rats were then randomly divided into the following groups: ddH2O high-fat diet model group (MC), 20 mg/kg/day Orlistat positive control group (Orlistat), 1.62 g/kg/day low-dose LGZGD group (LGZGL), and 3.24 g/kg/day high-dose LGZGD group (LGZGH) for 8 weeks. We evaluated changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) levels. Fat and liver tissues were collected for pathological analysis. Intestinal contents were aseptically collected for 16S rRNA gene sequencing and gas chromatography–mass spectrometry (GC–MS) to assess gut microbiota and SCFA levels.

Results

LGZGD reduces body weight, TC, TG, LDL, and HDL levels, significantly reducing hepatic steatosis. Besides, it restored the richness and diversity of gut microbiota, which was reduced by HFD, altering the overall structure. Specifically, LGZGD significantly promoted the growth of Muribaculaceae and Dubosiella while inhibiting the growth of Christensenellaceae_R_7_group and UCG_005. It also restricts the production of caproic acid. Correlation analysis indicated positive correlations: Muribaculaceae with Butyric acid and Isovaleric acid; UCG_005 with TC, LDL, and HDL; and Christensenellaceae_R_7_group with TC and LDL.

Conclusion

LGZGD increased the abundance of beneficial gut microbiota in HFD-induced obese rats, improved gut microbiota dysbiosis, and inhibited the increase in caproic acid content. These results suggest that LGZGD can mitigate HFD-induced obesity, and its active components warrant further investigation.
Specific structural changes in Parkinson’s disease-related olfactory dysfunction compared to others forms of olfactory dysfunction
Authors: Brosse Sarah , Tremblay Cécilia , Mérida Inés , Frasnelli Johannes
Published: November 2024

Context

Olfactory dysfunction (OD) is a common early symptom of Parkinson’s disease (PD). However, OD is not specific to PD, as approximatively 20% of the general population exhibit different forms of OD. To use olfactory measures for early Parkinson screening, it is crucial to distinguish PD-related OD from Non-Parkinsonian OD (NPOD).

Objectives and hypothesis

This study aimed to compare the structural changes associated with PD-related OD (n = 15) with NPOD (n = 15), focusing on gray matter volumes and white matter fiber integrity in chemosensory regions. We hypothesized that PD-related OD presents specific structural alterations in these regions.

Methods

Participants underwent a 3 T MRI scan, which included anatomical T1 and diffusion-weighted imaging. Gray and white matter integrity were assessed using both whole-brain analyses (voxel-based morphometry—VBM and tract-based spatial statistics—TBSS, respectively) and localized approaches, including regions of interest and tractography.

Results

PD patients exhibited significantly higher gray matter volume in the left insula using restricted regions-of-interest analyses, while no other significant gray or white matter differences were found between groups.

Conclusion

Structural imaging of the gray matter, particularly the insula, but not of white matter, differentiates PD-related OD from NPOD.