bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Mesoporous CuOx Using Inverse Micelle Sol–gel Process for NO2 Gas Sensing
Authors: Heo Sung Gue , Kim Sangwoo , Seo Seok-Jun , Sim Jae Jin , Shin Jiyeon , Mirzaei Ali , Choi Myung Sik
Published: August 2024

Nitrogen dioxide (NO2) is a highly dangerous gas, mostly emitting emitted from fossil fuels, and a major contributor to air pollution. It has negatively effects affects on the human health as well asand contributes to environmental issues like acid rain. In this study, mesoporous CuOx nanoparticles (NPs) were successfully synthesized using a low-temperature inverse micelle sol–gel method. Subsequently, the synthesized NPs were annealed at temperatures of 250, 350, and 450 °C. Advanced characterization of the synthesized samples revealed that upon with increasing the annealing temperature, the sizes of the NPs increased, whileereas their surface areas decreased. The sample annealed at 250°C showed a remarkably higher surface area (161.85 m2/g) compared with the samples annealed at 350 °C (39.88 m2/g) and 450 °C (22.52 m2/g) thanks to finer particle sizes and a mesoporous nature. Resistive gas sensors incorporating these samples were successfully fabricated and tested for sensitivity towards both NO2 (oxidizing gas) and H2S (reducing gas) at 200 °C. The sensor with the mesoporous CuOx NPs annealed at the lowest temperature (250 °C) exhibited an enhanced response to NO2 gas but no response to H2S. The strong response to NO2 gas is considered to be due to the high surface area of the sensing layer which provides plenty of adsorption sites for gas molecules and the oxidizing nature of NO2 gas with high affinity to electrons. These findings highlight the effectiveness of the inverse micelle sol–gel method forin synthesizing mesoporous CuOx NPs for gas sensing, as well as the need for to optimizing optimize the annealing temperature to maximize the sensor response.
Microwave Absorption Characteristics of M2+, 3+ (M = Mn3+, Zn2+, Ni2+)-substituted Sr3Co2Fe24O41 Hexaferrite Composites
Authors: Heo Jae-Hee , Kang Young-Min
Published: August 2024

Mn, Zn, Ni-substituted Z-type hexaferrites, Sr3Co2Fe24O41 (Sr3Co2Fe24-xMnxO41, Sr3Co2-yZnyFe24O41, Sr3Co1-zNizZnFe24O41), were prepared by sol-gel synthesis processes and their high-frequency magnetic, dielectric and electromagnetic (EM) wave absorption characteristics were investigated. Substituting Mn for Fe by x = 0.5 maintained the single-phase Z phase while shifting the μ' , μ″ spectra towards lower frequencies. Substituting Zn for Co by y = 1.0 resulted in the single-phase Z phase and effectively shifted the μ' , μ″ spectra towards lower frequencies. Additionally, substituting Ni by z = 0.5, 1.0 gradually shifted the μ' , μ″ spectra towards higher frequencies. The Sr3Co2Fe24O41 with a single Z-type hexaferrite phase and epoxy (10 wt.%) composite showed strong ferromagnetic resonance (FMR) at 3.05 GHz and exhibited primary and secondary strong EM wave absorption characteristics at the thicknesses where impedance matching occurred near the FMR frequency and at frequencies higher than this. Substitution of Mn and Zn tended to decrease the FMR frequency, while substitution of Ni tended to increase it. The samples with substituted compositions also showed changes in the primary and secondary strong EM wave absorption frequency regions, depending on the FMR frequency changes. They demonstrated excellent EM wave absorption performance with the absolute value of the minimum reflection loss (RLmin) ranging from 42 to 58 dB. The FMR-tunable Z-type hexaferrite is a promising EM wave absorption material that can modulate EM wave absorption characteristics by cation substitution in in L-S-band (1~4 GHz) and X-band (8~12 GHz) ranges.
Investigation of Atomic-Scale η1 Precipitate Growth in Aluminum-Zinc-Magnesium Alloys
Authors: Kim Hwangsun , Han Heung Nam
Published: August 2024

Aluminum-Zinc-Magnesium (Al-Zn-Mg) alloys are extensively utilized in aerospace and automotive industries because of their exceptional mechanical properties and light weight. These properties of Al-Zn-Mg alloys are significantly influenced by the morphology, distribution, and size of the precipitates within the alloy, which result from the formation of numerous nanoscale precipitates. Among the various types of precipitates, η precipitates are the most representative, with the η1 variant comprising approximately 50% of the total η precipitates. In this study, we investigated the atomic-scale growth mechanism of η1 precipitates in Al-Zn-Mg alloys using high-resolution scanning transmission electron microscopy (STEM). The investigation revealed that the growth of η1 precipitates is driven by the separation of Mg and Zn atomic columns along the aluminum atomic arrangement near the interface, which facilitates the stepwise growth of the precipitates. Additionally, it was observed that a unique interfacial segregation layer forms in the direction of η1 precipitate growth, and energy-dispersive X-ray spectroscopy (EDS) confirmed that this layer is composed of Mg and Zn. These findings provide critical insights into the microscopic interactions and transformations that govern the precipitate formation process. This research offers valuable information for optimizing the microstructure and enhancing the mechanical performance of Al-Zn-Mg alloys for various high-performance applications.
Native Customary Rights Land: Indigenous Perspectives
Authors: Langub Jayl
Published: August 2024

Indigenous perspectives on natives’ customary rights to land are often marginalised in the development discourse in Sarawak. This paper argues that it is important for us to understand how indigenous communities claim customary rights to their territorial domain based on their adat that existed even before the Brooke administration in the mid-19th century. The state’s policies concerning land tenure and resource use systems in Sarawak have dramatically changed since the 100-year Brooke administration, followed by the British colonisation, and the eventual independence of Sarawak within Malaysia in 1963. These changes have directly impacted the different indigenous communities’ customary land tenure systems in Sarawak.
Adjuvant-independent airway sensitization and infection mouse models leading to allergic asthma
Authors: Radhouani Mariem , Starkl Philipp
Published: August 2024

Asthma is a chronic respiratory disease of global importance. Mouse models of allergic asthma have been instrumental in advancing research and novel therapeutic strategies for patients. The application of relevant allergens and physiological routes of exposure in such models has led to valuable insights into the complexities of asthma onset and development as well as key disease mechanisms. Furthermore, environmental microbial exposures and infections have been shown to play a fundamental part in asthma pathogenesis and alter disease outcome. In this review, we delve into physiological mouse models of allergic asthma and explore literature reports on most significant interplays between microbial infections and asthma development with relevance to human disease.
Microbial signatures predictive of short-term prognosis in severe pneumonia
Authors: Huang Shen-Shen , Qiu Jia-Yong , Li Shuang-Ping , Ma Ya-Qing , He Jun , Han Li-Na , Jiao Long-Long , Xu Chong , Mao Yi-Min , Zhang Yong-Mei
Published: August 2024

Objective

This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis.

Methods

A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis.

Results

The overall 28-day mortality rate was 37.7% in severe pneumonia. Non-survival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and β diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera.

Conclusion

Our study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings.
Cardiac magnetic resonance imaging for discrimination of hypertensive heart disease and hypertrophic cardiomyopathy: a systematic review and meta-analysis
Authors: Zhao Qingyuan , Chen Zhiyu , Qi Chengcheng , Xu Sunan , Ren Ruichen , Li Wenting , Zhang Xiaoxue , Zhang Yang
Published: August 2024

Introduction

Differentiating hypertensive heart disease (HHD) from hypertrophic cardiomyopathy (HCM) is crucial yet challenging due to overlapping clinical and morphological features. Recent studies have explored the use of various cardiac magnetic resonance (CMR) parameters to distinguish between these conditions, but findings have remained inconclusive. This study aims to identify which CMR parameters effectively discriminate between HHD and HCM and to investigate their underlying pathophysiological mechanisms through a meta-analysis.

Methods

The researchers conducted a systematic and comprehensive search for all studies that used CMR to discriminate between HHD and HCM and calculated the Hedges'g effect size for each of the included studies, which were then pooled using a random-effects model and tested for the effects of potential influencing variables through subgroup and regression analyses.

Results

In this review, 26 studies encompassing 1,349 HHD and 1,581 HCM cases were included for meta-analysis. Analysis revealed that HHD showed a significant lower in T1 mapping (g = −0.469, P < 0.001), extracellular volume (g = −0.417, P = 0.024), left ventricular mass index (g = −0.437, P < 0.001), and maximal left ventricular wall thickness (g = −2.076, P < 0.001), alongside a significant higher in end-systolic volume index (g = 0.993, P < 0.001) and end-diastolic volume index (g = 0.553, P < 0.001), compared to HCM.

Conclusion

This study clearly demonstrates that CMR parameters can effectively differentiate between HHD and HCM. HHD is characterized by significantly lower diffuse interstitial fibrosis and myocardial hypertrophy, along with better-preserved diastolic function but lower systolic function, compared to HCM. The findings highlight the need for standardized CMR protocols, considering the significant influence of MRI machine vendors, post-processing software, and study regions on diagnostic parameters. These insights are crucial for improving diagnostic accuracy and optimizing treatment strategies for patients with HHD and HCM.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023470557, PROSPERO (CRD42023470557).
Study on fragmentation characteristics of rock mass in bench blasting with different coupling media
Authors: Li Tong , Chen Ming , Guo Bo-wen , Song Li , Fan Bing , Cui Shan-shan
Published: August 2024

The fragmentation size distribution is an important index to evaluate blasting effect. Based on stress wave theory, a blasting fragmentation distribution model is established, and the key influencing factors were clarified. Then, the distribution characteristics of rock fragmentation in water-coupled blasting and air-coupled blasting were compared and verified by numerical simulation and field test. The results show that the rock blasting fragmentation size is negatively correlated with borehole pressure and unit explosive consumption when blasting rock is determined. The existence of water slows down the attenuation of blasting load, prolongs the duration, and makes the blasting pressure transmitted to hole wall significantly greater than air-coupled one, which is equivalent to increasing the unit explosive consumption. Moreover, the rock fracture development speed and fragmentation degree of water-coupled blasting is significantly higher than air-coupled blasting. Comprehensively determined in same charging parameters, water-coupled blasting compared with air-coupled blasting can improve the degree of rock fragmentation, the average size of rock after blasting is smaller, more uniform particle size distribution. The research results for the control of blasting and optimization of explosive energy utilization have important reference significance.
Causal effects of gut microbiota on diabetic neuropathy: a two-sample Mendelian randomization study
Authors: Xu Ming , Hao Jinxuan , Qi Yijie , Wu Baofeng , Li Ru , Yang Xifeng , Zhang Yi , Liu Yunfeng
Published: August 2024

Objective

Previous observational studies have suggested an association between gut microbiota and diabetic neuropathy (DN). However, confounding factors and reverse causality make the causal relationship between gut microbiota and DN uncertain. We aimed to investigate the interactive causal relationships between the abundance of gut microbiota and DN.

Methods

We conducted a Mendelian randomization (MR) analysis to examine the causal relationship between gut microbiota and DN. Genomic data on gut microbiota at the genus level were obtained from the MiBioGen Consortium, including 18,340 individuals of European descent. Data on diabetic polyneuropathy (DPN) were obtained from the FinnGen Consortium, which included 1,048 cases and 374,434 controls, while data on diabetic autonomic neuropathy (DAN) were also obtained from the FinnGen Consortium, including 111 cases and 374,434 controls. Causal effects were primarily estimated using inverse variance weighted (IVW) analysis, supplemented with four validation methods, and additional sensitivity analyses to assess the pleiotropy, heterogeneity, and robustness of instrumental variables.

Results

The IVW analysis indicated that Prevotella 9 had a protective effect on DPN (OR = 0.715, 95% CI: 0.521-0.982, P = 0.038), and Bacteroides also showed a protective effect (OR = 0.602, 95% CI: 0.364-0.996, P = 0.048). On the other hand, Ruminococcus 2 had a promoting effect on DPN (OR = 1.449, 95% CI: 1.008-2.083, P = 0.045). Blautia (OR = 0.161, 95% CI: 0.035-0.733, P = 0.018), Clostridium innocuum group (OR = 3.033, 95% CI: 1.379-6.672, P = 0.006), and Howardella (OR = 2.595, 95% CI: 1.074-6.269, P = 0.034) were causally associated with DAN in the IVW analysis, with no evidence of heterogeneity or pleiotropy. Sensitivity analyses showed no significant pleiotropy or heterogeneity.

Conclusion

Our study identified a causal relationship between gut microbiota and the increased or decreased risk of diabetic neuropathy. These findings underscore the importance of adopting a comprehensive approach that combines gut microbiota modulation with other therapeutic interventions in the management of diabetic neuropathy.
Broadening horizons: the role of ferroptosis in polycystic ovary syndrome
Authors: Wang Min , Zhang Bo-Qi , Ma Shuai , Xu Ying , Zhao Dong-Hai , Zhang Jing-Shun , Li Chun-Jin , Zhou Xu , Zheng Lian-Wen
Published: August 2024

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.
Impacts of a partially connected wastewater treatment plant on the water quality of stormwater drains used as an irrigation source
Authors: Samaraweera S. A. P. T. , Najim M. M. M. , Alotaibi Bader Alhafi , Traore Abou
Published: August 2024

Urban stormwater drains in Kurunegala City collect runoff and untreated wastewater, leading to public health problems. The Greater Kurunegala Sewage Treatment Plant (GKSTP) was commissioned in 2018 and currently operates at 73% of its capacity to combat public health issues. This study assessed the water quality of canals, comparing it with standards and pre-GKSTP conditions. Water samples were collected from seven sites during dry and wet seasons, and physicochemical parameters were measured. The data underwent spatial and temporal analysis using the general linear model (GLM). Additionally, cluster analysis and distance-based redundancy analysis were employed. The water quality index (WQI) was employed to evaluate the effectiveness of the treatment plant. The study revealed significant spatial and temporal variations in physicochemical parameters along the canals (p < 0.05, GLM), with higher pollution levels during wet months. The WQI improved from 35 (2005) to 49 at present, indicating enhanced water quality (p < 0.05, ANOVA), although it remains unsatisfactory. This study provides novel insights into the limitations of conventional wastewater treatment practices, demonstrating that merely treating wastewater and discharging it back into canals is insufficient. Research underscores the importance of rethinking treated wastewater reuse in achieving multiple sustainable development goals (SDGs). This approach offers a pragmatic path forward for enhancing water security and environmental sustainability globally.
Immune-targeted therapy with transarterial chemo(embolization) for unresectable HCC: a systematic review and meta-analysis
Authors: Fang Huipeng , Ke Qiao , Wu Shiji , Tu Qiang , Wang Lei
Published: August 2024

Background

Transarterial chemo(embolization) is preferred for treating unresectable hepatocellular carcinoma (uHCC); however, because of emerging immune-targeted therapies, its efficacy is at stake. This systematic review pioneers to evaluate the clinical efficacy and safety of transarterial chemo(embolization) combined with immune-targeted therapy for uHCC patients.

Methods

PubMed, Embase, and Cochrane Library were searched for studies comparing immune-targeted therapy with or without transarterial chemo(embolization) until 31 May 2024. The complete response (CR) rate, objective response rate (ORR), and disease control rate (DCR) were considered to be the primary outcomes calculated for the clinical outcomes of transarterial chemo(embolization) combined with immune-targeted therapy, along with progression-free survival (PFS) and overall survival (OS). The incidence of treatment-related severe adverse events was set as the major measure for the safety outcome.

Results

Sixteen studies, encompassing 1,789 patients receiving transarterial chemo(embolization) plus immune-targeted therapy and 1,215 patients receiving immune-targeted therapy alone, were considered eligible. The combination of transarterial chemo(embolization) and immune-targeted therapy demonstrated enhanced outcomes in CR (OR = 2.12, 95% CI = 1.35–3.31), ORR (OR = 2.78, 95% CI = 2.15–3.61), DCR (OR = 2.46, 95% CI = 1.72–3.52), PFS (HR = 0.59, 95% CI = 0.50–0.70), and OS (HR = 0.51, 95% CI = 0.44–0.59), albeit accompanied by a surge in ALT (OR = 2.17, 95% CI = 1.28–3.68) and AST (OR = 2.28, 95% CI = 1.42–3.65). The advantages of additional transarterial chemo(embolization) to immune-targeted therapy were also verified in subgroups of first-line treatment, intervention techniques, with or without extrahepatic metastasis, Child–Pugh grade A or B, and with or without tumor thrombus.

Conclusion

The combination of transarterial chemo(embolization) and immune-targeted therapy seems to bolster local control and long-term efficacy in uHCC, albeit at the expense of hepatic complications.

Systematic review registration

http://www.crd.york.ac.uk/PROSPERO/, identifier 474669.
Development and validation of a survival prediction model for patients with advanced non-small cell lung cancer based on LASSO regression
Authors: Guo Yimeng , Li Lihua , Zheng Keao , Du Juan , Nie Jingxu , Wang Zanhong , Hao Zhiying
Published: August 2024

Introduction: Lung cancer remains a significant global health burden, with non-small cell lung cancer (NSCLC) being the predominant subtype. Despite advancements in treatment, the prognosis for patients with advanced NSCLC remains unsatisfactory, underscoring the imperative for precise prognostic assessment models. This study aimed to develop and validate a survival prediction model specifically tailored for patients diagnosed with NSCLC. Methods: A total of 523 patients were randomly divided into a training dataset (n=313) and a validation dataset (n=210). We conducted initial variable selection using three analytical methods: univariate Cox regression, LASSO regression, and random survival forest (RSF) analysis. Multivariate Cox regression was then performed on the variables selected by each method to construct the final predictive models. The optimal model was selected based on the highest bootstrap C-index observed in the validation dataset. Additionally, the predictive performance of the model was evaluated using time-dependent receiver operating characteristic (Time-ROC) curves, calibration plots, and decision curve analysis (DCA). Results: The LASSO regression model, which included N stage, neutrophil-lymphocyte ratio (NLR), D-dimer, neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC), driver alterations, and first-line treatment, achieved a bootstrap C-index of 0.668 (95% CI: 0.626-0.722) in the validation dataset, the highest among the three models tested. The model demonstrated good discrimination in the validation dataset, with area under the ROC curve (AUC) values of 0.707 (95% CI: 0.633-0.781) for 1-year survival, 0.691 (95% CI: 0.616-0.765) for 2-year survival, and 0.696 (95% CI: 0.611-0.781) for 3-year survival predictions, respectively. Calibration plots indicated good agreement between predicted and observed survival probabilities. Decision curve analysis demonstrated that the model provides clinical benefit at a range of decision thresholds. Conclusion: The LASSO regression model exhibited robust performance in the validation dataset, predicting survival outcomes for patients with advanced NSCLC effectively. This model can assist clinicians in making more informed treatment decisions and provide a valuable tool for patient risk stratification and personalized management.
Isolation and characterization of bacteriophages for controlling Rhizobium radiobacter – causing stem and crown gall of highbush blueberry
Authors: Chantapakul Bowornnan , Sabaratnam Siva , Wang Siyun
Published: August 2024

Introduction

Stem and crown gall disease caused by the plant pathogen Rhizobium radiobacter has a significant impact on highbush blueberry (Vaccinium corymbosum) production. Current methods for controlling the bacterium are limited. Lytic phages, which can specifically target host bacteria, have been widely gained interest in agriculture.

Methods

In this study, 76 bacteriophages were recovered from sewage influent and screened for their inhibitory effect against Rhizobium spp. The phages were genetically characterized through whole-genome sequencing, and their lytic cycle was confirmed.

Results

Five potential candidate phages (isolates IC12, IG49, AN01, LG08, and LG11) with the ability to lyse a broad range of hosts were chosen and assessed for their morphology, environmental stability, latent period, and burst size. The morphology of these selected phages revealed a long contractile tail under transmission electron microscopy. Single-step growth curves displayed that these phages had a latent period of 80–110 min and a burst size ranging from 8 to 33 phages per infected cell. None of these phages contained any antimicrobial resistance or virulence genes in their genomes. Subsequently, a combination of two-, three- and four-phage cocktails were formulated and tested for their efficacy in a broth system. A three-phage cocktail composed of the isolates IC12, IG49 and LG08 showed promising results in controlling a large number of R. radiobacter strains in vitro. In a soil/peat-based model, the three-phage cocktail was tested against R. radiobacter PL17, resulting in a significant reduction (p < 0.05) of 2.9 and 1.3 log10 CFU/g after 24 and 48 h of incubation, respectively.

Discussion

These findings suggest that the three-phage cocktail (IC12, IG49 and LG08) has the potential to serve as a proactive antimicrobial solution for controlling R. radiobacter on blueberry.
Optimal cut-off values of visceral fat area for predicting metabolic syndrome among patients with ischemic stroke: a cross-sectional study
Authors: Lu Xueyan , Wang Jing , Sun Huijie , Liu Dandan , Yan Xiuli , Liu Zhuo
Published: August 2024

Objectives

The prevalence of metabolic syndrome (MetS) among patients with ischemic stroke is relatively high. The visceral fat area (VFA) is a predictor of MetS. This study aimed to estimate sex-specific optimal cut-off values of VFA and MetS risk factors among patients with ischemic stroke.

Methods

A cross-sectional study including 851 patients with ischemic stroke was conducted between March 2019 and January 2020 in a tertiary hospital in the northeast of China. VFA was measured using the dual bioelectrical impedance method. Binary logistic regression analysis was used to investigate MetS risk factors, and the VFA cut-off value was assessed using receiver operating characteristic curve analysis.

Results

The overall prevalence of MetS was 43.4%. After adjusting for potential confounders, female sex (odds ratio [OR] = 2.86, p < 0.001), the presence of visceral obesity according to VFA (OR = 7.45, p < 0.001), being overweight (OR = 2.75, p < 0.001) or obesity (OR = 6.00, p < 0.001) were associated with an increased risk of MetS. The correlation between VFA and MetS in patients with ischemic stroke was strongest with cut-off values of 104.3 cm2 (sensitivity 73.0%, specificity 83.1%) for men, and 94.1 cm2 (sensitivity 70.9%, specificity 72.9%) for women.

Conclusion

MetS affected approximately a half of patients with ischemic stroke. Female sex, visceral obesity, and body mass index were independent risk factors for the development of MetS. Sex-specific reference values for VFA are proposed for the prediction of incident MetS in patients with ischemic stroke.
Iterative Data-adaptive Autoregressive (IDAR) whitening procedure for long and short TR fMRI
Authors: Yue Kun , Webster Jason , Grabowski Thomas , Shojaie Ali , Jahanian Hesamoddin
Published: August 2024

Introduction

Functional magnetic resonance imaging (fMRI) has become a fundamental tool for studying brain function. However, the presence of serial correlations in fMRI data complicates data analysis, violates the statistical assumptions of analyses methods, and can lead to incorrect conclusions in fMRI studies.

Methods

In this paper, we show that conventional whitening procedures designed for data with longer repetition times (TRs) (>2 s) are inadequate for the increasing use of short-TR fMRI data. Furthermore, we comprehensively investigate the shortcomings of existing whitening methods and introduce an iterative whitening approach named “IDAR” (Iterative Data-adaptive Autoregressive model) to address these shortcomings. IDAR employs high-order autoregressive (AR) models with flexible and data-driven orders, offering the capability to model complex serial correlation structures in both short-TR and long-TR fMRI datasets.

Results

Conventional whitening methods, such as AR(1), ARMA(1,1), and higher-order AR, were effective in reducing serial correlation in long-TR data but were largely ineffective in even reducing serial correlation in short-TR data. In contrast, IDAR significantly outperformed conventional methods in addressing serial correlation, power, and Type-I error for both long-TR and especially short-TR data. However, IDAR could not simultaneously address residual correlations and inflated Type-I error effectively.

Discussion

This study highlights the urgent need to address the problem of serial correlation in short-TR (< 1 s) fMRI data, which are increasingly used in the field. Although IDAR can address this issue for a wide range of applications and datasets, the complexity of short-TR data necessitates continued exploration and innovative approaches. These efforts are essential to simultaneously reduce serial correlations and control Type-I error rates without compromising analytical power.
Unveiling the therapeutic potential of airpotato yam rhizome against colorectal cancer: a network pharmacology approach
Authors: Xie Yiwen , Xu Sumei , Chen Zhiyun , Song Caiping , Yan Wenxi
Published: August 2024

Objective

The objective of this investigation was to elucidate the key active compounds and molecular mechanisms underlying the therapeutic potential of airpotato yam rhizome (AYR) in colorectal cancer (CRC) treatment.

Methods

By utilizing network pharmacology and molecular docking, key targets and signaling pathways of AYR against CRC were predicted and subsequently validated in cellular and mouse xenograft models.

Results

This study initially predicted that quercetin was the primary compound in AYR that might have potential efficacy against CRC and that EGFR and AKT1 could be the main targets of AYR, with the EGF/EGFR-induced PI3K/AKT signaling pathway potentially playing a crucial role in the anti-CRC effects of AYR. Molecular docking analysis further indicated a strong binding affinity between quercetin and EGFR, primarily through hydrogen bonds. Additionally, the AYR-derived drug-containing serum was found to inhibit the PI3K/AKT signaling pathway, as demonstrated by decreased levels of p-PI3K, p-AKT, and BCL2, which ultimately led to enhanced apoptosis of HCT116 and HT29 cells. The potential antitumor effects of AYR were investigated in nude mouse xenograft models of human HCT116 and HT29 cells, in which AYR was found to induce tumor cell apoptosis and inhibit tumor formation.

Conclusion

AYR may promote CRC cell apoptosis by suppressing the PI3K/AKT signaling pathway, which provides a basis for further research on the safe and effective use of AYR for the treatment of CRC.
Case report: Germline POT1 mutation in a patient with GIST and lung adenocarcinoma
Authors: Martino Stefania , De Summa Simona , Pilato Brunella , Digennaro Maria , Laera Letizia , Tommasi Stefania , Patruno Margherita
Published: August 2024

The gene protection of telomere 1 (POT1) is involved in telomere maintenance and stability and plays a crucial role in the preservation of genomic stability. POT1 is considered a high-penetrance melanoma susceptibility gene; however, the number of cancer types associated with the pathogenic germline variants of POT1 is gradually increasing, including chronic lymphocytic leukemia (CLL), angiosarcomas, and gliomas, even though many associations are still elusive. Here, we reported a case of a 60-year-old man who showed early-onset multiple neoplasms, including multiple melanomas, gastrointestinal stromal tumor (GIST), and lung adenocarcinoma. Next-generation sequencing (NGS) analyses revealed a germline heterozygous pathogenic variant in the POT1 gene. Notably, GIST and lung adenocarcinoma were not previously reported in association with the POT1 germline variant. Lung cancer susceptibility syndrome is very rare and the actual knowledge is limited to a few genes although major genetic factors are unidentified. Recently, genome-wide association studies (GWAS) have pointed out an association between POT1 variants and lung cancer. This case report highlights the clinical relevance of POT1 alterations, particularly their potential involvement in lung cancer. It also suggests that POT1 testing may be warranted in patients with familial cancer syndrome, particularly those with a history of melanoma and other solid tumors.
Perceived social support and quality of life in endometrial cancer patients: a longitudinal study
Authors: Mandato Vincenzo Dario , Paterlini Marcella , Torricelli Federica , Rabitti Elisa , Mastrofilippo Valentina , Aguzzoli Lorenzo
Published: August 2024

Objective

This study aimed to assess the influence of medical history, perceived physician-patient communication, and perceived social support on changes in the quality of life (QoL) during the first year of follow-up in patients undergoing surgery for endometrial cancer (EC), the most prevalent gynecological cancer in Western countries, especially in Central and Eastern Europe and North America.

Methods

This prospective longitudinal study included 98 EC patients. All participants completed the Short Form 36 (SF-36) and the Multidimensional Scale of Perceived Social Support (MSPSS) one month and one year after surgery. Additionally, one month after surgery, they responded to a questionnaire designed by the researchers concerning the key aspects of physician-patient communication.

Results

Our findings revealed that patients reporting high social support one month after surgery demonstrated significantly improved emotional well-being (EWB) at both one month and one year after the surgery, with statistically significant higher scores in the dimension of EWB (p<0.05). The support from a significant other at one year correlates with greater PF (p<0.005), fewer limitations due to physical health (p<0.05), less pain (p<0.05), less fatigue (p<0.05), and better general and EWB (p<0.05).

Conclusion

This study underscores the significance of perceived social support for patients cross endometrial cancer. The multifaceted nature of social support, encompassing emotional assistance and information sharing, emerges as a pivotal factor aiding patients in confronting the challenges inherent to EC. This form of support contributes to bolstering psychological well-being and enhancing overall QoL.
Using a collaborative learning health system approach to improve disease activity outcomes in children with juvenile idiopathic arthritis in the Pediatric Rheumatology Care and Outcomes Improvement Network
Authors: Harris Julia G. , Bingham Catherine A. , Vora Sheetal S. , Yildirim-Toruner Cagri , Batthish Michelle , Bullock Danielle R. , Burnham Jon M. , Fair Danielle C. , Ferraro Kerry , Ganguli Suhas , Gilbert Mileka , Gottlieb Beth S. , Halyabar Olha , Hazen Melissa M. , Laxer Ronald M. , Lee Tzielan C. , Liu Alice , Lovell Daniel J. , Mannion Melissa L. , Oberle Edward J. , Pan Nancy , Shishov Michael , Weiss Jennifer E. , Morgan Esi M.
Published: August 2024

Introduction

The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023.

Methods

Twenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care.

Results

Five outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6.

Conclusions

PR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.
Intranasal dexmedetomidine reduces pain scores in preterm infants during retinopathy of prematurity screening
Authors: Ozkan Zarif Nurten , Arayici Sema , Celik Kiymet , Kihtir Zeynep , Ongun Hakan
Published: August 2024

Background

This study aimed to investigate the effectiveness of intranasal dexmedetomidine in reducing pain scores during retinopathy of prematurity (ROP) screening examinations in preterm infants.

Methods

Infants born at ≤32 weeks of gestational age, undergoing routine ROP examinations in the neonatal intensive care unit, were included in the study and divided into two groups: the standard protocol group (n = 43) and the dexmedetomidine group (n = 56), over a 1-year period. Both groups received standard procedural preparation including swaddling, oral dextrose, and topical anesthesia with proparacaine. The dexmedetomidine group additionally received intranasal dexmedetomidine at a dose of 1 mcg/kg before the procedure. Pain scores (PIPP score), heart rate, respiratory rate, blood pressure, and oxygen saturation were compared at baseline, 1-min, and 5-min during the procedure.

Results

There were no significant differences between the groups regarding descriptive and pre-procedure characteristics. In the dexmedetomidine group, the median (25-75p) PIPP score, heart rate, systolic blood pressure and mean (±SD) respiratory rate measured at the 1st minute of the procedure were significantly lower than those in the standard group [PIPP score 10 (8–13) vs. 14 (10–16), p < 0.001; heart rate 165 (153–176) beats/min vs. 182 (17–190) beats/min, p < 0.001; respiratory rate 60 (±7) breaths/min vs. 65(±9) breaths/min, p = 0.002; systolic blood pressure 78 (70–92) mmHg vs. 87 (78–96) mmHg, p = 0.024; respectively] whereas the saturation value was significantly higher (88% (81–95) vs. 84% (70–92), p = 0.036; respectively). By the 5th minute of the procedure, the median (25-75p) PIPP score [4 (2–6) vs. 6 (4–10), p < 0.001], heart rate [148 (143–166) beats/min vs. 162 (152–180) beats/min, p = 0.001] and respiratory rate [56 (54–58) breaths/min vs. 58 (54–62) breaths/min, p = 0.034] were significantly lower, and the saturation level was significantly higher [96% (94–97) vs. 93% (91–96), p = 0.003] in the dexmedetomidine group. Additionally, the frequency of adverse effects was significantly lower in the dexmedetomidine group compared to the standard protocol group (11% vs. 47%, p = 0.001).

Conclusion

Administering intranasal dexmedetomidine before ROP screening examinations was associated with a decrease in pain scores among preterm infants. This suggests its potential as an effective and well-tolerated method for pain management during ROP screenings.
Therapeutic effect of Sheng Mai San, a traditional Chinese medicine formula, on inflammatory bowel disease via inhibition of NF-κB and NLRP3 inflammasome signaling
Authors: Lee Magnolia Muk-Lan , Chan Brandon Dow , Ng Yuen-Wa , Leung Tsz-Wing , Shum Tan-Yu , Lou Jian-Shu , Wong Wing-Yan , Tai William Chi-Shing
Published: August 2024

Introduction

Inflammatory bowel disease (IBD) is a globally emergent chronic inflammatory disease which commonly requires lifelong care. To date, there remains a pressing need for the discovery of novel anti-inflammatory therapeutic agents against this disease. Sheng Mai San (SMS) is a traditional Chinese medicine prescription with a long history of use for treating Qi and Yin deficiency and recent studies have shown that SMS exhibits anti-inflammatory potential. However, the effects of SMS on the gastrointestinal system remain poorly studied, and its therapeutic potential and underlying molecular mechanisms in IBD have yet to be discovered. In this study, we examined the therapeutic efficacy of SMS in IBD and its anti-inflammatory activity and underlying molecular mechanism, in vivo and in vitro.

Methods

The therapeutic efficacy of SMS in IBD was assessed in the DSS-induced acute colitis mouse model. Body weight, stool consistency, rectal bleeding, colon length, organ coefficient, cytokine levels in colon tissues, infiltration of immune cells, and colon pathology were evaluated. The anti-inflammatory activity of SMS and related molecular mechanisms were further examined in lipopolysaccharide (LPS)-induced macrophages via assessment of pro-inflammatory cytokine secretion and NF-κB, MAPK, STAT3, and NLRP3 signalling.

Results

SMS significantly ameliorated the severity of disease in acute colitis mice, as evidenced by an improvement in disease activity index, colon morphology, and histological damage. Additionally, SMS reduced pro-inflammatory cytokine production and infiltration of immune cells in colon tissues. Furthermore, in LPS-induced macrophages, we demonstrated that SMS significantly inhibited the production of cytokines and suppressed the activation of multiple pro-inflammatory signalling pathways, including NF-κB, MAPK, and STAT3. SMS also abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion, suggesting a new therapeutic target for the treatment of IBD. These mechanistic findings were also confirmed in in vivo assays.

Conclusion

This study presents the anti-inflammatory activity and detailed molecular mechanism of SMS, in vitro and in vivo. Importantly, we highlight for the first time the potential of SMS as an effective therapeutic agent against IBD.
Artificial intelligence integration in the drug lifecycle and in regulatory science: policy implications, challenges and opportunities
Authors: Oualikene-Gonin Wahiba , Jaulent Marie-Christine , Thierry Jean-Pierre , Oliveira-Martins Sofia , Belgodère Laetitia , Maison Patrick , Ankri Joël ,   The Scientific Advisory Board of ANSM
Published: August 2024

Artificial intelligence tools promise transformative impacts in drug development. Regulatory agencies face challenges in integrating AI while ensuring reliability and safety in clinical trial approvals, drug marketing authorizations, and post-market surveillance. Incorporating these technologies into the existing regulatory framework and agency practices poses notable challenges, particularly in evaluating the data and models employed for these purposes. Rapid adaptation of regulations and internal processes is essential for agencies to keep pace with innovation, though achieving this requires collective stakeholder collaboration. This article thus delves into the need for adaptations of regulations throughout the drug development lifecycle, as well as the utilization of AI within internal processes of medicine agencies.
A phantom for 2D dose measurements in the vicinity of metal implants for photon and proton beams
Authors: Lechner Wolfgang , Knäusl Barbara , Brunner Jacob , Georg Dietmar , Kuess Peter
Published: August 2024

This work aimed to characterize a dedicated phantom for assessing the dose near metal implants for radiotherapy with photons and protons. A dosimetry audit phantom was redesigned to position a Gafchromic EBT-3 film within a bisected titanium pedicle screw (6.5 mm diameter). The mass density and the water equivalent thickness (WET) of the phantom material were determined. The phantom was irradiated using a photon arc and a horizontal proton beam in combination with a couch rotation of 20°, with three repeated measurements each. Treatment plans utilizing a single field covering the screw and the EBT-3 film were optimized to deliver a physical dose of 2 Gy using a collapsed cone and Monte Carlo dose engine for photons and protons, respectively. The mass density and the WET of the phantom were determined as (1.033 ± 0.010) gcm−3 and (1.022 ± 0.013), respectively. Ionisation chamber measurements agreed within 1% (photons) and 0.5% (protons) with the calculated dose values. Relative photon dosimetry measurements using EBT-3 films revealed an agreement between measured and calculated horizontal profiles within the confidence interval for areas beyond 5 mm from the center. For photon plans, significant deviations of more than 10% were found at the interfaces between phantom material and screw. The proton measurements showed a gradual decrease of 3% across both profiles. In contrast to photon plans, no dose increase was measured within the screw, but significant dose fluctuations (>5%) in the beam’s exit region. This study showed that the behavior of dose engine is affected by metal implants and thus dosimetric measurements are highly recommended. The presented phantom can serve as foundation for dedicated end-2-end phantoms.