bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive analysis on the safety of two biologics dupilumab and omalizumab
Authors: Xiao Yu , Yang Wanying , Wang Muyang
Published: August 2024

Dupilumab was approved for the treatment of several dermatologic immune-mediated inflammatory diseases, such as atopic dermatitis and bullous pemphigoid; whereas omalizumab is the first biological agent which was approved to treat chronic spontaneous urticaria. None of the published meta-analyses has provided the sufficient data regarding the safety of these two biologics, especially regarding their potential serious adverse events (SAEs). The aim of this study was, to comprehensively evaluate the safety of the two biologics dupilumab and omalizumab. In this study, we included 32 randomized trials, and performed meta-analyses on 113 types of SAEs regarding dupilumab and 61 types of SAEs regarding omalizumab. We identified that: (1) use of dupilumab was significantly associated with the lower incidence of atopic dermatitis, while use of omalizumab was significantly associated with the lower incidence of asthma; and (2) use of dupilumab was not significantly associated with the incidences of 112 other kinds of SAEs including various infectious diseases, while use of omalizumab was not significantly associated with the incidences of 60 other kinds of SAEs including various infectious diseases. This meta-analysis for the first time assessed the association between use of dupilumab or omalizumab and incidences of various SAEs, and identified that neither dupilumab use nor omalizumab use was associated with the increased risks of any SAEs including various infectious diseases. These findings further confirm the general safety of the two biologics dupilumab and omalizumab. This informs clinicians that there is no need to worry too much about the safety issues of these two biologics.
The microwave bacteriome: biodiversity of domestic and laboratory microwave ovens
Authors: Iglesias Alba , Martínez Lorena , Torrent Daniel , Porcar Manuel
Published: August 2024

Microwaves have become an essential part of the modern kitchen, but their potential as a reservoir for bacterial colonization and the microbial composition within them remain largely unexplored. In this study, we investigated the bacterial communities in microwave ovens and compared the microbial composition of domestic microwaves, microwaves used in shared large spaces, and laboratory microwaves, using next-generation sequencing and culturing techniques. The microwave oven bacterial population was dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes, similar to the bacterial composition of human skin. Comparison with other environments revealed that the bacterial composition of domestic microwaves was similar to that of kitchen surfaces, whereas laboratory microwaves had a higher abundance of taxa known for their ability to withstand microwave radiation, high temperatures and desiccation. These results suggest that different selective pressures, such as human contact, nutrient availability and radiation levels, may explain the differences observed between domestic and laboratory microwaves. Overall, this study provides valuable insights into microwave ovens bacterial communities and their potential biotechnological applications.
Survey of the fecal microbiota of indigenous small ruminants living in different areas of Guizhou
Authors: Guo Wei , Liu Tingmei , Wang Weiwei , Yu Yinshu , Neves André Luis Alves , Zhou Mi , Chen Xiang
Published: August 2024

Introduction

Gut microbiota are associated with the health and performance of ruminant species, and they are affected by altitude, host genetics, and sex. However, there has been little research on comparing the fecal microbiota of indigenous small ruminants such as sheep and goats in Guizhou province, China. In the present study, we revealed the effect of altitude, genetics, and sex on fecal microbiota profiles and enterotypes in indigenous small ruminants of Guizhou province, China.

Methods

Fecal samples were collected from Hei and Qianbei Ma goats and Weining sheep in the Chinese province of Guizhou. 16S rRNA gene sequencing targeting the V3–V4 region was performed using the Illumina MiSeq platform. Sequences were processed using QIIME2, and the qualified sequences were processed using the plugin DADA2 to generate amplicon sequence variants (ASVs). The statistical analysis was performed using R studio.

Results

The fecal microbial profile was found to vary by herd (influenced by genetics/altitude) and sex. All samples were categorized into two enterotypes. The first enterotype is dominated by UCG-005, and the second enterotype is dominated by the Christensenellaceae_R-7_group, which may be highly driven by the host's genetics (breed). The predicted functional profiles of the fecal microbiota were also assigned to two clusters that corresponded exactly to the enterotypes. Cluster 1 of the functional profiling was characterized by biosynthesis pathways, and cluster 2 was characterized by energy metabolism pathways.

Discussion

Our findings may provide new insights into the fecal microbial community and enterotypes in small ruminants by herds, offering clues for understanding the mechanisms by which the fecal microbiota contribute to divergent host phenotypes in indigenous small ruminants in Guizhou.
Trichoderma and Bacillus multifunctional allies for plant growth and health in saline soils: recent advances and future challenges
Authors: Santoyo Gustavo , Orozco-Mosqueda Ma. del Carmen , Afridi Muhammad Siddique , Mitra Debasis , Valencia-Cantero Eduardo , Macías-Rodríguez Lourdes
Published: August 2024

Saline soils pose significant challenges to global agricultural productivity, hindering crop growth and efficiency. Despite various mitigation strategies, the issue persists, underscoring the need for innovative and sustainable solutions. One promising approach involves leveraging microorganisms and their plant interactions to reclaim saline soils and bolster crop yields. This review highlights pioneering and recent advancements in utilizing multi-traits Trichoderma and Bacillus species as potent promoters of plant growth and health. It examines the multifaceted impacts of saline stress on plants and microbes, elucidating their physiological and molecular responses. Additionally, it delves into the role of ACC deaminase in mitigating plant ethylene levels by Trichoderma and Bacillus species. Although there are several studies on Trichoderma-Bacillus, much remains to be understood about their synergistic relationships and their potential as auxiliaries in the phytoremediation of saline soils, which is why this work addresses these challenges.
Licorice processing involving functions of Evodiae Fructus on liver inflammation and oxidative stress are associated with intestinal mucosal microbiota
Authors: Liang Xuejuan , Tian Qixue , Chen Linglong , Zhang Yanbing , Peng Yanmei
Published: August 2024

Background

This study aimed to investigate the effects of licorice processing of different Evodiae Fructus (EF) specifications on liver inflammation and oxidative stress associated with the intestinal mucosal microbiota.

Materials and methods

The 25 Kunming mice were divided into control (MCN), raw small-flowered Evodiae Fructus (MRSEF), raw medium-flowered EF (MRMEF), licorice-processed small-flowered EF (MLSEF), and licorice-processed medium-flowered EF (MLSEF) groups. The EF intervention groups were given different specifications of EF extract solutions by gavage. After 21 days, indices of liver inflammation and oxidative stress and intestinal mucosal microbiota were measured in mice.

Results

Compared with the MCN, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were significantly increased in the MRMEF. Although the trends of oxidative stress and inflammatory indexes in the MLSEF and MLMEF were consistent with those in the raw EF groups, the changes were smaller than those in the raw EF groups. Compared to the raw EF groups, the MLSEF and MLMEF showed closer approximations of metabolic function to the MCN. The abundance of Corynebacterium in MRMEF was significantly lower than that in the MCN, and it was not significantly different from the MCN after licorice processing. The probiotic Candidatus Arthromitus was enriched in the MLSEF. The probiotic Lactobacillus was enriched in the MLMEF. Correlation analysis revealed significant negative correlations between IL-1β, some metabolic functions and Corynebacterium.

Conclusion

The effects of medium-flowered EF on oxidative stress and inflammatory factors in the liver of mice were stronger than those of small-flowered EF. The licorice processing can reduce this difference by modulating the abundance of Corynebacterium and intestinal mucosal metabolic function.
A novel mitochondria-related algorithm for predicting the survival outcomes and drug sensitivity of patients with lung adenocarcinoma
Authors: Wu Xianqiao , Chen Hang , Ge Zhen , Luo Binyu , Pan Hanbo , Shen Yiming , Xie Zuorun , Zhou Chengwei
Published: August 2024

Background

Mitochondria have always been considered too be closely related to the occurrence and development of malignant tumors. However, the bioinformatic analysis of mitochondria in lung adenocarcinoma (LUAD) has not been reported yet.

Methods

In the present study, we constructed a novel and reliable algorithm, comprising a consensus cluster analysis and risk assessment model, to predict the survival outcomes and tumor immunity for patients with terminal LUAD.

Results

Patients with LUAD were classified into three clusters, and patients in cluster 1 exhibited the best survival outcomes. The patients in cluster 3 had the highest expression of PDL1 (encoding programmed cell death 1 ligand 11) and HAVCR2 (encoding Hepatitis A virus cellular receptor 2), and the highest tumor mutation burden (TMB). In the risk assessment model, patients in the low-risk group tended to have a significantly better survival outcome. Furthermore, the risk score combined with stage could act as a reliable independent prognostic indicator for patients with LUAD. The prognostic signature is a novel and effective biomarker to select anti-tumor drugs. Low-risk patients tended to have a higher expression of CTLA4 (encoding cytotoxic T-lymphocyte associated protein 4) and HAVCR2. Moreover, patients in the high-risk group were more sensitive to Cisplatin, Docetaxel, Erlotinib, Gemcitabine, and Paclitaxel, while low-risk patients would probably benefit more from Gefitinib.

Conclusion

We constructed a novel and reliable algorithm comprising a consensus cluster analysis and risk assessment model to predict survival outcomes, which functions as a reliable guideline for anti-tumor drug treatment for patients with terminal LUAD.
The aryl hydrocarbon receptor pathway: a linking bridge between the gut microbiome and neurodegenerative diseases
Authors: Coretti Lorena , Buommino Elisabetta , Lembo Francesca
Published: August 2024

The Aryl hydrocarbon receptor (AHR) is a cytosolic receptor and ligand-activated transcription factor widely expressed across various cell types in the body. Its signaling is vital for host responses at barrier sites, regulating epithelial renewal, barrier integrity, and the activities of several types of immune cells. This makes AHR essential for various cellular responses during aging, especially those governing inflammation and immunity. In this review, we provided an overview of the mechanisms by which the AHR mediates inflammatory response at gut and brain level through signals from intestinal microbes. The age-related reduction of gut microbiota functions is perceived as a trigger of aberrant immune responses linking gut and brain inflammation to neurodegeneration. Thus, we explored gut microbiome impact on the nature and availability of AHR ligands and outcomes for several signaling pathways involved in neurodegenerative diseases and age-associated decline of brain functions, with an insight on Parkinson’s and Alzheimer’s diseases, the most common neurodegenerative diseases in the elderly. Specifically, we focused on microbial tryptophan catabolism responsible for the production of several AHR ligands. Perspectives for the development of microbiota-based interventions targeting AHR activity are presented for a healthy aging.
Physical exercise for brain plasticity promotion an overview of the underlying oscillatory mechanism
Authors: Li Xueyang , Qu Xuehong , Shi Kaixuan , Yang Yichen , Sun Jizhe
Published: August 2024

The global recognition of the importance of physical exercise (PE) for human health has resulted in increased research on its effects on cortical activity. Neural oscillations, which are prominent features of brain activity, serve as crucial indicators for studying the effects of PE on brain function. Existing studies support the idea that PE modifies various types of neural oscillations. While EEG-related literature in exercise science exists, a comprehensive review of the effects of exercise specifically in healthy populations has not yet been conducted. Given the demonstrated influence of exercise on neural plasticity, particularly cortical oscillatory activity, it is imperative to consolidate research on this phenomenon. Therefore, this review aims to summarize numerous PE studies on neuromodulatory mechanisms in the brain over the past decade, covering (1) effects of resistance and aerobic training on brain health via neural oscillations; (2) how mind-body exercise affects human neural activity and cognitive functioning; (3) age-Related effects of PE on brain health and neurodegenerative disease rehabilitation via neural oscillation mechanisms; and (4) conclusion and future direction. In conclusion, the effect of PE on cortical activity is a multifaceted process, and this review seeks to comprehensively examine and summarize existing studies' understanding of how PE regulates neural activity in the brain, providing a more scientific theoretical foundation for the development of personalized PE programs and further research.
Clinical concentration of sevoflurane had no short-term effect on the myelin sheath in prefrontal cortex of aged marmosets
Authors: Miao Zhengjie , Jiang Yi , Wang Fangfang , Shi Lingling , Zhou Ren , Niu Yixuan , Zhang Lei
Published: August 2024

Introduction

The fragile brain includes both the developing brain in childhood and the deteriorating brain in elderly. While the effects of general anesthesia on the myelin sheath of developing brain have been well-documented, limited research has explored its impact on degenerating brain in elderly individuals.

Methods

In our study, aged marmosets in control group were only anesthetized with 6–8% sevoflurane and 100% oxygen (2 L/min) for 1–2 min for anesthesia induction. In addition to anesthesia induction, the anesthesia group was exposed to a clinical concentration of sevoflurane (1.5–2%) for 6 h to maintain anesthesia. After anesthesia, scanning electron microscopy (SEM) and artificial intelligence-assisted image analysis were utilized to observe the effects of general anesthesia on the myelin sheath in prefrontal cortex (PFC) of aged marmosets.

Results

Compared with the control group, our findings revealed no evidence that 6 h of sevoflurane general anesthesia altered the thickness of myelin sheath, the diameter of myelinated axons, and the g-ratio in prefrontal cortex of aged marmosets.

Conclusion

Clinical concentration of sevoflurane may have no short-term effect on the myelin sheath in prefrontal cortex of aged marmosets.
How psychological ownership over nutritional products affects purchase intentions of high-pressure working groups
Authors: Liang Boyu , Yang Dajun , Tan Fuqiang , Sun Dajun , Li Jianshu
Published: August 2024

This study aims to investigate the influence of psychological ownership of nutritional products on the purchase intention of high-pressure working groups, as well as the underlying mechanisms and boundary conditions of this influence. This study aims to investigate the impact of psychological ownership of nutritional products on the purchase intention of high-pressure working groups, as well as the underlying mechanisms and boundary conditions of this influence. The research contributes through the use of variance analysis, mediation models, and moderation models on data from adult participants over the age of 18, across three experiments. Experiment 1, conducted on the Credamo platform, randomly recruited 285 participants, with 148 males (51.9%) and 137 females (48.1%), and the results indicated a direct impact of psychological ownership on purchase intention. Building upon this, Experiment 2, which also utilized the Credamo platform and recruited 280 participants consisting of 136 males (48.6%) and 144 females (51.4%), further revealed the mediating role of perceived value. Experiment 3, with 265 participants randomly recruited on the Credamo platform, including 131 males (49.4%) and 134 females (50.6%), identified the moderating effect of nutritional awareness. The theoretical contribution of this study lies primarily in its in-depth exploration of the impact of psychological ownership of nutritional products. By integrating the factors of perceived value and nutritional awareness, it provides a systematic explanation for better understanding the purchase intentions of high-pressure working groups. Additionally, this study offers valuable strategies for merchants to enhance the purchase intentions of high-pressure living groups.
Crosstalk between breast cancer-derived microRNAs and brain microenvironmental cells in breast cancer brain metastasis
Authors: Khan Munazza S. , Wong Grace L. , Zhuang Chuling , Najjar Mariana K. , Lo Hui-Wen
Published: August 2024

Breast cancer is the most frequent malignancy in women, constituting 15.2% of all new cancers diagnosed in the United States. Distant breast cancer metastasis accounts for the majority of breast cancer-related deaths; brain metastasis is the third most common site for metastatic breast cancer but is associated with worst prognosis of approximately eight months of survival. Current treatment options for breast cancer brain metastasis (BCBM) are limited and ineffective. To help identify new and effective therapies for BCBM, it is important to investigate the mechanisms by which breast cancer cells metastasize to the brain and thrive in the brain microenvironment. To this end, studies have reported that primary breast tumor cells can prime brain microenvironmental cells, including, astrocytes and microglia, to promote the formation of BCBM through the release of extracellular vesicle-microRNAs (miRNAs). Breast tumor-derived miRNAs can also promote breast cancer cell invasion through the blood-brain barrier by disrupting the integrity of the brain microvascular endothelial cells. In this review, we summarize current literature on breast cancer-derived BCBM-promoting miRNAs, cover their roles in the complex steps of BCBM particularly their interactions with microenvironmental cells within the brain metastatic niche, and finally discuss their therapeutic applications in the management of BCBM.
Case Report: Plummer's adenoma in Prader–Willi syndrome
Authors: Corica Domenico , Toscano Fabio , Moleti Mariacarla , Pepe Giorgia , Campenni Alfredo , Fadda Guido , Dionigi Gianlorenzo , Romeo Carmelo , Aversa Tommaso , Wasniewska Malgorzata
Published: August 2024

Thyroid nodules in children are less common than in adults but they are approximately two- to three-fold more likely to be malignant in children. Among thyroid nodular diseases, Plummer's adenoma occurs very rarely in pediatrics, and currently, there is no literature providing evidence of this diagnosis in patients with Prader–Willi syndrome (PWS). We report the case of a 9-year-old Caucasian boy affected by PWS presenting with a rapidly growing palpable mass in the thyroid lodge associated with subclinical hyperthyroidism. Laboratory and other examinations (thyroid ultrasound, fine-needle aspiration of the nodule, and scintigraphy) were strongly suggestive for Plummer's adenoma; therefore, the patient underwent left hemithyroidectomy surgery, and anatomo-pathological examination confirmed the diagnosis. Our case describes the first evidence of an isolated follicular adenoma in children with PWS. Surgery is the only therapeutic option in younger children. Further evidence is needed to assess the possible correlation between these two conditions and the existence of potential risk factors.
Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids
Authors: Jäger Marie-Christin , González-Ruiz Víctor , Joos Friedrich L. , Winter Denise V. , Boccard Julien , Degenhardt Thorsten , Brand Steve , Rudaz Serge , Thompson George R. , Odermatt Alex
Published: August 2024

The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia, edema, and gynecomastia by inhibiting steroid synthesis and metabolism. Mechanisms underlying pseudohyperaldosteronism include inhibition of adrenal 11β-hydroxylase cytochrome-P450 (CYP) 11B1 and 17α-hydroxylase (CYP17A1) as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazoles have been developed. This study employed H295R adrenocortical cells and enzyme activity assays to assess the potential risk of oteseconazole and two other tetrazoles, VT-1598 and quilseconazole, to inhibit adrenal steroidogenesis or 11β-HSD2. Steroidomic footprint analyses of H295R cell supernatants using untargeted liquid-chromatography-high-resolution mass-spectrometry (LC-HRMS) indicated overall patterns common to oteseconazole, quilseconazole and itraconazole, as well as similarities between VT-1598 and isavuconazole. Additionally, more specific features of the steroid signatures were observed. Targeted quantification of nine adrenal steroids in supernatants from treated H295R cells revealed an overall inhibition of adrenal steroidogenesis by the three tetrazoles, itraconazole and isavuconazole, providing an explanation for their similar steroidomic pattern. Applying recombinant enzymes indicated that this effect is not due to direct inhibition of steroidogenic enzymes because no or only weak inhibition could be observed. Moreover, oteseconazole and the two other tetrazoles did not inhibit 11β-HSD2, suggesting that they do not pose a risk of pseudohyperaldosteronism. Furthermore, oteseconazole did not alter steroid concentrations in a recent clinical study. Nevertheless, follow-up studies should assess the mechanism underlying the observed overall steroidogenesis inhibition by tetrazoles, itraconazole and isavuconazole, and whether concentrations achievable in a subgroup of susceptible patients might cause adrenal insufficiency and hyperplasia.
Pioglitazone treatment mitigates cardiovascular bioprosthetic degeneration in a chronic kidney disease model
Authors: Katahira Shintaro , Barth Mareike , Döpp Robin , Sugimura Yukiharu , Schmidt Vera , Selig Jessica Isabel , Saiki Yoshikatsu , Jankowski Joachim , Marx Nikolaus , Jahnen-Dechent Willi , Lichtenberg Artur , Akhyari Payam
Published: August 2024

Aims

Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular diseases, e.g., atherosclerosis and calcific aortic valve disease, leading inevitably to valve replacement surgery. CKD patients with bioprosthetic cardiovascular grafts, in turn, have a higher risk of premature graft degeneration. Peroxisome proliferator-activated receptor gamma (PPARγ) activation by pioglitazone has cardio-renal protective properties, and research using a heterotopic valve implantation model has shown anti-degenerative effects of PPARγ activation on bioprosthetic valved grafts (BVG) in rats. The present work aims to analyze a potential protective effect of pioglitazone treatment on BVG in an adenine-induced rat model of CKD.

Methods and Results

BVG of Sprague Dawley rats were heterotopically implanted in Wistar rats in an infrarenal position for 4 and 8 weeks. Animals were distributed into three groups for each time point: 1) control group receiving standard chow, 2) CKD group receiving 0.25% adenine and 3) CKD + pioglitazone group (300 mg per kg of 0.25% adenine chow). BVG function was analyzed by echocardiography. Plasma analytes were determined and explanted grafts were analyzed by semi-quantitative real-time PCR, Western blot analysis, histology and immunohistology.

PPARγ activation significantly reduced CKD-induced calcification of aortic and valvular segments of BVG by 44% and 53%, respectively. Pioglitazone treatment significantly also reduced CKD-induced intima hyperplasia by 60%. Plasma analysis revealed significantly attenuated potassium and phosphate levels after pioglitazone treatment. Moreover, PPARγ activation led to significantly decreased interleukin-6 gene expression (by 57%) in BVG compared to CKD animals. Pioglitazone treatment leads to functional improvement of BVG.

Conclusion

This study broadens the understanding of the potential value of PPARγ activation in cardio-renal diseases and delineates pioglitazone treatment as a valuable option to prevent bioprosthetic graft failure in CKD. Further mechanistic studies, e.g., using small molecules activating PPARγ signaling pathways, are necessary for the evaluation of involved mechanisms. Additionally, the translation into pre-clinical studies using large animals is intended as the next research project.
Multidimensional role of adapalene in regulating cell death in multiple myeloma
Authors: Cao Xinya , Xiang Jie , Zhang Qi , Liu Jinwen , Zhou Dongming , Xu Yong , Xu Peipei , Chen Bing , Bai Hua
Published: August 2024

Aims

Multiple myeloma (MM) remains a challenging condition to cure, with persistent drug resistance negating the benefits of treatment advancements. The unraveling complexities in programmed cell death (PCD), inclusive of apoptosis, autophagy, and ferroptosis, have highlighted novel therapeutic avenues. Our study focuses on deciphering how adapalene (ADA), a small molecule compound, accelerates the demise of MM cells via targeting their compensatory survival mechanisms.

Methods

To assess the impact of ADA on MM, we employed flow cytometry and trypan blue exclusion assays to determine cell viabilities across MM cell lines and primary patient samples post-treatment. To delineate ADA’s therapeutic targets and mechanisms, we conducted RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), molecular docking, and molecular dynamics simulations. We further designed pre-clinical trials emphasizing MM, exploring the efficacy of ADA as a standalone and in combination with bortezomib (BTZ).

Results

ADA elicited a dose-responsive induction of MM cell death. Building upon ADA’s anti-MM capabilities as a single agent, we proposed that ADA-BTZ co-treatment might amplify this lethality. Indeed, ADA and BTZ together greatly potentiated MM cell death. ADA proved beneficial in restoring BTZ susceptibility in BTZ-resistant relapsed or refractory MM (RRMM) patient cells. Molecular simulations highlighted ADA’s high affinity (−9.17 kcal/mol) for CD138, with MM-GBSA revealing a binding free energy of −27.39 kcal/mol. Detailed interaction analyses indicated hydrogen-bonding of ADA with CD138 at the Asp35 and Gln34 residues. Additionally, ADA emerged as a versatile instigator of both ferroptosis and apoptosis in MM cells. Furthermore, ADA disrupted activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway triggered by BTZ, fostering cell death in BTZ-resistant MM subsets.

Conclusion

ADA demonstrates a comprehensive capability to orchestrate MM cell death, exerting pronounced anti-MM activity while disrupting NF-κB-related drug resistance. ADA sensitization of MM cells to BTZ unravels its potential as a novel therapeutic drug for MM management.
Long-term effects of mepolizumab in patients with severe eosinophilic asthma: a 6-year real-life experience
Authors: Stanziola Anna Agnese , Candia Claudio , Nazzaro Gerardo , Caso Antonio , Merola Claudia , Gallotti Lorena , Maniscalco Mauro
Published: August 2024

Background

Severe eosinophilic asthma (SEA) is often linked to a dysregulation in the Interleukin-(IL)-5 axis. Mepolizumab, a humanized monoclonal antibody, reduces eosinophils by directly binging to IL-5, potentially restoring homeostatic eosinophil biology, with a significant impact on quality of life, acute exacerbations and oral corticosteroids (OCS) elimination in SEA patients. While its short- and middle-term effects are well described, no study has so far investigated its long-lasting effects in SEA patients. The aim of our study was therefore to explore the effects of a long-term, six-year continuous treatment with mepolizumab on clinical control and clinical remission in a cohort of SEA patients.

Methods

We conducted a retrospective review of clinical records of patients who were prescribed mepolizumab between June 2017 and April 2018. We collected demographical, functional, and clinical data from visits performed at baseline and then at the specified timepoints and checked if patients had reached clinical remission after 6 years. We assessed asthma control test (ACT), exacerbation rate, and OCS elimination dose at 6 years. Clinical Remission (CR) was defined on the basis of the elimination of OCS and the contemporary presence of all the following: 1) stable lung function; 2) no exacerbation in the previous 12 months; 3) acceptable symptom control (ACT ≥ 20).

Results

Of 86 patients screened, 62 were included in the final analysis. Our study suggests that mepolizumab is effective and well tolerated after a six-year course of continuous treatment in patients with SEA. We reported a prevalence of 28 (46.8%) patients who reached complete CR at 72 months from the treatment start. 75% of patients eliminated the maintenance OCS already after 1 year of treatment; this proportion reached the 87% within the sixth year of treatment.

Conclusion

Mepolizumab proved to be effective in real-life after 6 years of treatment, inducing a complete clinical remission in the 46.8% of patients, with sustained improvements in quality of life, exacerbation rate, OCS intake and lung function.
Characterising cerebrovascular reactivity and the pupillary light response–a comparative study
Authors: Sparks Sierra , Hayes Genevieve , Pinto Joana , Bulte Daniel
Published: August 2024

Introduction

Smooth muscle is integral to multiple autonomic systems, including cerebrovascular dynamics through vascular smooth muscle cells and in ocular muscle dynamics, by regulating pupil size. In the brain, smooth muscle function plays a role in cerebrovascular reactivity (CVR) that describes changes in blood vessel calibre in response to vasoactive stimuli. Similarly, pupil size regulation can be measured using the pupillary light response (PLR), the pupil’s reaction to changes in light levels. The primary aim of this study was to explore the interplay between cerebral blood flow and pupil dynamics, evaluated using CVR and PLR, respectively.

Methods

A total of 20 healthy adults took part in a CVR gas stimulus protocol and a light and dark flash PLR protocol. CVR was calculated as the blood flow velocity change in the middle cerebral artery, measured using transcranial Doppler ultrasound in response to a 5% increase in CO2. Multiple PLR metrics were evaluated with a clinical pupillometer.

Results

CVR and PLR metrics were all within the expected physiological ranges for healthy adults. Nine different PLR metrics, assessed through the light and dark flash protocols, were compared against CVR. A significant negative relationship was observed between the latency of the PLR in the dark flash protocol and CVR. No statistically significant relationships were found between CVR and other PLR metrics.

Conclusion

This is the first study to investigate the relationship between cerebral blood flow and pupil dynamics. A significant relationship between dark flash latency and CVR was observed. Future work includes evaluating these relationships using more robust CVR and PLR measurement techniques in a larger, more diverse cohort. Notably, more research is warranted into the PLR using a dark flash protocol and its connection to cerebrovascular function.
Automatic cardiothoracic ratio calculation based on lung fields abstracted from chest X-ray images without heart segmentation
Authors: Yang Yingjian , Zheng Jie , Guo Peng , Wu Tianqi , Gao Qi , Guo Yingwei , Chen Ziran , Liu Chengcheng , Ouyang Zhanglei , Chen Huai , Kang Yan
Published: August 2024

Introduction

The cardiothoracic ratio (CTR) based on postero-anterior chest X-rays (P-A CXR) images is one of the most commonly used cardiac measurement methods and an indicator for initially evaluating cardiac diseases. However, the hearts are not readily observable on P-A CXR images compared to the lung fields. Therefore, radiologists often manually determine the CTR’s right and left heart border points of the adjacent left and right lung fields to the heart based on P-A CXR images. Meanwhile, manual CTR measurement based on the P-A CXR image requires experienced radiologists and is time-consuming and laborious.

Methods

Based on the above, this article proposes a novel, fully automatic CTR calculation method based on lung fields abstracted from the P-A CXR images using convolutional neural networks (CNNs), overcoming the limitations to heart segmentation and avoiding errors in heart segmentation. First, the lung field mask images are abstracted from the P-A CXR images based on the pre-trained CNNs. Second, a novel localization method of the heart’s right and left border points is proposed based on the two-dimensional projection morphology of the lung field mask images using graphics.

Results

The results show that the mean distance errors at the x-axis direction of the CTR’s four key points in the test sets T1 (21 × 512 × 512 static P-A CXR images) and T2 (13 × 512 × 512 dynamic P-A CXR images) based on various pre-trained CNNs are 4.1161 and 3.2116 pixels, respectively. In addition, the mean CTR errors on the test sets T1 and T2 based on four proposed models are 0.0208 and 0.0180, respectively.

Discussion

Our proposed model achieves the equivalent performance of CTR calculation as the previous CardioNet model, overcomes heart segmentation, and takes less time. Therefore, our proposed method is practical and feasible and may become an effective tool for initially evaluating cardiac diseases.
Integrated physiological and metabolomic responses reveal mechanisms of Cd tolerance and detoxification in kenaf (Hibiscus cannabinus L.) under Cd stress
Authors: Saeed Wajid , Mubeen Samavia , Pan Jiao , Rehman Muzammal , Fang Wangqiang , Luo Dengjie , Liu Pingwu , Li Yun , Chen Peng
Published: August 2024

Introduction

Cadmium (Cd) is a highly toxic trace element that occurs in large quantities in agricultural soils. The cultivation of industrial crops with high phytoremediation potential, such as kenaf, could effectively reduce soil Cd contamination, but the mechanisms of toxicity, tolerance, and detoxification remain unclear.

Methods

In this study, the effects of different Cd concentrations (0, 100, 250, and 400 µM) on growth, biomass, Cd uptake, physiological parameters, metabolites and gene expression response of kenaf were investigated in a hydroponic experiment.

Results and discussion

The results showed that Cd stress significantly altered the ability of kenaf to accumulate and transport Cd; increased the activity of hydrogen peroxide (H2O2), superoxide anion (O2−), and malondialdehyde (MDA); reduced the activities of superoxide dismutase (SOD) and catalase (CAT); and decreased the content of photosynthetic pigments, resulting in significant changes in growth and biomass production. Exposure to Cd was found to have a detrimental effect on the ascorbate–glutathione (AsA–GSH) cycle in the roots, whereas it resulted in an elevation in AsA levels and a reduction in GSH levels in the leaves. The increased content of cell wall polysaccharides under Cd stress could contribute to Cd retention in roots and limited Cd transport to above-ground plant tissues. Metabolomic analyses revealed that alanine, aspartate, and glutamate metabolism, oxidative phosphorylation, ABC transporter, and carbon metabolism were the major metabolic pathways associated with Cd stress tolerance. Cd stress increased gene expression of IRT1 and MTP1 in roots, which resulted in kenaf roots accumulating high Cd concentrations. This study extends our knowledge of the factors regulating the response of kenaf to Cd stress. This work provided a physiological and metabolomic perspective on the mechanism controlling the response of kenaf to Cd stress.
The eyes as the exclamation mark of the face: exploring the relationship between eye size, intensity of female facial expressions and attractiveness in a range of emotions
Authors: Esté Jaloveckas Alanís , Granero Roser
Published: August 2024

Background-objective

The eyes play an important role in communicating emotions and shape the determination of other facial attributes. Here, we explored the relationship between eye size, perceived intensity and attractiveness of facial expressions.

Methods

A sample of N = 63 participants (men and women, aged 18–35) rated attractiveness and emotional intensity for images displaying emotionally expressive women’s faces with digitally manipulated eye size (15% smaller, unchanged, or 15% larger).

Results

The analysis of perceived intensity showed an interaction parameter between eye size and gender. Female individuals reported differences when comparing unchanged and larger eyes; male participants showed differences across all eye size comparisons (smaller-unchanged, smaller-larger, unchanged-larger). Regarding perceived attractiveness, faces with smaller eyes registered lower mean scores than both unchanged and larger. The lowest intensity level was associated with neutral faces and the highest with fearful ones. Faces displaying happiness were perceived as the most attractive.

Conclusion

Larger eyes seem to make emotions more intense and attractive. We suggest that the more intense phenomenon serves an evolutive purpose, as it might encourage caretaking behavior.
Evaluating deep learning techniques for identifying tongue features in subthreshold depression: a prospective observational study
Authors: Han Bo , Chang Yue , Tan Rui-rui , Han Chao
Published: August 2024

Objective

This study aims to evaluate the potential of using tongue image features as non-invasive biomarkers for diagnosing subthreshold depression and to assess the correlation between these features and acupuncture treatment outcomes using advanced deep learning models.

Methods

We employed five advanced deep learning models—DenseNet169, MobileNetV3Small, SEResNet101, SqueezeNet, and VGG19_bn—to analyze tongue image features in individuals with subthreshold depression. These models were assessed based on accuracy, precision, recall, and F1 score. Additionally, we investigated the relationship between the best-performing model’s predictions and the success of acupuncture treatment using Pearson’s correlation coefficient.

Results

Among the models, SEResNet101 emerged as the most effective, achieving an impressive 98.5% accuracy and an F1 score of 0.97. A significant positive correlation was found between its predictions and the alleviation of depressive symptoms following acupuncture (Pearson’s correlation coefficient = 0.72, p<0.001).

Conclusion

The findings suggest that the SEResNet101 model is highly accurate and reliable for identifying tongue image features in subthreshold depression. It also appears promising for assessing the impact of acupuncture treatment. This study contributes novel insights and approaches to the auxiliary diagnosis and treatment evaluation of subthreshold depression.
Altered dynamic neural activities in individuals with obsessive-compulsive disorder and comorbid depressive symptoms
Authors: Shang Tinghuizi , Chen Yunhui , Ding Zhenning , Qin Weiqi , Li Shancong , Wei Siyi , Ding Zhipeng , Yang Xu , Qi Jiale , Qin Xiaoqing , Lv Dan , Li Tong , Pan Zan , Zhan Chuang , Xiao Jian , Sun Zhenghai , Wang Na , Yu Zengyan , Li Chengchong , Li Ping
Published: August 2024

Objectives

Depressive symptoms are the most prevalent comorbidity in individuals with obsessive-compulsive disorder (OCD). The objective of this study was to investigate the dynamic characteristics of resting-state neural activities in OCD patients with depressive symptoms.

Methods

We recruited 29 OCD patients with depressive symptoms, 21 OCD patients without depressive symptoms, and 27 healthy controls, and collected data via structural and functional magnetic resonance imaging (fMRI). We analyzed the fMRI results using the dynamic amplitude of low-frequency fluctuation (dALFF) and support vector machine (SVM) techniques.

Results

Compared with OCD patients without depressive symptoms, OCD patients with depressive symptoms exhibited an increased dALFF in the left precuneus and decreased dALFF in the right medial frontal gyrus. The SVM indicated that the integration of aberrant dALFF values in the left precuneus and right medial frontal gyrus led to an overall accuracy of 80%, a sensitivity of 79%, and a specificity of 100% in detecting depressive symptoms among OCD patients.

Conclusion

Therefore, our study reveals that OCD patients with depressive symptoms display neural activities with unique dynamic characteristics in the resting state. Accordingly, abnormal dALFF values in the left precuneus and right medial frontal gyrus could be used to identify depressive symptoms in OCD patients.
Automatic speech analysis for detecting cognitive decline of older adults
Authors: Huang Lihe , Yang Hao , Che Yiran , Yang Jingjing
Published: August 2024

Background

Speech analysis has been expected to help as a screening tool for early detection of Alzheimer’s disease (AD) and mild-cognitively impairment (MCI). Acoustic features and linguistic features are usually used in speech analysis. However, no studies have yet determined which type of features provides better screening effectiveness, especially in the large aging population of China.

Objective

Firstly, to compare the screening effectiveness of acoustic features, linguistic features, and their combination using the same dataset. Secondly, to develop Chinese automated diagnosis model using self-collected natural discourse data obtained from native Chinese speakers.

Methods

A total of 92 participants from communities in Shanghai, completed MoCA-B and a picture description task based on the Cookie Theft under the guidance of trained operators, and were divided into three groups including AD, MCI, and heathy control (HC) based on their MoCA-B score. Acoustic features (Pitches, Jitter, Shimmer, MFCCs, Formants) and linguistic features (part-of-speech, type-token ratio, information words, information units) are extracted. The machine algorithms used in this study included logistic regression, random forest (RF), support vector machines (SVM), Gaussian Naive Bayesian (GNB), and k-Nearest neighbor (kNN). The validation accuracies of the same ML model using acoustic features, linguistic features, and their combination were compared.

Results

The accuracy with linguistic features is generally higher than acoustic features in training. The highest accuracy to differentiate HC and AD is 80.77% achieved by SVM, based on all the features extracted from the speech data, while the highest accuracy to differentiate HC and AD or MCI is 80.43% achieved by RF, based only on linguistic features.

Conclusion

Our results suggest the utility and validity of linguistic features in the automated diagnosis of cognitive impairment, and validated the applicability of automated diagnosis for Chinese language data.
Rotavirus outbreaks in China, 1982–2021: a systematic review
Authors: Tian Yi , Yu Fan , Zhang Guanhua , Tian Chunyu , Wang Xinxin , Chen Yanwei , Yan Hanqiu , Jia Lei , Zhang Daitao , Wang Quanyi , Gao Zhiyong
Published: August 2024

Background

Rotavirus is globally recognized as an important cause of acute gastroenteritis in young children. Whereas previous studies focused more on sporadic diarrhea, the epidemiological characteristics of rotavirus outbreaks have not been systematically understood.

Methods

This systematic review was carried out according to the Preferred Reporting Items for Systematic Review and Meta-Analysis standards, WANFANG, China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science databases were searched from database inception to February 20, 2022. We used SPSS 21.0 statistical software for data analysis, RStudio1.4.1717, and ArcGIS trial version for plotting bar graphs and maps.

Results

Among 1,596 articles, 78 were included, with 92 rotavirus outbreaks and 96,128 cases. Most outbreaks (67.39%, 62/92) occurred in winter and spring. The number of rotavirus outbreaks reported in the eastern region was more than that in the western region. Outbreaks were most commonly reported in villages (33/92, 35.87%), followed by hospitals (19, 20.65%). The outbreak duration was longer in factories and workers’ living places, and villages, while it was shorter in hospitals. Waterborne transmission was the main transmission mode, with the longest duration and the largest number of cases. Rotavirus groups were identified in 66 outbreaks, with 40 outbreaks (60.61%) caused by Group B rotaviruses and 26 outbreaks (39.39%) caused by Group A rotaviruses. Significant differences were found in duration, number of cases, settings, population distribution, and transmission modes between Groups A and B rotavirus outbreaks.

Conclusion

Rotavirus is an important cause of acute gastroenteritis outbreaks in China. It should also be considered in the investigation of acute gastroenteritis outbreaks, especially norovirus-negative outbreaks.
The prevalence of Black/African American individuals in concussion literature: a systematic review and meta-analysis
Authors: MacEachern Taia , John-Baptiste Ava , Christie Anita
Published: August 2024

Introduction

Comprising approximately 13.6% of the United States population, Black/African American individuals are overrepresented in sports associated with a high risk of concussion. However, there has been a notable absence of systematic reviews examining whether concussion literature accurately reflects the participation and experiences of Black/African American individuals. Therefore, this study aims to systematically review the prevalence of Black/African American individuals compared to White individuals diagnosed with concussions in the literature.

Methods

A systematic search was performed across four electronic databases: PubMed, MEDLINE (Ovid), Scopus and Web of Science. Articles were searched from inception to January 5, 2022. Prevalence data were extracted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A meta-analysis of proportions was conducted within hospital records and national survey data.

Results

Among 447 identified studies, 11 were included, representing 1,839,901 individuals diagnosed with a concussion, with 73.6% identifying as White and 12.5% identifying as Black/African American. The mean proportion of Black/African American diagnosed with a concussion in hospital records (13.9%; 95% CI [12.8, 15.1]) exceeded that in national surveys (6.4%; 95% CI [3.5, 11.3]) but lower than sports-centered studies (16%).

Discussion

These findings underscore the need to address racial disparities in healthcare within the broader context of social determinants of health and systemic inequities. By identifying gaps in the current research, this study lays the foundation for future investigation aimed at elucidating and addressing healthcare disparities.