bluuebunny/crossref_metadata_2025 huggingface dataset:
Early re-emerging tremor after MRgFUS thalamotomy: case–control analysis of procedural and imaging features
Authors: Bruno Federico , Badini Pierfrancesco , Innocenzi Antonio , Saporito Gennaro , Catalucci Alessia , Sucapane Patrizia , Barile Antonio , Cesare Ernesto Di , Marini Carmine , Pistoia Francesca , Splendiani Alessandra
Published: June 2024

Purpose

This study aimed to identify possible prognostic factors determining early tremor relapse after Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) thalamotomy in patients with essential tremor (ET) and Parkinson’s disease (PD).

Methods

Nine patients (six ET and three PD) who underwent Vim MRgFUS thalamotomy in a single institution and developed early re-emergent tremor were analyzed. A control group of patients matched pairwise for sex, pathology, age, disease duration, and skull density ratio (SDR) was selected to compare the technical-procedural data and MR imaging evidence. MR imaging findings compared between groups included lesion shape and volume in multiparametric sequences, as well as Fractiona Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) values derived from Diffusion Tensor Imaging Diffusion Weighted Imaging (DTI) and Diffusion Weighted Imaging (DWI) sequences.

Results

We did not find statistically significant differences in gender and age between the two groups. Technical and procedural parameters were also similar in both treatment groups. In MRI analysis, we found lesions of similar size but with greater caudal extension in the control group with stable outcomes compared to patients with tremor relapse.

Conclusion

In our analysis of early recurrences after thalamotomy with focused ultrasound, there were neither technical and procedural differences nor prognostic factors related to lesion size or ablation temperatures. Greater caudal extension of the lesion in patients without recurrence might suggest the importance of spatial consolidation during treatment.
Therapeutic targets for age-related macular degeneration: proteome-wide Mendelian randomization and colocalization analyses
Authors: Pu Kun-Lin , Kang Hong , Li Li
Published: June 2024

Background

Currently, effective therapeutic drugs for age-related macular degeneration (AMD) are urgently needed, and it is crucial to explore new treatment targets. The proteome is indispensable for exploring disease targets, so we conducted a Mendelian randomization (MR) of the proteome to identify new targets for AMD and its related subtypes.

Methods

The plasma protein level data used in this study were obtained from two large-scale studies of protein quantitative trait loci (pQTL), comprising 35,559 and 54,219 samples, respectively. The expression quantitative trait loci (eQTL) data were sourced from eQTLGen and GTEx Version 8. The discovery set for AMD data and subtypes was derived from the FinnGen study, consisting of 9,721 AMD cases and 381,339 controls, 5,239 wet AMD cases and 273,920 controls, and 6,651 dry AMD cases and 272,504 controls. The replication set for AMD data was obtained from the study by Winkler TW et al., comprising 14,034 cases and 91,234 controls. Summary Mendelian randomization (SMR) analysis was employed to assess the association between QTL data and AMD and its subtypes, while colocalization analysis was performed to determine whether they share causal variants. Additionally, chemical exploration and molecular docking were utilized to validate potential drugs targeting the identified proteins.

Results

SMR and colocalization analysis jointly identified risk-associated proteins for AMD and its subtypes, including 5 proteins (WARS1, BRD2, IL20RB, TGFB1, TNFRSF10A) associated with AMD, 2 proteins (WARS1, IL20RB) associated with Dry-AMD, and 9 proteins (COL10A1, WARS1, VTN, SDF2, LBP, CD226, TGFB1, TNFRSF10A, CSF2) associated with Wet-AMD. The results revealed potential therapeutic chemicals, and molecular docking indicated a good binding between the chemicals and protein structures.

Conclusion

Proteome-wide MR have identified risk-associated proteins for AMD and its subtypes, suggesting that these proteins may serve as potential therapeutic targets worthy of further clinical investigation.
Interactive effects of Composite Dietary Antioxidant Index with Body Mass Index for the risk of stroke among U.S. adults: insight from NHANES 2001–2018
Authors: Li Xi , Hu Xin , You Chao
Published: June 2024

Background

This cross-sectional study aims to explore the interactive effects of the Composite Dietary Antioxidant Index (CDAI) and Body Mass Index (BMI) on stroke risk among U.S. adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2018.

Methods

The analysis involved 42,042 participants from a representative sample of non-institutionalized U.S. civilians, selected through a stratified, multistage probability sampling method. Dietary intake data were collected over two 24-h periods using the Automated Multiple-Pass Method. The study calculated a modified CDAI to assess dietary antioxidant intake, excluding supplements and water sources. Statistical methods included multivariable logistic regression and Generalized Additive Models (GAM) to evaluate the interaction between CDAI scores and BMI in relation to stroke risk, adjusting for a wide range of demographic, lifestyle, and health covariates.

Results

The research identified a significant interaction between CDAI scores and BMI categories in stroke risk assessment. While a negative correlation was observed between CDAI scores and stroke risk across the total population (OR 0.97, 95% CI 0.96–0.99), this relationship varied notably across different BMI groups. In participants with a BMI ≥25, a statistically significant negative association persisted, displaying a non-linear pattern. The study also revealed an inflection point in the CDAI score, indicating a shift in the relationship between dietary antioxidants and stroke risk.

Conclusion

This study underscores the complex interaction between dietary antioxidant intake and BMI in determining stroke risk among U.S. adults. The findings suggest that individuals with higher BMI may experience more pronounced benefits from dietary antioxidants in stroke prevention. These insights could inform targeted dietary recommendations and public health strategies aimed at reducing stroke risk, particularly in populations with higher BMI. Further research is needed to fully understand these interactions and their implications for stroke prevention guidelines.
An expert panel on the adequacy of safety data and physiological roles of dietary bovine osteopontin in infancy
Authors: Fleming Stephen A. , Reyes Sarah M. , Donovan Sharon M. , Hernell Olle , Jiang Rulan , Lönnerdal Bo , Neu Josef , Steinman Lawrence , Sørensen Esben S. , West Christina E. , Kleinman Ronald , Wallingford John C.
Published: June 2024

Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN’s concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8–24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN’s physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity. The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.
Case report: Sustained remission after combined sintilimab, anti-VEGF therapy, and chemotherapy in a patient with non-small cell lung cancer harboring acquired EGFR 19Del/T790M/cis-C797S mutation resistance
Authors: He Wanming , Tong Lihua , Yang Wen , Yuan Yanling , Li Yu , Tang Wubing
Published: June 2024

Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are highly effective against tumors harboring the T790M mutation. However, patients treated with these inhibitors ultimately develop resistance, and the most common mechanism is the emergence of the EGFR C797S mutation. Few treatment regimens have been reported for this condition. In this report, we present a successful combination treatment with the programmed cell death 1 (PD-1) inhibitor sintilimab, anti-vascular endothelial growth factor (VEGF) therapy, and chemotherapy with pemetrexed and cisplatin in a patient with non-small cell lung cancer (NSCLC) who developed acquired resistance with EGFR 19 exon deletion (19Del)/T790M/cis-C797S mutation following progression with ametinib therapy. This regimen was well tolerated, and the patient has remained progression-free for 15 months. Our case provides clinical evidence that the combination of PD-1 inhibitor, anti-VEGF therapy, and chemotherapy may be an efficacious therapeutic strategy for NSCLC patients with acquired EGFR 19Del/T790M/cis-C797S mutation resistance following progression with EGFR TKI therapy.
Immune cell related signature predicts prognosis in esophageal squamous cell carcinoma based on single-cell and bulk-RNA sequencing
Authors: Wang Xian , Peng Wei , Zhao Yali , Sha Jiming , Li Na , Huang Shan , Wang Hua
Published: June 2024

Background

It has been reported that tumor immune microenvironment performs a vital role in tumor progress. However, acting mechanism of immune cell related genes (IRGs) in esophageal squamous cell carcinoma (ESCC) is uncertain.

Methods

TCGA-ESCC, GSE23400, GSE26886, GSE75241, and GSE196756 datasets were gained via public databases. First, differentially expressed genes (DEGs) between ESCC and control samples from GSE23400, GSE26886, and GSE75241 were screened out by differential expression analysis, and overlapping DEGs were identified. Single-cell transcriptome data of GSE196756 were applied to explore immune cells that might be involved in regulation of ESCC. Then, weighted gene co-expression network analysis was applied to screen IRGs. Next, differentially expressed IRGs (DE-IRGs) were identified by overlapping IRGs and DEGs, and were incorporated into univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox to acquire prognosis-related genes, and ESCC samples were grouped into high-/low-risk groups on the basis of median risk score. Finally, the role of prognosis model in immunotherapy was analyzed.

Results

Totally 248 DEGs were yielded by overlapping 3,915 DEGs in GSE26886, 459 DEGs in GSE23400, and 1,641 DEGs in GSE75241. Single-cell analysis found that B cells, dendritic cells, monocytes, neutrophils, natural killer cells, and T cells were involved in ESCC development. Besides, MEred, MEblack, MEpink, MEblue and MEbrown modules were considered as key modules because of their highest correlations with immune cell subtypes. A total of 154 DE-IRGs were yielded by taking intersection of DEGs and genes in key modules. Moreover, CTSC, ALOX12, and RMND5B were identified as prognosis-related genes in ESCC. Obviously, Exclusion and TIDE scores were notably lower in high-risk group than in the other one, indicating that high-risk group was more responsive to immunotherapy.

Conclusions

Through bioinformatic analysis, we identified a prognosis model consisting of IRGs (CTSC, ALOX12, and RMND5B) in ESCC, providing new ideas for studies related to treatment and prognosis of ESCC.
Triple-negative breast cancer survival prediction: population-based research using the SEER database and an external validation cohort
Authors: Qiu Yu , Chen Yan , Shen Haoyang , Yan Shuixin , Li Jiadi , Wu Weizhu
Published: June 2024

Introduction

Triple-negative breast cancer (TNBC) is linked to a poorer outlook, heightened aggressiveness relative to other breast cancer variants, and limited treatment choices. The absence of conventional treatment methods makes TNBC patients susceptible to metastasis. The objective of this research was to assess the clinical and pathological traits of TNBC patients, predict the influence of risk elements on their outlook, and create a prediction model to assist doctors in treating TNBC patients and enhancing their prognosis.

Methods

We included 23,394 individuals with complete baseline clinical data and survival information who were diagnosed with primary TNBC between 2010 and 2015 based on the SEER database. External validation utilised a group from The Affiliated Lihuili Hospital of Ningbo University. Independent risk factors linked to TNBC prognosis were identified through univariate, multivariate, and least absolute shrinkage and selection operator regression methods. These characteristics were chosen as parameters to develop 3- and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) nomogram models. Model accuracy was assessed using calibration curves, consistency indices (C-indices), receiver operating characteristic curves (ROCs), and decision curve analyses (DCAs). Finally, TNBC patients were divided into groups of high, medium, and low risk, employing the nomogram model for conducting a Kaplan-Meier survival analysis.

Results

In the training cohort, variables such as age at diagnosis, marital status, grade, T stage, N stage, M stage, surgery, radiation, and chemotherapy were linked to OS and BCSS. For the nomogram, the C-indices stood at 0.762, 0.747, and 0.764 in forecasting OS across the training, internal validation, and external validation groups, respectively. Additionally, the C-index values for the training, internal validation, and external validation groups in BCSS prediction stood at 0.793, 0.755, and 0.811, in that order. The findings revealed that the calibration of our nomogram model was successful, and the time-variant ROC curves highlighted its effectiveness in clinical settings. Ultimately, the clinical DCA showcased the prospective clinical advantages of the suggested model. Furthermore, the online version was simple to use, and nomogram classification may enhance the differentiation of TNBC prognosis and distinguish risk groups more accurately.

Conclusion

These nomograms are precise tools for assessing risk in patients with TNBC and forecasting survival. They can help doctors identify prognostic markers and create more effective treatment plans for patients with TNBC, providing more accurate assessments of their 3- and 5-year OS and BCSS.
Long-read sequencing for brain tumors
Authors: Shelton William J. , Zandpazandi Sara , Nix J Stephen , Gokden Murat , Bauer Michael , Ryan Katie Rose , Wardell Christopher P. , Vaske Olena Morozova , Rodriguez Analiz
Published: June 2024

Brain tumors and genomics have a long-standing history given that glioblastoma was the first cancer studied by the cancer genome atlas. The numerous and continuous advances through the decades in sequencing technologies have aided in the advanced molecular characterization of brain tumors for diagnosis, prognosis, and treatment. Since the implementation of molecular biomarkers by the WHO CNS in 2016, the genomics of brain tumors has been integrated into diagnostic criteria. Long-read sequencing, also known as third generation sequencing, is an emerging technique that allows for the sequencing of longer DNA segments leading to improved detection of structural variants and epigenetics. These capabilities are opening a way for better characterization of brain tumors. Here, we present a comprehensive summary of the state of the art of third-generation sequencing in the application for brain tumor diagnosis, prognosis, and treatment. We discuss the advantages and potential new implementations of long-read sequencing into clinical paradigms for neuro-oncology patients.
Preliminary exploration of amide proton transfer weighted imaging in differentiation between benign and malignant bone tumors
Authors: Li Ying , Lin Liangjie , Zhang Yong , Ren Cuiping , Zhang Wenhua , Cheng Jingliang
Published: June 2024

Purpose

To explore the value of 3D amide proton transfer weighted imaging (APTWI) in the differential diagnosis between benign and malignant bone tumors, and to compare the diagnostic performance of APTWI with traditional diffusion-weighted imaging (DWI).

Materials and methods

Patients with bone tumors located in the pelvis or lower limbs confirmed by puncture or surgical pathology were collected from January 2021 to July 2023 in the First Affiliated Hospital of Zhengzhou University. All patients underwent APTWI and DWI examinations. The magnetization transfer ratio with asymmetric analysis at the frequency offset of 3.5 ppm [MTRasym(3.5 ppm)] derived by APTWI and the apparent diffusion coefficient (ADC) derived by DWI for the tumors were measured. The Kolmogorou-Smirnou and Levene normality test was used to confirm the normal distribution of imaging parameters; and the independent sample t test was used to compare the differences in MTRasym(3.5 ppm) and ADC between benign and malignant bone tumors. In addition, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different imaging parameters in differentiation between benign and malignant bone tumors. P<0.05 means statistically significant.

Results

Among 85 bone tumor patients, 33 were benign and 52 were malignant. The MTRasym(3.5 ppm) values of malignant bone tumors were significantly higher than those of benign tumors, while the ADC values were significantly lower in benign tumors. ROC analysis shows that MTRasym(3.5 ppm) and ADC values perform well in the differential diagnosis of benign and malignant bone tumors, with the area under the ROC curve (AUC) of 0.798 and 0.780, respectively. Combination of MTRasym(3.5 ppm) and ADC values can further improve the diagnostic performance with the AUC of 0.849 (sensitivity = 84.9% and specificity = 73.1%).

Conclusion

MTRasym(3.5 ppm) of malignant bone tumors was significantly higher than that of benign bone tumors, reflecting the abnormal increase of protein synthesis in malignant tumors. APTWI combined with DWI can achieve a high diagnostic efficacy in differentiation between benign and malignant bone tumors.
Tailoring advanced breast cancer treatment after cyclin-dependent kinase 4/6 inhibitors progression - real-world data analysis
Authors: Kubeczko Marcin , Polakiewicz-Gilowska Anna , Świderska Katarzyna , Leśniak Aleksandra , Mianowska-Malec Marta , Łanoszka Barbarba , Chomik Konstanty , Grandys Barbara , Lisovska Natalya , Bobek-Billewicz Barbara , Chmielik Ewa , Jarząb Michał
Published: June 2024

Background

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression.

Methods

We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone.

Results

Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1–76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6–26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3–94.8%] compared to 21.1% [95% CI 12.2–31.7%] for patients with non-tailored treatment.

Conclusions

Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.
Wnt signaling in gastric cancer: current progress and future prospects
Authors: Han Ruyue , Yang Jing , Zhu Yingying , Gan Runliang
Published: June 2024

Levels of the Wnt pathway components are abnormally altered in gastric cancer cells, leading to malignant cell proliferation, invasion and metastasis, poor prognosis and chemoresistance. Therefore, it is important to understand the mechanism of Wnt signaling pathway in gastric cancer. We systematically reviewed the molecular mechanisms of the Wnt pathway in gastric cancer development; and summarize the progression and the challenges of research on molecular agents of the Wnt pathway.
Enhancing ectasia screening using advanced AS-OCT: a case series of challenging refractive candidates
Authors: Mohr Niklas , Kassumeh Stefan , Luft Nikolaus , Dirisamer Martin , Priglinger Siegfried G. , Mayer Wolfgang J.
Published: June 2024

Purpose

Ectasia screening in candidates for laser refractive surgery is mandatory during preoperative evaluation. Despite the availability of modern imaging techniques, refractive surgeons often face borderline decisions when patients present with suspicious tomographic findings. This case series presents refractive candidates with suspicious tomographic findings and demonstrates how to interpret them using Scheimpflug imaging and additional anterior segment optical coherence tomography (AS-OCT).

Setting

Department of Ophthalmology, University Hospital, LMU Munich.

Case series

This case series examines six potential candidates for refractive surgery with a mean age of 29.2 ± 3.9 years, whose corneal assessments using Scheimpflug imaging raised suspicion for ectasia. Each candidate was additionally examined with AS-OCT and reevaluated. The mean manifest subjective spherical equivalent was -3.67 ± 1.8 diopters. The total corneal thickness measured 537 µm ± 30 µm at its thinnest point. None of the candidates had any reported underlying corneal or ophthalmic diseases, and slit lamp examinations revealed no abnormal morphological findings.

Conclusions

Both Scheimpflug imaging and AS-OCT are appropriate tools for screening refractive candidates for ectasia. While topographic and elevation analyses yielded comparable results regarding corneal structure, the epithelial mapping provided by AS-OCT played a critical role in decision-making for cases with borderline tomographic findings. Establishing a global consensus on the use of epithelial mapping in ectasia screening is necessary.
Drawbacks of work intensification during the COVID-19 pandemic for procrastination and irritation: work from home as a further risk and social support as a potential buffer?
Authors: Bendixen Lydia , Scheel T.E.
Published: June 2024

The use of information and communication technologies while working from home during the COVID-19 pandemic may have increased flexibility and compatibility of different life domains, but may have also increased work intensification – which in turn may jeopardize wellbeing and task performance. While work intensification is assumed to relate positively to procrastination as well as irritation, the extent of work from home was expected to strengthen these relationships. Social support may attenuate these moderations. The assumptions were tested in two independent, comparable samples (S1, N = 347; S2, N = 1,066) during two stages of the COVID-19 pandemic (November 2020, 2021). Data were collected via online questionnaires using established scales (preregistered before analyses). Work intensification was significantly positively related to procrastination as well as cognitive and affective irritation in both samples. The extent of work from home strengthened the relationship between work intensification and procrastination (S2), while in S1 this held true only when persons reported not having their own study at home. Social support did not moderate the moderations. By replicating results in two different samples, this study contributes by being the first to examine the relationship between work intensification and procrastination, while further confirming the positive relationship between work intensification and irritation. The extent of work from home seems to pose an additional risk for procrastination. Our research extends the research on remote work by showing the downsides, such as work intensification, which is positively related to irritation and procrastination, which are precursors to impaired wellbeing and task performance. This highlights the different negative outcomes that can result from non-ideal working conditions when working from home during the COVID-19 pandemic. Especially given that the pandemic paved the way for a high prevalence of work from home, future research should investigate beneficial contextual factors to provide the evidence base for the design of healthy and productive working conditions.
Hyponatremia in babies: a 11-year single-center study
Authors: Liu Xu , Xie Yanshu , Tang Jing , Zhong Jingzi , Lan Dan
Published: June 2024

Introduction

Hyponatremia is one of the most prevalent water-electrolyte disturbances encountered in clinical practice in pediatrics and can arise from various conditions. However, there are limited reports on hyponatremia in hospitalized infants. The objective of this study was to provide an overview of the incidence, etiologies, and clinical characteristics of hyponatremia in hospitalized babies (from birth to 3 years old) at a tertiary hospital.

Method

Computer records of all hospitalized babies (from birth to 3 years old) with hyponatremia were extracted from the First Affiliated Hospital of Guangxi Medical University's clinical databases.

Results

801 patients from 39,019 hospital admissions were found to have hyponatremia and the overall prevalence of this condition was 2.05% in babies. Patients with hyponatremia due to aldosterone signaling abnormalities, neurological disorders, and liver diseases exhibited more severe outcomes than those with other etiologies.

Conclusions

Various conditions can result in hyponatremia in hospitalized babies. Aldosterone signaling abnormalities were not that uncommon and it could lead to severe hyponatremia in babies.
Sputum microbe community alterations induced by long-term inhaled corticosteroid use are associated with airway function in chronic obstructive pulmonary disease patients based on metagenomic next-generation sequencing (mNGS)
Authors: Yue Yuanyi , Zhang Baohui , He Zhong , Zheng Yuling , Wang Xueqing , Zhang Qiang
Published: June 2024

Objective: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD) patients as a treatment option. However, ICS may also increase the risk of pneumonia and alter the composition of airway microbiota. In clinical application, the overuse of ICS exists pervasively and may potentially lead to adverse effects. Whether the long-term use of ICS confers enough benefit to COPD patients to justify its use so far remains unknown. Therefore, this study employed a single-center retrospective cohort study to compare alterations in airway function and the sputum microbial community structure between COPD patients who had undergone either long-term or short-term treatment with ICS.

Methods: Sixty stable COPD patients who had used ICS were recruited and classified into the long-term use group (more than 3 months) and short-term use group (less than 3 months). The demographic features and clinical information of the subjects were investigated and their sputum samples were collected and subjected to metagenomic next-generation sequencing (mNGS).

Results: The study found that compared with short-term ICS use, long-term ICS use did not further improve the clinical airway function, decrease the number of acute exacerbations, or decrease hospital readmission. In terms of sputum microbiota, the long-term use of ICS significantly altered the beta diversity of the microbial community structure (p < 0.05) and the top three phyla differed between the two groups. At the genus level, long-term ICS induced higher relative abundances of Abiotrophia, Schaalia, Granulicatella, Mogibacterium, Sphingobium, and Paraeggerthella compared to short-term ICS use. Additionally, alpha diversity was positively associated with clinical airway indicators (pre-bronchodilatory FEV1 and pre-bronchodilatory FVC) in the long-term ICS group. The relative abundances of Rothia, Granulicatella, Schaalia, and Mogibacterium genera had positive correlations with the eosinophil % (of all white blood cells).

Conclusion: This study reveals the effect of long-term and short-term ICS use on sputum microbiota among COPD patients and provides a reference for the appropriate application of clinical ICS treatment in COPD patients.
Pre-clinical studies comparing the anti-inflammatory potential of artemisinic compounds by targeting NFκB/TNF-α/NLRP3 and Nrf2/TRX pathways in Balb/C mice
Authors: Kazmi Syeda Tayyaba Batool , Fatima Humaira , Naz Iffat , Kanwal Nosheen , Haq Ihsan-ul
Published: June 2024

Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p<0.05) attenuated the memory deficit, anxiety, and depressive-like behavior. Moreover, histopathological, hematological, serological, and endogenous antioxidant profiles indicated substantial AIP of ACs. Findings of comet assay further bolstered the compelling evidence as DNA damage was significantly (p<0.05) curbed down after ACs (100 mg/kg) treatment. All these outcomes implied that ACs exhibited AIP in a dose-dependent manner with maximal AIP imparted by artemisinin (100 mg/kg). This pre-clinical investigation avers the tremendous AIP of ACs targeting key molecular pathways. The current study divulges artemisinin as the most potent antiinflammatory agent among the tested compounds.
Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning
Authors: Glajzner Paulina , Bernat Agnieszka , Jasińska-Stroschein Magdalena
Published: June 2024

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics. The use of drug repositioning in searching for new therapeutic options has brought promising results for many viral infectious diseases, such as Ebola, ZIKA, Dengue, and HCV. This review describes the most favorable results for repositioned drugs for the treatment of bacterial infections. It comprises publications from various databases including PubMed and Web of Science published from 2015 to 2023. The following search keywords/strings were used: drug repositioning and/or repurposing and/or antibacterial activity and/or infectious diseases. Treatment options for infections caused by multidrug-resistant bacteria were taken into account, including methicillin-resistant staphylococci, multidrug-resistant Mycobacterium tuberculosis, or carbapenem-resistant bacteria from the Enterobacteriaceae family. It analyses the safety profiles of the included drugs and their synergistic combinations with antibiotics and discusses the potential of antibacterial drugs with antiparasitic, anticancer, antipsychotic effects, and those used in metabolic diseases. Drug repositioning may be an effective response to public health threats related to the spread of multidrug-resistant bacterial strains and the growing antibiotic resistance of microorganisms.
Malnutrition alters protein expression of KNDy neuropeptides in the arcuate nucleus of mature ewes
Authors: Thorson Jennifer F. , Prezotto Ligia D.
Published: June 2024

The neuropeptides kisspeptin, neurokinin B, and dynorphin A are imperative for the pulsatile secretion of gonadotropin-releasing hormone and luteinizing hormone to ultimately regulate reproductive cyclicity. A population of neurons co-expressing these neuropeptides, KNDy neurons, within the arcuate nucleus of the hypothalamus (ARC) are positioned to integrate energy status from afferent neuronal and glial cells. We hypothesized that KNDy-expressing neurons in the ARC of mature ewes are influenced by energy balance. To test this hypothesis, ovary-intact, mature ewes were fed to lose, maintain, or gain body weight and hypothalamic tissue harvested during the luteal phase of the estrous cycle. Fluorescent, multiplex immunohistochemistry with direct antibody conjugation was employed to identify and quantify neurons expressing a single neuropeptide, as well as for the first time report co-expression of kisspeptin, neurokinin B, and dynorphin A protein in the ARC. Previous reports using this population of ewes demonstrated that concentrations of insulin and leptin differed between ewes fed to achieve different body weights and that ewes fed to gain body weight had increased concentrations of progesterone. Moreover, within this population of ewes tanycyte density and cellular penetration into the ARC was increased in ewes fed to gain body weight. Within the current report we have revealed that the number of neurons in the ARC expressing kisspeptin, neurokinin B, and dynorphin A protein was increased in ewes fed to gain body weight. Moreover, the number of KNDy neurons in the ARC expressing all three neuropeptides within a single neuron was decreased in ewes fed to lose body weight and increased in ewes fed to gain body weight when compared to ewes fed to maintain body weight. The cumulative findings of this experimental model suggest that expression of kisspeptin, neurokinin B, and dynorphin A protein in the ARC during the luteal phase of the estrous cycle are influenced by energy balance-induced alterations in circulating concentrations of progesterone that drive changes in morphology and density of tanycytes to ultimately regulate central perception of global energy status. Moreover, these results demonstrate that changes in KNDy neurons within the ARC occur as an adaptation to energy balance, potentially regulated divergently by metabolic milieu via proopiomelanocortin afferents.
Climber, mediator, and marathoner: narrative inquiry of career motivation changes of pre-service CSL teachers throughout teaching practicum
Authors: Zhou Rubing , Wang Tianmiao , Lin Hanzhao
Published: June 2024

Introduction

The growing global demand for foreign language learning contrasts sharply with the shortage of second language teachers. In Chinese as a second language (CSL) education, although the number of pre-service CSL teachers is increasing, few continue in the profession after completing their teacher education courses.

Methods

To investigate the reasons behind this trend, this longitudinal narrative inquiry examined the career motivations of three participants during their teaching practicum. The study focused on identifying key narrative clues based on metaphors emerging from their narratives.

Results

The research found that the participants’ career motivations were influenced by their teaching practice and experienced various dynamic changes. Key motivational factors included self-efficacy and intrinsic self-fulfillment, with a notable influence from the unique cross-cultural motivation associated with second language teaching.

Discussion

The study underscores the significant role of narratives and metaphors in understanding changes in teacher career motivations. It suggests that enhancing self-efficacy and intrinsic motivation, alongside recognizing cross-cultural motivations, could be crucial in addressing the retention issues among pre-service CSL teachers.
It’s about time! Exploring time allocation patterns of adults with lower literacy skills on a digital assessment
Authors: Kaldes Gal , Tighe Elizabeth L. , He Qiwei
Published: June 2024

Introduction

Despite the necessity for adults with lower literacy skills to undergo and succeed in high-stakes computer-administered assessments (e.g., GED, HiSET), there remains a gap in understanding their engagement with digital literacy assessments.

Methods

This study analyzed process data, specifically time allocation data, from the Program for the International Assessment of Adult Competencies (PIAAC), to investigate adult respondents’ patterns of engagement across all proficiency levels on nine digital literacy items. We used cluster analysis to identify distinct groups with similar time allocation patterns among adults scoring lower on the digital literacy assessment. Finally, we employed logistic regression to examine whether the groups varied by demographic factors, in particular individual (e.g., race/ethnicity, age) and contextual factors (e.g., skills-use at home).

Results

Adults with lower literacy skills spent significantly less time on many of the items than adults with higher literacy skills. Among adults with lower literacy skills, two groups of time allocation patterns emerged: one group (Cluster 1) exhibited significantly longer engagement times, whereas the other group (Cluster 2) demonstrated comparatively shorter durations. Finally, we found that adults who had a higher probability of Cluster 1 membership (spending more time) exhibited relatively higher literacy scores, higher self-reported engagement in writing skills at home, were older, unemployed, and self-identified as Black.

Discussion

These findings emphasize differences in digital literacy engagement among adults with varying proficiency levels. Additionally, this study provides insights for the development of targeted interventions aimed at improving digital literacy assessment outcomes for adults with lower literacy skills.
How do differences in native language affect out-of-body experiences?
Authors: Uchitomi Hirotaka , Yamamoto Yuma , Ueno Kishiko , Nomura Yuko , Miyake Yoshihiro
Published: June 2024

Out-of-body experiences are scientifically inducible cognitive phenomena attracting global attention due to their application in the Metaverse and medical care. Despite previous studies suggesting that one’s native language influences one’s cognition, the out-of-body experiences of humans with different native languages have not been investigated separately. This study replicated an experiment from a 2007 study to investigate whether differences in native language affect the ability to have scientifically induced out-of-body experiences. A total of 19 age-matched native English and Japanese speakers completed the experiment in two blocks. Thereafter, their experiences were evaluated using questionnaires, and their responses were compared. Importantly, no significant differences between the English and Japanese native-speaker conditions were found. The results showed that out-of-body experiences were induced similarly in both groups, suggesting that people can have out-of-body experiences as a response to similar stimuli, regardless of their native language. However, differences in participants’ introspective reports suggested that their experiences may differ qualitatively, possibly, due to the different linguistic backgrounds. The elucidation of the mechanisms of science-assisted out-of-body experiences that consider different cultural and cognitive characteristics, such as native language, could lead to the investigation of their applications in the borderless Metaverse and medicine.
Visual search strategies and game knowledge in junior Australian rules football players: testing potential in talent identification and development
Authors: Kassem Lael , Pang Bonnie , Dogramaci Sera , MacMahon Clare , Quinn John , Steel Kylie A.
Published: June 2024

This study explored video-based decision-making and eye-movement behavior as a complementary method to assess the decision-making skills and knowledge of elite junior Australian Rules (AR) Football players. Performance was measured twice over an 18-month period. This approach tested a practical and reliable assessment of decision-making and game knowledge that does not contribute to physical training load. N = 59 participants were categorized based on their training age groups, U14 (N = 38, Mage13.37 ± 0.47) and U16 (N = 21, Mage14.80 ± 0.39). Participants watched 14 brief video clips and provided action choices while wearing eye-movement recording glasses that captured visual search patterns (e.g., fixations). Decision accuracy and speed of decision-making were also recorded. Participants with accurate decisions made significantly faster decisions compared to less skilled players (p < 0.001). Further, skilled participants had significantly fewer fixations of shorter duration compared to less skilled participants at both the initial and follow-up testing sessions (p < 0.0001). This suggests that eye-movement characteristics, remain a relatively stable measure over moderate periods of time. With the ability to differentiate between more and less skilled decision-makers, this proof-of-concept study proposes that examining eye movements in relation to decision-making and game knowledge is a viable tool for Talent Identification and Development (TID) to complement current measures. We provide a platform for further development and research in the quest for efficient and effective talent identification processes.
Mixed-methods analysis of satisfaction during a 12-session mindfulness-based intervention for women with a substance use disorder and trauma symptomatology
Authors: Bautista Tara G. , Ware Orrin D. , Macias Burgos Miracle A. , Rivas Veronica D. , Cruz-Carrillo Yesenia , Davidson Alec , Mezhenska Mariia , Sanchez Mariana , Amaro Hortensia
Published: June 2024

Satisfaction with an intervention influences the uptake of behavior changes and the long-term efficacy of the intervention. Therefore, it is crucial to assess satisfaction by participant profile when creating and adapting behavior interventions for minoritized populations. Qualitative and quantitative data on participant trauma symptom severity and intervention satisfaction were collected through self-report surveys from 54 women. The sample was 59.3% Hispanic, with an average age of 33.21 (SD = 10.42), who were in residential treatment for substance use disorders (SUDs) and participated in a 12-session mindfulness-based intervention. Qualitative responses were coded using thematic analysis, and an integrative mixed-methods approach was used to compare qualitative theme frequency between high-trauma (N = 28) and low-trauma (N = 26) groups at session 2 and session 11. High- and low-trauma groups were determined by interquartile ranges (bottom 25% = low; top 75% = high). In session 2, the low-trauma group reported significantly higher satisfaction (M = 4.20, SD = 0.55) than the high-trauma group (M = 3.77, SD = 0.89); t(43) = 1.90, p = 0.03. In session 11, there was no significant difference between groups. The mixed-methods analysis revealed that “trouble focusing” appeared more frequently in the high-trauma group than in the low-trauma group during session 2, but the theme was not present in either group at session 11, suggesting that this might pose an initial barrier for individuals with high trauma but subsides as the intervention progresses. This speaks to the importance of retention strategies tailored for participants with SUDs and high trauma while they adjust to the intervention. Assessing initial challenges with satisfaction may help facilitators intervene to increase participant satisfaction.
On assessing trait rumination using the Ruminative Response Scale
Authors: Int-Veen Isabell , Ehlis Ann-Christine , Fallgatter Andreas J. , Rosenbaum David
Published: June 2024

Introduction

This study explores the stability of scores on psychometrically validated trait questionnaires over time. We illustrate potential pitfalls through a larger study that used the Ruminative Response Scale (RRS) to categorize participants prior to study inclusion into two groups based on their habitual tendency to ruminate. Surprisingly, when we re-administered the RRS at the start of an experimental session, significant score changes occurred, resulting in participants shifting between the two groups.

Methods

To address this, we modified our recruitment process, aiming to reduce careless responses, including an online RRS assessment a week before the lab appointment. We analyzed the different samples prior to and after changing the recruitment procedure, as well as the total sample regarding the psychometric properties of the RRS. We also explored various indices to identify and predict score changes due to careless responding; however, only a subgroup of participants was successfully identified.

Results

Our findings suggest that Mahalanobis distances are effective for identifying substantial score changes, with baseline state rumination emerging as a marginally significant predictor.

Discussion

We discuss the importance of conducting manipulation checks and offer practical implications for research involving psychometrically validated trait questionnaires.