bluuebunny/crossref_metadata_2025 huggingface dataset:
Feature evaluation of accelerometry signals for cough detection
Authors: Diab Maha S. , Rodriguez-Villegas Esther
Published: March 2024

Cough is a common symptom of multiple respiratory diseases, such as asthma and chronic obstructive pulmonary disorder. Various research works targeted cough detection as a means for continuous monitoring of these respiratory health conditions. This has been mainly achieved using sophisticated machine learning or deep learning algorithms fed with audio recordings. In this work, we explore the use of an alternative detection method, since audio can generate privacy and security concerns related to the use of always-on microphones. This study proposes the use of a non-contact tri-axial accelerometer for motion detection to differentiate between cough and non-cough events/movements. A total of 43 time-domain features were extracted from the acquired tri-axial accelerometry signals. These features were evaluated and ranked for their importance using six methods with adjustable conditions, resulting in a total of 11 feature rankings. The ranking methods included model-based feature importance algorithms, first principal component, leave-one-out, permutation, and recursive features elimination (RFE). The ranking results were further used in the feature selection of the top 10, 20, and 30 for use in cough detection. A total of 68 classification models using a simple logistic regression classifier are reported, using two approaches for data splitting: subject-record-split and leave-one-subject-out (LOSO). The best-performing model out of the 34 using subject-record-split obtained an accuracy of 92.20%, sensitivity of 90.87%, specificity of 93.52%, and F1 score of 92.09% using only 20 features selected by the RFE method. The best-performing model out of the 34 using LOSO obtained an accuracy of 89.57%, sensitivity of 85.71%, specificity of 93.43%, and F1 score of 88.72% using only 10 features selected by the RFE method. These results demonstrate the ability for future implementation of a motion-based wearable cough detector.
When best friendships end: young adolescents' responses to hypothetical best friendship dissolution and associations with real-life friendship outcomes
Authors: Bowker Julie C. , Weingarten Jenna P. , Etkin Rebecca G. , Dirks Melanie A.
Published: March 2024

Introduction

This study examined young adolescents' responses to two types of hypothetical best friendship dissolution (complete and downgrade dissolutions). Responses included their attributions, emotional reactions, and coping strategies. It also considered whether responses vary across dissolution type and are related to the real-life friendship-specific outcomes of best friendship dissolution and friendship quantity.

Method

Data were collected from 318 young adolescents at two time points (Time 1 (T1): Mage = 11.87 years) and included a newly-developed vignette measure of responses to hypothetical complete and downgrade dissolutions (T1), real-life complete and downgrade dissolutions experienced by participants (T2), and friendship (T1, T2).

Results

Findings showed that adolescents responded differently in their emotional reactions and coping strategies to hypothetical complete and downgrade dissolutions. Path models revealed unique linkages between several responses, such as vengeful coping and the real-life friendship-specific outcomes.

Discussion

Findings suggest variability in how young adolescents respond to hypothetical best friendship dissolutions and that such variability may explain differences in their real-life friendships.
Gamifying the university classroom: a comparative analysis of game dimensions through educational Escape Room and a digital board game
Authors: Mauri-Medrano Marta , González-Yubero Sara , Falcón-Linares Carolina , Cardoso-Moreno María Jesús
Published: March 2024

Introduction

University education is looking for innovative ways to enrich the teaching-learning process.

Methods

This study aims to describe and compare two gamified experiences: an educational Escape Room and a digital goose board game with Genially. The design of this research follows a quantitative correlational methodology. A total of 135 university students in the first year of the Bachelor’s Degree in Primary Education participated in the study.

Results

Data were collected using the Gamified Game Experience Scale (GAMEX). The results of contrasting means for the game dimensions between both gamified experiences reveal a significant variability (p < 0.01) in favor of the Escape Room in fun, absorption, creative thinking, activation and mastery. On the other hand, the absence of negative affect was significant (p < 0.05) in favor of the digital board game.

Discussion

It could be said that the educational Escape Room manifests itself as a powerful resource for learning. However, it can induce a high level of stress, generating discomfort, hostility and frustration in students, so its implementation is not free of negative effects. These findings provide additional empirical evidence that could guide the design of gamified experiences in the Higher Education environment.
A brief neuro-affirming resource to support school absences for autistic learners: development and program description
Authors: Johnston Lorna , Maciver Donald , Rutherford Marion , Gray Anna , Curnow Eleanor , Utley Izy
Published: March 2024

Background

Education should be inclusive, nurturing each individual’s potential, talents, and creativity. However, criticisms have emerged regarding support for autistic learners, particularly in addressing disproportionately high absence levels within this group. The demand for accessible, person-centered, neuro-affirming approaches is evident. This paper provides a program description of a structured absence support framework, developed and implemented during and following the Covid-19 pandemic. We detail creation, content, and implementation.

Methods

We collaborated with stakeholders, reviewed literature and drew on existing theoretical frameworks to understand absence in autistic learners, and produced draft guidance detailing practical approaches and strategies for supporting their return to school. The final resource was disseminated nationally and made freely available online with a supporting program of work around inclusive practices.

Results

The resource is rooted in neuro-affirming perspectives, rejecting reward-based systems and deficit models of autism. It includes key messages, case studies and a planning framework. It aims to cultivate inclusive practices with an autism-informed lens. The principles promoted include recognizing the child’s 24-hour presentation, parental partnership, prioritizing environmental modifications, and providing predictable, desirable and meaningful experiences at school. Feedback to date has been positive in terms of feasibility, face validity, and utility.

Conclusion

This novel, freely available resource provides a concise, practical framework for addressing absence in autistic learners by cultivating a more inclusive, equitable, and supportive educational system in which autistic individuals can thrive.
Interaction between anemia and hyperuricemia in the risk of all-cause mortality in patients with chronic kidney disease
Authors: Lu Zhaoxuan , Lu Fangping , Zhang Ruixue , Guo Shuting
Published: March 2024

Aim

Both hyperuricemia and anemia are not only the manifestation of chronic kidney disease (CKD) but also related to its occurrence and development. A recent study has found that there was a synergetic effect between hyperuricemia and anemia on new-onset CKD. Herein we aimed to explore the roles of hyperuricemia and anemia in the all-cause mortality in patients with CKD.

Methods

Data of adult patients with CKD were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2009–2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were used to investigate the associations of hyperuricemia and anemia with all-cause mortality, and the evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). The interaction effect between hyperuricemia and anemia on the risk of all-cause mortality was assessed via relative excess risk due to interaction (RERI) and attributable proportion of interaction (AP). Subgroup analyses of age, gender, CVD, hypertension, DM, and cancer were also performed to assess this interaction effect.

Results

Among 3,678 eligible patients, 819 died from all causes. After adjusting for covariables, we found that CKD patients with anemia (HR = 1.72, 95%CI: 1.42–2.09) or hyperuricemia (HR = 1.21, 95%CI: 1.01–11.45) had a higher risk of all-cause mortality. There was a potential synergetic effect between anemia and hyperuricemia on all-cause mortality, with RERI of 0.630 and AP of 0.291. Moreover, this synergetic effect was also observed in ≥65 years old (AP = 0.330), male (AP = 0.355), hypertension (AP = 0.736), non-hypertension (AP = 0.281), DM (AP = 0.371), and cancer (AP = 0.391) subgroups.

Conclusion

A potential synergetic effect between anemia and hyperuricemia on all-cause mortality was found in patients with CKD. However, further studies are needed to clarify the causal relationship between them.
Association of serum uric acid with right cardiac chamber remodeling assessed by cardiovascular magnetic resonance feature tracking in patients with connective tissue disease
Authors: Tang Yuanyuan , Yang Zhaoxia , Wen Jinyang , Tang Dazhong , Luo Yi , Xiang Chunlin , Huang Lu , Xia Liming
Published: March 2024

Background

Right cardiac chamber remodeling is widespread in patients with connective tissue disease (CTD). Serum uric acid (SUA) is considered a potential independent risk factor for cardiovascular disease, and elevated SUA levels are often observed in patients with CTD. The correlation between SUA levels and right cardiac chamber remodeling remains unclear. This study investigated the association of SUA with right cardiac chamber remodeling as assessed by cardiac magnetic resonance feature-tracking (CMR-FT) in CTD patients.

Methods and results

In this cross-sectional study, a total of 104 CTD patients and 52 age- and sex-matched controls were consecutively recruited. All individuals underwent CMR imaging, and their SUA levels were recorded. The patients were divided into three subgroups based on the tertiles of SUA level in the present study. CMR-FT was used to evaluate the right atrial (RA) longitudinal strain and strain rate parameters as well as right ventricular (RV) global systolic peak strain and strain rate in longitudinal and circumferential directions for each subject. Univariable and multivariable linear regression analyses were used to explore the association of SUA with RV and RA strain parameters. Compared with the controls, the CTD patients showed significantly higher SUA levels but a lower RV global circumferential strain (GCS) and RA phasic strain parameters (all p < 0.05), except the RA booster strain rate. RV GCS remained impaired even in CTD patients with preserved RV ejection fraction. Among subgroups, the patients in the third tertile had significantly impaired RV longitudinal strain (GLS), RV GCS, and RA reservoir and conduit strain compared with those in the first tertile (all p < 0.05). The SUA levels were negatively correlated with RV GLS and RV GCS as well as with RA reservoir and conduit strain and strain rates (the absolute values of β were 0.250 to 0.293, all P < 0.05). In the multivariable linear regression analysis, the SUA level was still an independent determinant of RA conduit strain (β = -0.212, P = 0.035) and RV GCS (β = 0.207, P = 0.019).

Conclusion

SUA may be a potential risk factor of right cardiac chamber remodeling and is independently associated with impaired RA conduit strain and RV GCS in CTD patients.
BmSPP is a virus resistance gene in Bombyx mori
Authors: Feng Yu-ting , Yang Chun-yan , Wu Lin , Wang Yuan-cheng , Shen Guan-wang , Lin Ping
Published: March 2024

Introduction

Signal peptide peptidase (SPP) is an intramembrane protease involved in a variety of biological processes, it participates in the processing of signal peptides after the release of the nascent protein to regulate the endoplasmic reticulum associated degradation (ERAD) pathway, binds misfolded membrane proteins, and aids in their clearance process. Additionally, it regulates normal immune surveillance and assists in the processing of viral proteins. Although SPP is essential for many viral infections, its role in silkworms remains unclear. Studying its role in the silkworm, Bombyx mori , may be helpful in breeding virus-resistant silkworms.

Methods

First, we performed RT-qPCR to analyze the expression pattern of BmSPP. Subsequently, we inhibited BmSPP using the SPP inhibitor 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucylaminopropanone ((Z-LL)2-ketone) and downregulated the expression of BmSPP using CRISPR/Cas9 gene editing. Furthermore, we assessed the impact of these interventions on the proliferation of Bombyx mori nucleopolyhedrovirus (BmNPV).

Results

We observed a decreased in the expression of BmSPP during viral proliferation. It was found that higher concentration of the inhibitor resulted in greater inhibition of BmNPV proliferation. The down-regulation of BmSPP in both in vivo and in vitro was found to affect the proliferation of BmNPV. In comparison to wild type silkworm, BmSPPKO silkworms exhibited a 12.4% reduction in mortality rate.

Discussion

Collectively, this work demonstrates that BmSPP plays a negative regulatory role in silkworm resistance to BmNPV infection and is involved in virus proliferation and replication processes. This finding suggests that BmSPP servers as a target gene for BmNPV virus resistance in silkworms and can be utilized in resistance breeding programs.
Taxonomic and functional dynamics of nirS denitrifiers along a salinity gradient in the Pearl River Estuary
Authors: Zhou Hongwei , Zhang Hao , He Xinping , Liu Cheng , Fozia  , Cui Qian , Yang Hongjun , Zhao Chunyu , Zhang Han , Hu Huanhuan , Zhang Zongxiao
Published: March 2024

Understanding the factors that shape the diversity, distribution, and function of denitrifying microbes is vital for managing nitrogen cycling in these ecosystems. This study explores the diversity, biogeographic distribution, assembly processes, interaction, and denitrification potential of the nirS-encoding microbial community (nirS denitrifier) in the Pearl River Estuary based on high-throughput and metagenomics sequencing dataset. The results of this study show that salinity is a crucial regulatory environmental factor that determines the spatial distribution, phylogenetic turnover, and co-occurrence patterns of nirS denitrifiers. Additionally, the dissolved organic carbon (DOC), suspended sediment concentration (SSC), and dissolved oxygen (DO) in water also significantly impact the biodiversity and abundance of nirS denitrifiers. Furthermore, our findings demonstrate that, in comparison to environmental factors, the ecological and evolutionary characteristics of nirS denitrifiers play a more prominent role in regulating their denitrification potential, suggesting that alterations in the microbial community within dynamic changes in estuarine water can profoundly affect its denitrification function. Our results indicate the significant roles of denitrification microbial structure and phylogenetic characteristics in maintaining their ecological functions. Future studies should continue to explore the interactions between microbial communities and environmental factors to further elucidate the denitrification process in estuaries and its implications for ecosystem health and water quality.
Molecular cloning and characterization of three carnitine palmitoyltransferase (cpt) isoforms from mud crab (Scylla paramamosain) and their roles in respond to fasting and ambient salinity stress
Authors: Lin Zhideng , Huang Chaoyang , Zhuo Zhengrui , Xie Jun , Lan Hongliang , Hu Bixing , Zhang Chengkang , Han Kunhuang , Huang Weiqing
Published: March 2024

As rate-limiting enzymes of β-oxidation of fatty acids in mitochondria, the carnitine palmitoyltransferase (CPT) played an important role in regulating energy homeostasis of aquatic animals. However, there was very little research on β-oxidation of fatty acids in crustaceans. In the present study, the full-length cDNA sequences of cpt-1a, cpt-1b and cpt-2 were isolated from the hepatopancreas of Scylla paramamosain, and contained 4206, 5303 and 3486 bp respectively. Sequence analysis showed that the CPT-1A, CPT-1B and CPT-2 encoded proteins with 777, 775 and 672 amino acids respectively, and only the CPT-1A possessed a transmembrane region. In addition, both the CPT-1B and CPT-2 contained conservative functional domains like N-terminal domain and acyltransferases choActase 2, while the CPT-1A lacked. The results of phylogenetic tree indicated that the CPT-1A, CPT-1B and CPT-2 of S. paramamosain gathered together with their corresponding orthologues from crustaceans. The tissue distribution exhibited that the cpt-1a was highly expressed in hepatopancreas, followed by muscle, eyestalk and cranial ganglia, and the muscle, eyestalk and heart were main expressed tissues of cpt-1b. Furthermore, the high expression levels of cpt-2 were mainly detected in hepatopancreas, muscle and heart. The transcriptional levels of cpt-1a, cpt-1b and cpt-2 were significantly up-regulated under chronic low salinity stress. Besides, at the acute low salinity stress condition, the expression levels of cpt-1a, cpt-1b and cpt-2 in hepatopancreas were dramatically increased in 14‰ and 4‰ salinity groups at the 6h and 48h, while the transcriptional levels of cpt-1a, cpt-1b and cpt-2 in muscle were signally up-regulated in 14‰ and 4‰ salinity groups at the 12h and 24h, showing an alternate response pattern. Similarly, the present study found that fasting could markedly increase the expression levels of cpt-1a, cpt-1b and cpt-2 in hepatopancreas and muscle, especially cpt-1a in hepatopancreas as well as cpt-1a and cpt-1b in muscle. The results above indicated that the cpt-1a, cpt-1b and cpt-2 played a crucial part in providing energy for coping with fasting and salinity stress. These results would contribute to enhancing the knowledge of cpt phylogenetic evolution and their roles in energy metabolism of crustaceans.
A mRNA panel for differentiation between acute exacerbation or pneumonia in COPD patients
Authors: Bertrams Wilhelm , Wilhelm Jochen , Veeger Pia-Marie , Hanko Carolina , Brinke Kristina auf dem , Klabunde Björn , Pott Hendrik , Weckler Barbara , Greulich Timm , Vogelmeier Claus F. , Schmeck Bernd
Published: March 2024

Introduction

Patients suffering from chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations (AECOPD) or community acquired pneumonia (CAP), both posing severe risk of morbidity and mortality. There is no available biomarker that correctly separates AECOPD from COPD. However, because CAP and AECOPD differ in aetiology, treatment and prognosis, their discrimination would be important.

Methods

This study analysed the ability of selected candidate transcripts from peripheral blood mononuclear cells (PBMCs) to differentiate between patients with AECOPD, COPD & CAP, and CAP without pre-existing COPD.

Results

In a previous study, we identified differentially regulated genes between CAP and AECOPD in PBMCs. In the present new cohort, we tested the potential of selected candidate PBMC transcripts to differentiate at early time points AECOPD, CAP+COPD, and CAP without pre-existing COPD. Expression of YWHAG, E2F1 and TDRD9 held predictive power: This gene set predicted diseases markedly better (model accuracy up to 100%) than classical clinical markers like CRP, lymphocyte count and neutrophil count (model accuracy up to 82%).

Discussion

In summary, in our cohort expression levels of YWHAG, E2F1 and TDRD9 differentiated with high accuracy between COPD patients suffering from acute exacerbation or CAP.
Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis
Authors: Desaintjean Charlene , Ahmad Kaïs , Traclet Julie , Gerfaud-Valentin Mathieu , Durel Cecile-Audrey , Glerant Jean-Charles , Hot Arnaud , Lestelle François , Mainbourg Sabine , Nasser Mouhamad , Seve Pascal , Turquier Ségolène , Devouassoux Gilles , Cottin Vincent
Published: March 2024

Introduction

Asthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma.

Objective

Our aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under “real-world” conditions.

Methods

This was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0.

Results

Twenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable.

Conclusion

In this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function.
Causal associations of genetically predicted gut microbiota and blood metabolites with inflammatory states and risk of infections: a Mendelian randomization analysis
Authors: Liu Yingjian , Zhu Qian , Guo Gongjie , Xie Zhipeng , Li Senlin , Lai Chengyang , Wu Yonglin , Wang Liansheng , Zhong Shilong
Published: March 2024

Background

Inflammation serves as a key pathologic mediator in the progression of infections and various diseases, involving significant alterations in the gut microbiome and metabolism. This study aims to probe into the potential causal relationships between gut microbial taxa and human blood metabolites with various serum inflammatory markers (CRP, SAA1, IL-6, TNF-α, WBC, and GlycA) and the risks of seven common infections (gastrointestinal infections, dysentery, pneumonia, bacterial pneumonia, bronchopneumonia and lung abscess, pneumococcal pneumonia, and urinary tract infections).

Methods

Two-sample Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW), maximum likelihood, MR-Egger, weighted median, and MR-PRESSO.

Results

After adding other MR models and sensitivity analyses, genus Roseburia was simultaneously associated adversely with CRP (Beta IVW = −0.040) and SAA1 (Beta IVW = −0.280), and family Bifidobacteriaceae was negatively associated with both CRP (Beta IVW = −0.034) and pneumonia risk (Beta IVW = −0.391). After correction by FDR, only glutaroyl carnitine remained significantly associated with elevated CRP levels (Beta IVW = 0.112). Additionally, threonine (Beta IVW = 0.200) and 1-heptadecanoylglycerophosphocholine (Beta IVW = −0.246) were found to be significantly associated with WBC levels. Three metabolites showed similar causal effects on different inflammatory markers or infectious phenotypes, stearidonate (18:4n3) was negatively related to SAA1 and urinary tract infections, and 5-oxoproline contributed to elevated IL-6 and SAA1 levels. In addition, 7-methylguanine showed a positive correlation with dysentery and bacterial pneumonia.

Conclusion

This study provides novel evidence confirming the causal effects of the gut microbiome and the plasma metabolite profile on inflammation and the risk of infection. These potential molecular alterations may aid in the development of new targets for the intervention and management of disorders associated with inflammation and infections.
A Mendelian randomization investigation of the causal association between the gut microbiota and sleep disorders
Authors: Yan Wei , Zhuang Zhenzhen , Gao Yuhao , Wang Yuntao , He Daikun
Published: March 2024

Background

Increasing numbers of people are suffering from sleep disorders. The gut microbiota of these individuals differs significantly. However, no reports are available on the causal associations between specific gut microbiota and sleep disorders.

Methods

Data on gut genera were obtained from the MiBioGen consortium. Twenty-four cohorts with 18,340 individuals of European origin were included. Sleep disorder data, which included 216,454 European individuals, were retrieved from the FinnGen Biobank. Subsequently, two-sample Mendelian randomization was performed to analyze associations between sleep disorders and specific components of the gut microbiota.

Results

Inverse variance weighting (IVW) revealed a negative correlation between Coprobacter and sleep disorders (OR = 0.797, 95% CI = 0.66–0.96, and p = 0.016), a positive correlation between Lachnospiraceae and sleep disorders (OR = 1.429, 95% CI = 1.03–1.98, and p = 0.032), a negative association between Oscillospira and sleep disorders (OR = 0.745, 95% CI = 0.56–0.98, and p = 0.038), and a negative association between Peptococcus and sleep disorders (OR = 0.858, 95% CI = 0.74–0.99, p = 0.039).

Conclusion

A significant causal relationship was found between four specific gut microbiota and sleep disorders. One family, Lachnospiraceae, was observed to increase the risk of sleep disorders, while three genera, namely, Coprobacter, Oscillospira, and Peptococcus, could reduce the risk of sleep disorders. However, further investigations are needed to confirm the specific mechanisms by which the gut microbiota affects sleep.
Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson’s disease: a Chinese cross-sectional and longitudinal study
Authors: He Raoli , Zeng Yuqi , Wang Chaodong , Chen Lina , Cai Guoen , Chen Ying , Wang Yingqing , Ye Qinyong , Chen Xiaochun
Published: March 2024

Background

Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson’s disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively.

Methods

The study consisted of three parts: a case–control study, a cross-sectional study, and a longitudinal cohort study. The case–control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression.

Results

In the case–control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: β = −5.42, p < 0.001, interaction ptime × genotype < 0.001) and non-motor symptoms (NMSS score: β = −4.78, p = 0.030, interaction ptime × genotype < 0.001).

Conclusion

Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression.
Causal role of immune cells on risk of Parkinson’s disease: a Mendelian randomization study
Authors: Gu Jian , Qiao Yue , Cong Shuyan
Published: March 2024

Background

Previous observational studies have suggested a correlation between immune cells and Parkinson’s disease (PD), yet specific investigations into the causal relationship between the two remain limited. This study aims to explore this potential causal relationship.

Methods

We utilized genome-wide association study (GWAS) data on immune cells and Parkinson’s Disease, conducting a two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms (SNPs). To estimate causality, we employed inverse variance weighting (IVW), MR-Egger, and weighted median (WM) methods. For sensitivity analysis, we used Cochran’s Q-test, MR-Egger intercept, leave-one-out analysis, and funnel plots.

Results

After false discovery rate (FDR) correction, the effects of PD on immune cells, and vice versa, were not statistically significant. These include CX3CR1 on CD14+ CD16-monocyte (OR = 0.91, 95% CI = 0.86–0.96, p = 0.0003 PFDR = 0.152), CD62L-CD86+ myeloid DC AC (OR = 0.93, 95% CI = 0.89–0.97, p = 0.0005, PFDR = 0.152),CD11b on Mo (OR = 1.08, 95% CI = 1.03–1.13, p = 0.001, PFDR = 0.152), CD38 on igd+ cd24− (OR = 1.14, 95% CI = 1.06–1.23, p = 0.001, PFDR = 0.152), D14+ cd16+ monocyte %monocyte (OR = 1.10, 95% CI = 1.04–1.17, p = 0.001, PFDR = 0.159). Additionally, PD may be causally related to the immune phenotype of CM CD8br %T cell (beta = 0.10, 95% CI = 1.14–1.16, p = 0.0004, PFDR = 0.151), SSC-A on monocyte (beta = 0.11, 95% CI = 1.15–1.18, p = 0.0004, PFDR = 0.1 SSC-A on monocyte). No pleiotropy was determined.

Conclusion

This study suggested a potential causal link between immune cells and Parkinson’s Disease through the MR method, which could provide a new direction for the mechanistic research and clinical treatment of PD.
The ratio of the maximum density values: a new method for predicting hemorrhagic transformation in acute ischemic stroke patients undergoing mechanical thrombectomy
Authors: Qiao Xiaohong , Zheng Fuhao , Wei Manman , Zhao Zhenming
Published: March 2024

Background

It is challenging yet critical to differentiate between hemorrhagic transformation (HT) and contrast extravasation on non-contrast-enhanced computed tomography (NCCT) scans following mechanical thrombectomy (MT) in patients with acute ischemic stroke. We propose a new method called the ratio of maximum density values (RMDV) to minimize the confusion of contrast extravasation and to evaluate the diagnostic significance of RMDV in predicting HT on immediate post-interventional NCCT scans.

Methods

We conducted a retrospective analysis of the prospective patients’ database who received MT for acute ischemic stroke caused by occlusion of the intracranial large artery and showed postinterventional cerebral hyperdensities (PCHDs) on NCCT scans immediately after MT. Based on the subsequent NCCT scans, we divided patients with PCHDs into the HT and the non-HT groups. The clinical characters and radiological details were collected and compared to the two groups. We assessed the ability of RMDV >1 to predict HT by analyzing the receiver operating characteristic curve.

Results

One hundred and three patients showed PCHDs; 58 (56.31%) were classified as HT, while 45 (43.69%) were classified as non-HT. The only notable distinction between the two groups was the proportion of RMDV >1 in the HT group. The correlation between HT and RMDV >1 with an area under the curve of 0.826 (95% confidence interval, 0.739 to 0.894). The sensitivity, specificity, positive, and negative predictive values of RMDV >1 on NCCT for predicting HT were 89.66, 75.56, 82.54, and 85.00%, respectively.

Conclusion

The utilization of RMDV >1 on immediate NCCT scans after MT can predict early HT with good sensitivity and specificity.
Early cortico-muscular coherence and cortical network changes in Parkinson’s patients treated with MRgFUS
Authors: Visani Elisa , Panzica Ferruccio , Franceschetti Silvana , Golfrè Andreasi Nico , Cilia Roberto , Rinaldo Sara , Rossi Sebastiano Davide , Lanteri Paola , Eleopra Roberto
Published: March 2024

Introduction

To investigate cortical network changes using Magnetoencephalography (MEG) signals in Parkinson’s disease (PD) patients undergoing Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thalamotomy.

Methods

We evaluated the MEG signals in 16 PD patients with drug-refractory tremor before and after 12-month from MRgFUS unilateral lesion of the ventralis intermediate nucleus (Vim) of the thalamus contralateral to the most affected body side. We recorded patients 24 h before (T0) and 24 h after MRgFUS (T1). We analyzed signal epochs recorded at rest and during the isometric extension of the hand contralateral to thalamotomy. We evaluated cortico-muscular coherence (CMC), the out-strength index from non-primary motor areas to the pre-central area and connectivity indexes, using generalized partial directed coherence. Statistical analysis was performed using RMANOVA and post hoct-tests.

Results

Most changes found at T1 compared to T0 occurred in the beta band and included: (1) a re-adjustment of CMC distribution; (2) a reduced out-strength from non-primary motor areas toward the precentral area; (3) strongly reduced clustering coefficient values. These differences mainly occurred during motor activation and with few statistically significant changes at rest. Correlation analysis showed significant relationships between changes of out-strength and clustering coefficient in non-primary motor areas and the changes in clinical scores.

Discussion

One day after MRgFUS thalamotomy, PD patients showed a topographically reordered CMC and decreased cortico-cortical flow, together with a reduced local connection between different nodes. These findings suggest that the reordered cortico-muscular and cortical-networks in the beta band may represent an early physiological readjustment related to MRgFUS Vim lesion.
Explainable artificial intelligence (xAI) in neuromarketing/consumer neuroscience: an fMRI study on brand perception
Authors: Marques dos Santos José Paulo , Marques dos Santos José Diogo
Published: March 2024

Introduction

The research in consumer neuroscience has identified computational methods, particularly artificial intelligence (AI) and machine learning, as a significant frontier for advancement. Previously, we utilized functional magnetic resonance imaging (fMRI) and artificial neural networks (ANNs) to model brain processes related to brand preferences in a paradigm exempted from motor actions. In the current study, we revisit this data, introducing recent advancements in explainable artificial intelligence (xAI) to gain insights into this domain. By integrating fMRI data analysis, machine learning, and xAI, our study aims to search for functional brain networks that support brand perception and, ultimately, search for brain networks that disentangle between preferred and indifferent brands, focusing on the early processing stages.

Methods

We applied independent component analysis (ICA) to overcome the expected fMRI data’s high dimensionality, which raises hurdles in AI applications. We extracted pertinent features from the returned ICs. An ANN is then trained on this data, followed by pruning and retraining processes. We then apply explanation techniques, based on path-weights and Shapley values, to make the network more transparent, explainable, and interpretable, and to obtain insights into the underlying brain processes.

Results

The fully connected ANN model obtained an accuracy of 54.6%, which dropped to 50.4% after pruning. However, the retraining process allowed it to surpass the fully connected network, achieving an accuracy of 55.9%. The path-weights and Shapley-based analysis concludes that, regarding brand perception, the expected initial participation of the primary visual system is followed. Other brain areas participate in early processing and discriminate between preferred and indifferent brands, such as the cuneal and the lateral occipital cortices.

Discussion

The most important finding is that a split between processing brands|preferred from brands|indifferent may occur during early processing stages, still in the visual system. However, we found no evidence of a “decision pipeline” that would yield if a brand is preferred or indifferent. The results suggest the existence of a “tagging”-like process in parallel flows in the extrastriate. Network training dynamics aggregate specific processes within the hidden nodes by analyzing the model’s hidden layer. This yielded that some nodes contribute to both global brand appraisal and specific brand category classification, shedding light on the neural substrates of decision-making in response to brand stimuli.
Comparative development of the serotonin- and FMRFamide-immunoreactive components of the nervous system in two distantly related ribbon worm species (Nemertea, Spiralia)
Authors: von Döhren Jörn
Published: March 2024

Introduction

Neurodevelopment in larval stages of non-model organisms, with a focus on the serotonin- and FMRFamide-immunoreactive components, has been in the focus of research in the recent past. However, some taxonomic groups remain understudied. Nemertea (ribbon worms) represent such an understudied clade with only few reports on nervous system development mostly from phylogenetically or developmentally derived species. It would be insightful to explore neurodevelopment in additional species to be able to document the diversity and deduce common patterns to trace the evolution of nervous system development.

Methods

Fluorescent immunohistochemical labeling with polyclonal primary antibodies against serotonin and FMRF-amide and a monoclonal antibody against synapsin performed on series of fixed larval stages of two nemertean species Cephalothrix rufifrons (Archinemertea, Palaeonemertea) and Emplectonema gracile (Monostilifera, Hoplonemertea) were analyzed with confocal laser scanning microscopy.

Results

This contribution gives detailed accounts on the development of the serotonin- and FMRFamide-immunoreactive subsets of the nervous system in two nemertean species from the first appearance of the respective signals. Additionally, data on synapsin-like immunoreactivity illustrates the general structure of neuropil components. Events common to both investigated species are the appearance of serotonin-like immunoreactive signals before the appearance of FMRF-like immunoreactive signals and the strict progression of the development of the lateral nerve cords from the anteriorly located, ring-shaped brain toward the posterior pole of the larva. Notable differences are (1) the proboscis nervous system that is developing much earlier in investigated larval stages of E. gracile and (2) distinct early, but apparently transient, serotonergic neurons on the frontal and caudal pole of the larva in E. gracile that seem to be absent in C. rufifrons.

Discussion

According to the results from this investigation and in line with previously published accounts on nervous system development, the hypothetical last common ancestor of Nemertea had a ring-shaped brain arranged around the proboscis opening, from which a pair of ventro-lateral nerve cords develops in anterior to posterior progression. Early frontal and caudal serotonergic neurons that later degenerate or cease to express serotonin are an ancestral character of Nemertea that they share with several other spiralian clades.
The correlation between fruit intake and all-cause mortality in hypertensive patients: a 10-year follow-up study
Authors: Sun Chuang , Li Jie , Zhao Zeyuan , Ren Shupeng , Guan Yue , Zhang Miaoan , Li Tianfeng , Tan Linglin , Yao Qiying , Chen Liang
Published: March 2024

Objective

Extensive research has consistently shown the beneficial impact of fruit consumption on overall health. While some studies have proposed a potential association between fruit consumption and hypertension management, the influence of fruit consumption on mortality rates among hypertensive individuals remains uncertain. Consequently, aim of this study is to evaluate whether fruit consumption is associated with all-cause mortality among hypertensive patients.

Methods

Data were obtained from the National Health and Nutrition Examination Survey (NHANES), conducted between 2003 and 2006. Ten-year follow-up data from the National Death Index (NDI) were used to assess all-cause mortality. Cox proportional hazard model was utilized to explore the impact of fruit intake on all-cause mortality among hypertensive individuals.

Results

The study included a cohort of 2,480 patients diagnosed with hypertension, and during the follow-up period, a total of 658 deaths from various causes were recorded. The COX regression analysis demonstrated that hypertensive patients who consumed apples three to six times per week exhibited a significantly reduced risk of all-cause mortality (HR = 0.60, 95%CI: 0.45–0.78, p < 0.001) in comparison to those who consumed apples less than once per month. Likewise, consuming bananas three to six times per week also led to a comparable outcome (HR = 0.76, 95%CI: 0.59–0.97, p = 0.027). Moreover, Combined consumption of bananas and apples three to six times per week exhibited a noteworthy decrease in all-cause mortality (HR = 0.57, 95%CI: 0.39–0.84, p = 0.005) when compared to individuals who consumed these fruits less frequently. Conversely, no significant association was found between the consumption of other fruits, including pears, pineapples, and grapes, and all-cause mortality.

Conclusion

The study discovered that moderate consumption of apples and bananas was associated with a reduced risk of all-cause mortality in patients with hypertension.
Practical management of disease-related manifestations and drug toxicities in patients with multiple myeloma
Authors: Geraldes Catarina , Roque Adriana , Sarmento-Ribeiro Ana Bela , Neves Manuel , Ionita Alina , Gerivaz Rita , Tomé Ana , Afonso Sofia , Silveira Maria Pedro , Sousa Patrícia , Bergantim Rui , João Cristina
Published: March 2024

Multiple myeloma (MM) is a very heterogeneous disease with multiple symptoms and clinical manifestations. MM affects mainly elderly patients and is difficult to manage in the presence of comorbidities, polypharmacy, frailty and adverse events of disease-targeted drugs. The rapid changes in MM treatment resulting from constant innovations in this area, together with the introduction of numerous new drugs with distinct mechanisms of action and toxicity profiles, have led to an increased complexity in the therapeutic decision-making and patient management processes. The prolonged exposure to novel agents, sometimes in combination with conventional therapies, makes this management even more challenging. A careful balance between treatment efficacy and its tolerability should be considered for every patient. During treatment, a close monitoring of comorbidities, disease-related manifestations and treatment side effects is recommended, as well as a proactive approach, with reinforcement of information and patient awareness for the early recognition of adverse events, allowing prompt therapeutic adjustments. In this review, we discuss various issues that must be considered in the treatment of MM patients, while giving practical guidance for monitoring, prevention and management of myeloma-related manifestations and treatment-related toxicities.
Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review
Authors: Wang Lumin , Qiu Qining , Yang Dawei , Cao Chang , Lu Yanqin , Zeng Yulan , Jiang Weiwen , Shen Yun , Ye Yanrong
Published: March 2024

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus’s clinical applications.
Synergizing biotechnology and natural farming: pioneering agricultural sustainability through innovative interventions
Authors: Badiyal Anila , Mahajan Rishi , Rana Ranbir Singh , Sood Ruchi , Walia Abhishek , Rana Tanuja , Manhas Shilpa , Jayswal D. K.
Published: March 2024

The world has undergone a remarkable transformation from the era of famines to an age of global food production that caters to an exponentially growing population. This transformation has been made possible by significant agricultural revolutions, marked by the intensification of agriculture through the infusion of mechanical, industrial, and economic inputs. However, this rapid advancement in agriculture has also brought about the proliferation of agricultural inputs such as pesticides, fertilizers, and irrigation, which have given rise to long-term environmental crises. Over the past two decades, we have witnessed a concerning plateau in crop production, the loss of arable land, and dramatic shifts in climatic conditions. These challenges have underscored the urgent need to protect our global commons, particularly the environment, through a participatory approach that involves countries worldwide, regardless of their developmental status. To achieve the goal of sustainability in agriculture, it is imperative to adopt multidisciplinary approaches that integrate fields such as biology, engineering, chemistry, economics, and community development. One noteworthy initiative in this regard is Zero Budget Natural Farming, which highlights the significance of leveraging the synergistic effects of both plant and animal products to enhance crop establishment, build soil fertility, and promote the proliferation of beneficial microorganisms. The ultimate aim is to create self-sustainable agro-ecosystems. This review advocates for the incorporation of biotechnological tools in natural farming to expedite the dynamism of such systems in an eco-friendly manner. By harnessing the power of biotechnology, we can increase the productivity of agro-ecology and generate abundant supplies of food, feed, fiber, and nutraceuticals to meet the needs of our ever-expanding global population.