bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: eosinophilic myocarditis in hypereosinophilic syndrome: a journey to heart transplantation
Authors: Sharma Shriya , Desai Smruti , Leoni Juan , Paghdar Smit , Ruiz Jose , Goswami Rohan
Published: June 2024

Introduction

Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management.

Case presentation

A 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation.

Discussion

EM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition.

Conclusion

Advancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM.
Challenges in the diagnosis and control of female genital schistosomiasis in sub-Saharan Africa: an exemplar case report associated with mixed and putative hybrid schistosome infection in Nsanje District, Southern Malawi
Authors: Kayuni Sekeleghe A. , Cunningham Lucas J. , Kumwenda Dingase , Mainga Bright , Lally David , Chammudzi Priscilla , Kapira Donales , Namacha Gladys , Ntaba Bessie , Chisale Alice , Nchembe Tereza , Kinley Luis , Chibwana Ephraim , Juhasz Alexandra , Jones Sam , Archer John , Makaula Peter , Chiphwanya John , LaCourse E. James , Musaya Janelisa , Stothard J. Russell
Published: June 2024

Female genital schistosomiasis (FGS) remains an often overlooked chronic complication of urogenital schistosomiasis in adolescent girls and women. Moreover, the role of zoonotic or hybrid schistosome infection(s) is poorly appreciated, but is increasingly becoming an emerging public health concern in sub-Saharan Africa. In Southern Malawi, during the “Hybridization in UroGenital Schistosomiasis (HUGS)” study visit, we describe the case of a 33-year-old woman with suspected FGS who partook in a detailed external assessment with internal cervical examination using a portable colposcope. She provided several biological samples for analysis with traditional and molecular parasitological methods—urine, cervicovaginal lavage (CVL), cervical swabs, and external mass and cervical biopsies—alongside provision of detailed demographic information after a thorough medical history questionnaire and an in-depth interview. These samples were screened for the presence of Schistosoma ova on microscopy and DNA genotyping using a novel real-time PCR assay in parallel to pre-published probe-based PCR assays capable of identifying and discriminating up to six named Schistosoma species. A further molecular screen of sexually transmitted infections (STIs) including Trichomonas vaginalis, Chlamydia spp., and human papilloma virus (HPV) was conducted on her genital swab and CVL. Overt FGS was diagnosed on clinical colposcopy alongside inspection of the cervical biopsy by microscopy, real-time PCR, and histopathology. The urine filtration, microscopy and real-time PCR of the CVL and swab were negative. This evidences the typical diagnostic challenge, and cases such as this will pose an unmet need in satisfactory patient management. In addition to Schistosoma haematobium, the presence of the zoonotic species Schistosoma mattheei and concurrent STIs raise questions as to the long-term effectiveness of the current control strategies of the National Control Programme to eliminate schistosomiasis as a public health problem. Improved availability of and regular accessibility to praziquantel treatment for women at risk such as this are urgently needed. Furthermore, targeted health education, increased community awareness, and dovetailing of synergistic activities and strategies with other health stakeholders such as those in sexual and reproductive health, as well as HIV/AIDS programs in the Ministry of Health, are needed here and in neighboring countries.
Caught in transition: changes in brachyuran diversity following mangrove encroachment into saltmarshes at a southern distribution limit
Authors: Katharoyan Chaitanya , Rajkaran Anusha , Peer Nasreen
Published: June 2024

Mangroves are expanding polewards due to global change, often encroaching into adjacent temperate saltmarshes. In both vegetated ecosystems, brachyurans are responsible for ecological processes and functions such as nutrient cycling and sediment bioturbation. South African mangroves occur at a latitudinal limit and are establishing further south due to past planting events and global change, making these ideal study systems for the effects of mangrove expansion and encroachment. Here, we investigated the effect of mangrove encroachment on brachyuran community composition at two saltmarsh sites with planted mangrove stands of different ages. Transects were laid perpendicular to each estuary where three habitat types were demarcated (mangrove, ecotone, saltmarsh). Sediment samples were collected for analyses and quadrats were used to measure pneumatophore density, saltmarsh cover, and brachyuran abundance and diversity. We found that brachyuran community structure at each site has significantly changed over seven years, with two mangrove-associated fiddler crab species, Tubuca urvillei and Paraleptuca chlorophthalmus, now recorded at the younger planted site, indicating a new southern distributional limit. Community structure was also significantly different amongst habitat types (p < 0.05) with Parasesarma catenatum dominating saltmarshes while Danielella edwardsii was more prominent in mangroves. However, community composition did not differ significantly between the two (differently aged) sites (p > 0.05). Pneumatophore density had a proportional relationship with crab abundance, diversity and richness, while saltmarsh cover had an inversely proportional relationship with crab abundance, diversity and richness. It is likely that as mangroves continue to expand into saltmarshes, more mangrove-associated species will move into saltmarshes, potentially altering ecosystem processes in this unique habitat.
The salinity anomalies due to nutrients and inorganic carbon in the Bohai Sea
Authors: Ji Fengying , Yang Jinkun , Ding Feng , Zheng Bing , Ning Pengfei
Published: June 2024

As a new seawater standard, the International Thermodynamic Equation of Seawater-2010 (TEOS-10) has made it possible to accurately calculate salinity changes caused by small changes in the relative proportions of inorganic dissolved constituents in the open ocean and thus to accurately calculate the thermodynamic properties of seawater. However, offshore and semi-enclosed seas are subject to the dual influence of geo-biochemical processes and terrestrial inputs, and the spatial and temporal variations in the relative composition of their seawater are more complex, resulting in very few studies of salinity change due to changes in the relative composition in these regions, and the applicability of the TEOS-10 in these seas needs to be further evaluated. The Bohai Sea is a typical semi-enclosed sea that has accumulated a large amount of physical oceanography and marine chemistry measurements, making it an ideal area to study the effects of changes in the relative composition of seawater on salinity. Based on repeated measurements of Section B in the Bohai Sea from 1985 to 2020, complemented by quasi-synchronous large-scale measurements of the Bohai Sea from 2006 to 2007, this study found that [HCO3−] and [Ca2+] ions anomalies dominate the relative composition anomalies of dissolved substances in this sea relative to the Standard Sea Water (SSW). These additional components could increase the absolute salinity SA by up to 0.1 g·kg-1 and the practical salinity SP by 0~0.04 according to the TEOS-10 algorithm and the mathematical model Pa08. Based on the specific environmental characteristics of the Bohai Sea, the sources, spatial and temporal variations, and influencing factors of the relative compositional anomalies are analyzed, and the empirical formulas of the absolute salinity anomaly δSA and practical salinity anomaly δSP for the Bohai Sea are further fitted, with the uncertainty of 0.007~0.021 g·kg-1 for δSA and 0.003~0.008 for δSP. The above results can not only improve the accuracy of the thermodynamic properties of the Bohai Seawater, but also provide the compatibility level of the long-term salinity changes in the Bohai Sea and its adjacent waters.
Optimization of machining path for integral impeller side milling based on SA-PSO fusion algorithm in CNC machine tools
Authors: Zhao Yu
Published: June 2024

The five axis linkage Computer Numerical Control machine tool for integral impeller can achieve blade machining through side milling, which is of great significance for improving the machining accuracy, production efficiency, and long-term stability of integral impeller blades. This study is based on non-uniform rational B-spline curves and aims to reduce the surface over cutting or under cutting of integral turbine blades. The path planning of non deployable ruled surfaces was analyzed in depth through side milling, and the path planning model of the side milling cutter axis was solved through a fusion algorithm of simulated annealing algorithm and particle swarm optimization algorithm, in order to find the optimal path through iterative process. As the number of iterations increased, the error values of particle swarm optimization algorithm and simulated annealing particle swarm optimization fusion algorithm gradually decreased, with convergence times of about 7 and 6, respectively. The stable error value of the fusion algorithm was 0.253, which is 30.45% lower than that of the particle swarm optimization algorithm. The optimal number of iterations for solving the model using particle swarm optimization algorithm and fusion algorithm was the 7th, with range values of 0.0213 and 0.0165 mm, respectively. The tool axis trajectory surface optimized by the fusion algorithm was closer to the tool axis motion state compared to the initial tool axis trajectory surface. The range of the sum of mean squared deviations for single and global cutting was 0.0011–0.0198 and 0.046–0.0341, but the overall error value was relatively small. This study effectively reduces the envelope error of machining tools and improves machining accuracy, thereby solving the principle error of non expandable ruled surfaces in the motion trajectory of the blade axis of the integral turbine. This provides new research ideas for the intelligent development of Computer Numerical Control machining technology.
Knowledge and attitude toward geriatric nursing care and associated factors among nurses working at hospitals in Hawassa City, Ethiopia, 2022
Authors: Abera Workineh , Daba Alemneh Kabeta , Gebre Bereket Beyene , Ashagere Mathewos , Yeheyis Tomas , Addisu Dereje , Amlaku Tsegahun , Tadesse Fikru , Samuel Tinbete
Published: June 2024

Background

Globally, the fastest growth in the number of older people combined with chronic and age-related medical conditions experienced by the older adult placed great demand on geriatric care. Thus, nurses are required to be knowledgeable and have a desirable attitude toward geriatric nursing care. Therefore, this study aimed to assess knowledge and attitude toward geriatric nursing care and associated factors among nurses working at hospitals in Hawassa City, Ethiopia.

Methods

Hospital-based cross-sectional study was conducted from June 30 to July 30, 2022, among 365 nurses. The hospitals and study participants were selected by using purposive and simple random sampling methods, respectively. Data were collected using self-administered questionnaires. Descriptive statistics were computed to generate descriptive results. Binary and multivariable logistic regressions were used to identify predictors at p-value <0.05.

Results

About 39.2% of nurses had good knowledge and 49.3% of the nurses showed a positive attitude toward geriatric nursing care. Nurses with BSc degree or above [AOR 2.5, 95% CI, (1.2–5.6)], having lived with older people [AOR 2.2, 95% CI, (1.4–3.6)], nurses with 6–10 years [AOR, 2.8, 95% CI, (1.4–5.57)] and >10 years of work experience [AOR 4.2, 95% CI, (1.6–10.8)] were more likely to have knowledge about geriatric nursing care. Having BSc degree or above [AOR 2.7, 95% C.I, (1.2–6)], 6–10 years [AOR 3, 95% CI, (1.48–6.3)], and >10 years [AOR 3.9, 95% CI, (1.4–10.99)] of work experience, living experience with older people [AOR 1.7, 95% C.I:1.05–2.7], knowledge about geriatric care [AOR 3, 95% CI,(1.85–4.92)], and having worked at adequate space [AOR 1.7, 95% CI: 1.009–2.8] increased odds of good attitude toward geriatric nursing care.

Conclusion

Less than half of nurses demonstrated good knowledge and positive attitude toward geriatric nursing care. Higher level of education, higher work experience, living with older people were significantly associated with knowledge and attitude toward geriatric nursing care. Additionally, working in an adequate space and having knowledge about geriatric care positively influenced attitude toward geriatric nursing care. Therefore, nursing schools and hospitals should conduct training and consider incorporating more content about geriatric care into nursing education to enhance nurses’ knowledge and attitude.
The interplay between the microbiota and opioid in the treatment of neuropathic pain
Authors: Gong Zexiong , Xue Qingsheng , Luo Yan , Yu Buwei , Hua Bo , Liu Zhiheng
Published: June 2024

Neuropathic pain (NP) is characterized by its complex and multifactorial nature and limited responses to opioid therapy; NP is associated with risks of drug resistance, addiction, difficulty in treatment cessation, and psychological disorders. Emerging research on gut microbiota and their metabolites has demonstrated their effectiveness in alleviating NP and augmenting opioid-based pain management, concurrently mitigating the adverse effects of opioids. This review addresses the following key points: (1) the current advances in gut microbiota research and the challenges in using opioids to treat NP, (2) the reciprocal effects and benefits of gut microbiota on NP, and (3) the interaction between opioids with gut microbiota, as well as the benefits of gut microbiota in opioid-based treatment of NP. Through various intricate mechanisms, gut microbiota influences the onset and progression of NP, ultimately enhancing the efficacy of opioids in the management of NP. These insights pave the way for further pragmatic clinical research, ultimately enhancing the efficacy of opioid-based pain management.
The sweating process promotes toxigenic fungi expansion and increases the risk of combined contamination of mycotoxins in Radix Dipsaci
Authors: Ge Yangyan , Wang Lulu , Su Dapeng , Yuan Qingsong , Xiao Chenghong , Hu Min , Kang Chuanzhi , Guo Lanping , Zhou Tao , Zhang Jinqiang
Published: June 2024

Sweating is one of the most important processing methods of Chinese medicinal herbs. However, the high temperature and humidity environment required for sweating Chinese medicinal herbs makes it very easy for fungi to breed, especially toxigenic fungi. The mycotoxins produced by these fungi will then contaminate the Chinese medicinal herbs. In this study, we explored the changes in mycobiota, toxigenic fungi, and mycotoxins with and without sweating in Radix Dipsaci (RD), a typical representative of traditional Chinese medicine that requires processing through sweating. We also isolated and identified the toxigenic fungi from RD, whether they were subjected to sweating treatment or not, and examined their toxigenic genes and ability. The results showed that the detection rate of mycotoxins (aflatoxins, ochratoxins, zearalenone, and T-2 toxin) in RD with sweating was 36%, which was 2.25-fold higher than that in RD without sweating. We also detected T-2 toxin in the RD with sweating, whereas it was not found in the RD without sweating. The sweating process altered the fungal composition and increased the abundance of Fusarium and Aspergillus in RD. Aspergillus and Fusarium were the most frequently contaminating fungi in the RD. Morphological and molecular identification confirmed the presence of key toxigenic fungal strains in RD samples, including A. flavus, A. westerdijkiae, F. oxysporum and F. graminearum. These four fungi, respectively, carried AflR, PKS, Tri7, and PKS14, which were key genes for the biosynthesis of aflatoxins, ochratoxins, zearalenone, and T-2 toxin. The toxigenic ability of these four fungal strains was verified in different matrices. We also found that A. flavus, A. westerdijkiae, and F. oxysporum were isolated in RD both with sweating and without sweating, but their isolation frequency was significantly higher in the RD with sweating than in the RD without sweating. F. graminearum was not isolated from RD without sweating, but it was isolated from RD with sweating. These findings suggest that the sweating process promotes the expansion of toxigenic fungi and increases the risk of combined mycotoxin contamination in RD.
Comprehensive toxicological, metabolomic, and transcriptomic analysis of the biodegradation and adaptation mechanism by Achromobacter xylosoxidans SL-6 to diuron
Authors: Hu Zhixu , Qian Cancan , Wang Haodong , Sun Lanlan , Wu Cailan , Zhang Guoqiang , Han Xiaoqiang , Wang Chunjuan , Ma Ting , Yang Desong
Published: June 2024

Biodegradation was considered a promising and environmentally friendly method for treating environmental pollution caused by diuron. However, the mechanisms of biodegradation of diuron required further research. In this study, the degradation process of diuron by Achromobacter xylosoxidans SL-6 was systematically investigated. The results suggested that the antioxidant system of strain SL-6 was activated by adding diuron, thereby alleviating their oxidative stress response. In addition, degradation product analysis showed that diuron in strain SL-6 was mainly degraded by urea bridge cleavage, dehalogenation, deamination, and ring opening, and finally cis, cis-muconic acid was generated. The combined analysis of metabolomics and transcriptomics revealed the biodegradation and adaptation mechanism of strain SL-6 to diuron. Metabolomics analysis showed that after the strain SL-6 was exposed to diuron, metabolic pathways such as tricarboxylic acid cycle (cis, cis-muconic acid), glutathione metabolism (oxidized glutathione), and urea cycle (arginine) were reprogrammed in the cells. Furthermore, diuron could induce the production of membrane transport proteins in strain SL-6 cells and overexpress antioxidant enzyme genes, finally ultimately promoting the up-regulation of genes encoding amide hydrolases and dioxygenases, which was revealed by transcriptomics studies. This work enriched the biodegradation mechanism of phenylurea herbicides and provided guidance for the removal of diuron residues in the environment and promoting agriculture sustainable development.
Biosynthesis of β-nicotinamide mononucleotide from glucose via a new pathway in Bacillus subtilis
Authors: Tan Zhilei , Yang Yihang , Wu Yannan , Yan Jiajia , Zhang Bin , Hou Ying , Jia Shiru
Published: June 2024

Introduction

β-nicotinamide mononucleotide (β-NMN) is an essential precursor of nicotinamide adenine dinucleotide (NAD+) and plays a key role in supplying NAD+ and maintaining its levels. Existing methods for NMN production have some limitations, including low substrate availability, complex synthetic routes, and low synthetic efficiency, which result in low titers and high costs.

Methods

We constructed high-titer, genetically engineered strains that produce NMN through a new pathway. Bacillus subtilis WB600 was used as a safe chassis strain. Multiple strains overexpressing NadE, PncB, and PnuC in various combinations were constructed, and NMN titers of different strains were compared via shake-flask culture.

Results

The results revealed that the strain B. subtilis PncB1-PnuC exhibited the highest total and extracellular NMN titers. Subsequently, the engineered strains were cultured in a 5-L fermenter using batch and fed-batch fermentation. B. subtilis PncB1-PnuC achieved an NMN titer of 3,398 mg/L via fed-batch fermentation and glucose supplementation, which was 30.72% higher than that achieved via batch fermentation.

Discussion

This study provides a safe and economical approach for producing NMN on an industrial scale.
The contribution of circadian clock to the biological processes
Authors: Luo Beibei , Song Jiangyuan , Zhang Jiaqi , Han Jun , Zhou Xin , Chen Lili
Published: June 2024

All organisms have various circadian, behavioral, and physiological 24-h periodic rhythms, which are controlled by the circadian clock. The circadian clock controls various behavioral and physiological rhythms. In mammals, the primary circadian clock is present in the suprachiasmatic nucleus of the hypothalamus. The rhythm of the circadian clock is controlled by the interaction between negative and positive feedback loops, consisting of crucial clock regulators (including Bmal1 and Clock), three cycles (mPer1, mPer2, and mPer3), and two cryptochromes (Cry1 and Cry2). The development of early mammalian embryos is an ordered and complex biological process that includes stages from fertilized eggs to blastocysts and undergoes important morphological changes, such as blastocyst formation, cell multiplication, and compaction. The circadian clock affects the onset and timing of embryonic development. The circadian clock affects many biological processes, including eating time, immune function, sleep, energy metabolism, and endocrinology, therefore, it is also crucial for overall health, growth and development after birth. This review summarized the effects of the circadian clock in the body’s physiological activities. A new strategy is proposed for the prevention of malformations or diseases by regulating the circadian clock or changing circadian rhythms.
RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma
Authors: Ala Ugo , Fagoonee Sharmila
Published: June 2024

Primary Sclerosing Cholangitis (PSC) is a persistent inflammatory liver condition that affects the bile ducts and is commonly diagnosed in young individuals. Despite efforts to incorporate various clinical, biochemical and molecular parameters for diagnosing PSC, it remains challenging, and no biomarkers characteristic of the disease have been identified hitherto. PSC is linked with an uncertain prognosis, and there is a pressing need to explore multiomics databases to establish a new biomarker panel for the early detection of PSC’s gradual progression into Cholangiocarcinoma (CCA) and for the development of effective therapeutic interventions. Apart from non-coding RNAs, other components of the Ribonucleoprotein (RNP) complex, such as RNA-Binding Proteins (RBPs), also hold great promise as biomarkers due to their versatile expression in pathological conditions. In the present review, an update on the RBP transcripts that show dysregulated expression in PSC and CCA is provided. Moreover, by utilizing a bioinformatic data mining approach, we give insight into those RBP transcripts that also exhibit differential expression in liver and gall bladder, as well as in body fluids, and are promising as biomarkers for diagnosing and predicting the prognosis of PSC. Expression data were bioinformatically extracted from public repositories usingTCGA Bile Duct Cancer dataset for CCA and specific NCBI GEO datasets for both PSC and CCA; more specifically, RBPs annotations were obtained from RBP World database. Interestingly, our comprehensive analysis shows an elevated expression of the non-canonical RBPs, FANCD2, as well as the microtubule dynamics regulator, ASPM, transcripts in the body fluids of patients with PSC and CCA compared with their respective controls, with the same trend in expression being observed in gall bladder and liver cancer tissues. Consequently, the manipulation of tissue expression of RBP transcripts might be considered as a strategy to mitigate the onset of CCA in PSC patients, and warrants further experimental investigation. The analysis performed herein may be helpful in the identification of non-invasive biomarkers for the early detection of PSC and for predicting its progression into CCA. In conclusion, future clinical research should investigate in more depth the full potential of RBP transcripts as biomarkers for human pathologies.
Correlation between hearing loss and mild cognitive impairment in the elderly population: Mendelian randomization and cross-sectional study
Authors: Xu Tong , Zong Tao , Liu Jing , Zhang Le , Ge Hai , Yang Rong , Liu Zongtao
Published: June 2024

Background

Hearing loss and tinnitus have been linked to mild cognitive impairment (MCI); however, the evidence is constrained by ethical and temporal constraints, and few prospective studies have definitively established causation. This study aims to utilize Mendelian randomization (MR) and cross-sectional studies to validate and analyze this association.

Methods

This study employs a two-step approach. Initially, the genetic data of the European population from the Genome-wide association studies (GWAS) database is utilized to establish the causal relationship between hearing loss and cognitive impairment through Mendelian randomization using the inverse variance weighted (IVW) method. This is achieved by identifying strongly correlated single nucleotide polymorphisms (SNPs), eliminating linkage disequilibrium, and excluding weak instrumental variables. In the second step, 363 elderly individuals from 10 communities in Qingdao, China are assessed and examined using methods questionnaire survey and pure tone audiology (PTA). Logistic regression and multiple linear regression were used to analyze the risk factors of MCI in the elderly and to calculate the cutoff values.

Results

Mendelian randomization studies have shown that hearing loss is a risk factor for MCI in European populations, with a risk ratio of hearing loss to MCI loss of 1. 23. The findings of this cross-sectional study indicate that age, tinnitus, and hearing loss emerged as significant risk factors for MCI in univariate logistic regression analysis. Furthermore, multivariate logistic regression analysis identified hearing loss and tinnitus as potential risk factors for MCI. Consistent results were observed in multiple linear regression analysis, revealing that hearing loss and age significantly influenced the development of MCI. Additionally, a notable finding was that the likelihood of MCI occurrence increased by 9% when the hearing threshold exceeded 20 decibels.

Conclusion

This study provides evidence from genomic and epidemiological investigations indicating that hearing loss may serve as a risk factor for cognitive impairment. While our epidemiological study has found both hearing loss and tinnitus as potential risk factors for cognitive decline, additional research is required to establish a causal relationship, particularly given that tinnitus can manifest as a symptom of various underlying medical conditions.
A more objective PD diagnostic model: integrating texture feature markers of cerebellar gray matter and white matter through machine learning
Authors: Chen Yini , Qi Yiwei , Li Tianbai , Lin Andong , Ni Yang , Pu Renwang , Sun Bo
Published: June 2024

Objective

The purpose of this study is to explore whether machine learning can be used to establish an effective model for the diagnosis of Parkinson's disease (PD) by using texture features extracted from cerebellar gray matter and white matter, so as to identify subtle changes that cannot be observed by the naked eye.

Method

This study involved a data collection period from June 2010 to March 2023, including 374 subjects from two cohorts. The Parkinson's Progression Markers Initiative (PPMI) served as the training set, with control group and PD patients (HC: 102 and PD: 102) from 24 global sites. Our institution's data was utilized as the test set (HC: 91 and PD: 79). Machine learning was employed to establish multiple models for PD diagnosis based on texture features of the cerebellum's gray and white matter. Results underwent evaluation through 5-fold cross-validation analysis, calculating the area under the receiver operating characteristic curve (AUC) for each model. The performance of each model was compared using the Delong test, and the interpretability of the optimized model was further augmented by employing Shapley additive explanations (SHAP).

Results

The AUCs for all pipelines in the validation dataset were compared using FeAture Explorer (FAE) software. Among the models established by Kruskal-Wallis (KW) and logistic regression via Lasso (LRLasso), the AUC was highest using the “one-standard error” rule. 'WM_original_glrlm_GrayLevelNonUniformity' was considered the most stable and predictive feature.

Conclusion

The texture features of cerebellar gray matter and white matter combined with machine learning may have potential value in the diagnosis of Parkinson's disease, in which the heterogeneity of white matter may be a more valuable imaging marker.
Astrocytic Calcium Signaling Toolkit (astroCaST): efficient analysis of dynamic astrocytic calcium events
Authors: Reising Jan Philipp , Gonzalez-Sanchez Ana Cristina , Samara Athina , Herlenius Eric
Published: June 2024

The Astrocytic Calcium Signaling Toolkit (astroCaST) is a novel solution to a longstanding challenge in neuroscience research: the specialized analysis of astrocytic calcium events within fluorescence time-series imaging. Distinct from existing neuron-centric tools, astroCaST is adept at detecting and clustering astrocytic calcium events based on their unique spatiotemporal characteristics, thus filling a gap in astrocytic research methodologies. This toolkit not only facilitates the detection of such events but also extends its utility to provide comprehensive end-to-end analysis. This feature is absent in most tools targeting astrocytic activity. AstroCaST's development was motivated by the critical need for dedicated software that supports researchers in transitioning from raw video data to insightful experimental conclusions, efficiently managing large-scale datasets without compromising computational speed. It offers a user-friendly interface that caters to both novice and expert users, incorporating both a graphical user interface (GUI) for detailed explorations and a command-line interface (CLI) for extensive analyses. Expected outcomes from utilizing astroCaST include the ability to process and analyze a significantly larger volume of data. This enables a more profound and comprehensive analysis than previously possible, addressing the demands of large-scale astrocytic studies. In summary, astroCaST aims to advance astrocytic calcium imaging analysis, offering a tailored, efficient, and comprehensive toolset that enhances our understanding of astrocytic functions and their implications in neuroscience.
Degree centrality-based resting-state functional magnetic resonance imaging explores central mechanisms in lumbar disc herniation patients with chronic low back pain
Authors: Mei Jianbing , Hu Yong
Published: June 2024

Objective

To investigate the central mechanism of lumbar disc herniation in patients with chronic low back pain (LDHCP) using resting-state functional magnetic resonance imaging (rs-fMRI) utilizing the Degree Centrality (DC) method.

Methods

Twenty-five LDHCP and twenty-two healthy controls (HCs) were enrolled, and rs-fMRI data from their brains were collected. We compared whole-brain DC values between the LDHCP and HC groups, and examined correlations between DC values within the LDHCP group and the Visual Analogue Score (VAS), Oswestry Dysfunction Index (ODI), and disease duration. Diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curve analysis.

Results

LDHCP patients exhibited increased DC values in the bilateral cerebellum and brainstem, whereas decreased DC values were noted in the left middle temporal gyrus and right post-central gyrus when compared with HCs. The DC values of the left middle temporal gyrus were positively correlated with VAS (r = 0.416, p = 0.039) and ODI (r = 0.405, p = 0.045), whereas there was no correlation with disease duration (p > 0.05). Other brain regions showed no significant correlations with VAS, ODI, or disease duration (p > 0.05). Furthermore, the results obtained from ROC curve analysis demonstrated that the Area Under the Curve (AUC) for the left middle temporal gyrus was 0.929.

Conclusion

The findings indicated local abnormalities in spontaneous neural activity and functional connectivity in the bilateral cerebellum, bilateral brainstem, left middle temporal gyrus, and right postcentral gyrus among LDHCP patients.
Leptomeningeal enhancement in multiple sclerosis: a focus on patients treated with hematopoietic stem cell transplantation
Authors: Marchi Leonardo , Mariottini Alice , Viti Vittorio , Bianchi Andrea , Nozzoli Chiara , Repice Anna Maria , Boncompagni Riccardo , Ginestroni Andrea , Damato Valentina , Barilaro Alessandro , Chiti Stefano , Saccardi Riccardo , Fainardi Enrico , Massacesi Luca
Published: June 2024

Background

Leptomeningeal enhancement (LME) is considered an MRI marker of leptomeningeal inflammation in inflammatory neurological disorders, including multiple sclerosis (MS). To our knowledge, no disease-modifying therapies (DMTs) have been demonstrated to affect LME number or morphology so far.

Methods

Monocentric study investigating the frequency and number of LME in a cohort of people with (pw)MS who performed a 3 T brain MRI with a standardized protocol (including a post-contrast FLAIR sequence), and exploring the impact of autologous hematopoietic stem cell transplantation (AHSCT) on this marker. In a longitudinal pilot study, consecutive MRIs were also analyzed in a subgroup of pwMS, including patients evaluated both pre- and post-AHSCT.

Results

Fifty-five pwMS were included: 24/55 (44%) had received AHSCT (AHSCT group) and 31 other treatments (CTRL group). At least one LME was identified in 19/55 (35%) cases (42 and 29% in the AHSCT and CTRL groups, respectively; p = 0.405). In the AHSCT group, LME number correlated with age at AHSCT (R = 0.50; p = 0.014), but not with age at post-treatment MRI. In the longitudinal pilot study (n = 8), one LME disappeared following AHSCT in 1/4 patients, whereas LME number was unchanged in the remaining four pwMS from the CTRL group.

Discussion

These results suggest that AHSCT may affect development and persistence of LME, strengthening the indication for early use of effective therapies bioavailable within the central nervous system (CNS), and therefore potentially targeting compartmentalized inflammation.
The rate-pressure product combined model within 24 h on admission predicts the 30-day mortality rate in conservatively treated patients with intracerebral hemorrhage
Authors: Zheng Hui , Tang Yuguang , Zhou Hai , Ji Xiang
Published: June 2024

Background and objectives

Recently, some literature has proposed new indicators such as rate-pressure product, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, etc. However, there has been no literature that has utilized these new indicators to establish a predictive model for assessing the risk of mortality in patients within 24 h on admission. Therefore, this study aims to build a predictive model that can rapidly assess the likelihood of mortality in patients within 24 h of admission.

Methods

The datasets used in this study are available from the corresponding author upon reasonable request. Patients were randomly assigned to the training or validation cohort based on a ratio of 7:3, which was implemented as internal validations for the final predictive models. In the training set, least absolute shrinkage and selection operator (LASSO) regression was employed to select predictive factors, followed by both univariate and subsequent multivariate analysis. The predictive ability was assessed by the area under the receiver operating characteristic (ROC) curve.

Results

A total of 428 patients were included in our research. The final model included 4 independent predictors (Glasgow Coma Scale, hematoma volume, rate-pressure product, c-reactive protein) and was developed as a simple-to-use nomogram. The training set and internal validation set model’s C-index are 0.933 and 0.954, demonstrating moderate predictive ability with regard to risks of mortality. Compared to ICH score (AUC: 0.910 and 0.925), the net reclassification index (NRI) is 0.298 (CI = −0.105 to 0.701, p: 0.147) and integrated discrimination improvement (IDI) is 0.089 (CI = −0.049 to 0.228, p: 0.209). Our model is equally excellent as the classic ICH score model.

Conclusion

We developed a model with four independent risk factors to predict the mortality of ICH patients. Our predictive model is effective in assessing the risk of mortality in patients within 24 h on admission, which might be worth considering in clinical settings after further external validation.
Dual antiplatelet therapy for ischemic stroke with intracranial arterial stenosis: a systematic review and meta-analysis
Authors: Shao Haifeng , He Song , Ni Ping , Zheng Danni , Yu Nengwei , Chen Qiao , Leng Xinyi , Lin Yan , Li Suping , Yang Jie , Wang Xia
Published: June 2024

Background

The safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious.

Aims

This study evaluates DAPT’s effectiveness and safety for these patients.

Methods

This review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4.

Results

Analysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46–0.59, p < 0.001) and recurrent stroke (RR = 0.37; 95% CI: 0.30–0.44, p < 0.001) compared to SAPT. There was no significant increase in bleeding events (RR = 1.34; 95% CI: 0.97–1.85, p = 0.07) or cerebral hemorrhage (RR = 0.47; 95% CI: 0.17–1.31, p = 0.15).

Conclusion

DAPT proveed to be effective and safe for ischemic stroke patients with ICAS and significantly reduced stroke and the composite endpoint of ischemic and bleeding events without elevating bleeding risks.
Patisiran for the treatment of patients with p.Ile88Leu hereditary transthyretin amyloidosis: an Italian real-life experience
Authors: Urbinati Giacomo , Cani Ilaria , Currò Dossi Marco , Longhi Simone , Carigi Samuela , Gagliardi Christian , Biagini Elena , Galiè Nazzareno , Cortelli Pietro , Guaraldi Pietro
Published: June 2024

Objectives

Evidence on the activity of patisiran therapy in specific subgroups of patients with hereditary transthyretin amyloidosis variant (ATTRv) is still scarce. This prospective real-world study was designed to provide the first in-depth clinical data on the effectiveness of patisiran in patients with ATTRv reporting the p.Ile88Leu variant, the most widespread variant in the Emilia-Romagna regional area, which has been less represented in previous clinical trials.

Patients and methods

This prospective study evaluated all the patients with genetically proven ATTRv (p.Ile88Leu) and polyneuropathy treated with patisiran in the Emilia-Romagna referral centers for ATTRv (Institute of Neurological Sciences in Bologna and Division of Neurology in Rimini) from March 2021 to April 2023. All subjects underwent clinical and neurological evaluations at baseline and after 9–12 months of treatment.

Results

A total of 22 patients were included in the study; the median age was 73 years (IQR: 9), the age at diagnosis was 72 years (IQR: 10), and the disease duration was 1.6 years (IQR: 2.3). We observed stability of all considered neurological and cardiological parameters at 9–12 months after the beginning of patisiran treatment.

Conclusion

Our findings support the clinical data regarding the effectiveness of patisiran in stabilizing the disease course and extend this activity to the subset of patients with the p.Ile88Leu variant.
Paradigm shift in Parkinson's disease: using continuous telemonitoring to improve symptoms control. Results from a 2-years journey
Authors: Konitsiotis Spyridon , Alexoudi Athanasia , Zikos Panagiotis , Sidiropoulos Christos , Tagaris George , Xiromerisiou Georgia , Tsamis Konstantinos , Kostikis Nicholas , Kanellos Foivos , Ntanis Adamantios , Kontaxis Spyridon , Rigas George
Published: June 2024

Introduction

Conventional care in Parkinson's disease (PD) faces limitations due to the significant time and location commitments needed for regular assessments, lacking quantitative measurements. Telemonitoring offers clinicians an opportunity to evaluate patient symptomatology throughout the day during activities of daily living.

Methods

The progression of PD symptoms over a two-year period was investigated in patients undergoing traditional evaluation, supplemented by insights from ambulatory measurements. Physicians integrated a telemonitoring device, the PDMonitor®, into daily practice, using it for informed medication adjustments.

Results

Statistical analyses examining intra-subject changes for 17 subjects revealed a significant relative decrease of −43.9% in the device-reported percentage of time spent in “OFF” state (from 36.2 to 20.3%). Following the 24-month period, the majority of the subjects improved or exhibited stable symptom manifestation. In addition to positively impacting motor symptom control, telemonitoring was found to enhance patient satisfaction about their condition, medication effectiveness, and communication with physicians.

Discussion

Considering that motor function is significantly worsened over time in patients with PD, these findings suggest a positive impact of objective telemonitoring on symptoms control. Patient satisfaction regarding disease management through telemonitoring can potentially improve adherence to treatment plans. In conclusion, remote continuous monitoring paves the way for a paradigm shift in PD, focusing on actively managing and potentially improve symptoms control.
Age-related changes of dopamine D1 and D2 receptors expression in parvalbumin-positive cells of the orbitofrontal and prelimbic cortices of mice
Authors: Dong Jihui , Wei Xiaoyan , Huang Ziran , Tian Jing , Zhang Wen
Published: June 2024

Dopamine (DA) plays a pivotal role in reward processing, cognitive functions, and emotional regulation. The prefrontal cortex (PFC) is a critical brain region for these processes. Parvalbumin-positive (PV+) neurons are one of the major classes of inhibitory GABAergic neurons in the cortex, they modulate the activity of neighboring neurons, influencing various brain functions. While DA receptor expression exhibits age-related changes, the age-related changes of these receptors in PV+ neurons, especially in the PFC, remain unclear. To address this, we investigated the expression of DA D1 (D1R) and D2 (D2R) receptors in PV+ neurons within the orbitofrontal (OFC) and prelimbic (PrL) cortices at different postnatal ages (P28, P42, P56, and P365). We found that the expression of D1R and D2R in PV+ neurons showed both age- and region-related changes. PV+ neurons in the OFC expressed a higher abundance of D1 than those in the PrL, and those neurons in the OFC also showed higher co-expression of D1R and D2R than those in the PrL. In the OFC and PrL, D1R in PV+ neurons increased from P28 and reached a plateau at P42, then receded to express at P365. Meanwhile, D2R did not show significant age-related changes between the two regions except at P56. These results showed dopamine receptors in the prefrontal cortex exhibit age- and region-specific changes, which may contribute to the difference of these brain regions in reward-related brain functions.
Fluorescence lifetime imaging of AMPA receptor endocytosis in living neurons: effects of Aβ and PP1
Authors: Prinkey Katie , Thompson Emily , Saikia Junmi , Cid Tania , Dore Kim
Published: June 2024

The relative amount of AMPA receptors expressed at the surface of neurons can be measured using superecliptic pHluorin (SEP) labeling at their N-terminus. However, the high signal variability resulting from protein overexpression in neurons and the low signal observed in intracellular vesicles make quantitative characterization of receptor trafficking difficult. Here, we establish a real-time live-cell assay of AMPAR trafficking based on fluorescence lifetime imaging (FLIM), which allows for simultaneous visualization of both surface and intracellular receptors. Using this assay, we found that elevating amyloid-beta (Aβ) levels leads to a strong increase in intracellular GluA1 and GluA2-containing receptors, indicating that Aβ triggers the endocytosis of these AMPARs. In APP/PS1 Alzheimer's disease model mouse neurons, FLIM revealed strikingly different AMPAR trafficking properties for GluA1- and GluA3-containing receptors, suggesting that chronic Aβ exposure triggered the loss of both surface and intracellular GluA3-containing receptors. Interestingly, overexpression of protein phosphatase 1 (PP1) also resulted in GluA1 endocytosis as well as depressed synaptic transmission, confirming the important role of phosphorylation in regulating AMPAR trafficking. This new approach allows for the quantitative measurement of extracellular pH, small changes in receptor trafficking, as well as simultaneous measurement of surface and internalized AMPARs in living neurons, and could therefore be applied to several different studies in the future.