bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delivering synaptic protein mRNAs via extracellular vesicles ameliorates cognitive impairment in a mouse model of Alzheimer’s disease
Authors: Cai Huimin , Pang Yana , Ren Ziye , Fu Xiaofeng , Jia Longfei 
Published: March 2024

Abstract
Background
Synaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer’s disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD.

Methods
In this study, we included 57 patients with AD and 56 healthy controls. We evaluated their brain atrophy through magnetic resonance imaging using the medial temporal lobe atrophy score. We measured the levels of four synaptic proteins, including synaptosome-associated protein 25 (SNAP25), growth-associated protein 43 (GAP43), neurogranin, and synaptotagmin 1 in both plasma neuronal-derived EVs and cerebrospinal fluid (CSF). We further examined the association of synaptic protein levels with brain atrophy. We also evaluated the levels of these synaptic proteins in the brains of 5×FAD mice. Then, we loaded rabies virus glycoprotein-engineered EVs with messenger RNAs (mRNAs) encoding GAP43 and SNAP25 and administered these EVs to 5×FAD mice. After treatment, synaptic proteins, dendritic density, and cognitive function were evaluated.

Results
The results showed that GAP43, SNAP25, neurogranin, and synaptotagmin 1 were decreased in neuronal-derived EVs but increased in CSF in patients with AD, and the changes corresponded to the severity of brain atrophy. GAP43 and SNAP25 were decreased in the brains of 5×FAD mice. The engineered EVs efficiently and stably delivered these synaptic proteins to the brain, where synaptic protein levels were markedly upregulated. Upregulation of synaptic protein expression could ameliorate cognitive impairment in AD by promoting dendritic density. This marks the first successful delivery of synaptic protein mRNAs via EVs in AD mice, yielding remarkable therapeutic effects.

Conclusions
Synaptic proteins are closely related to AD processes. Delivery of synaptic protein mRNAs via EVs stands as a promising effective precision treatment strategy for AD, which significantly advances the current understanding of therapeutic approaches for the disease.
Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin
Authors: Li Zhenxian , Zhu Haimei , Liu Hao , Liu Dayue , Liu Jianhe , Zhang Yi , Qin Zhang , Xu Yijia , Peng Yuan , Ruan Lihua , Li Jintao , He Yao , Liu Bin , Long Yun 
Published: March 2024

AbstractThe development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.
Association between intensive care unit nursing grade and mortality in patients with cardiogenic shock and its cost-effectiveness
Authors: Choi Ki Hong , Kang Danbee , Lee Jin , Park Hyejeong , Park Taek Kyu , Lee Joo Myung , Song Young Bin , Hahn Joo-Yong , Choi Seung-Hyuk , Gwon Hyeon-Cheol , Cho Juhee , Yang Jeong Hoon 
Published: March 2024

Abstract
Background
Despite the high workload of cardiac intensive care unit (ICU), there is a paucity of evidence on the association between nurse workforce and mortality in patients with cardiogenic shock (CS). This study aimed to evaluate the prognostic impact of the ICU nursing grade on mortality and cost-effectiveness in CS.

Methods
A nationwide analysis was performed using the K-NHIS database. Patients diagnosed with CS and admitted to the ICU at tertiary hospitals were enrolled. ICU nursing grade was defined according to the bed-to-nurse ratio: grade1 (bed-to-nurse ratio < 0.5), grade2 (0.5 ≤ bed-to-nurse ratio < 0.63), and grade3 (0.63 ≤ bed-to-nurse ratio < 0.77) or above. The primary endpoint was in-hospital mortality. Cost-effective analysis was also performed.

Results
Of the 72,950 patients with CS, 27,216 (37.3%) were in ICU nursing grade 1, 29,710 (40.7%) in grade 2, and 16,024 (22.0%) in grade ≥ 3. The adjusted-OR for in-hospital mortality was significantly higher in patients with grade 2 (grade 1 vs. grade 2, 30.6% vs. 37.5%, adjusted-OR 1.14, 95% CI1.09–1.19) and grade ≥ 3 (40.6%) with an adjusted-OR of 1.29 (95% CI 1.23–1.36) than those with grade 1. The incremental cost-effectiveness ratio of grade1 compared with grade 2 and ≥ 3 was $25,047/year and $42,888/year for hospitalization and $5151/year and $5269/year for 1-year follow-up, suggesting that grade 1 was cost-effective. In subgroup analysis, the beneficial effects of the high-intensity nursing grade on mortality were more prominent in patients who received CPR or multiple vasopressors usage.

Conclusions
For patients with CS, ICU grade 1 with a high-intensity nursing staff was associated with reduced mortality and more cost-effectiveness during hospitalization compared to grade 2 and grade ≥ 3, and its beneficial effects were more pronounced in subjects at high risk of CS.

Graphical abstract
A validated restriction enzyme ddPCR cg05575921 (AHRR) assay to accurately assess smoking exposure
Authors: Fitzgerald Sandra , Bhat Basharat , Print Cristin , Jones Gregory T. 
Published: March 2024

Abstract
Background & Methods
In this study, a novel restriction enzyme (RE) digestion-based droplet digital polymerase chain reaction (ddPCR) assay was designed for cg005575921 within the AHRR gene body and compared with matching results obtained by bisulfite conversion (BIS) ddPCR and Illumina DNA methylation array.

Results
The RE ddPCR cg05575921 assay appeared concordant with BIS ddPCR (r2 = 0.94, P < 0.0001) and, when compared with the Illumina array, had significantly better smoking status classification performance for current versus never smoked (AUC 0.96 versus 0.93, P < 0.04) and current versus ex-smoker (AUC 0.88 versus 0.83, P < 0.04) comparisons.

Conclusions
The RE ddPCR cg05575921 assay accurately predicts smoking status and could be a useful component of ‘precision-medicine’ chronic disease risk screening tools.
Pediatric emergency department-based asthma education tools and parent/child asthma knowledge
Authors: Goodman Kina , Arriaga Rosa I. , Korman Rawan , Zafar Farzina , Stephens Cal , Kumari Polly , Jayaprakash Karthika , Fitzpatrick Anne M. , Cooper Nicholas , Morris Claudia R. 
Published: March 2024

AbstractAsthma exacerbations are a leading cause of pediatric hospitalizations despite multiple efforts to educate patients and families on disease course and medication management. Asthma education in the pediatric emergency department (ED) is challenging, and although the use of written action plans has been associated with reduction in hospitalizations and ED visits, written tools may not be useful for individuals with low health literacy. Moreover, asthmatic children should participate in their asthma education. In this prospective randomized study of 53 families presenting to a pediatric ED with a child experiencing an asthma exacerbation, education on asthma was presented via an interactive mobile-based video-game versus a standard-of-care asthma education video (SAV). Median age was 10 years; 64% were males. Many patients had moderate-to-severe asthma, with 57% experiencing ≥ 2 asthma-related ED visits in the last year, 58% requiring hospitalization and 32% reporting a critical care admission. In this cohort, the mobile-based video-game was found to be a feasible, acceptable educational tool; 86% of parents and 96% of children liked the game, while 96% of parents and 76% of children preferred playing the game over watching a SAV. Despite a history of persistent asthma, only 34% of children used an inhaled corticosteroid while 70% required rescue inhaler use in the prior week. Basic asthma knowledge was sub-optimal with only 60% of parents and 43% of children correctly recognizing symptoms that should prompt immediate medical care. This reflects a major gap in asthma knowledge that coexists with parental misconceptions regarding optimal asthma management.
Predicting three or more metastatic nodes using contrast-enhanced lymphatic US findings in early breast cancer
Authors: Niu Zihan , Hao Yunxia , Gao Yuanjing , Zhang Jing , Xiao Mengsu , Mao Feng , Zhou Yidong , Cui Ligang , Jiang Yuxin , Zhu Qingli 
Published: March 2024

Abstract
Objectives
To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs).

Materials and methods
Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis.

Results
One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80–0.81; Brier = 0.066–0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs.

Conclusion
Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making.

Trial registration
This trial is registered on www.chictr.org.cn: ChiCTR2000031231. Registered March 25, 2020.

Critical relevance statement
A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer.

Key points
• CEUS can help identify and diagnose SLN in early breast cancer preoperatively.
• Combining lymphatic and grayscale US findings can predict axillary tumor burden.
• The nomogram showed a high diagnostic value in validation cohorts.

Graphical Abstract
Time-aware outlier detection in health physique monitoring in edge-aided sport education decision-makings
Authors: Li Yanjie , Kang Liqin , Li Zhaojin , Jiang Fugao , Bi Nan , Du Tao , Abiri Maryam 
Published: March 2024

AbstractThe increasing popularity of various intelligent sensor and mobile communication technologies has enabled quick health physique sensing, monitoring, collection and analyses of students, which significantly promoted the development of sport education. Through collecting the students’ physiological signals and transmitted them to edge servers, we can precisely analyze and judge whether a student is in poor health (e.g., an outlier). However, with time elapsing, the accumulated physiological signals of students become massive, which places a heavy burden on the quick storage and in-time processing of physiological data of students. In this situation, it is becoming a necessity to develop a time-aware outlier detection technique for health physique evaluation of students in a time-efficient way. Considering this challenge, we propose a novel time-aware outlier detection method named TOD based on Locality-Sensitive Hashing. TOD condenses extensive physiological student data into a concise set of health indices. Leveraging these indices, we can efficiently identify potential student outliers from a large pool of candidates with precision and speed. Finally, we have designed a group of simulated experiments based on WS-DREAM dataset. Experiment results prove the feasibility and superiority of the TOD method compared with other existing methods.
Accurate and fast congestion feedback in MEC-enabled RDMA datacenters
Authors: He Xin , Liang Feifan , Fan Weibei , Wang Junchang , Han Lei , Xiao Fu , Dou Wanchun 
Published: March 2024

AbstractMobile edge computing (MEC) is a novel computing paradigm that pushes computation and storage resources to the edge of the network. The interconnection of edge servers forms small-scale data centers, enabling MEC to provide low-latency network services for mobile users. Nowadays, Remote Direct Memory Access (RDMA) has been widely deployed in such data centers to reduce CPU overhead and network latency. Plenty of congestion control mechanisms have been proposed for RDMA data centers, aiming to provide low-latency data delivery and high throughput network services. However, our fine-grained experimental analysis reveals that existing congestion control mechanisms still have performance limitations due to inappropriate congestion notifications and the long congestion feedback cycle. In this paper, we propose Mercury, which is an accurate and fast congestion feedback mechanism. Mercury comprises two key components: (1) the state-driven congestion detection and (2) the window-based congestion notification. Specifically, the state-driven congestion detection monitors the queue length and the number of packets received at the switch egress port when the PFC is triggered. It determines the states of egress ports and identifies flows that really contribute to congestion. Then, window-based congestion notification calculates the window sizes for congested flows and rapidly returns Congestion Notification Packets (CNPs) with the window information to the sender. It facilitates the rate adjustment of congested flows. Mercury is compatible with existing RDMA CC mechanisms and can be easily implemented in switches. We employ real-world data sets and conduct both micro-benchmark and large-scale simulations to evaluate the performance of Mercury. The results indicate that, thanks to the accurate and fast congestion feedback, Mercury achieves a reduction in the 99th tail flow completion time by up to 45.1%, 41.8%, 38.7%, 30.9%, and 37.9% compared with Timely, DCQCN, DCQCN+TCD, PACC, and HPCC, respectively.
2- to 20-year myelomeningocele follow-up outcomes from a referral center in Southern Iran: the Shiraz experience
Authors: Zoghi Sina , Mosayebi Mohammad Amin , Feili Maryam , Eskandari Hossein , Jalalinezhad Hadis , Masoudi Mohammad Sadegh , Taheri Reza 
Published: March 2024

Abstract
Background
The current convention for treatment of children with myelomeningocele (MMC) is timely surgical intervention combined with long-term follow-up by a multidisciplinary specialized team. This study aims to investigate the outcomes of MMC patients treated at Namazi Hospital.

Methods
All children presenting to Namazi Hospital with myelomeningocele between May 2001 and August 2020 were eligible for this study. For those with a documented telephone number, follow-up phone surveys with the patient’s caregivers, on top of the review of the medical documents were carried out to assess mortality, morbidities, and the functional outcome of the care provided to them.

Results
A total of 125 patients were studied (62 females). All of the patients were followed up for a mean duration of 6.28 years (range 1–23 years). The majority were located in the lumbosacral area. All of the patients underwent postnatal surgical intervention for MMC in Namazi Hospital. Mean age at surgery was 9.51 days. There were statistically significant differences between urinary and bowel incontinence and presence of scoliosis, MMT grading of the lower limbs, school attendance, number of readmissions, and requirement of laminectomy at the initial surgical intervention.

Conclusions
This study is the first to characterize the long-term outcomes of MMC patients in Iran. This study illustrates that there is a great need for improved access to and coordination of care in antenatal, perioperative, and long-term stages to improve morbidity and mortality.
Pediatric hospital utilization for patients with avoidant restrictive food intake disorder
Authors: Milliren Carly E. , Crowley McGreggor , Carmody Julia K. , Bern Elana M. , Eldredge Olivia , Richmond Tracy K. 
Published: March 2024

Abstract
Background
Avoidant restrictive food intake disorder (ARFID) is a relatively new feeding and eating disorder added to the DSM-5 in 2013 and ICD-10 in 2018. Few studies have examined hospital utilization for patients with ARFID specifically, and none to date have used large administrative cohorts. We examined inpatient admission volume over time and hospital utilization and 30-day readmissions for patients with ARFID at pediatric hospitals in the United States.

Methods
Using data from the Pediatric Health Information System (PHIS), we identified inpatient admissions for patients with ARFID (by principal International Classification of Diseases, 10th Revision, ICD-10 diagnosis code) discharged October 2017–June 2022. We examined the change over time in ARFID volume and associations between patient-level factors (e.g., sociodemographic characteristics, co-morbid conditions including anxiety and depressive disorders and malnutrition), hospital ARFID volume, and hospital utilization including length of stay (LOS), costs, use of enteral tube feeding or GI imaging during admission, and 30-day readmissions. Adjusted regression models were used to examine associations between sociodemographic and clinical factors on LOS, costs, and 30-day readmissions.

Results
Inpatient ARFID volume across n = 44 pediatric hospitals has increased over time (β = 0.36 per month; 95% CI 0.26–0.46; p < 0.001). Among N = 1288 inpatient admissions for patients with ARFID, median LOS was 7 days (IQR = 8) with median costs of $16,583 (IQR = $18,115). LOS and costs were highest in hospitals with higher volumes of ARFID patients. Younger age, co-morbid conditions, enteral feeding, and GI imaging were also associated with LOS. 8.5% of patients were readmitted within 30 days. In adjusted models, there were differences in the likelihood of readmission by age, insurance, malnutrition diagnosis at index visit, and GI imaging procedures during index visit.

Conclusions
Our results indicate that the volume of inpatient admissions for patients with ARFID has increased at pediatric hospitals in the U.S. since ARFID was added to ICD-10. Inpatient stays for ARFID are long and costly and associated with readmissions. It is important to identify effective and efficient treatment strategies for ARFID in the future.
Exploring the potential effects of forest urbanization on the interplay between small mammal communities and their gut microbiota
Authors: Bouilloud Marie , Galan Maxime , Pradel Julien , Loiseau Anne , Ferrero Julien , Gallet Romain , Roche Benjamin , Charbonnel Nathalie 
Published: March 2024

AbstractUrbanization significantly impacts wild populations, favoring urban dweller species over those that are unable to adapt to rapid changes. These differential adaptative abilities could be mediated by the microbiome, which may modulate the host phenotype rapidly through a high degree of flexibility. Conversely, under anthropic perturbations, the microbiota of some species could be disrupted, resulting in dysbiosis and negative impacts on host fitness. The links between the impact of urbanization on host communities and their gut microbiota (GM) have only been scarcely explored. In this study, we tested the hypothesis that the bacterial composition of the GM could play a role in host adaptation to urban environments. We described the GM of several species of small terrestrial mammals sampled in forested areas along a gradient of urbanization, using a 16S metabarcoding approach. We tested whether urbanization led to changes in small mammal communities and in their GM, considering the presence and abundance of bacterial taxa and their putative functions. This enabled to decipher the processes underlying these changes. We found potential impacts of urbanization on small mammal communities and their GM. The urban dweller species had a lower bacterial taxonomic diversity but a higher functional diversity and a different composition compared to urban adapter species. Their GM assembly was mostly governed by stochastic effects, potentially indicating dysbiosis. Selection processes and an overabundance of functions were detected that could be associated with adaptation to urban environments despite dysbiosis. In urban adapter species, the GM functional diversity and composition remained relatively stable along the urbanization gradient. This observation can be explained by functional redundancy, where certain taxa express the same function. This could favor the adaptation of urban adapter species in various environments, including urban settings. We can therefore assume that there are feedbacks between the gut microbiota and host species within communities, enabling rapid adaptation.
Some aspects of Morris-Thorne wormhole in
gravity
Authors: Chalavadi Chaitra Chooda , Venkatesha V. 
Published: March 2024

Abstract
The aim of this manuscript is to study traversable wormhole geometries in the non-metricity and matter coupling gravity. We investigate the Morris-Thorne wormhole metric within the framework of extended symmetric teleparallel gravity. With an anisotropic matter distribution, we explore two distinct wormhole models under two different scenarios. First, we consider the equations of state, and then we assume specific shape functions for each scenario. In both cases, the shape function satisfies all fundamental criteria for a traversable wormhole. We present our results through graphical representations and analyze the energy conditions. Furthermore, we examine the behavior of the wormhole through the anisotropic parameter. Finally, we present our conclusions based on the obtained results.