bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole blood ratio of CDK1/CX3CR1 mRNA expression combined to lactate refines the prediction of ICU mortality in septic patients in the Sepsis-3 era: a proof-of-concept study
Authors: Cazalis Marie-Angélique , Kreitmann Louis , Monneret Guillaume , Pachot Alexandre , Brengel-Pesce Karen , Llitjos Jean-François
Published: January 2025

Background

Transcriptomics biomarkers have been widely used to predict mortality in patients with sepsis. However, the association between mRNA levels and outcomes shows substantial variability over the course of sepsis, limiting their predictive performance. We aimed to: (a) identify and validate an mRNA biomarker signature whose association with all-cause intensive care unit (ICU) mortality is consistent at several timepoints; and (b) evaluate how this mRNA signature could be used in association with lactate levels for predictive and prognostic enrichment in sepsis.

Methods

We conducted a gene expression analysis study at two timepoints (day 1 and day 2–3 following ICU admission) using microarray data from adult septic patients to identify candidate biomarkers predictive of all-cause ICU mortality. We validated mRNA biomarkers using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) on an external validation cohort. The predictive performance of the mRNA biomarkers combination was assessed in association with lactate level to refine ICU mortality prediction.

Main results

Among 180 chips from 100 septic patients, we identified 39 upregulated and 2 downregulated differentially expressed genes (DEGs) in survivors vs. non-survivors, both at day 1 and days 2–3 following ICU admission. We combined CDK1, the hub gene of upregulated DEGs, and CX3CR1 and IL1b to compute expression ratios. The CDK1/CX3CR1 ratio had the best performance to predict all-cause ICU mortality, with an area under the ROC curve (AUROC) of 0.77 (95% confidence interval [CI] 0.88–0.66) at day 1 and of 0.82 (95% CI 0.91–0.72) at days 2–3 after ICU admission. This performance was better than that of each individual mRNA biomarker. In the external validation cohort, the predictive performance of the CDK1/CX3CR1 ratio, measured using RT-qPCR, was similar to that of lactate when measure at day 1, and higher when measured at days 2–3. Combining lactate levels and the CDK1/CX3CR1 ratio, we identify 3 groups of patients with an increasing risk of ICU-mortality, ranging from 9 to 60% with an intermediate-risk group mortality rate of 28%.

Conclusion

With stable predictive performance over the first 3 days following ICU admission, the CDK1/CX3CR1 ratio identifies three groups of septic patients with increasing ICU mortality risk. In combination with lactate, this novel biomarker strategy may be useful for sepsis patient stratification for personalized medicine trials and ICU management.
Marital status and risk of type 2 diabetes among middle-aged and elderly population: a systematic review and meta-analysis
Authors: Karimi Mohammad Amin , Binaei Sara , Hashemi Seyed Hadi , Refahi Pegah , Olama Ensiyeh , Olama Elnaz , Mohammadpour Aydin , Yonjali Reza Mostafaei , Poudineh Mohadeseh , Deravi Niloofar
Published: January 2025

Background

Marital status is among the factors influencing type 2 diabetes mellitus (T2DM). However, the precise relationship remains incompletely understood. This meta-analysis aims to evaluate the association between marital status and the incidence of T2DM.

Methods

A review and meta-analysis of observational studies were conducted to investigate the relationship between marital status and diabetes incidence. We searched three databases, including PubMed, Google Scholar, and Scopus, for relevant studies published up to August 16th, 2023. In our initial search, we identified a total of 358 articles. After a demanding screening process involving evaluating titles, abstracts, and full-text content, we ultimately included six studies for our meta-analysis.

Result

Comprising a total of 1,440,904 participants, our study found that in comparison to married individuals, unmarried participants exhibited a higher likelihood of developing diabetes [odds ratio (OR): 1.47, 95% confidence interval (CI): 0.88–2.45, I2: 91%, p-value = 0.14]. Divorced participants had a reduced likelihood of developing diabetes compared to married participants (OR: 0.84, 95% CI: 0.77–0.91, I2: 17%, p < 0.001). Similarly, widowed participants showed a lower risk of developing diabetes compared to divorced participants (OR: 0.35, 95% CI: 0.26–0.46, I2: 83%, p < 0.00001).

Conclusion

This study provides strong evidence of links between marital status and type 2 diabetes risk. Unmarried individuals are more susceptible to T2DM, divorced individuals have a lower risk, and widowed individuals exhibit reduced T2DM risk. Further research should investigate underlying mechanisms and confounding factors.
Antiphospholipid antibodies positivity as a potential risk factor for restenosis following arteriovenous fistula stenting in hemodialysis patients: a pilot study
Authors: Taghavi Maxime , Lengelé Adrien , Laureys Marc , Jacobs Lucas , Kaysi Saleh , Collart Frédéric , Demulder Anne , Nortier Joëlle
Published: January 2025

Background

The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. AVF stenosis is a common complication, often requiring balloon angioplasty. For recurrent stenosis, AVF stenting may be an option. Persistent antiphospholipid antibody (aPL) positivity is frequently observed in hemodialysis (HD) patients and is associated with AVF thrombosis and stenosis. This study aimed to evaluate AVF stent survival without stenosis in aPL-positive hemodialysis patients.

Methods

A monocentric retrospective observational study was conducted on 35 patients who underwent AVF stenting between 1st January 2014 and 31st December 2023. The patients were divided into two groups: the aPL+ group [defined by a score of 3 or more based on the laboratory criteria of the 2023 ACR/EULAR for antiphospholipid syndrome (APS)] and the control group. Intrastent restenosis was defined as a chronic change in the AVFphysical examination or blood flow, confirmed by ultrasound (US) or angiography. Kaplan–Meier survival analysis was used to estimate the probability of stent survival without restenosis.

Results

The prevalence of intrastent restenosis was significantly higher in the aPL+ group at 24 months. The Kaplan–Meier survival analysis showed a significantly lower probability of AVF stent survival without restenosis in the aPL+ group (age-adjusted Hazard Ratio, 2.13 [IC95%, 1.70–2.69]).

Conclusion

To the best of our knowledge, we describe for the first time a statistically significant association between aPL+ and AVF intrastent restenosis. Intimal hyperplasia is a non-thrombotic lesion associated with aPL+ and is linked to the mammalian target of rapamycin (mTOR) signaling pathway. We hypothesize that aPL may contribute to intrastent restenosis by inducing intimal hyperplasia. Whether this phenomenon is mTOR-mediated and whether sirolimus-eluting stents or balloons could be a better option for aPL+ patients requires further study.
Bacterial community profiling and identification of bacteria with lignin-degrading potential in different gut segments of African palm weevil larvae (Rhynchophorus phoenicis)
Authors: Lenka Jessica , González-Tortuero Enrique , Kuba Shweta , Ferry Natalie
Published: January 2025

The microbiota within the guts of insects plays beneficial roles for their hosts, such as facilitating digestion and extracting energy from their diet. The African palm weevil (APW) lives within and feeds on the high lignin-containing trunk of palm trees; therefore, their guts could harbour a large community of lignin-degrading microbes. In this study, we aimed to explore the bacterial community within the gut of the APW larvae, specifically with respect to the potential for lignin degradation in various gut segments as a first step to determining the viability of mining bacterial lignin-degrading enzymes for the bioconversion of lignocellulosic biomass to biofuels and biomaterials. Bacterial metagenomic DNA was extracted from the foregut, midgut, and hindgut of larvae of the APW, and the V3–V4 hypervariable region of the 16S rRNA gene was sequenced using the Illumina MiSeq platform. The generated data were analysed and taxonomically classified to identify the different bacterial phylotypes within the gut community cumulatively and per gut segment. We then determined the presence, diversity, and abundance of bacteria associated with lignin degradation within each larval gut compartment as a basis for suggesting the gut segment(s) where lignin degradation occurs the most. All sequences were classified and belonged to the bacterial kingdom. Firmicutes (54.3%) and Proteobacteria (42.5%) were the most dominant phyla within the gut, followed distantly by Bacteroidota (1.7%) and Actinobacteriota (1.4%). Enterococcus, Levilactobacillus, Lactococcus, Shimwellia, Megasphaera, Klebsiella, Pectinatus, Salmonella, Lelliotia, and Enterobacter constituted the most abundant genera found across all gut segments. The foregut and midgut had many similar genera, whilst the hindgut appeared unique. Overall, 29.5% of total gut bacteria comprising 21 genera were lignin degraders found predominantly in the Firmicutes and Proteobacteria phyla (56.8 and 39.5%, respectively), then moderately in Actinobacteriota (2.5%) and Bacteroidota (1.1%). The most abundant ligninolytic genera were Levilactobacillus (46.4%), Klebsiella (22.9%), Enterobacter (10.7%), Lactiplantibacillus (5.9%), Citrobacter (2.2%), Corynebacterium (1.8%), Paucilactobacillus (1.8%), Serratia (1.5%), Bacteroides (1.1%), and Leucobacter (1.0%) found in different amounts in different gut compartments. The foregut had the most diverse and highest abundance of lignin-degrading phylotypes, and we present reasons that point to the foregut as the main location for the depolymerization of lignin in the APW larval gut.
Traditional pediatric massage enhanced the skeletal muscle mass in OVA-exposed adolescent rats via regulating SCFAs-FFAR2-IGF-1/AKT pathway
Authors: Lin Lin , Li Siyuan , Liu Que , Zhang Xingxing , Xiong Ying , Zhao Shaoyun , Cao Liyue , Gong Jiaxuan , Liu Yaping , Wu Rong
Published: January 2025

Objective

This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.

Methods

Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.

Results

OVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.

Conclusion

The retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.
High-affinity promotor binding of YhaJ mediates a low signal leakage for effective DNT detection
Authors: Kim Myeongbin , Kang Ryun , Park Hye Min , Cho Eun Bi , Lee Hye Rim , Ryu Seong Eon
Published: January 2025

The YhaJ transcription factor responds to dinitrophenol (DNT) and its metabolic products. The YhaJ-involving cells have been exploited for whole-cell biosensors of soil-buried landmines. Such biosensors would decrease the damage to personnel who approach landmine fields. By the structure determination of the DNA-binding domain (DBD) of YhaJ and the structure-guided mutagenesis, we found that the mutation increasing the DNA binding affinity decreases the signal leakage in the absence of an effector, resulting in a significant enhancement of the response ratio for the DNT metabolite detection. The decrease in signal leakage explains the LysR-type transcriptional regulators’ (LTTRs’) unique mechanism of signal absence repression by choosing between two different activation binding sites. We showed that the biosensor performance enhancement by the decrease in signal leakage could combine with the previous signal-enhancing mutations. The novel mechanism of performance enhancement of YhaJ shed light on bacterial transcription regulation and the optimization of biosensors that involve the large family of LTTRs.
Development and evaluation of the recombinant BP26 protein-based C-ELISA for human brucellosis diagnosis
Authors: Xie Yujia , Lin Shaoqing , Guo Liping , Qi Xinru , Zhao Shiqi , Pei Qichuan , Chen Yixiao , Wu Qi , Wang Yun , Yao Meixue , Yin Dehui
Published: January 2025

Introduction

Timely and accurate diagnosis is crucial for the effective treatment and prevention of brucellosis. Current serological diagnostics, primarily based on lipopolysaccharide (LPS), suffer from cross-reactivity with other Gram-negative bacteria, which limits their specificity. Periplasmic protein 26 (BP26), a highly immunogenic antigen found in Brucella, has emerged as a promising alternative for enhancing diagnostic specificity. This study aimed to develop and evaluate a competitive enzyme-linked immunosorbent assay (C-ELISA) utilizing monoclonal antibodies against BP26 for the diagnosis of human brucellosis, thereby providing a more accurate and specific diagnostic approach.

Methods

The study produced monoclonal antibody (mAb) against the BP26 protein through traditional mouse hybridoma technology and developed the C-ELISA method, and compared with a C-ELISA method based on LPS mAb. The detection performance was validated through the analysis of 190 human serum samples, which included 95 brucellosis serum samples and 95 negative serum samples collected by the Xuzhou Center for Disease Control and Prevention, and a comparative analysis was conducted on the diagnostic efficacy of indirect ELISA for brucellosis using both BP26 and LPS-based methods.

Results

The BP26 mAb based C-ELISA achieved 100% sensitivity and specificity in detecting human brucellosis, significantly outperforming the C-ELISA based LPS mAb. Furthermore, the accuracy of the indirect enzyme-linked immunosorbent assay (I-ELISA) using BP26 protein was 98.95%, compared to an accuracy of LPS diagnosis was 99.47%. These results indicated that the BP26 mAb can effectively and accurately detected human brucellosis infections.

Conclusion

This study successfully developed and evaluated a BP26 protein-based C-ELISA method for diagnosing human brucellosis, establishing a foundation for identifying alternative diagnostic antigens for brucellosis.
Unveiling and validating biomarkers related to the IL-10 family in chronic sinusitis with nasal polyps: insights from transcriptomics and single-cell RNA sequencing analysis
Authors: Liu Xinghong , Peng Yi , Guo Ling , Xiong Weilan , Liao Weijiang , Fan Jiangang
Published: January 2025

Introduction

Extensive efforts have been made to explore members of the IL-10 family as potential therapeutic strategies for various diseases; however, their biological role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains underexplored.

Methods

Gene expression datasets GSE136825, GSE179265, and GSE196169 were retrieved from the Gene Expression Omnibus (GEO) for analysis. Candidate genes were identified by intersecting differentially expressed genes (DEGs) between the CRSwNP and control groups (DEGsall) with those between the high- and low-score groups within the CRSwNP cohort (DEGsNP). Biomarker selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and the Boruta algorithm. Further refinement of biomarkers was carried out using receiver operating characteristic (ROC) analysis, with genes demonstrating an area under the curve (AUC) greater than 0.7 being considered significant. Genes exhibiting consistent expression trends and significant differences across both GSE136825 and GSE179265 were selected as potential biomarkers. Cell-type annotation was performed on GSE196169, and the expression profiles of the biomarkers across various cell types were analyzed. A competing endogenous RNA (ceRNA) network and a biomarker-drug interaction network were also established. Additionally, the mRNALocater database was utilized to determine the cellular localization of the identified biomarkers.

Results

The intersection of 1817 DEGsall and 24 DEGsNP yielded 15 candidate genes. Further filtering through LASSO, SVM-RFE, and Boruta led to the identification of seven candidate biomarkers: PRB3, KRT16, MUC6, SPAG4, FGFBP1, NR4A1, and GSTA2. Six of these genes demonstrated strong diagnostic performance in GSE179265, while four biomarkers, showing both significant differences and consistent expression trends, were validated in both GSE179265 and GSE136825. Single-cell sequencing analysis of GSE196169 revealed seven distinct cell types, including endothelial cells, with the biomarkers predominantly expressed in epithelial cells. The ceRNA network comprised nine nodes and eleven edges, with only FGFBP1 exhibiting a complete lncRNA-miRNA-mRNA interaction.

Discussion

This study identifies several novel biomarkers and their associated drugs for CRSwNP therapy, as well as potential therapeutic targets, such as spiperone and arnenous acid, identified through molecular docking. Ultimately, this work underscores the identification of four IL-10 family-related biomarkers, providing a theoretical foundation for future clinical research in CRSwNP.
LncRNA HOXA10-AS as a novel biomarker and therapeutic target in human cancers
Authors: Hu Xin , Wang Yong , Zhang Sijia , Gu Xiaosi , Zhang Xiaoyu , Li Lianlian
Published: January 2025

Long non-coding RNAs (lncRNAs) are crucial regulatory molecules that participate in numerous cellular development processes, and they have gathered much interest recently. HOXA10 antisense RNA (HOXA10-AS, also known as HOXA-AS4) is a novel lncRNA that was identified to be dysregulated in some prevalent malignancies. In this review, the clinical significance of HOXA10-AS for the prognosis of various cancers is analyzed. In addition, the major advances in our understanding of the cellular biological functions and mechanisms of HOXA10-AS in different human cancers are summarized. These cancers include esophageal carcinoma (ESCA), gastric cancer (GC), glioma, laryngeal squamous cell carcinoma (LSCC), acute myeloid leukemia (AML), lung adenocarcinoma (LUAD), nasopharyngeal carcinoma (NPC), oral squamous cell carcinoma (OSCC), and pancreatic cancer. We also note that the aberrant expression of HOXA10-AS promotes malignant progression through various underlying mechanisms. In conclusion, HOXA10-AS is expected to serve as an ideal clinical biomarker and an effective cancer therapy target.
Sleep structure of short-term insomnia disorder with mild cognitive impairment in older adults and their correlation with cognitive function: a case-control study
Authors: Zeng Jinkun , Wei Jia , Qi Ruobing
Published: January 2025

Objectives

This study seeks to delineate the sleep architecture characteristics in older adults with short-term insomnia and mild cognitive impairment (MCI) and to explore their association with cognitive performance.

Methods

Ninety elderly individuals with short-term insomnia were enrolled and stratified into two cohorts based on their Montreal Cognitive Assessment (MoCA) scores: the Short-Term Insomnia Group (STID) comprising 35 participants and the Short-Term Insomnia with Cognitive Impairment Group (STID-MCI) with 55 participants. Demographic data, Pittsburgh Sleep Quality Index (PSQI), MoCA, Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and polysomnography (PSG) parameters were compared between groups. Correlations between MoCA scores and PSG metrics were also analyzed.

Results

No significant disparities were noted between groups in terms of HAMD-17, HAMA, and PSQI scores (p > 0.05). However, marked differences were identified in MoCA scores and its subdomains (p < 0.05). Significant variations were also observed in the duration and proportion of slow-wave sleep (N3) between groups (p < 0.05). In STID-MCI patients, memory scores correlated positively with N3 duration and percentage (p < 0.05), while verbal functions and attention were positively associated with rapid eye movement (REM) sleep duration.

Conclusion

This study highlights the potential of PSG in the clinical assessment of cognitive function and underscores the need for targeted interventions to improve sleep quality in this vulnerable population.
Architectural planning robot driven by unsupervised learning for space optimization
Authors: Zhang Zhe , Zheng Yuchun
Published: January 2025

Introduction

Space optimization in architectural planning is a crucial task for maximizing functionality and improving user experience in built environments. Traditional approaches often rely on manual planning or supervised learning techniques, which can be limited by the availability of labeled data and may not adapt well to complex spatial requirements.

Methods

To address these limitations, this paper presents a novel architectural planning robot driven by unsupervised learning for automatic space optimization. The proposed framework integrates spatial attention, clustering, and state refinement mechanisms to autonomously learn and optimize spatial configurations without the need for labeled training data. The spatial attention mechanism focuses the model on key areas within the architectural space, clustering identifies functional zones, and state refinement iteratively improves the spatial layout by adjusting based on learned patterns. Experiments conducted on multiple 3D datasets demonstrate the effectiveness of the proposed approach in achieving optimized space layouts with reduced computational requirements.

Results and discussion

The results show significant improvements in layout efficiency and processing time compared to traditional methods, indicating the potential for real-world applications in automated architectural planning and dynamic space management. This work contributes to the field by providing a scalable solution for architectural space optimization that adapts to diverse spatial requirements through unsupervised learning.
Cycloastragenol promotes dorsal column axon regeneration in mice
Authors: Zihan Tao , Wenwen Teng , Yanxia Ma , Saijilafu
Published: January 2025

Introduction

Cycloastragenol (CAG) has a wide range of pharmacological effects, including anti-inflammatory, antiaging, antioxidative, and antitumorigenic properties. In addition, our previous study showed that CAG administration can promote axonal regeneration in peripheral neurons. However, whether CAG can activate axon regeneration central nervous system (CNS) remains unknown.

Methods

Here, we established a novel mouse model for visualizing spinal cord dorsal column axon regeneration involving the injection of AAV2/9-Cre into the lumbar 4/5 dorsal root ganglion (DRG) of Rosa-tdTomato reporter mice. We then treated mice by intraperitoneal administration of CAG.

Results

Our results showed that intraperitoneal CAG injections significantly promoted the growth of vitro-cultured DRG axons as well as the growth of dorsal column axons over the injury site in spinal cord injury (SCI) mice. Our results further indicate that CAG administration can promote the recovery of sensory and urinary function in SCI mice.

Conclusion

Together, our findings highlight the therapeutic potential of CAG in spinal cord injury repair.
Role of insulin-like growth factor-2 in Alzheimer’s disease induced memory impairment and underlying mechanisms
Authors: Chen Ruiqi , Lu Xing , Xiao Anqi , Ma Junpeng
Published: January 2025

Alzheimer’s disease (AD) is the most prevalent type of dementia. Treatments for AD do not reverse the loss of brain function; rather, they decrease the rate of cognitive deterioration. Current treatments are ineffective in part because they do not address neurotrophic mechanisms, which are believed to be critical for functional recovery. Given that structural losses are assumed to be the root cause of cognitive impairment in AD, strengthening neurotrophic pathways may be a useful preventative therapeutic approach. Insulin-like growth factor-2 (IGF2), which is widely expressed in the central nervous system (CNS), has emerged as a crucial mechanism of synaptic plasticity and learning and memory, and many studies have indicated that this neurotrophic peptide is a viable candidate for treating and preventing AD-induced cognitive decline. An increase in IGF2 levels improves memory in healthy animals and alleviates several symptoms associated with neurodegenerative disorders. These effects are primarily caused by the IGF2 receptor, which is widely expressed in neurons and controls protein trafficking, synthesis, and degradation. However, the use of IGF2 as a potential target for the development of novel pharmaceuticals to treat AD-induced memory impairment needs further investigation. We compiled recent studies on the role of IGF2 in AD-associated memory issues and summarized the current knowledge regarding IGF2 expression and function in the brain, specifically in AD-induced memory impairment.
A machine learning model to predict neurological deterioration after mild traumatic brain injury in older adults
Authors: Abe Daisu , Inaji Motoki , Hase Takeshi , Suehiro Eiichi , Shiomi Naoto , Yatsushige Hiroshi , Hirota Shin , Hasegawa Shu , Karibe Hiroshi , Miyata Akihiro , Kawakita Kenya , Haji Kohei , Aihara Hideo , Yokobori Shoji , Maeda Takeshi , Onuki Takahiro , Oshio Kotaro , Komoribayashi Nobukazu , Suzuki Michiyasu , Maehara Taketoshi
Published: January 2025

Objective

Neurological deterioration after mild traumatic brain injury (TBI) has been recognized as a poor prognostic factor. Early detection of neurological deterioration would allow appropriate monitoring and timely therapeutic interventions to improve patient outcomes. In this study, we developed a machine learning model to predict the occurrence of neurological deterioration after mild TBI using information obtained on admission.

Methods

This was a retrospective cohort study of data from the Think FAST registry, a multicenter prospective observational study of elderly TBI patients in Japan. Patients with an admission Glasgow Coma Scale (GCS) score of 12 or below or who underwent surgical treatment immediately upon admission were excluded. Neurological deterioration was defined as a decrease of 2 or more points from a GCS score of 13 or more within 24 h of hospital admission. The model predictive accuracy was judged with the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC), and the Youden index was used to determine the cutoff value.

Results

A total of 421 of 721 patients registered in the Think FAST registry between December 2019 and May 2021 were included in our study, among whom 25 demonstrated neurological deterioration. Among several machine learning algorithms, eXtreme Gradient Boosting (XGBoost) demonstrated the highest predictive accuracy in cross-validation, with an AUROC of 0.81 (±0.07) and an AUPRC of 0.33 (±0.08). Through SHapley Additive exPlanations (SHAP) analysis, five important features (D-dimer, fibrinogen, acute subdural hematoma thickness, cerebral contusion size, and systolic blood pressure) were identified and used to construct a better performing model (cross-validation AUROC of 0.84 and AUPRC of 0.34; testing data AUROC of 0.77 and AUPRC of 0.19). At the cutoff value from the Youden index, the model showed a sensitivity, specificity, and positive predictive value of 60, 96, and 38%, respectively. When neurosurgeons attempted to predict neurological deterioration using the same testing data, their values were 20, 94, and 19%, respectively.

Conclusion

In this study, our predictive model showed an acceptable performance in detecting neurological deterioration after mild TBI. Further validation through prospective studies is necessary to confirm these results.
Oxidative imbalance as a co-player in jaw functional limitations and biopsychosocial profile in patients with temporomandibular disorder—myofascial pain with referral
Authors: Kuć Joanna , Szarejko Krzysztof Dariusz , Maciejczyk Mateusz , Dymicka-Piekarska Violetta , Żendzian-Piotrowska Małgorzata , Zalewska Anna
Published: January 2025

Introduction

Temporomandibular disorders have a multifactorial etiology including biological, biomechanical, neuromuscular, and biopsychosocial factors. Current research on temporomandibular disorders focuses on identifying clinically relevant biomarkers thus creating a new way of thinking about this dysfunction. The aim of the study was to determine the relationship between salivary/blood concentrations of oxidative/nitrosative stress biomarkers and biopsychosocial findings in patients with temporomandibular disorder—myofascial pain with referral.

Methods

The sample enrolled a total of 26 individuals with temporomandibular myofascial pain with referral (twenty women, six men). The procedure included clinical examination according to the Diagnostic Criteria for Temporomandibular Disorders, saliva and blood collection. Biochemical analysis concerned, among others, the content of reduced glutathione, uric acid, total antioxidant capacity, advanced glycation end products, malondialdehyde, total lipid hydroperoxides, kynurenine, N-formylkynurenine, and peroxynitrite. All determinations were considered with respect to the Patient Health Questionnaire-4 (PHQ-4), Patient Health Questionnaire-9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), Generalized Anxiety Disorder-7 (GAD-7), Jaw Functional Limitation Scale-20 (JFLS-20), Perceived Stress Scale-10 (PSS-10), and Beck Depression Inventory (BDI).

Results and discussion

The average age of participants was 24.2 ± 1.23. High content of kynurenine and N-formylkynurenine in plasma was related to intensified psychological distress (PHQ-4) and anxiety (GAD-7). Low concentration of plasma malondialdehyde and total lipid hydroperoxides was linked with severe somatization (PHQ-15) and stress (PSS-10), respectively. Reduced levels of non-enzymatic antioxidants were associated with greater jaw functional mobility restrictions as well as limited mastication and communication factor with respect to JFLS-20. These findings indicate that oxidative stress biomarkers are significantly related to the biopsychosocial profile in patients with temporomandibular disorder.
Leveraging deep learning for robust EEG analysis in mental health monitoring
Authors: Liu Zixiang , Zhao Juan
Published: January 2025

Introduction

Mental health monitoring utilizing EEG analysis has garnered notable interest due to the non-invasive characteristics and rich temporal information encoded in EEG signals, which are indicative of cognitive and emotional conditions. Conventional methods for EEG-based mental health evaluation often depend on manually crafted features or basic machine learning approaches, like support vector classifiers or superficial neural networks. Despite the potential of these approaches, they often fall short in capturing the intricate spatiotemporal relationships within EEG data, leading to lower classification accuracy and poor adaptability across various populations and mental health scenarios.

Methods

To overcome these limitations, we introduce the EEG Mind-Transformer, an innovative deep learning architecture composed of a Dynamic Temporal Graph Attention Mechanism (DT-GAM), a Hierarchical Graph Representation and Analysis (HGRA) module, and a Spatial-Temporal Fusion Module (STFM). The DT-GAM is designed to dynamically extract temporal dependencies within EEG data, while the HGRA models the brain's hierarchical structure to capture both localized and global interactions among different brain regions. The STFM synthesizes spatial and temporal elements, generating a comprehensive representation of EEG signals.

Results and discussion

Our empirical results confirm that the EEG Mind-Transformer significantly surpasses conventional approaches, achieving an accuracy of 92.5%, a recall of 91.3%, an F1-score of 90.8%, and an AUC of 94.2% across several datasets. These findings underline the model's robustness and its generalizability to diverse mental health conditions. Moreover, the EEG Mind-Transformer not only pushes the boundaries of state-of-the-art EEG-based mental health monitoring but also offers meaningful insights into the underlying brain functions associated with mental disorders, solidifying its value for both research and clinical settings.
Postoperative evaluation of visual and cognitive functions following cataract surgery in patients with age-related cataracts: a prospective longitudinal study
Authors: Zhao Chenzhu , Li Xuan , Deng Bolin , Shui Bingyue , Zhou Lin , Wu Zhengzheng
Published: January 2025

Introduction

Cataracts are associated with a decline in both cognitive and visual functions. This study examines postoperative changes in cognitive and visual functions in patients with age-related cataracts, focusing on the differential effects of unilateral and bilateral cataract surgeries on these functions. Additionally, the study evaluates changes in cognitive function following cataract surgery in individuals with mild cognitive impairment (MCI).

Methods

A cohort of patients (n = 35, 59 eyes) aged 60 years and older (69.9 ± 7.0 years) with age-related cataracts who underwent unilateral or bilateral cataract surgery between May and June 2024 was selected. Cognitive and visual functions were evaluated preoperatively and at 1 week, 1 month, and 3 months postoperatively. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). Visual function was assessed using a binocular visual function testing system based on virtual reality (VR) technology, which evaluated low spatial frequency suppression, simultaneous vision, stereopsis, and perceptual eye position under 3D viewing conditions without glasses. Based on preoperative MoCA scores, patients were classified into cognitively normal and mild cognitive impairment (MCI) groups.

Results

Patients with age-related cataracts demonstrated significant improvements in both cognitive and visual functions at 1 week, 1 month, and 3 months postoperatively, compared to preoperative assessments (p < 0.05). Specifically, both the bilateral surgery group and the MCI group exhibited substantial improvements in cognitive function at these time points (p < 0.05). Additionally, the bilateral surgery group outperformed the unilateral surgery group in cognitive function throughout the follow-up period (p < 0.05). In terms of visual function, the bilateral surgery group showed significant improvements in low spatial frequency suppression, simultaneous vision, and stereopsis at 1 week, 1 month, and 3 months postoperatively, compared to preoperative measurements (p < 0.05).

Conclusion

Both cognitive and visual functions significantly improved after cataract surgery. Bilateral cataract surgery is more effective in increasing the cognitive functions than unilateral surgery. Additionally, cataract surgery plays a critical role in facilitating cognitive recovery in patients with mild cognitive impairment (MCI).
Parental intentions and requests to provide pain care for their infants in neonatal intensive care units
Authors: Shimizu Aya , Arimitsu Takeshi , Harada Kana , Ozawa Mio
Published: January 2025

Purpose

The Japan Association of Neonatal Nursing evaluated the pain care provided by parents to their infants admitted to the neonatal intensive care unit (NICU). However, further collaborations with families based on family-centered care are necessary to clarify the parental intentions and requests regarding pain care for their infants. This study aimed to describe the experiences and content of nonpharmacological pain care provided by parents to their infants, the intentions and requests of parents regarding each type of recommended pain care (irrespective of whether they had provided pain care at the NICU), and the reasons for their hesitation to implement specific pain management methods.

Methods

A total of 108 parents with NICU-hospitalized infants, including 66 (65.6%) infants with a birth weight of <1,000 g, voluntarily responded to an anonymous self-administered online electronic survey. Sociodemographic and clinical data were quantitatively analyzed.

Results

In our study population, 30.6% (N = 33) had provided pain care to their infants, 56.5% (N = 61) hoped to provide pain care in the future, and 40.7% (N = 44) expected advice for pain care options from healthcare professionals (HCPs). Swaddling, facilitated tucking, and skin-to-skin contact were the most popular options (≥60%). By contrast, the use of sucrose and breastfeeding (both 13.0%), skin-to-skin contact (7%), and use of expressed breast milk and non-nutritive sucking (both 3.7%) were less frequently used due to indifference or doubts, lack of knowledge about pain care, differences between recommended pain care methods and parental values, and pain care methods being inappropriate for the child's condition.

Conclusions

This survey demonstrated that when parents provide pain care for their children in the NICU, they are required to make choices based on the advice and knowledge offered by HCPs, taking into account the diverse values of parents as well as the overall condition of their infant and their breastfeeding status. Therefore, we suggest that HCPs support parents in choosing not only the recommended care but also the most appropriate pain care for the condition of their infant.
A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis
Authors: Tian Xirong , Gao Yamin , Li Chunyu , Ma Wanli , Zhang Jingran , Ju Yanan , Ding Jie , Zeng Sanshan , Hameed H. M. Adnan , Aung Htin Lin , Zhong Nanshan , Cook Gregory M. , Hu Jinxing , Zhang Tianyu
Published: January 2025

The efficacy of many compounds against Mycobacterium tuberculosis is often limited when administered via conventional oral or injection routes due to suboptimal pharmacokinetic characteristics. Inhalation-based delivery methods have been investigated to achieve high local therapeutic doses in the lungs. However, previous models, typically employing wild-type M. tuberculosis strains, were intricate, time-consuming, labor-intensive, and with poor reproducibility. In this study, we developed an autoluminescence-based inhalation administration model to evaluate drug activity by quantifying relative light units (RLUs) emitted from live mice infected with autoluminescent M. tuberculosis. This novel approach offers several advantages: (1) it eliminates the need for anesthesia in mice during administration and simplifies the instrument manipulation; (2) it is cost-effective by utilizing mice instead of larger animals; (3) it shortens the time from several months to 16 or 17 days for obtaining result; (4) it is non-invasive by directly measuring the live RLUs of mice as a surrogate marker for colony-forming units for in vivo drug activity testing; (5) up to six mice can be administrated daily and simultaneously, even 2–3 times/day; (6) results are relatively objective and reproducible results minimizing human factors. Proof-of-concept experiments demonstrated that inhalable rifampicin, isoniazid, and ethambutol showed anti-M. tuberculosis activity at concentrations as low as 0.5, 0.5, and 0.625 mg/mL, respectively, as evidenced by comparing the live RLUs of mice. Furthermore, consistency between RLUs and colony-forming units of the autoluminescent M. tuberculosis in lungs reaffirms the reliability of RLUs as an indicator of drug efficacy, highlighting the potential of this approach for accurately assessing anti-M. tuberculosis activity in vivo. This autoluminescence-based, non-invasive inhalation model offers a substantial reduction in the time, effort, and cost required for evaluating the efficacy of screening new drugs and repurposing old drugs in vivo via inhalation administration.
Integrated serum pharmacochemistry, pharmacokinetics, and network analysis to explore active components of BuShao Tiaozhi Capsule on hyperlipidemia
Authors: Tang Ruiyin , Xiao Guanlin , Liu Yanchang , Jia Dezheng , Zeng Zhihao , Jia Canchao , Li Dongmei , Li Yangxue , Jiang Jieyi , Li Sumei , Bi Xiaoli
Published: January 2025

BuShao Tiaozhi Capsule (BSTZC), a novel drug in China, has been used to treat hyperlipidemia (HLP) in clinical practice for many years. Despite our previous studies suggesting that BSTZC can treat HLP, there is a lack of a rapid and systematic method to explore its active components. Therefore, in this study, we aimed to investigate the active components and mechanisms of BSTZC in treating HLP by integrating serum pharmacology, pharmacokinetics, network analysis, and experimental validation. We first established UPLC fingerprints, calibrated 23 common peaks, and identified 13 common peaks, and the similarity was greater than 0.99 for 10 batches. A total of nine metabolites from BSTZC were identified in serum and considered as PK markers. The pharmacokinetic parameters of the PK markers were compared between the control group and the model group through the pharmacokinetics study to determine the dynamic changes of representative components in rats. Compared with the control group, the Cmax and AUC0→t of OXY, IVT, IVL, and KPF-3-G were significantly higher (P< 0.05); the AUC0→∞ of OXY, PN, and IVT was significantly higher (P< 0.05); and the t1/2 of IVT, SA, and KPF-3-G was significantly different (P< 0.05). In vivo experiments showed that BSTZC and its active components could effectively alleviate lipid metabolism disorders and liver injury, with obvious lipid-lowering effects. Further studies showed that BSTZC alleviated HLP by inhibiting the PI3K/Akt signaling pathway, which was consistent with the results of the network analysis study. Our results revealed the active components and mechanisms of BSTZC in the treatment of HLP, which could provide useful information to guide the clinical application of BSTZC.
Effect of bromelain on ischemia-reperfusion injury in the torsion model created in polycystic and normal ovarian tissues
Authors: Ulusoy Tangul Sevgi , Onat Taylan , Aydoğan Kirmizi Demet , Doganyigit Zuleyha , Kaymak Emin , Oflamaz Aslı , Şenayli Atilla , Somuncu Salih
Published: January 2025

Purpose

Due to its increased volume, polycystic ovarian tissue is more prone to torsion than normal ovarian tissue. In treating ovarian torsion, detorsion is applied to ensure oxygenation of hypoxic tissues. However, the resulting oxygen radicals cause tissue damage. Bromelain is a substance obtained from pineapple, and studies in the literature show it is used as an antioxidant. This study aimed to evaluate the damage caused by ischemia-reperfusion (I/R) in the torsion-detorsion model created in normal and polycystic ovarian tissue and investigate the role of bromelain in this damage.

Methods

Polycystic ovarian tissue was created by applying dihydroepiandrosterone sulfate to rats. Afterward, a torsion-detorsion model was used for all rats. The rats were divided into six groups: the polycystic ovary sham-operated group (P-S), the normal ovary sham-operated group (N-S), the polycystic ovary ischemia/reperfusion group (P-IR), the normal ovary ischemia/reperfusion group (N-IR), the polycystic ovary ischemia/reperfusion group treated with bromelain (P-IRB), and the normal ovary ischemia/reperfusion group treated with bromelain (N-IRB). After the procedure, tissues were collected for histopathological examination, and MDA, TUNEL, and NF-κB levels were measured.

Results

This study detected significant decreases in MDA and NF-κB levels and apoptotic cell numbers assessed by TUNEL staining in groups with IR damage and given bromelain compared to the control groups. The number of TUNEL-positive cells was found to be highest in the P-IR group (8.80 ± 2.98) and significantly lower in the bromelain-administered P-IRB (1.04 ± 1.09) and N-IRB (0.52 ± 0.58) groups (p< 0.05). NF-κB expression was also high in P-IR and N-IR groups, while it was significantly decreased in bromelain-treated groups (P-IRB and N-IRB) (p< 0.05). In addition, IR damage was more pronounced in polycystic ovary tissue than in normal ovary tissue.

Conclusion

Ischemia perfusion damage may be more pronounced in polycystic ovarian tissue than in normal ovarian tissue. Bromelain may be preferred to prevent I/R injury caused by ovarian torsion. It is also thought that bromelain may function in treating polycystic ovaries, and further studies can be conducted on this subject.
Using intermediate energy knockout, pickup, and charge exchange reactions with invariant mass spectroscopy for investigating nuclear structure beyond the proton drip line
Authors: Sobotka L. G. , Charity R. J.
Published: January 2025

The continuum structure of light p-rich elements has been extensively studied in recent years by invariant-mass spectroscopy. The feeble Coulomb barrier for light proton-rich nuclei makes proton decay an essential tool in this region not unlike alpha decay is in the trans-Pb region and neutron-deficient rare earths. Unlike binary alpha decay, the part of the Chart of the Nuclides this mini review will focus on can undergo decay into many-particle final states and invariant-mass spectroscopy is the frame-invariant and multi-particle replacement for simple binary alpha-particle spectroscopy. Here we highlight how pairing is reflected in the zig-zaggy pattern of the drip line, the decay of nuclides beyond the drip lines, and what the masses of nuclides exterior to the p-drip line have taught us about shell structure. In this context, the subtlety of removing the Wigner, or n-p congruence, energy when interpreting nucleon separation-energy systematics is discussed. We also present examples of where isospin symmetry is maintained in the continuum and where it is not.