bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of lactylation in plasma cells and its impact on rheumatoid arthritis pathogenesis: insights from single-cell RNA sequencing and machine learning
Authors: Fu Weicong , Wang Tianbao , Lu Yehong , Shi Tiejun , Yang Qining
Published: October 2024

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, systemic inflammation, and autoantibody production. This study aims to explore the role of lactylation in plasma cells and its impact on RA pathogenesis.

Methods

We utilized single-cell RNA sequencing (scRNA-seq) data and applied bioinformatics and machine learning techniques. A total of 10,163 cells were retained for analysis after quality control. Clustering analysis identified 13 cell clusters, with plasma cells displaying the highest lactylation scores. We performed pathway enrichment analysis to examine metabolic activity, such as oxidative phosphorylation and glycolysis, in highly lactylated plasma cells. Additionally, we employed 134 machine learning algorithms to identify seven core lactylation-promoting genes and constructed a diagnostic model with an average AUC of 0.918.

Results

The RA lactylation score (RAlac_score) was significantly elevated in RA patients and positively correlated with immune cell infiltration and immune checkpoint molecule expression. Differential expression analysis between two plasma cell clusters revealed distinct metabolic and immunological profiles, with cluster 2 demonstrating increased immune activity and extracellular matrix interactions. qRT-PCR validation confirmed that NDUFB3, NGLY1, and SLC25A4 are highly expressed in RA.

Conclusion

This study highlights the critical role of lactylation in plasma cells for RA pathogenesis and identifies potential biomarkers and therapeutic targets, which may offer insights for future therapeutic strategies.
The causality between rheumatoid arthritis and postural deformities: bidirectional Mendelian randomization study and mediation analysis
Authors: Zhao Piqian , Chen Zhe , Wen Ya , Zhang Hongtao , Wen Liangyuan , Pei Zijie
Published: October 2024

Background

To better understand the preventive or therapeutic clinical interventions that may be supported by the association between rheumatoid arthritis (RA) and postural deformities including hallux valgus, flat foot, and scoliosis, this study was conducted using Mendelian randomization (MR) analysis. It aimed to investigate whether RA is causally associated with postural deformities in European populations.

Methods

Summary-level data on RA and postural deformities were obtained from the IEU OpenGWAS project and Finngen database, respectively. LDSC regression analysis was conducted to assess the genetic correlation between these diseases. The inverse variance weighting (IVW) method was employed as the primary approach for two-sample MR analyses to evaluate causality. Supplementary methods included MR-Egger, maximum likelihood, weighted median, and cML-MA. To test for potential horizontal pleiotropy, we performed the MR-Egger intercept test, cML-MA, and secondary analyses after excluding confounders. Additionally, mediation analyses were conducted using two-step MR.

Results

The IVW method revealed RA to be causally associated with hallux valgus (OR 1.132, 95% CI 1.087-1.178, P < 0.001) and flat foot (OR 1.197, 95% CI 1.110-1.291, P < 0.001). Among postural deformities, hallux valgus was causally associated with flat foot (OR 1.823, 95% CI 1.569-2.119, P < 0.001) and scoliosis (OR 1.150, 95% CI 1.027-1.287, P < 0.05). No significant horizontal pleiotropy was detected. Moreover, mediation analyses indicated that hallux valgus mediates the effect of RA on flat foot (mediation effect 0.024, 95% CI 0.005-0.044, P < 0.05), with a mediation proportion of 41.31%.

Conclusion

These findings indicate a potential causal association between genetically predicted RA and both hallux valgus and flat foot. Furthermore, hallux valgus serves as a mediator in the pathway from RA to flat foot. This underscores the importance of early screening and preventive treatment of foot deformities in RA patients. Further research is necessary to determine the applicability of these findings in non-European populations.
CD19: a promising target for systemic sclerosis
Authors: Komura Kazuhiro
Published: October 2024

Systemic sclerosis (SSc) is an autoimmune disease characterized by immune dysregulation, vascular damage, and fibrosis. B cells play a significant role in SSc through autoantibody production, cytokine secretion, and T cell regulation. Autoantibodies like anti-topoisomerase I and anti-RNA polymerase III are specific to SSc and linked to clinical features such as skin and lung involvement. B cell depletion therapies, particularly anti-CD20 antibodies like rituximab, have shown benefits in treating SSc, improving skin and lung disease symptoms. However, CD19, another B cell marker, is more widely expressed and has emerged as a promising target in autoimmune diseases. CD19-targeted therapies, such as CAR T cells and Uplizna® (inebilizumab), have demonstrated potential in treating refractory autoimmune diseases, including SSc. Uplizna® offers advantages over rituximab by targeting a broader range of B cells and showing higher efficacy in specific patient subsets. Clinical trials currently investigate Uplizna®’s effectiveness in SSc, particularly in severe cases. While these therapies offer hope, long-term safety and efficacy remain unknown. SSc is still a complex disease, but advancing B cell-targeted treatments could significantly improve patient outcomes and knowledge about the pathogenesis.
scRNA+TCR-seq reveals the pivotal role of dual receptor T lymphocytes in the pathogenesis of Kawasaki disease and during IVIG treatment
Authors: Xu Yuanyuan , Yuan Yi , Mou Lanlan , Hui Linhu , Zhang Xing , Yao Xinsheng , Li Jun
Published: October 2024

Introduction

Kawasaki disease (KD), a common cause of acquired heart disease in children in developed countries, is primarily treated with intravenous immunoglobulin (IVIG), but some children demonstrate IVIG resistance with increased coronary artery injury risk. T cells have been demonstrated to be involved in the pathogenesis of KD and its treatment with IVIG. However, the role and mechanism of dual TCR T lymphocytes in the occurrence of KD and IVIG therapy remain unclear.

Methods

This study, based on scRNA-seq combined with TCR-seq technology, clustered the peripheral blood mononuclear cells of 3 healthy controls and 6 KD patients before and after IVIG treatment. Comparative analysis was conducted to investigate the differences in the proportion of single/dual receptor T cells, the characteristics of CDR3 repertoires, cell types, and the expression of transcription factors among the three groups. The study aimed to explore the correlation between dual TCR T cells and KD as well as IVIG treatment.

Results

In our experimental results, we observed the presence of dual TCR T cells in all three groups. However, compared to the healthy control group and the IVIG-treated group, the KD patients before IVIG treatment exhibited a lower proportion of dual TCR T cells, with variability between samples, ranging from 4% to 15%. Notably, after IVIG treatment, the proportion of dual TCR T cells significantly increased, stabilizing above 12%, and these T cells also exhibited clonal expansion and a preference for V gene usage. In addition we found differences in dual TCR T cell subsets among the three groups, for example, IVIG treatment increases the proportion of dual TCR Treg cells, but it still remains below that of healthy control groups, significantly higher proportions of both dual TCR CD8 central and effector memory T cells in IVIG-treated KD patients, and differences in the expression of transcription factors between single and dual TCR T cells. These results suggest dual TCR T cells correlate with KD and IVIG treatment.

Conclusion

Dual TCR T lymphocytes, especially dual TCR CD8 T cells and Treg cells, play crucial roles in the pathogenesis of KD and during IVIG treatment, providing strong support for further elucidating KD pathogenesis and optimizing treatment strategies.
Comparative genomics of the Natural Killer Complex in carnivores
Authors: Futas Jan , Jelinek April L. , Burger Pamela A. , Horin Petr
Published: October 2024

Background

The mammalian Natural Killer Complex (NKC) harbors genes and gene families encoding a variety of C-type lectin-like proteins expressed on various immune cells. The NKC is a complex genomic region well-characterized in mice, humans and domestic animals. The major limitations of automatic annotation of the NKC in non-model animals include short-read based sequencing, methods of assembling highly homologous and repetitive sequences, orthologues missing from reference databases and weak expression. In this situation, manual annotations of complex genomic regions are necessary.

Methods

This study presents a manual annotation of the genomic structure of the NKC region in a high-quality reference genome of the domestic cat and compares it with other felid species and with representatives of other carnivore families. Reference genomes of Carnivora, irrespective of sequencing and assembly methods, were screened by BLAST to retrieve information on their killer cell lectin-like receptor (KLR) gene content. Phylogenetic analysis of in silico translated proteins of expanded subfamilies was carried out.

Results

The overall genomic structure of the NKC in Carnivora is rather conservative in terms of its C-type lectin receptor gene content. A novel KLRH-like gene subfamily (KLRL) was identified in all Carnivora and a novel KLRJ-like gene was annotated in the Mustelidae. In all six families studied, one subfamily (KLRC) expanded and experienced pseudogenization. The KLRH gene subfamily expanded in all carnivore families except the Canidae. The KLRL gene subfamily expanded in carnivore families except the Felidae and Canidae, and in the Canidae it eroded to fragments.

Conclusions

Knowledge of the genomic structure and gene content of the NKC region is a prerequisite for accurate annotations of newly sequenced genomes, especially of endangered wildlife species. Identification of expressed genes, pseudogenes and gene fragments in the context of expanded gene families would allow the assessment of functionally important variability in particular species.
Expanding the VEXAS diagnostic workup: the role of peripheral blood cytological analysis
Authors: Baggio Chiara , Oliviero Francesca , Padoan Roberto , Iorio Luca , Bixio Riccardo , Orsolini Giovanni , Bertoldo Eugenia , Bernardi Cristina , Colavito Davide , Paiero Barbara , Pregnolato Giovanna , Ramonda Roberta , Doria Andrea , Bindoli Sara , Sfriso Paolo
Published: October 2024

VEXAS syndrome is a newly described autoinflammatory entity characterized by somatic mutations in the UBA1 X-linked gene in hematopoietic progenitor cells. Several studies have demonstrated that the presence of vacuoles in progenitor cells from bone marrow aspirates is a hallmark finding for this syndrome. Therefore, this study aimed to characterize leukocytes from VEXAS patients versus patients with ANCA-associated vasculitis (AAV), familial Mediterranean fever (FMF), and healthy donors (HD) to define a specific cytological pattern that can support VEXAS diagnosis. Twelve VEXAS patients were included in the study. Blood samples from FMF (n = 16), AAV (n = 16) and HDs (n = 20) acted as controls. May-Grünwald Giemsa (MGG) staining was used for studying cellular morphology, including cytoplasm, granules, and vacuoles and to perform a cytogenic evaluation of leucocytes. Plasma IL-1β, IL-1α, TNFα, IL-18 and IL-8 were measured using ELISA assay. The cytological analysis from blood smears confirmed the presence of immature neutrophils in VEXAS patients. We found a greater number of vacuoles in VEXAS patients vs. FMF, AAV and HD. Micronuclei (MNi) and cell death rate were higher in VEXAS patients vs. HD. Cell death correlated with IL-1β and IL-8 levels. MNi were positively associated with IL-8 and IL-1β levels, and with the percentage of immature neutrophils and vacuoles. In conclusion, our findings suggested that cytological test may be supportive for VEXAS diagnosis, despite genetical analysis is mandatory for confirming the disease. Finally, we identified several cytological hallmarks that may distinguish the VEXAS “cytotype” not only from HD but also from other inflammatory diseases.
Population connectivity of the swordtip squid Uroteuthis edulis between southern Japan and northern Taiwan using statolith trace elemental analysis
Authors: Pang Yumeng , Yokoyama Yusuke , Aze Takahiro , Irie Takahiro , Chen Chih-Shin , Kawamura Tomohiko , Iwata Yoko
Published: October 2024

Uroteuthis edulis (Hoyle, 1885) is an Indo-Pacific squid species widely distributing in the western Pacific, and commercially important especially in Japan and Taiwan. It has been suggested that some individuals are possibly transported from the spawning ground in north Taiwan to the coasts of Japan, however, the strength of population connectivity between those areas and its influence on U. edulis population dynamics were unveiled. To understand the U. edulis population connectivity in this area, the correlations between statolith trace elements and abiotic/biotic factors were examined first, and then squid experienced environments were postulated throughout their entire life cycle. Sr/Ca ratio showed a strongly negative correlation with ambient water temperature but no correlation with individual growth rate, suggesting that Sr/Ca ratio can be used to reflect squid experienced temperatures. Most squid caught in the Sea of Japan hatched in the areas having similar water temperature with where Taiwanese squid hatched, that would be off the north Taiwan or even warmer area. Statolith trace elements successfully distinguished the catch locations but not the hatching grounds, implying that hatching grounds of Japan and Taiwan squid were largely overlapped. Thus, we suggest that there is strong population connectivity of U. edulis population between southern Japan and northern Taiwan. As there was no clear evidence for existence of local population hatched in the Sea of Japan in this study, U. edulis population might display a source-sink population dynamics, that is, population in Taiwanese waters and/or further south as the source, and the one in the Sea of Japan as a sink population. As U. edulis should be considered as a metapopulation, collaboration among countries in the northwestern Pacific is required for sustainable fishery management of this species.
The association of social networks with the job performance of primary health care professionals: the mediating effect of knowledge sharing
Authors: Wang Xiubo , Hou Shengchao , Lv Qiongxin , Liu Yuxin , Wu Huan , Liu Zhiyong
Published: October 2024

Background and aims

Social networks formed through social media platforms have facilitated knowledge sharing among primary health care professionals (PHCPs). However, the impact of these networks on PHCPs’ job performance and the mediating role of knowledge sharing remain underexplored. This study aimed to investigate the association between social networks formed via social media and the job performance of PHCPs, and to explore the mediating role of knowledge sharing in this association.

Methods

A cross-sectional survey was carried out among PHCPs in Henan Province, China, involving 655 valid responses. Validated scales measured the key variables, and structural equation modeling (SEM) tested the proposed hypotheses, including the mediating effect of knowledge sharing through bootstrap method. Statistical analysis was performed using SPSS 24.0 and AMOS 24.0.

Results

The degree centrality (β = 0.225; p = 0.001) and network heterogeneity (β = 0.093; p = 0.043) of the social network had a significant direct association with job performance, whereas the direct associations of betweenness centrality and network tie strength with job performance were not significant. Knowledge sharing mediated the relationship between degree centrality (β = 0.147; p = 0.001), network heterogeneity (β = 0.251; p = 0.043), and job performance.

Conclusion

The study revealed the internal mechanisms by which social network characteristics influence PHCPs’ job performance, highlighting the mediating role of knowledge sharing. Social networks formed within social media contexts have multifaceted effects on job performance, with knowledge sharing as a critical mediating variable. These findings underscore the importance of leveraging social media for professional networking and knowledge exchange to enhance PHCPs’ job performance.
Cost-effectiveness of home care compared to hospital care in patients with chronic obstructive pulmonary disease (COPD): a systematic review
Authors: Vidigal Maria Tereza Campos , Borges Guilherme Henrique , Rabelo Diogo Henrique , de Andrade Vieira Walbert , Nascimento Gustavo G. , Lima Rafael Rodrigues , Costa Márcio Magno , Herval Álex Moreira , Paranhos Luiz Renato
Published: October 2024

Background

To compare, through a systematic literature review, the cost-effectiveness ratio of home care compared to hospital care for following up patients with chronic obstructive pulmonary disease (COPD).

Methods

This review was registered in PROSPERO, and the bibliographic search was performed in six primary databases [MedLine (via PubMed), Scopus, LILACS, SciELO, Web of Science, and Embase], two dedicated databases for economic studies (NHS Economic Evaluation Database (NHS EED) and Cost-Effectiveness Analysis (CEA) Registry), and two databases for partially searching the “gray literature” (DansEasy and ProQuest). This review only included studies that compared home and hospital care for patients diagnosed with COPD, regardless of publication year or language. Two reviewers selected the studies, extracted the data, and assessed the risk of bias independently. A JBI tool was used for risk of bias assessment.

Results and discussion

7,279 studies were found, of which 14 met the eligibility criteria. Only one study adequately met all items of the risk of bias assessment. Thirteen studies found lower costs and higher effectiveness for home care. Home care showed a better cost-effectiveness ratio than hospital care for COPD patients. Regarding effectiveness, there is no possibility of choosing a more effective care for COPD patients, given the incipience of the data presented on eligible studies. However, considering the analyzed data refer only to high-income countries, caution is required when extrapolating this conclusion to low- and low-middle-income countries.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022319488.
Survival prediction for heart failure complicated by sepsis: based on machine learning methods
Authors: Zhang Qitian , Xu Lizhen , He Weibin , Lai Xinqi , Huang Xiaohong
Published: October 2024

Background

Heart failure is a cardiovascular disorder, while sepsis is a common non-cardiac cause of mortality. Patients with combined heart failure and sepsis have a significantly higher mortality rate and poor prognosis, making early identification of high-risk patients and appropriate allocation of medical resources critically important.

Methods

We constructed a survival prediction model for patients with heart failure and sepsis using the eICU-CRD database and externally validated it using the MIMIC-IV database. Our primary outcome is the 28-day all-cause mortality rate. The Boruta method is used for initial feature selection, followed by feature ranking using the XGBoost algorithm. Four machine learning models were compared, including Logistic Regression (LR), eXtreme Gradient Boosting (XGBoost), Adaptive Boosting (AdaBoost), and Gaussian Naive Bayes (GNB). Model performance was assessed using metrics such as area under the curve (AUC), accuracy, sensitivity, and specificity, and the SHAP method was utilized to visualize feature importance and interpret model results. Additionally, we conducted external validation using the MIMIC-IV database.

Results

We developed a survival prediction model for heart failure complicated by sepsis using data from 3891 patients in the eICU-CRD and validated it externally with 2928 patients from the MIMIC-IV database. The LR model outperformed all other machine learning algorithms with a validation set AUC of 0.746 (XGBoost: 0.726, AdaBoost: 0.744, GNB: 0.722), alongside accuracy (0.685), sensitivity (0.666), and specificity (0.712). The final model incorporates 10 features: age, ventilation, norepinephrine, white blood cell count, total bilirubin, temperature, phenylephrine, respiratory rate, neutrophil count, and systolic blood pressure. We employed the SHAP method to enhance the interpretability of the model based on the LR algorithm. Additionally, external validation was conducted using the MIMIC-IV database, with an external validation AUC of 0.699.

Conclusion

Based on the LR algorithm, a model was constructed to effectively predict the 28-day all-cause mortality rate in patients with heart failure complicated by sepsis. Utilizing our model predictions, clinicians can promptly identify high-risk patients and receive guidance for clinical practice.
Shedding light on the DICER1 mutational spectrum of uncertain significance in malignant neoplasms
Authors: Bug D. S. , Moiseev I. S. , Porozov Yu. B. , Petukhova N. V.
Published: October 2024

The Dicer protein is an indispensable player in such fundamental cell pathways as miRNA biogenesis and regulation of protein expression in a cell. Most recently, both germline and somatic mutations in DICER1 have been identified in diverse types of cancers, which suggests Dicer mutations can lead to cancer progression. In addition to well-known hotspot mutations in RNAase III domains, DICER1 is characterized by a wide spectrum of variants in all the functional domains; most are of uncertain significance and unstated clinical effects. Moreover, various new somatic DICER1 mutations continuously appear in cancer genome sequencing. The latest contemporary methods of variant effect prediction utilize machine learning algorithms on bulk data, yielding suboptimal correlation with biological data. Consequently, such analysis should be conducted based on the functional and structural characteristics of each protein, using a well-grounded targeted dataset rather than relying on large amounts of unsupervised data. Domains are the functional and evolutionary units of a protein; the analysis of the whole protein should be based on separate and independent examinations of each domain by their evolutionary reconstruction. Dicer represents a hallmark example of a multidomain protein, and we confirmed the phylogenetic multidomain approach being beneficial for the clinical effect prediction of Dicer variants. Because Dicer was suggested to have a putative role in hematological malignancies, we examined variants of DICER1 occurring outside the well-known hotspots of the RNase III domain in this type of cancer using phylogenetic reconstruction of individual domain history. Examined substitutions might disrupt the Dicer function, which was demonstrated by molecular dynamic simulation, where distinct structural alterations were observed for each mutation. Our approach can be utilized to study other multidomain proteins and to improve clinical effect evaluation.
The utility of point-of-care ultrasound in critical care nephrology
Authors: Passos Rogério da Hora , Flato Uri Adrian Prync , Sanches Paula Rodrigues , Pellegrino Carolina Moraes , Cordioli Ricardo Luiz , Silva Bruno Caldin , Campos Felipe Galdino , Barros Dalton de Souza , Coelho Fernanda Oliveira , Bravim Bruno de Arruda , Corrêa Thiago Domingos
Published: October 2024

Point-of-care ultrasonography (POCUS) is gaining heightened significance in critical care settings as it allows for quick decision-making at the bedside. While computerized tomography is still considered the standard imaging modality for many diseases, the risks and delays associated with transferring a critically ill patient out of the intensive care unit (ICU) have prompted physicians to explore alternative tools. Ultrasound guidance has increased the safety of invasive procedures in the ICU, such as the placement of vascular catheters and drainage of collections. Ultrasonography is now seen as an extension of the clinical examination, providing quick answers for rapidly deteriorating patients in the ICU. The field of nephrology is increasingly acknowledging the value of diagnostic point-of-care ultrasound (POCUS). By employing multi-organ POCUS, nephrologists can address specific queries that arise during the diagnosis and treatment of patients with acute kidney injury. This approach aids in ruling out hydronephrosis and offers immediate information on hemodynamics, thereby consolidating patient data and facilitating the development of personalized treatment strategies.
Renal hypouricemia type 2 with SLC2A9 compound heterozygous variants: a case report of recurrent acute kidney injury triggered by low-intensity exercise
Authors: Paladugu Niranjana Rekha , Vukkadala Muralinath
Published: October 2024

Renal hypouricemia (RHUC) is a rare genetic disorder characterized by impaired uric acid reabsorption which leads to persistently low serum uric acid levels. This condition predisposes individuals to complications such as uric acid kidney stones and exercise-induced acute kidney injury (EIAKI). Although mutations in SLC22A12 and SLC2A9 are commonly implicated in RHUC, the precise pathophysiological mechanisms, particularly those contributing to AKI, remain incompletely understood. We report the case of a 30-year-old male who experienced recurrent episodes of EIAKI despite the absence of high-intensity exercise, suggesting the involvement of factors beyond the traditional risk. Genetic analysis confirmed the diagnosis of RHUC type 2 (RHUC2) and identified compound heterozygous variants of SLC2A9. Although these variants are not novel, this case contributes to the limited literature on RHUC2, particularly in male patients with recurrent EIAKI. These findings highlight the importance of maintaining a high index of suspicion for RHUC in cases of unexplained AKI, especially when recurrent episodes follow physical activity, and the need for targeted genetic testing for an accurate diagnosis. The genomic data related to this case are available in Mendeley Data: Vukkadala, Muralinath; Paladugu, Niranjana Rekha (2024), “Renal hypouricemia,” Mendeley Data, V2, doi: 10.17632/7z84mkdgn9.2.
Predicting cerebral edema in patients with spontaneous intracerebral hemorrhage using machine learning
Authors: Xu Jiangbao , Yuan Cuijie , Yu Guofeng , Li Hao , Dong Qiutong , Mao Dandan , Zhan Chengpeng , Yan Xinjiang
Published: October 2024

Background

The early prediction of cerebral edema changes in patients with spontaneous intracerebral hemorrhage (SICH) may facilitate earlier interventions and result in improved outcomes. This study aimed to develop and validate machine learning models to predict cerebral edema changes within 72 h, using readily available clinical parameters, and to identify relevant influencing factors.

Methods

An observational study was conducted between April 2021 and October 2023 at the Quzhou Affiliated Hospital of Wenzhou Medical University. After preprocessing the data, the study population was randomly divided into training and internal validation cohorts in a 7:3 ratio (training: N = 150; validation: N = 65). The most relevant variables were selected using Support Vector Machine Recursive Feature Elimination (SVM-RFE) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms. The predictive performance of random forest (RF), GDBT, linear regression (LR), and XGBoost models was evaluated using the area under the receiver operating characteristic curve (AUROC), precision–recall curve (AUPRC), accuracy, F1-score, precision, recall, sensitivity, and specificity. Feature importance was calculated, and the SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) methods were employed to explain the top-performing model.

Results

A total of 84 (39.1%) patients developed cerebral edema changes. In the validation cohort, GDBT outperformed LR and RF, achieving an AUC of 0.654 (95% CI: 0.611–0.699) compared to LR of 0.578 (95% CI, 0.535–0.623, DeLong: p = 0.197) and RF of 0.624 (95% CI, 0.588–0.687, DeLong: p = 0.236). XGBoost also demonstrated similar performance with an AUC of 0.660 (95% CI, 0.611–0.711, DeLong: p = 0.963). However, in the training set, GDBT still outperformed XGBoost, with an AUC of 0.603 ± 0.100 compared to XGBoost of 0.575 ± 0.096. SHAP analysis revealed that serum sodium, HDL, subarachnoid hemorrhage volume, sex, and left basal ganglia hemorrhage volume were the top five most important features for predicting cerebral edema changes in the GDBT model.

Conclusion

The GDBT model demonstrated the best performance in predicting 72-h changes in cerebral edema. It has the potential to assist clinicians in identifying high-risk patients and guiding clinical decision-making.
Can micro-expressions be used as a biomarker for autism spectrum disorder?
Authors: Ruan Mindi , Zhang Na , Yu Xiangxu , Li Wenqi , Hu Chuanbo , Webster Paula J. , K. Paul Lynn , Wang Shuo , Li Xin
Published: October 2024

Introduction

Early and accurate diagnosis of autism spectrum disorder (ASD) is crucial for effective intervention, yet it remains a significant challenge due to its complexity and variability. Micro-expressions are rapid, involuntary facial movements indicative of underlying emotional states. It is unknown whether micro-expression can serve as a valid bio-marker for ASD diagnosis.

Methods

This study introduces a novel machine-learning (ML) framework that advances ASD diagnostics by focusing on facial micro-expressions. We applied cutting-edge algorithms to detect and analyze these micro-expressions from video data, aiming to identify distinctive patterns that could differentiate individuals with ASD from typically developing peers. Our computational approach included three key components: (1) micro-expression spotting using Shallow Optical Flow Three-stream CNN (SOFTNet), (2) feature extraction via Micron-BERT, and (3) classification with majority voting of three competing models (MLP, SVM, and ResNet).

Results

Despite the sophisticated methodology, the ML framework's ability to reliably identify ASD-specific patterns was limited by the quality of video data. This limitation raised concerns about the efficacy of using micro-expressions for ASD diagnostics and pointed to the necessity for enhanced video data quality.

Discussion

Our research has provided a cautious evaluation of micro-expression diagnostic value, underscoring the need for advancements in behavioral imaging and multimodal AI technology to leverage the full capabilities of ML in an ASD-specific clinical context.
Cathepsins and neurological diseases: a Mendelian randomization study
Authors: Sun Haitao , Tang Qingqing , Yan Xue , Xie Wanying , Xu Yueshan , Zhang Weimin
Published: October 2024

Background

The causal relationship between cathepsins and neurological diseases remains uncertain. To address this, we utilized a two-sample Mendelian randomization (MR) approach to assess the potential causal effect of cathepsins on the development of neurological diseases.

Methods

This study conducted a two-sample two-way MR study using pooled data from published genome-wide association studies to evaluate the relationship between 10 cathepsins (B, D, E, F, G, H, L2, O, S, and Z) and 7 neurological diseases, which included ischemic stroke, cerebral hemorrhage, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and epilepsy. The analysis employed various methods such as inverse variance weighting (IVW), weighted median, MR Egger regression, MR pleiotropy residual sum and outlier, Cochran Q statistic, and leave-one-out analysis.

Results

We found a causal relationship between cathepsins and neurological diseases, including Cathepsin B and Parkinson’s disease (IVW odds ratio (OR): 0.89, 95% confidence interval (CI): 0.83, 0.95, p = 0.001); Cathepsin D and Parkinson’s disease (OR: 0.80, 95%CI: 0.68, 0.95, p = 0.012); Cathepsin E and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.09, p = 0.015); Cathepsin O and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.021). Reverse MR analyses revealed that multiple sclerosis and Cathepsin E (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.030). There is currently no significant relationship has been found between other cathepsins and neurological diseases.

Conclusion

Our study reveals a causal relationship between Cathepsins B, D, E, and O and neurological diseases, offering valuable insights for research aimed at improving the diagnosis and treatment of such conditions.
A study of pre- and post-treatment hematologic markers of immune response in patients undergoing radiotherapy for soft tissue sarcoma
Authors: Ku Eric , Harada Garrett , Lee Grace , Munjal Akul , Peterson Nicholas , Park Jino , Chow Warren , Stitzlein Russell , Limoli Charles , Harris Jeremy
Published: October 2024

Introduction

This study investigates the impact of pre- and post-treatment hematologic markers, specifically neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on treatment outcomes in soft tissue sarcoma (STS) patients undergoing radiation therapy (RT).

Methods

Data from 64 patients who underwent RT for curative management of STS were reviewed. Pre-RT and post-RT hematologic measures were evaluated for associations with survival outcomes. A normal tissue complication probability (NTCP) curve for predicting ΔPLR ≥ 75 was modeled using a probit function.

Results

Elevated baseline NLR was associated with worse overall survival (OS) and disease-free survival (DFS), while elevated PLR was associated with worse DFS. Post-RT, elevated PLR was linked to worse OS and DFS. Increasing PLR change post-RT was associated with worse OS and DFS. Receiver operating characteristics analysis determined ΔPLR ≥ 75 to be a robust cutoff associated with worse DFS. Bone V10Gy ≥362 cc corresponded to a 50% risk of developing ΔPLR ≥ 75.

Discussion

These results suggest that hematologic markers could serve as prognostic biomarkers in both pre- and post-treatment settings for STS patients undergoing RT. Future studies can consider using bone V10Gy < 362 cc as a potential cutoff to reduce the risk of increased PLR after RT.
Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia
Authors: Salceda-Rivera Violeta , Ortiz-Lazareno Pablo C. , Hernández-Flores Georgina , Vazquez-Urrutia Jorge R. , Meza-Arroyo Jesus , Pardo-Zepeda Monzerrat , Romo-Rubio Hugo , Barba-Barba Cesar , Sánchez-Zubieta Fernando , Barrón-Gallardo Carlos Alfredo , Gonzalez-Ramella Oscar , Bravo-Cuellar Alejandro
Published: October 2024

Introduction

Despite the improvement in survival in acute lymphoblastic leukemia (ALL), there are still cases with evasion of chemotherapy-induced apoptosis. The IKK/NF-κB signaling pathway contributes to antiapoptotic gene expression. Pentoxifylline (PTX) inhibits IkB phosphorylation, blocking NF-κB and antiapoptotic activity.

Methods

We conducted a randomized, double-blind clinical trial on pediatric ALL patients undergoing induction therapy, assigning them to PTX or placebo group. Bone marrow aspirates were obtained on days 1, 8, 15, and 22. Apoptosis was assessed using Annexin-V/propidium iodide.

Results

Results indicated that the PTX group exhibited higher apoptosis on day-8 (41.3% vs. 19.4%, p =0.029) and day-15 (35.0% vs. 14.2%, p <0.01). On day-8, the PTX group displayed an MRD of 0.25% vs. 18.2% (p <0.01) in placebo group; on day-15, the PTX group demonstrated an MRD of 0.09% vs. 1.4% (p =0.02). Patients achieving an MRD <0.01% on day-8 demonstrated a 3-year Overall Survival (OS) of 81.6% vs. 58.3% (p =0.03); on day-15, patients with MRD <0.01% had a 3-year OS of 77.9% vs. 54.5% (p =0.03). The PTX group achieved an MRD of <0.01% earlier on days-8 and 15, along with a higher apoptosis rate, indicating a more favorable therapeutic response. In the entire cohort, patients achieving MRD <0.01% on day-8 or 15 displayed superior OS.

Conclusion

Our study demonstrates that PTX enhances apoptosis and reduces MRD in pediatric acute lymphoblastic leukemia patients.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT02451774.
Real world clinical outcomes from targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer: data from a large cohort at a national cancer institute
Authors: Vinante Lorenzo , Vaidya Jayant Sharad , Caroli Angela , Mileto Mario , Piccoli Erica , Avanzo Michele , Barresi Loredana , Marson Marta , Montico Marcella , Baboci Lorena , Perin Tiziana , Urbani Martina , Puglisi Fabio , Mascarin Maurizio , Massarut Samuele
Published: October 2024

Introduction

Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT.

Methods

This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the risk-adapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events.

Results

The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality (“exclusive IORT” group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the “exclusive IORT” cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%-3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%).

Conclusions

This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This “real world” experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice.
The efficacy of azithromycin combined with seven types of Chinese medicine injections in the treatment of Mycoplasma pneumoniae pneumonia in children: a systematic review and Bayesian network meta-analysis
Authors: Huang Xinggui , Tao Sian , Liu Chenhao , Sun Xiaoluo , Hao Yule , Ma Yuqi , Liu Yi , Liu Jibin
Published: October 2024

Mycoplasma pneumoniae pneumonia (MPP) is the predominant community-acquired pneumonia (CAP) in children aged 5 years or older. In recent decades, the annual increase in drug resistance rates of macrolide antibiotics, particularly azithromycin (AZ), has led to complex clinical treatment strategies and substantial healthcare costs associated with MPP. Chinese medicine injections (CMIs), recognized as an effective supplementary therapy, are acknowledged by clinicians in China. It is necessary to explore the efficacy of azithromycin in combination with CMIs.

Methods

Randomized controlled trials (RCTs) evaluating azithromycin in combination with seven types of CMIs for MPP in children were identified based on inclusion criteria and assessed using the revised Cochrane risk of bias tool (RoB 2.0). R 4.3.1 and STATA 15.0 were employed to generate ranking probabilities and perform network meta-analysis. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities.

Results

A comprehensive analysis was performed on 155 RCTs involving 15,014 patients and 8 therapeutic strategies within this Bayesian network meta-analysis (BNMA). The results indicated that AZ combined with seven types of CMIs was more effective than azithromycin alone in overall outcomes. Notably, azithromycin combined with Chuanhuning injection (AZ + CHN) achieved the highest ranking in improving the clinical effectiveness rate (SUCRA, 80.89%); regarding secondary outcome measures, azithromycin combined with Yanhuning injection (AZ + YHN) had the highest probability of improving four different outcomes: disappearance time of cough (SUCRA, 80.01%), disappearance time of pulmonary rale (SUCRA, 87.77%), disappearance time of fever (SUCRA, 95.70%), and disappearance time of pulmonary shadows in X-ray (SUCRA, 97.34%); furthermore, azithromycin combined with Qingkailing injection (AZ + QKL) was more likely to reduce average hospitalization time (SUCRA, 94.60%).

Conclusion

This study highlights the potential benefits of seven types of Chinese medicine injections as adjunctive therapy for Mycoplasma pneumoniae pneumonia in children. However, further support and validation of these findings are needed through high-quality randomized controlled trials with larger sample sizes and double-blind designs.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails/.
How teacher behaviors and perceptions, air change rates, and portable air purifiers affect indoor air quality in naturally ventilated schools
Authors: Xia Tian , Raneses Julia , Schmiesing Brixon , Garcia Raquel , Walding Alison , DeMajo Richardo , Schulz Amy , Batterman Stuart A.
Published: October 2024

Introduction

Many school buildings have inadequate ventilation, rudimentary if any air filtration, and aging and poorly maintained mechanical systems, all of which can lead to poor indoor air quality (IAQ). These issues are especially acute in environmental justice (EJ) communities where schools are located in polluted areas. This community-based participatory research examines how IAQ in naturally ventilated school buildings is affected by the use of air purifiers, air change rates, outdoor pollution levels, and teacher and staff behavior.

Methods

IAQ assessments were performed at two schools in Detroit, Michigan, which included building walk-through inspections and continuous indoor and outdoor measurements of black carbon (BC), particulate matter (PM10 and PM2.5), carbon dioxide (CO2), air change rates (ACRs), temperature, humidity, and sound pressure levels. Air purifiers with usage monitors were then installed, and the IAQ assessments were repeated. Teachers were surveyed before and after purifier deployment.

Results

At baseline, classrooms had low ACRs (0.58–1.38 h−1), moderate PM2.5 levels (2.8–8.9 μg/m3), highly variable PM10 concentrations (4.7–37.5 μg/m3), and elevated BC levels (0.3–0.7 μg/m3), reflecting emissions from local traffic, industry and other sources. The installation and use of purifiers reduced pollutant levels and the overall performance matched the predictions of a single compartment model. However, daily reductions varied widely among classrooms, reflecting differences in teacher behavior regarding the frequency of opening windows and the operation of purifiers, including differences in purifier fan speed settings and whether purifiers were used at night. Survey responses indicated that many teachers were aware of IAQ problems. The higher rates reported for health symptoms and dissatisfaction at one school may have lowered the teachers’ tolerance to noise and reduced purifier use.

Discussion

The study helps explain the variation reported in prior studies using purifiers, and it reinforces the need to monitor IAQ and purifier use, use enhanced filtration and increase ventilation, and engage with teachers and school staff to support and maintain IAQ programs in schools.
Design and psychometrics of the family caregivers burnout inventory of older adults with chronic disease
Authors: Farokhmanesh Kataneh , Shamsalinia Abbas , Kordbageri Mohammad Reza , Saadati Kiyana , Ebrahimi Rad Reza , Ghaffari Fatemeh
Published: October 2024

Background

Identifying the hidden and pervasive phenomenon of burnout among family caregivers of older adults with chronic disease requires the use of a valid and reliable tool tailored to the cultural structure of the target community. Therefore, the present study aimed to design and psychometrically evaluate the family caregivers burnout inventory (FCBI) of older adults with chronic disease.

Methods

This research is a sequential exploratory mixed-methods study focused on instrument design, conducted in Iran in 2024. The study employed classical theory, involving three stages to create a valid instrument: item design using inductive (semi-structured face-to-face interviews with 13 caregivers) and deductive (literature review) methods, tool design, and tool evaluation using face validity, content validity, construct validity [exploratory factor analysis (EFA) (N = 297) and confirmatory factor analysis (297 participants)], convergent validity, and reliability (internal consistency and stability). Data were analyzed using AMOS version 24 and SPSS version 26.

Results

Based on qualitative findings, participant quotes, and item adoption from other studies, a pool of 228 items was designed using a 5-point Likert scale (always to never). After several stages of review by the research team, 102 items remained. Following face validity (2 items), content validity (46 items), and construct validity (23 items due to factor loadings less than 0.4 and cross-loadings), 71 items were eliminated, leaving 31 items. EFA results indicated that the family caregiver’s burnout construct of older adults with chronic diseases comprises six factors include; “neurosis,” “feeling victimized,” “extreme fatigue and helplessness,” “neglect or abuse of self and others,” “adaptation deficiency” and “emotional separation” explaining 52.93% of the total variance. The fit indices showed acceptable model fit with the data. In this study, composite reliability and average variance extracted (AVE) for the six factors were greater than 0.7 and 0.5, respectively, and the (AVE) for each factor was higher than the composite reliability. Cronbach’s alpha coefficient for the entire scale was 0.975, and there was a significant correlation between test and retest scores (p < 0.001).

Conclusion

FCBI demonstrates suitable validity and reliability and can be used in various settings by health service providers to identify symptoms of burnout in family caregivers.