bluuebunny/crossref_metadata_2025_split huggingface dataset:
NAD metabolism-related genes provide prognostic value and potential therapeutic insights for acute myeloid leukemia
Authors: Cao Yuncan , Shu Wenjing , Jin Peng , Li Jianfeng , Zhu Hongming , Chen Xinjie , Zhu Yongmei , Huang Xi , Cheng Wenyan , Shen Yang 
Published: June 2024

IntroductionAcute myeloid leukemia (AML) is an aggressive blood cancer with high heterogeneity and poor prognosis. Although the metabolic reprogramming of nicotinamide adenine dinucleotide (NAD) has been reported to play a pivotal role in the pathogenesis of acute myeloid leukemia (AML), the prognostic value of NAD metabolism and its correlation with the immune microenvironment in AML remains unclear.MethodsWe utilized our large-scale RNA-seq data on 655 patients with AML and the NAD metabolism-related genes to establish a prognostic NAD metabolism score based on the sparse regression analysis. The signature was validated across three independent datasets including a total of 1,215 AML patients. ssGSEA and ESTIMATE algorithms were employed to dissect the tumor immune microenvironment. Ex vivo drug screening and in vitro experimental validation were performed to identify potential therapeutic approaches for the high-risk patients. In vitro knockdown and functional experiments were employed to investigate the role of SLC25A51, a mitochondrial NAD+ transporter gene implicated in the signature.ResultsAn 8-gene NAD metabolism signature (NADM8) was generated and demonstrated a robust prognostic value in more than 1,800 patients with AML. High NADM8 score could efficiently discriminate AML patients with adverse clinical characteristics and genetic lesions and serve as an independent factor predicting a poor prognosis. Immune microenvironment analysis revealed significant enrichment of distinct tumor-infiltrating immune cells and activation of immune checkpoints in patients with high NADM8 scores, acting as a potential biomarker for immune response evaluation in AML. Furthermore, ex vivo drug screening and in vitro experimental validation in a panel of 9 AML cell lines demonstrated that the patients with high NADM8 scores were more sensitive to the PI3K inhibitor, GDC-0914. Finally, functional experiments also substantiated the critical pathogenic role of the SLC25A51 in AML, which could be a promising therapeutic target.ConclusionOur study demonstrated that NAD metabolism-related signature can facilitate risk stratification and prognosis prediction in AML and guide therapeutic decisions including both immunotherapy and targeted therapies.
Agreement between serological data on schoolchildren and the number of malaria cases in the remaining high-burden villages of Indonesia
Authors: Kosasih Ayleen , Utami Retno Ayu Setya , Noviyanti Rintis , Elyazar Iqbal R. F. , Lestari Karina Dian , Raimanus Valentinus Seran , Longley Rhea J. , Baird J. Kevin , Robinson Leanne J. , Sutanto Inge , Mueller Ivo 
Published: June 2024

IntroductionIn areas where malaria transmission has been successfully reduced, surveillance based solely on clinical cases becomes increasingly challenging. Antibodies generated by the host in response to malaria infections may persist in the circulation for several months or longer. We assessed a serological surveillance tool to measure malaria transmission in eastern Indonesia where reported cases have been recently declining.MethodsIn June 2021, we conducted a cross-sectional survey of elementary schoolchildren aged 5 to 14 years residing in six villages in an endemic area of West Timor, Indonesia. Annual Parasite Incidence (API, cases/1,000 residents/year) of these villages ranged from 0.0 to 4.1 in 2021. Finger-prick plasma samples were tested using a multiplexed Luminex MAGPIX® bead array system to measure IgG antibodies against a panel of 8 Plasmodium vivax antigens. Using a random forest classification algorithm, individuals with predicted exposure to P. vivax in the prior 9 months were identified.Results15 of 398 (4%) schoolchildren were seropositive for recent P. vivax exposure. Remarkably, 87% (13/15) of seropositive children were from one village, the one with the highest API (4.1). In contrast, one seropositive child was from a village with an API of 1.3, and another from a village with an API of 0.0.ConclusionOur serological survey data confirms the reported malaria cases from PHC in the villages with likely ongoing transmission. Malaria programs may consider Lamea as the target for intervention.
Compact machine learning model for the accurate prediction of first 24-hour survival of mechanically ventilated patients
Authors: Nguyen Quynh T. , Tran Mai P. , Prabhakaran Vishnu , Liu Andrew , Nguyen Ghi H. 
Published: June 2024

BackgroundThe field of machine learning has been evolving and applied in medical applications. We utilised a public dataset, MIMIC-III, to develop compact models that can accurately predict the outcome of mechanically ventilated patients in the first 24 h of first-time hospital admission.Methods67 predictive features, grouped into 6 categories, were selected for the classification and prediction task. 4 tree-based algorithms (Decision Tree, Bagging, eXtreme Gradient Boosting and Random Forest), and 5 non-tree-based algorithms (Logistic Regression, K-Nearest Neighbour, Linear Discriminant Analysis, Support Vector Machine and Naïve Bayes), were employed to predict the outcome of 18,883 mechanically ventilated patients. 5 scenarios were crafted to mirror the target population as per existing literature. S1.1 reflected an imbalanced situation, with significantly fewer mortality cases than survival ones, and both the training and test sets played similar target class distributions. S1.2 and S2.2 featured balanced classes; however, instances from the majority class were removed from the test set and/or the training set. S1.3 and S 2.3 generated additional instances of the minority class via the Synthetic Minority Over-sampling Technique. Standard evaluation metrics were used to determine the best-performing models for each scenario. With the best performers, Autofeat, an automated feature engineering library, was used to eliminate less important features per scenario.ResultsTree-based models generally outperformed the non-tree-based ones. Moreover, XGB consistently yielded the highest AUC score (between 0.91 and 0.97), while exhibiting relatively high Sensitivity (between 0.58 and 0.88) on 4 scenarios (1.2, 2.2, 1.3, and 2.3). After reducing a significant number of predictors, the selected calibrated ML models were still able to achieve similar AUC and MCC scores across those scenarios. The calibration curves of the XGB and BG models, both prior to and post dimension reduction in Scenario 2.2, showed better alignment to the perfect calibration line than curves produced from other algorithms.ConclusionThis study demonstrated that dimension-reduced models can perform well and are able to retain the important features for the classification tasks. Deploying a compact machine learning model into production helps reduce costs in terms of computational resources and monitoring changes in input data over time.
Comparative microbiome diversity in root-nodules of three Desmodium species used in push-pull cropping system
Authors: Adan Isack H. , Asudi George Ochieng , Niassy Saliou , Jalloh Abdul A. , Mutua Johnstone Mutiso , Chidawanyika Frank , Khamis Fathiya , Khan Zeyaur , Subramanian Sevgan , Dubois Thomas , Mutyambai Daniel Munyao 
Published: June 2024

BackgroundDesmodium species used as intercrops in push-pull cropping systems are known to repel insect-pests, suppress Striga species weeds, and shift soil microbiome. However, the mechanisms through which Desmodium species impact the soil microbiome, either through its root exudates, changes in soil nutrition, or shading microbes from its nodules into the rhizosphere, are less understood. Here, we investigated the diversity of root-nodule microbial communities of three Desmodium species- Desmodium uncinatum (SLD), Desmodium intortum (GLD), and Desmodium incanum (AID) which are currently used in smallholder maize push-pull technology (PPT).MethodsDesmodium species root-nodule samples were collected from selected smallholder farms in western Kenya, and genomic DNA was extracted from the root-nodules. The amplicons underwent paired-end Illumina sequencing to assess bacterial and fungal populations.ResultsWe found no significant differences in composition and relative abundance of bacterial and fungal species within the root-nodules of the three Desmodium species. While a more pronounced shift was observed for fungal community compositions compared to bacteria, no significant differences were observed in the general diversity (evenness and richness) of fungal and bacterial populations among the three Desmodium species. Similarly, beta diversity was not significantly different among the three Desmodium species. The root-nodule microbiome of the three Desmodium species was dominated by Bradyrhizobium and Fusarium species. Nevertheless, there were significant differences in the proportion of marker gene sequences responsible for energy and amino acid biosynthesis among the three Desmodium species, with higher sequence proportions observed in SLD.ConclusionThere is no significant difference in the microbial community of the three Desmodium species used in PPT. However, root-nodule microbiome of SLD had significantly higher marker gene sequences responsible for energy and amino acid biosynthesis. Therefore, it is likely that the root-nodules of the three Desmodium species host similar microbiomes and influence soil health, consequently impacting plant growth and agroecosystem functioning.
Alterations in brain morphology and functional connectivity mediate cognitive decline in carotid atherosclerotic stenosis
Authors: Maimaitiaili Subinuer , Tang Chen , Liu Cheng , Lv Xiaochen , Chen Zhipeng , Zhang Mengqiang , Cai Jing , Liang Zishun , Zhao Biao , Zhang Wen , Qiao Tong 
Published: June 2024

BackgroundPatients with carotid atherosclerotic stenosis (CAS) often have varying degrees of cognitive decline. However, there is little evidence regarding how brain morphological and functional abnormalities impact the cognitive decline in CAS patients. This study aimed to determine how the brain morphological and functional changes affected the cognitive decline in patients with CAS.MethodsThe brain morphological differences were analyzed using surface and voxel-based morphometry, and the seed-based whole-brain functional connectivity (FC) abnormalities were analyzed using resting-state functional magnetic resonance imaging. Further, mediation analyses were performed to determine whether and how morphological and FC changes affect cognition in CAS patients.ResultsThe CAS-MCI (CAS patients with mild cognitive impairment) group performed worse in working memory, verbal fluency, and executive time. Cortical thickness (CT) of the left postcentral and superiorparietal were significantly reduced in CAS-MCI patients. The gray matter volume (GMV) of the right olfactory, left temporal pole (superior temporal gyrus) (TPOsup.L), left middle temporal gyrus (MTG.L), and left insula (INS.L) were decreased in the CAS-MCI group. Besides, decreased seed-based FC between TPOsup.L and left precuneus, between MTG.L and TPOsup.L, and between INS.L and MTG.L, left middle frontal gyrus, as well as Superior frontal gyrus, were found in CAS-MCI patients. Mediation analyses demonstrated that morphological and functional abnormalities fully mediated the association between the maximum degree of carotid stenosis and cognitive function.ConclusionMultiple brain regions have decreased GMV and CT in CAS-MCI patients, along with disrupted seed-based FC. These morphological and functional changes play a crucial role in the cognitive impairment in CAS patients.
Staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of bilateral essential tremor and Parkinson’s disease related tremor: a systematic review and critical appraisal of current knowledge
Authors: Cesarano Simone , Saporito Gennaro , Sucapane Patrizia , Bruno Federico , Catalucci Alessia , Pistoia Maria Letizia , Splendiani Alessandra , Ricci Alessandro , Di Cesare Ernesto , Totaro Rocco , Pistoia Francesca 
Published: June 2024

IntroductionEssential tremor (ET) and Parkinson’s Disease (PD) are debilitating neurodegenerative disorders characterized by tremor as a predominant symptom, significantly impacting patients’ quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) Thalamotomy is an innovative therapeutic option for the treatment of unilateral medically refractory tremor with fewer adverse effects compared to traditional surgical interventions. A recent CE approval allows appropriate patients to have their second side treated.ObjectiveThe objective of this systematic review was to analyze available current knowledge about the use of MRgFUS for the treatment of bilateral ET and PD related tremor, to identify the effectiveness and the risks associated with bilateral treatment.MethodsEligible studies were identified by searching published studies in PubMed and Scopus databases from May 2014 to January 2024 and by identifying ongoing studies registered on the clinicaltrials.gov website. Data were summarized by considering the following information topics: the number of patients involved, the selected lesion target, the assessment tool used to evaluate clinical changes, the observed improvement, the reported side effects, and the time interval between the two treatments. The study was registered in PROSPERO (ID: CRD42024513178).ResultsNine studies were eligible for this review, 7 for ET and 2 for PD. The involved population included a variable number of patients, ranging from 1 to 11 subjects for ET and from 10 to 15 subjects for PD. The main lesional targets were the ventral intermediate nucleus of the thalamus, the pallidothalamic tract and the cerebellothalamic tract bilaterally. All studies investigated the tremor relief through the Clinical Rating Scale for Tremor (CRST) in patients with ET, and through the Unified Parkinson’s Disease Rating Scale (UPDRS) in patients with PD. A variable degree of improvement was observed, with all patients expressing overall satisfaction with the bilateral treatment. Adverse events were mild and transient, primarily involving gait disturbances, dysarthria, and ataxia. A standardized protocol for administering the two consecutive treatments was not identifiable; typically, the timing of the second treatment was delayed by at least 6 months.ConclusionAvailable evidence supports the effectiveness and safety of staged bilateral MRgFUS treatments for ET and PD-related tremor.
The utility of methylmalonic acid, methylcitrate acid, and homocysteine in dried blood spots for therapeutic monitoring of three inherited metabolic diseases
Authors: Liu Yi , Ma Xue , Kang Lulu , Jin Ying , Li Mengqiu , Song Jinqing , Li Haixia , Cao Yongtong , Yang Yanling 
Published: June 2024

BackgroudRoutine metabolic assessments for methylmalonic acidemia (MMA), propionic acidemia (PA), and homocysteinemia involve detecting metabolites in dried blood spots (DBS) and analyzing specific biomarkers in serum and urine. This study aimed to establish a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the simultaneous detection of three specific biomarkers (methylmalonic acid, methylcitric acid, and homocysteine) in DBS, as well as to appraise the applicability of these three DBS metabolites in monitoring patients with MMA, PA, and homocysteinemia during follow-up.MethodsA total of 140 healthy controls and 228 participants were enrolled, including 205 patients with MMA, 17 patients with PA, and 6 patients with homocysteinemia. Clinical data and DBS samples were collected during follow-up visits.ResultsThe reference ranges (25th–95th percentile) for DBS methylmalonic acid, methylcitric acid, and homocysteine were estimated as 0.04–1.02 μmol/L, 0.02–0.27 μmol/L and 1.05–8.22 μmol/L, respectively. Following treatment, some patients achieved normal metabolite concentrations, but the majority still exhibited characteristic biochemical patterns. The concentrations of methylmalonic acid, methylcitric acid, and homocysteine in DBS showed positive correlations with urine methylmalonic acid (r = 0.849, p &lt; 0.001), urine methylcitric acid (r = 0.693, p &lt; 0.001), and serum homocysteine (r = 0.721, p &lt; 0.001) concentrations, respectively. Additionally, higher levels of DBS methylmalonic acid and methylcitric acid may be associated with increased cumulative complication scores.ConclusionThe LC–MS/MS method established in this study reliably detects methylmalonic acid, methylcitric acid, and homocysteine in DBS. These three DBS metabolites can be valuable for monitoring patients with MMA, PA, and homocysteinemia during follow-up. Further investigation is required to determine the significance of these DBS biomarkers in assessing disease burden over time.
Recurrent and transformation of borderline to malignant phyllodes tumour with osteoid differentiation: a case report and literature review
Authors: Balachandran Navin Raj , Abdullah Norlia , Ismail Muhammad Ishamuddin , Wong Yin Ping , Azmi Mohd Imree 
Published: June 2024

Phyllodes tumours or cystosarcoma phyllodes are fibroepithelial tumours of the breast and represent 1% of breast tumours. A 20-year-old nullipara presented with an enlarging left breast mass over 6 months. Although widely excised, it was reported to be a 12 × 10 × 5.5-cm borderline phyllodes tumour with involvement of the superior and inferior margins. Seven months later, she presented with a new ipsilateral breast lump measuring 8.5 × 7.5 × 4.6 cm. She underwent a left mastectomy, a three-rib resection with titanic rods for the thoracic cage reconstruction, and a latissimus dorsi flap wound closure. Histopathology revealed a high-grade malignant phyllodes tumour with features of osteoid differentiation with the nearest deep margin measuring 3 mm. She developed metastasis to the ipsilateral axillary lymph nodes and contralateral lung 2 months postoperatively. She was given palliative radiotherapy 60 Gy in 30 fractions to the left axilla. She developed sudden lower-limb weakness due to spinal metastases. The symptoms resolved with radiotherapy to the thoracic spine (T4–T8). As the lesion continued to grow rapidly from the anterior chest wall encircling towards the back, it was deemed unresectable. She was given palliative chemotherapy (doxorubicin six cycles, followed by ifosfamide one cycle) but had disease progression. She passed away 3 months later. The mainstay of treatment for phyllodes tumour is excision with a minimal margin of 1 cm. Although margins were involved after the first surgery, she was followed up as the pathology was a borderline phyllodes. When the lump recurred and had transformed, despite extensive surgery, it returned shortly and progressed. A borderline phyllodes should be excised to obtain a minimal margin of 1 cm, even if it means performing a mastectomy, to minimise recurrence. A recurrence may undergo malignant transformation which is largely chemotherapy and radiotherapy resistant. This will result in a poor outcome and decreased survival.
The survival and cost-effectiveness analysis of adjunctive Chinese medicine therapy for patients with non-small cell lung cancer: a nationwide cohort study in Taiwan
Authors: Tang Meng-Bin , Kuo Wei-Yin , Kung Pei-Tseng , Tsai Wen-Chen 
Published: June 2024

Introduction: Cancer, particularly lung cancer, is a significant global healthcare challenge. Non-Small Cell Lung Cancer (NSCLC) constitutes 85% of cases. Patients often seek alternative therapies like Chinese medicine alongside Western treatments. This study investigates the survival outcomes and cost-effectiveness of adjunctive Chinese medicine therapy for NSCLC patients in Taiwan.Methods: We utilized the National Health Insurance Research Database in a retrospective cohort study from 2000 to 2018, focusing on NSCLC patients diagnosed between 2007 and 2013. After propensity score matching 1:5 ratio, then compared patients with and without adjunctive Chinese medicine therapy. Survival outcomes, cost-effectiveness, and sensitivity analyses were conducted.Results: The study involved 43,122 NSCLC patients with 5.76% receiving adjunctive Chinese medicine. There is no significant associated between the risk of death and adjuvant Chinese medicine therapy until 181–365 days of adjuvant treatment could reduce the risk of death (HR = 0.88, 95% CI: 0.80–0.98). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 880,908 NT$/year.Conclusion: Adjunctive Chinese medicine therapy, particularly when administered for 181–365 days, significantly reduced the mortality risk among stage IV NSCLC patients. The cost-effectiveness aligns with willingness-to-pay thresholds, indicating economic benefit.
YOLO SSPD: a small target cotton boll detection model during the boll-spitting period based on space-to-depth convolution
Authors: Zhang Mengli , Chen Wei , Gao Pan , Li Yongquan , Tan Fei , Zhang Yuan , Ruan Shiwei , Xing Peng , Guo Li 
Published: June 2024

IntroductionCotton yield estimation is crucial in the agricultural process, where the accuracy of boll detection during the flocculation period significantly influences yield estimations in cotton fields. Unmanned Aerial Vehicles (UAVs) are frequently employed for plant detection and counting due to their cost-effectiveness and adaptability.MethodsAddressing the challenges of small target cotton bolls and low resolution of UAVs, this paper introduces a method based on the YOLO v8 framework for transfer learning, named YOLO small-scale pyramid depth-aware detection (SSPD). The method combines space-to-depth and non-strided convolution (SPD-Conv) and a small target detector head, and also integrates a simple, parameter-free attentional mechanism (SimAM) that significantly improves target boll detection accuracy.ResultsThe YOLO SSPD achieved a boll detection accuracy of 0.874 on UAV-scale imagery. It also recorded a coefficient of determination (R2) of 0.86, with a root mean square error (RMSE) of 12.38 and a relative root mean square error (RRMSE) of 11.19% for boll counts.DiscussionThe findings indicate that YOLO SSPD can significantly improve the accuracy of cotton boll detection on UAV imagery, thereby supporting the cotton production process. This method offers a robust solution for high-precision cotton monitoring, enhancing the reliability of cotton yield estimates.