bluuebunny/crossref_metadata_2025 huggingface dataset:
Traumatic brain injury and the pathways to cerebral tau accumulation
Authors: Flavin William P. , Hosseini Helia , Ruberti Jeffrey W. , Kavehpour H. Pirouz , Giza Christopher C. , Prins Mayumi L.
Published: August 2023

Tau is a protein that has received national mainstream recognition for its potential negative impact to the brain. This review succinctly provides information on the structure of tau and its normal physiological functions, including in hibernation and changes throughout the estrus cycle. There are many pathways involved in phosphorylating tau including diabetes, stroke, Alzheimer’s disease (AD), brain injury, aging, and drug use. The common mechanisms for these processes are put into context with changes observed in mild and repetitive mild traumatic brain injury (TBI). The phosphorylation of tau is a part of the progression to pathology, but the ability for tau to aggregate and propagate is also addressed. Summarizing both the functional and dysfunctional roles of tau can help advance our understanding of this complex protein, improve our care for individuals with a history of TBI, and lead to development of therapeutic interventions to prevent or reverse tau-mediated neurodegeneration.
Multiclass classification of imagined speech EEG using noise-assisted multivariate empirical mode decomposition and multireceptive field convolutional neural network
Authors: Park Hyeong-jun , Lee Boreom
Published: August 2023

Introduction

In this study, we classified electroencephalography (EEG) data of imagined speech using signal decomposition and multireceptive convolutional neural network. The imagined speech EEG with five vowels /a/, /e/, /i/, /o/, and /u/, and mute (rest) sounds were obtained from ten study participants.

Materials and methods

First, two different signal decomposition methods were applied for comparison: noise-assisted multivariate empirical mode decomposition and wavelet packet decomposition. Six statistical features were calculated from the decomposed eight sub-frequency bands EEG. Next, all features obtained from each channel of the trial were vectorized and used as the input vector of classifiers. Lastly, EEG was classified using multireceptive field convolutional neural network and several other classifiers for comparison.

Results

We achieved an average classification rate of 73.09 and up to 80.41% in a multiclass (six classes) setup (Chance: 16.67%). In comparison with various other classifiers, significant improvements for other classifiers were achieved (p-value < 0.05). From the frequency sub-band analysis, high-frequency band regions and the lowest-frequency band region contain more information about imagined vowel EEG data. The misclassification and classification rate of each vowel imaginary EEG was analyzed through a confusion matrix.

Discussion

Imagined speech EEG can be classified successfully using the proposed signal decomposition method and a convolutional neural network. The proposed classification method for imagined speech EEG can contribute to developing a practical imagined speech-based brain-computer interfaces system.
Human upper extremity motor cortex activity shows distinct oscillatory signatures for stereotyped arm and leg movements
Authors: Starkweather Clara Kwon , Morrison Melanie A. , Yaroshinsky Maria , Louie Kenneth , Balakid Jannine , Presbrey Kara , Starr Philip A. , Wang Doris D.
Published: August 2023

Introduction

Stepping and arm swing are stereotyped movements that require coordination across multiple muscle groups. It is not known whether the encoding of these stereotyped movements in the human primary motor cortex is confined to the limbs’ respective somatotopy.

Methods

We recorded subdural electrocorticography activities from the hand/arm area in the primary motor cortex of 6 subjects undergoing deep brain stimulation surgery for essential tremor and Parkinson’s disease who performed stepping (all patients) and arm swing (n = 3 patients) tasks.

Results

We show stepping-related low frequency oscillations over the arm area. Furthermore, we show that this oscillatory activity is separable, both in frequency and spatial domains, from gamma band activity changes that occur during arm swing.

Discussion

Our study contributes to the growing body of evidence that lower extremity movement may be more broadly represented in the motor cortex, and suggest that it may represent a way to coordinate stereotyped movements across the upper and lower extremities.
versaFlow: a versatile pipeline for resolution adapted diffusion MRI processing and its application to studying the variability of the PRIME-DE database
Authors: Valcourt Caron Alex , Shmuel Amir , Hao Ziqi , Descoteaux Maxime
Published: August 2023

The lack of “gold standards” in Diffusion Weighted Imaging (DWI) makes validation cumbersome. To tackle this task, studies use translational analysis where results in humans are benchmarked against findings in other species. Non-Human Primates (NHP) are particularly interesting for this, as their cytoarchitecture is closely related to humans. However, tools used for processing and analysis must be adapted and finely tuned to work well on NHP images. Here, we propose versaFlow, a modular pipeline implemented in Nextflow, designed for robustness and scalability. The pipeline is tailored to in vivo NHP DWI at any spatial resolution; it allows for maintainability and customization. Processes and workflows are implemented using cutting-edge and state-of-the-art Magnetic Resonance Imaging (MRI) processing technologies and diffusion modeling algorithms, namely Diffusion Tensor Imaging (DTI), Constrained Spherical Deconvolution (CSD), and DIstribution of Anisotropic MicrOstructural eNvironments in Diffusion-compartment imaging (DIAMOND). Using versaFlow, we provide an in-depth study of the variability of diffusion metrics computed on 32 subjects from 3 sites of the Primate Data Exchange (PRIME-DE), which contains anatomical T1-weighted (T1w) and T2-weighted (T2w) images, functional MRI (fMRI), and DWI of NHP brains. This dataset includes images acquired over a range of resolutions, using single and multi-shell gradient samplings, on multiple scanner vendors. We perform a reproducibility study of the processing of versaFlow using the Aix-Marseilles site's data, to ensure that our implementation has minimal impact on the variability observed in subsequent analyses. We report very high reproducibility for the majority of metrics; only gamma distribution parameters of DIAMOND display less reproducible behaviors, due to the absence of a mechanism to enforce a random number seed in the software we used. This should be taken into consideration when future applications are performed. We show that the PRIME-DE diffusion data exhibits a great level of variability, similar or greater than results obtained in human studies. Its usage should be done carefully to prevent instilling uncertainty in statistical analyses. This hints at a need for sufficient harmonization in acquisition protocols and for the development of robust algorithms capable of managing the variability induced in imaging due to differences in scanner models and/or vendors.
Identifying radiomics signatures in body composition imaging for the prediction of outcome following pancreatic cancer resection
Authors: van der Kroft Gregory , Wee Leonard , Rensen Sander S. , Brecheisen Ralph , van Dijk David P. J. , Eickhoff Roman , Roeth Anjali A. , Ulmer Florian T. , Dekker Andre , Neumann Ulf P. , Olde Damink Steven W. M.
Published: August 2023

Background

Computerized radiological image analysis (radiomics) enables the investigation of image-derived phenotypes by extracting large numbers of quantitative features. We hypothesized that radiomics features may contain prognostic information that enhances conventional body composition analysis. We aimed to investigate whether body composition-associated radiomics features hold additional value over conventional body composition analysis and clinical patient characteristics used to predict survival of pancreatic ductal adenocarcinoma (PDAC) patients.

Methods

Computed tomography images of 304 patients undergoing elective pancreatic cancer resection were analysed. 2D radiomics features were extracted from skeletal muscle and subcutaneous and visceral adipose tissue (SAT and VAT) compartments from a single slice at the third lumbar vertebra. The study population was randomly split (80:20) into training and holdout subsets. Feature ranking with Least Absolute Shrinkage Selection Operator (LASSO) followed by multivariable stepwise Cox regression in 1000 bootstrapped re-samples of the training data was performed and tested on the holdout data. The fitted regression predictors were used as “scores” for a clinical (C-Score), body composition (B-Score), and radiomics (R-Score) model. To stratify patients into the highest 25% and lowest 25% risk of mortality compared to the middle 50%, the Harrell Concordance Index was used.

Results

Based on LASSO and stepwise cox regression for overall survival, ASA ≥3 and age were the most important clinical variables and constituted the C-score, and VAT-index (VATI) was the most important body composition variable and constituted the B-score. Three radiomics features (SATI_original_shape2D_Perimeter, VATI_original_glszm_SmallAreaEmphasis, and VATI_original_firstorder_Maximum) emerged as the most frequent set of features and yielded an R-Score. Of the mean concordance indices of C-, B-, and R-scores, R-score performed best (0.61, 95% CI 0.56–0.65, p<0.001), followed by the C-score (0.59, 95% CI 0.55-0.63, p<0.001) and B-score (0.55, 95% CI 0.50–0.60, p=0.03). Kaplan-Meier projection revealed that C-, B, and R-scores showed a clear split in the survival curves in the training set, although none remained significant in the holdout set.

Conclusion

It is feasible to implement a data-driven radiomics approach to body composition imaging. Radiomics features provided improved predictive performance compared to conventional body composition variables for the prediction of overall survival of PDAC patients undergoing primary resection.
Global research status and hotspots of radiotherapy for prostate cancer: a bibliometric analysis based on Web of Science from 2010-2022
Authors: Xie Xiaodu , Zhang Peng , Ran Chongjun , Liu Lumiao , Hu Jian , Lei Pan , Liang Peihe
Published: August 2023

Background

Radiotherapy (RT) is one of the important treatments for various cancer types and its application to prostate cancer (PCa) has also gradually gained increasing attention. However, there is a lack of comprehensive and objective studies on the overall status of research on RT for PCa. This article aims to summarize and quantify the dynamic trends of RT in PCa by using bibliometrics.

Methods

Studies on RT for PCa were screened from the Web of Science Core Collection (WoSCC) database between 1 January 2010 and 21 November 2022 to collate and quantify information characteristics by analyzing parameters including annual publications, countries/regions, institutions and authors with the aid of the bibliometric software CiteSpace and VOSviewer. In addition, research trends and hotspots were explored by analyzing keywords and co-cited references.

Results

A total of 21338 documents were retrieved. The United States of America (USA) ranked first and maintained the leading position among all countries in the number of publications (8489) and total citations (266342). The University of Toronto was the most active institution in total publications (n=587). Paul L Nguyen enjoyed the most publications (n=179), and Michael J Zelefsky enjoyed the most co-citations (n=3376). INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS published the most papers (n=1026), and was the most frequently co-cited journal (n=78550). The largest and closest cluster in the reference cluster analysis was “oligorecurrent prostate cancer”. The timeline view of keywords reveals that cluster “biochemical recurrence(BCR)” is ongoing. Moreover, keywords burstness analysis showed that “radiation dosimetry”, “dose rate brachytherapy(BT)”, “salvage radiotherapy”, “stereotactic body radiotherapy(SBRT)”, “guideline”, and “multicenter” were the terms with great bursts in the past a few years.

Conclusion

The application of RT targeting oligometastatic prostate cancer(OMPC) has garnered considerable attention among researchers. SBRT and BT have become hot topics in the field. Additionally, the BCR of PCa has long been a critical issue requiring extensive research and resolution, and salvage radiotherapy has currently emerged as a closely related research focus. Related large-scale multicenter studies have been conducted over the past few years, providing valuable insights. More high-quality research is expected to be employed to guide clinical decision-making.
The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis
Authors: Pettersson Helna , Adamsson Jenni , Johansson Peter , Nilsson Staffan , Palmqvist Lars , Andréasson Björn , Asp Julia
Published: August 2023

Introduction

Myeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in CALR and MPL are also frequent. Mutations seen in additional genes are also often the same regardless of subtype of MPN. The aim of this study was to analyze a population based MPN cohort for genetic variants with prognostic value that can guide clinical decisions.

Methods

MPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy.

Results

Mutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN.

Discussion

In conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered.
Natural history of intraosseous low-grade chondroid lesions of the proximal humerus
Authors: LaPrade Christopher M. , Andryk Logan M. , Christensen Joshua L. , Neilson John C. , Wooldridge Adam N. , Hackbarth Donald A. , Bedi Manpreet , King David M.
Published: August 2023

Introduction

Enchondromas and grade 1 chondrosarcomas are commonly encountered low-grade chondroid tumors in the proximal humerus. While there is a concern for malignant transformation, few studies have evaluated the natural history of these lesions. The purpose of this study is to evaluate the natural history of proximal humerus low-grade chondroid lesions managed both conservatively and surgically, and to define management criteria using clinical and radiographic findings for these low-grade chondroid lesions.

Methods

The patient population included 90 patients intended for conservative treatment and 22 patients proceeding directly to surgery. Data collection was based on a combination of chart review and patient imaging and descriptive statistics were calculated for each group.

Results

No malignant transformations were noted amongst any group. In the conservative treatment group, 7 of 64 (11%) progressed to surgery after an average of 20.3 months of conservative treatment due to persistent pain unexplained by other shoulder pathology. Importantly, 71% experienced continued pain at a mean of 53.1 months post-operatively. The group that went directly to surgery also demonstrated pain in 41% at an average follow-up of 57.3 months.

Discussion

Low-grade cartilaginous lesions of the proximal humerus without concerning imaging findings can be managed with conservative treatment and the risk of malignant transformation is very low. Patients with a clear source of their shoulder pain unrelated to their tumor and without concerning characteristics on imaging can be managed with serial annual radiographic imaging. Patients undergoing surgery for these indolent tumors are likely to experience persistent pain even after surgery.
Typing and modeling of hepatocellular carcinoma based on disulfidptosis-related amino acid metabolism genes for predicting prognosis and guiding individualized treatment
Authors: Chen Xuenuo , Wang Zhijian , Wu Yilin , Lan Yinghua , Li Yongguo
Published: August 2023

Introduction

Hepatocellular carcinoma (HCC) is the most common type of cancer worldwide and is a major public health problem in the 21st century. Disulfidopathy, a novel cystine-associated programmed cell death, plays complex roles in various tumors. However, the relationship between disulfidoptosis and prognosis in patients with HCC remains unclear. This study aimed to explore the relationship between disulfideptosis and the prognosis of liver cancer and to develop a prognostic model based on amino acid metabolism and disulfideptosis genes.

Methods

We downloaded the clinicopathological information and gene expression data of patients with HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and classified them into different molecular subtypes based on the expression patterns of disulfidoptosis-associated amino acid metabolism genes (DRAGs). Patients were then classified into different gene subtypes using the differential genes between the molecular subtypes, and the predictive value of staging was assessed using survival and clinicopathological analyses. Subsequently, risk prognosis models were constructed based on Cox regression analysis to assess patient prognosis, receiver operating characteristic (ROC) curves, somatic mutations, microsatellite instability, tumor microenvironment, and sensitivity to antitumor therapeutic agents.

Results

Patients were classified into two subtypes based on differential DRAGs gene expression, with cluster B having a better survival outcome than cluster A. Three gene subtypes were identified based on the differential genes between the two DRAGs molecular subtypes. The patients in cluster B had the best prognosis, whereas those in cluster C had the worst prognosis. The heat map showed better consistency in the patient subtypes obtained using both typing methods. We screened six valuable genes and constructed a prognostic signature. By scoring, we found that patients in the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways compared to the high-risk group, which was consistent with the tumor subtype results.

Discussion

In conclusion, we developed a prognostic signature of disulfidptosis-related amino acid metabolism genes to assist clinicians in predicting the survival of patients with HCC and provide a reference value for targeted therapy and immunotherapy for HCC.
Characterization of engraftment dynamics in myelofibrosis after allogeneic hematopoietic cell transplantation including novel conditioning schemes
Authors: Jungius Sarah , Adam Franziska C. , Grosheintz Kerstin , Medinger Michael , Buser Andreas , Passweg Jakob R. , Halter Jörg P. , Meyer Sara C.
Published: August 2023

Introduction

Myelofibrosis (MF) is a rare hematopoietic stem cell disorder progressing to bone marrow (BM) failure or blast phase. Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative therapy for a limited subset of patients with advanced MF, who are eligible, but engraftment in MF vs. AML is delayed which promotes complications. As determinants of engraftment in MF are incompletely characterized, we studied engraftment dynamics at our center.

Methods

A longitudinal cohort of 71 allogeneic HCT performed 2000–2019 with >50% after 2015 was evaluated.

Results

Median time to neutrophil engraftment ≥0.5x109/l was +20 days post-transplant and associated with BM fibrosis, splenomegaly and infused CD34+ cell number. Engraftment dynamics were similar in primary vs. secondary MF and were independent of MF driver mutations in JAK2, CALR and MPL. Neutrophil engraftment occurred later upon haploidentical HCT with thiotepa-busulfan-fludarabine conditioning, post-transplant cyclophosphamide and G-CSF (TBF-PTCy/G-CSF) administered to 9.9% and 15.6% of patients in 2000-2019 and after 2015, respectively. Engraftment of platelets was similarly delayed, while reconstitution of reticulocytes was not affected.

Conclusions

Since MF is a rare hematologic malignancy, this data from a large number of HCT for MF is essential to substantiate that later neutrophil and platelet engraftment in MF relates both to host and treatment-related factors. Observations from this longitudinal cohort support that novel conditioning schemes administered also to rare entities such as MF, require detailed evaluation in larger, multi-center cohorts to assess also indicators of long-term graft function and overall outcome in patients with this infrequent hematopoietic neoplasm undergoing allogeneic transplantation.
Clinical implications and immune implications features of TARS1 in breast cancer
Authors: Gui Zhengwei , Liu Piao , Zhang Dong , Wang Wanju
Published: August 2023

Background

There has been an increase in the number of women suffering from breast cancer in recent years, and discovering new therapeutic targets and efficacy predictive markers is critical for comprehensive breast cancer treatment.

Methods

First, we used bioinformatics methods to analyze TARS1(encoding cytoplasmicthreonyl-tRNA synthetase) expression, prognosis, and clinicopathological characteristics in TCGA database breast cancers, and then we collected breast cancer specimens from our center for validation. TARS1 was then subjected to GSEA (Gene Set Enrichment Analysis) enrichment analysis, GO/KEGG pathway enrichment analysis, and breast cancer immune infiltration characterization. As a last step, we examined TARS1’s effects on breast cancer cell behavior with cellular assays.

Results

The overexpression of TARS1 has been found in several malignant tumors, including breast cancer, and has been linked to poor prognoses. Breast cancers with large primary tumors and negative hormone receptors are more likely to overexpress TARS1. Overexpression of TARS1 promotes the infiltration of T cells, such as Tregs and Th2s, while inhibiting the infiltration of NK cells and CD8+ T cells, which are anticancer cells in breast cancer. TARS1 was also found to be co-expressed with the majority of immune checkpoint-related genes, and breast cancer with TARS1 overexpression responded better to immunotherapy. By knocking down TARS1, breast cancer cells were prevented from proliferating and invading, as well as exhibiting other malignant biological properties.

Conclusion

According to our study, TARS1 may be an oncogene in breast cancer and may be a biomarker of efficacy or a target of immunotherapy in breast cancer.
Concurrent predictors of an immune responsive tumor microenvironment within tumor mutational burden-high breast cancer
Authors: Sammons Sarah , Elliott Andrew , Barroso-Sousa Romualdo , Chumsri Saranya , Tan Antoinette R. , Sledge George W. , Tolaney Sara M. , Torres Evanthia T. Roussos
Published: August 2023

Background

Data supporting high tumor mutational burden (TMB-H) as a lone biomarker for an immune-responsive tumor microenvironment (TME) in metastatic breast cancer (MBC) are weak, yet tumor agnostic approval in TMB-H advanced tumors provides immune checkpoint inhibition (ICI) as a clinical option. We evaluated concurrent predictors of immune-responsive and non-responsive TME within MBC.

Methods

Tumor samples from patients with MBC (N=5621) were analyzed by next-generation sequencing of DNA (592-gene panel or whole exome) and RNA (whole transcriptome) at Caris Life Sciences (Phoenix, AZ). TMB-H threshold was set to ≥ 10 muts/Mb. PDL-1 was evaluated using SP142 antibody. Gene expression profiling and RNA deconvolution were used to estimate immune and stromal cell population abundance in the TME, and transcriptomic signature of immunotherapy response (T cell-inflamed score).

Results

461 (8.2%) TMB-H MBC samples were identified. Consistent with prior studies, TMB-H tumors exhibited significant dMMR/MSI-H enrichment (7 vs. 0%, p<0.0001) and PD-L1+ expression (36 vs. 28%, p<0.05) compared to TMB-L. Across all samples, T cell-inflamed scores were weakly correlated with TMB. TMB-H was not associated with significantly increased immune responsive cell types (CD8+ T-cells, NK cells, or B cells) or immune response gene signatures (e.g. antigen presentation), yet positive trends were observed, while immunosuppressive fibroblasts were significantly decreased in TMB-H tumors (0.84-fold change compared to TMB-L, P<0.05). HR+/HER2- breast cancer was the only subtype in which TMB-H tumors exhibited increased T cell-inflamed scores vs. TMB-L. Concurrent PD-L1+ or dMMR/MSI-H with TMB-H was associated with high T cell-inflamed scores in both HR+/HER2- and TNBC. Among several associated biomarkers, B2M mutations and CD274 amplifications were positively associated with T-cell inflamed scores in TMB-H tumors; CDH1 and ERBB2 mutations were negatively associated.

Conclusion

High TMB alone does not strongly correlate with immune infiltrate or immune-related gene signatures in MBC. TMB-H predicts T-cell inflamed signature compared to TMB-L in HR+/HER2- tumors only. Along with MSI-H and PD-L1+, several biomarkers, including B2M mutation and CD274 amplification, may help predict ICI benefit amongst TMB-H tumors. Co-occurring biomarkers within TMB-H breast cancer warrant evaluation in larger cohorts for response or resistance to ICI to develop composite predictive biomarkers in MBC.
Quantitative non-nutritive sucking measurement as a predictor of oral feeding readiness in newborns
Authors: Lee Kyeong Jae , Shin Yong Beom , Park Ho Eun , Choi Suro , de Oliveira Jean G. , Hong Daun , Kim Sohee , Yoon Jin A
Published: August 2023

Background and purpose

The purpose of this study is to examine the relationship between the parameters of a silver nanowire-based flexible pressure sensor developed to measure the non-nutritive sucking (NNS) performance and predict the nutritive sucking status in preterm infants.

Methods

Preterm infants who were referred for feeding difficulty during the transition period from tubal feeding to oral feeding were enrolled in our study. A flexible pressure sensor was used to measure the non-nutritive sucking parameters of neonates. The evaluator stimulated the infants' lips and tongue with a pacifier integrated with a sucking pressure sensor, to check whether non-nutritive sucking had occurred. When the sucking reflex was induced, it was measured. The infants' sucking characteristics were subdivided into classifications according to the NOMAS criteria and full oral feeding (FOF) status. Quantitative NNS measurement according to the feeding state was compared between groups.

Results

When comparing the quantitative NNS measurement by feeding characteristics, the average sucking pressure was significantly higher in infants in the FOF capable group than those in the incomplete FOF group. In addition, the maximum and average sucking pressure was significantly higher in infants with a normal sucking pattern compared to those with a disorganized sucking pattern. The average NNS pressure was divided over the range of 0–3 kPa and the same weight was assigned to each item. When the optimal cut-off value for the sensitivity and specificity of the average NNS pressure to estimate the FOF was set, a pressure of 1.5 kPa yielded the highest sensitivity (84.62%) and specificity (67.65%) on the receiver operating characteristic (ROC) curve. The area under the curve (AUC) was 0.786, and this result was statistically significant.

Conclusions

This study presents a quantitative parameter for non-nutritive sucking in preterm infants with the use of a flexible pressure sensor. Results show possible quantitative indicators that can aid in predicting when preterm infants can transition to oral feeding and their prognosis. This will serve as a basis for future research on determining the feeding transition period of newborns with health conditions that affect oral feeding.
Centile reference curves of the ultrasound-based characteristics of the rectus femoris muscle composition in children at 4–11 years old
Authors: García-Alonso Yesenia , Alonso-Martínez Alicia M. , García-Hermoso Antonio , Legarra-Gorgoñon Gaizka , Izquierdo Mikel , Ramírez-Vélez Robinson
Published: August 2023

Quantitative diagnostic ultrasound has been proposed as a way to characterize muscle structure, but there is a lack of normative data for children. This study aims to establish age-specific normal ranges for echo-intensity (EI), cross-sectional area (CSA), muscular thickness (MT), and subcutaneous adipose thickness (SAT) values of the rectus femoris muscle in typically developing children. The study recruited 497 children (288 boys and 209 girls) aged 4–10.9 years (mean age 7.39 years), and muscle parameters were measured using 2D B-mode ultrasound. Percentile values and reference curves were calculated using the Lambda, Mu, and Sigma method (LMS). The results showed small variation between measurements for boys compared to girls, with the most significant difference in EI, CSA, and MT values. EI decreased with age, with the most pronounced curve in boys. SAT increased in both sexes, with a slightly higher increase in girls after the age of 9.0 years. This study provides the first age-specific reference norms for the rectus femoris muscle architecture in children, and further research is needed to validate these curves and determine their clinical utility.
Association between precocious puberty and obesity risk in children: a systematic review and meta-analysis
Authors: Song Yongfu , Kong Yibu , Xie Xiaofei , Wang Yongji , Wang Na
Published: August 2023

Objectives

The aim of this study was to evaluate the potential association between early onset puberty and the risk of different forms of obesity in children.

Methods

The databases PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched for relevant studies. The odds ratio (OR) and 95% confidence interval (CI) of obesity in precocious puberty were calculated using Stata software 14.0. A fixed-effects model was used if P > 0.1 and I2 ≤ 50%. Otherwise, a random-effects model was used. Publication bias was assessed using funnel plots and Egger's test.

Result

The pooling analysis showed that precocious puberty in girls was associated with a higher risk of obesity (OR = 1.98; 95% CI: 1.76–2.24; I2 = 0.00%, P < 0.001). Girls with a history of precocious puberty were found to have an increased risk of general obesity (OR = 2.03; 95% CI: 1.62–2.55; I2 = 22.2%, P < 0.001), central obesity (OR = 1.96; 95% CI: 1.70–2.26; I2 = 0.00%, P < 0.001), and overweight (OR = 2.03; 95% CI: 1.68–2.46; I2 = 5.1%, P < 0.001). The pooled analysis showed that precocious puberty in boys was not associated with an increased risk of obesity (OR = 1.14; 95% CI: 0.86–1.51; I2 = 50.6%, P = 0.369). In boys, the occurrence of precocious puberty was not associated with an elevated risk of general obesity (OR = 0.96; 95% CI: 0.40–2.27; I2 = 79.6%, P = 0.922), central obesity (OR = 1.17; 95% CI: 0.96–1.43; I2 = 0.00%, P = 0.125), or overweight (OR = 1.03; 95% CI: 0.56–1.88; I2 = 74.4%, P = 0.930).

Conclusion

This meta-analysis suggests that the onset of puberty at an early age in girls is associated with an increased risk of obesity, however precocious puberty in boy was not associated with an increased risk of obesity. These findings highlight that precocious puberty should be considered an independent risk factor for obesity in girls.

Systematic Review Registration

CRD42023404479.
Development of a membrane-based Gi-CASE biosensor assay for profiling compounds at cannabinoid receptors
Authors: Scott-Dennis Morgan , Rafani Fikri A. , Yi Yicheng , Perera Themiya , Harwood Clare R. , Guba Wolfgang , Rufer Arne C. , Grether Uwe , Veprintsev Dmitry B. , Sykes David A.
Published: August 2023

Introduction: The cannabinoid receptor (CBR) subtypes 1 (CB1R) and 2 (CB2R) are key components of the endocannabinoid system (ECS), playing a central role in the control of peripheral pain, inflammation and the immune response, with further roles in the endocrine regulation of food intake and energy balance. So far, few medicines targeting these receptors have reached the clinic, suggesting that a better understanding of the receptor signalling properties of existing tool compounds and clinical candidates may open the door to the development of more effective and safer treatments. Both CB1R and CB2R are Gαi protein-coupled receptors but detecting Gαi protein signalling activity reliably and reproducibly is challenging. This is due to the inherent variability in live cell-based assays and restrictions around the use of radioactive [35S]-GTPγS, a favoured technology for developing higher-throughput membrane-based Gαi protein activity assays.

Methods: Here, we describe the development of a membrane-based Gαi signalling system, produced from membrane preparations of HEK293TR cells, stably overexpressing CB1R or CB2R, and components of the Gαi-CASE biosensor. This BRET-based system allows direct detection of Gαi signalling in both cells and membranes by monitoring bioluminescence resonance energy transfer (BRET) between the α and the βγ subunits. Cells and membranes were subject to increasing concentrations of reference cannabinoid compounds, with 10 μM furimazine added to generate RET signals, which were detected on a PHERAstar FSX plate reader, then processed using MARS software and analysed in GraphPad PRISM 9.2.

Results: In membranes expressing the Gi-CASE biosensor, the cannabinoid ligands profiled were found to show agonist and inverse agonist activity. Agonist activity elicited a decrease in the BRET signal, indicative of receptor activation and G protein dissociation. Inverse agonist activity caused an increase in BRET signal, indicative of receptor inactivation, and the accumulation of inactive G protein. Our membrane-based Gi-CASE NanoBRET system successfully characterised the potency (pEC50) and efficacy (Emax) of CBR agonists and inverse agonists in a 384-well screening format. Values obtained were in-line with whole-cell Gi-CASE assays and consistent with literature values obtained in the GTPγS screening format.

Discussion: This novel, membrane-based Gαi protein activation assay is applicable to other Gαi-coupled GPCRs, including orphan receptors, allowing real-time higher-throughput measurements of receptor activation.
MBC and ECBL libraries: outstanding tools for drug discovery
Authors: Ginex Tiziana , Madruga Enrique , Martinez Ana , Gil Carmen
Published: August 2023

Chemical libraries have become of utmost importance to boost drug discovery processes. It is widely accepted that the quality of a chemical library depends, among others, on its availability and chemical diversity which help in rising the chances of finding good hits. In this regard, our group has developed a source for useful chemicals named Medicinal and Biological Chemistry (MBC) library. It originates from more than 30 years of experience in drug design and discovery of our research group and has successfully provided effective hits for neurological, neurodegenerative and infectious diseases. Moreover, in the last years, the European research infrastructure for chemical biology EU-OPENSCREEN has generated the European Chemical Biology library (ECBL) to be used as a source of hits for drug discovery. Here we present and discuss the updated version of the MBC library (MBC v.2022), enriched with new scaffolds and containing more than 2,500 compounds together with ECBL that collects about 100,000 small molecules. To properly address the improved potentialities of the new version of our MBC library in drug discovery, up to 44 among physicochemical and pharmaceutical properties have been calculated and compared with those of other well-known publicly available libraries. For comparison, we have used ZINC20, DrugBank, ChEMBL library, ECBL and NuBBE along with an approved drug library. Final results allowed to confirm the competitive chemical space covered by MBC v.2022 and ECBL together with suitable drug-like properties. In all, we can affirm that these two libraries represent an interesting source of new hits for drug discovery.
Enabling supra-aortic vessels inclusion in statistical shape models of the aorta: a novel non-rigid registration method
Authors: Scarpolini Martino Andrea , Mazzoli Marilena , Celi Simona
Published: August 2023

Statistical Shape Models (SSMs) are well-established tools for assessing the variability of 3D geometry and for broadening a limited set of shapes. They are widely used in medical imaging due to their ability to model complex geometries and their high efficiency as generative models. The principal step behind these techniques is a registration phase, which, in the case of complex geometries, can be a critical issue due to the correspondence problem, as it necessitates the development of correspondence mapping between shapes. The thoracic aorta, with its high level of morphological complexity, poses a multi-scale deformation problem due to the presence of several branch vessels with varying diameters. Moreover, branch vessels exhibit significant variability in shape, making the correspondence optimization even more challenging. Consequently, existing studies have focused on developing SSMs based only on the main body of the aorta, excluding the supra-aortic vessels from the analysis. In this work, we present a novel non-rigid registration algorithm based on optimizing a differentiable distance function through a modified gradient descent approach. This strategy enables the inclusion of custom, domain-specific constraints in the objective function, which act as landmarks during the registration phase. The algorithm’s registration performance was tested and compared to an alternative Statistical Shape modeling framework, and subsequently used for the development of a comprehensive SSM of the thoracic aorta, including the supra-aortic vessels. The developed SSM was further evaluated against the alternative framework in terms of generalisation, specificity, and compactness to assess its effectiveness.
Mining the chemical diversity of the hemp seed (Cannabis sativa L.) metabolome: discovery of a new molecular family widely distributed across hemp
Authors: Padilla-González Guillermo Federico , Rosselli Abigail , Sadgrove Nicholas J. , Cui Max , Simmonds Monique S.J.
Published: August 2023

Hemp (Cannabis sativa L.) is a widely researched industrial crop with a variety of applications in the pharmaceutical, nutraceutical, food, cosmetic, textile, and materials industries. Although many of these applications are related to its chemical composition, the chemical diversity of the hemp metabolome has not been explored in detail and new metabolites with unknown properties are likely to be discovered. In the current study, we explored the chemical diversity of the hemp seed metabolome through an untargeted metabolomic study of 52 germplasm accessions to 1) identify new metabolites and 2) link the presence of biologically important molecules to specific accessions on which to focus on in future studies. Multivariate analysis of mass spectral data demonstrated large variability of the polar chemistry profile between accessions. Five main groups were annotated based on their similar metabolic fingerprints. The investigation also led to the discovery of a new compound and four structural analogues, belonging to a previously unknown chemical class in hemp seeds: cinnamic acid glycosyl sulphates. Although variability in the fatty acid profiles was not as marked as the polar components, some accessions had a higher yield of fatty acids, and variation in the ratio of linoleic acid to α-linolenic acid was also observed, with some varieties closer to 3:1 (reported as optimal for human nutrition). We found that that cinnamic acid amides and lignanamides, the main chemical classes of bioactive metabolites in hemp seed, were more concentrated in the Spanish accession Kongo Hanf (CAN58) and the French accession CAN37, while the Italian cultivar Eletta Campana (CAN48) demonstrated the greatest yield of fatty acids. Our results indicate that the high variability of bioactive and novel metabolites across the studied hemp seed accessions may influence claims associated with their commercialization and inform breeding programs in cultivar development.
LC-MS/MS-based metabolomics approach identified novel antioxidant flavonoids associated with drought tolerance in citrus species
Authors: Rao Muhammad Junaid , Feng Bihong , Ahmad Muhammad Husnain , Tahir ul Qamar Muhammad , Aslam Muhammad Zeshan , Khalid Muhammad Fasih , Hussain Sajjad , Zhong Ruimin , Ali Qurban , Xu Qiang , Ma Chongjian , Wang Lingqiang
Published: August 2023

Citrus fruits are cultivated around the world, and they face drought stress frequently during their growth and development. Previous studies showed that citrus plants biosynthesized flavonoid compounds in response to abiotic stress. In this study, we have quantified 37 flavonoid compounds from the leaves of three distinct citrus species including sour orange (drought-tolerant), pummelo ‘Majia you pummelo’ (drought-sensitive), and lemon (drought-sensitive). The 37 flavonoids consisted of 12 flavones, 10 flavonols, 6 flavanones, 5 isoflavanones, and 1 each for chalcone, flavanol, flavanonol, and flavone glycoside. Drought stress differentially altered the flavonoid metabolism in drought-tolerant and drought-sensitive citrus species. The kaempferol 3-neohesperidoside was 17-fold higher in sour orange (124.41 nmol/L) after 18 days of drought stress than lemon (7.33 nmol/L). In sour orange, neohesperidin (69.49 nmol/L) was 1,407- and 37-fold higher than pummelo and lemon, respectively. In sour orange, some flavonoids were significantly increased, such as vitexin, neohesperidin, cynaroside, hyperoside, genistin, kaempferol 3-neohesperidoside, eriocitrin, and luteolin, in response to drought stress, whereas in lemon, these flavonoids were significantly decreased or not altered significantly in response to drought stress. Moreover, the total contents of flavonoids and antioxidant activity were increased in sour orange as compared with pummelo and lemon. The genes associated with flavonoid biosynthesis (PAL, CHI, FLS, GT1, F3H, F3’M, C4H, 4CL, FLS, FG2, FG3, and CYP81E1) were more highly expressed in sour orange leaves than in pummelo and lemon after drought stress. These outcomes showed that pummelo and lemon failed to biosynthesize antioxidant flavonoids to cope with the prolonged drought stress, whereas the sour orange biosynthesized fortified flavonoid compounds with increased antioxidant activity to detoxify the harmful effects of reactive oxygen species produced during drought stress.
A multi-attribute approach to evaluating the impact of biostimulants on crop performance
Authors: Mendes Rodrigo , de Barros Inácio , D’Andréa Paulo Antônio , D’Andréa-Kühl Maria Stefânia Cruanhes , Rodrigues Geraldo Stachetti
Published: August 2023

An ever-growing collection of commercial biostimulants is becoming available in a wide variety of forms and compositions to improve crop performance. Given the intricate nature of deciphering the underlying mechanisms of commercial products, which typically comprise various biological components, it is crucial for research in this area to have robust tools to demonstrate their effectiveness in field trials. Here, we took a multi-attribute approach to evaluating the impact of biostimulants on crop performance. First, we assessed the impact of a biostimulant on the soil and rhizosphere microbiomes associated to crops in eight reference farms, including corn (3 farms), soybean (2), cotton (2) and sugarcane (1), in different biomes and production contexts in Brazil and Paraguay. Second, we modeled a set of integrated indicators to measure crop responses to biostimulant application, including five analytical themes as follows: i) crop development and production (9 indicators), ii) soil chemistry (9), iii) soil physics (5), iv) soil biology (6) and v) plant health (10). Amplicon 16S rRNA and ITS sequencing revealed that the use of the biostimulant consistently changes the structure of bacterial and fungal communities associated with the production system for all evaluated crops. In the rhizosphere samples, the most responsive bacterial taxa to biostimulant application were Prevotella in cotton; Prauserella and Methylovirgula in corn; and Methylocapsa in sugar cane. The most responsive fungal taxa to biostimulant use were Arachnomyces in soybean and cotton; and Rhizophlyctis in corn. The proposed integrated indicators yielded highly favorable positive impact indices (averaging at 0.80), indicating that biostimulant-treated fields correlate with better plant development and crop performance. Prominent indices were observed for indicators in four themes: soil biology (average index 0.84), crop production (0.81), soil physics (compaction reduction 0.81), and chemical fertility (0.75). The multi-attribute approach employed in this study offers an effective strategy for assessing the efficacy of biostimulant products across a wide range of crops and production systems.
Pho1a (plastid starch phosphorylase) is duplicated and essential for normal starch granule phenotype in tubers of Solanum tuberosum L
Authors: Sharma Shrikant , Friberg Martin , Vogel Paul , Turesson Helle , Olsson Niklas , Andersson Mariette , Hofvander Per
Published: August 2023

Reserve starch from seeds and tubers is a crucial plant product for human survival. Much research has been devoted to quantitative and qualitative aspects of starch synthesis and its relation to abiotic factors of importance in agriculture. Certain aspects of genetic factors and enzymes influencing carbon assimilation into starch granules remain elusive after many decades of research. Starch phosphorylase (Pho) can operate, depending on metabolic conditions, in a synthetic and degradative pathway. The plastidial form of the enzyme is one of the most highly expressed genes in potato tubers, and the encoded product is imported into starch-synthesizing amyloplasts. We identified that the genomic locus of a Pho1a-type starch phosphorylase is duplicated in potato. Our study further shows that the enzyme is of importance for a normal starch granule phenotype in tubers. Null mutants created by genome editing display rounded starch granules in an increased number that contained a reduced ratio of apparent amylose in the starch.