bluuebunny/crossref_metadata_2025_split huggingface dataset:
True pattern-reversal LED stimulator and its comparison to LCD and CRT displays: visual evoked potential study
Authors: Voda P. , Kremláček J. , Kordek D. , Chutná M. , Bezrouk A. 
Published: February 2024

AbstractA rapid checkerboard pattern change is used to elicit pattern-reversal visual evoked potentials (PR VEPs). CRT or LCD monitors do not allow immediate reversal of the entire pattern. The study aimed to construct a new stimulator whose characteristics approximate an instantaneous reversal and verify whether the improvement is reflected in PR VEPs. A new stimulator using a matrix of 12 × 48 independent white square LEDs was designed and compared with LCDs and CRTs. The effect on the PR VEP peak times and amplitudes of N70, P100, and P140 waves was evaluated in ten subjects. The LED stimulator showed significantly better performance in the rate of change of illuminance, change of pattern, luminance settling and stability. The PR VEP amplitudes of N75, P100, and N140 did not show significant differences. The sum of interpeak amplitudes was significantly larger for the LCD than for the other monitors. The peak times of the waves evoked by the LED were shorter than those evoked by the LCD and CRT for the N75 wave and a check size of 30´. LED stimulators are a better alternative to CRTs for PR VEPs than current LCDs. LEDs also seem to be better than CRTs, but further research is necessary to obtain significant results.
New generative methods for single-cell transcriptome data in bulk RNA sequence deconvolution
Authors: Nishikawa Toui , Lee Masatoshi , Amau Masataka 
Published: February 2024

AbstractNumerous methods for bulk RNA sequence deconvolution have been developed to identify cellular targets of diseases by understanding the composition of cell types in disease-related tissues. However, issues of heterogeneity in gene expression between subjects and the shortage of reference single-cell RNA sequence data remain to achieve accurate bulk deconvolution. In our study, we investigated whether a new data generative method named sc-CMGAN and benchmarking generative methods (Copula, CTGAN and TVAE) could solve these issues and improve the bulk deconvolutions. We also evaluated the robustness of sc-CMGAN using three deconvolution methods and four public datasets. In almost all conditions, the generative methods contributed to improved deconvolution. Notably, sc-CMGAN outperformed the benchmarking methods and demonstrated higher robustness. This study is the first to examine the impact of data augmentation on bulk deconvolution. The new generative method, sc-CMGAN, is expected to become one of the powerful tools for the preprocessing of bulk deconvolution.
PDGFBB facilitates tumorigenesis and malignancy of lung adenocarcinoma associated with PI3K-AKT/MAPK signaling
Authors: Xiu-Ying He , Yue-Xiang Zheng , Hui-Si Yang , Hong-Zhou Yu , Qing-Jie Xia , Ting-Hua Wang 
Published: February 2024

AbstractLung adenocarcinoma (LUAD) remains one of the most aggressive tumors and the efficacy of conventional treatment has been bleak. Nowadays, gene-targeted therapy has become a new favorite in tumor therapy. Herein, we investigated the effect of platelet derived growth factor BB (PDGFBB) on LUAD. Firstly, PDGFBB was upregulated in LUAD patients and closely linked with poor survival. Furthermore, the expression of PDGFBB and PDGFRα/β in LUAD cells was higher than that in normal lung cells. By loss-of-function with herpes simplex virus (HSV)-PDGFi-shRNA, we found that PDGFBB knockdown caused a significant decrease in proliferation and migration, but evoked apoptosis of LUAD cells in vitro. Conversely, exogenous PDGFBB held adverse effect. Additionally, A549 cells with PDGFBB knockdown had a low probability of tumorigenesis in vivo. Moreover, PDGFBB knockdown restrained the growth of xenografts derived from normal A549 cells. Mechanistically, PDGFBB knockdown suppressed PI3K/AKT and Ras/MAPK signaling, while PDGFBB was the opposite. Therefore, we concluded that PDGFBB might facilitate the tumorigenesis and malignancy of LUAD through its functional downstream nodes—PI3K/AKT and Ras/MAPK signaling, which supported that PDGFBB could serve as a rational therapeutic target for LUAD.
Comparative physicochemical and structural characterisation studies establish high biosimilarity between BGL-ASP and reference insulin aspart
Authors: Ghade Nikhil S. , Thappa Damodar K. , Lona Jeseena , Krishnan Archana R. , Sonar Sanjay M. 
Published: February 2024

AbstractBiosimilar insulin analogues are increasing market access for diabetic patients globally. Scientific establishment of biosimilarity is cornerstone of this key change in the medical landscape. BGL-ASP is a biosimilar insulin aspart developed by BioGenomics Limited, India. BioGenomics has considered a stepwise approach in generating the totality of evidence required to establish similarity with reference product. Insulin aspart is a recombinant rapid-acting human insulin analogue utilised in the treatment of type-1 and type-2 diabetes mellitus. The single amino acid substitution at position B28 where proline is replaced with aspartic acid results in a decreased propensity to form hexamers, thus increasing the absorption rate on subcutaneous administration compared to native insulin. In order to establish the safety and efficacy of BGL-ASP, the critical quality attributes (CQAs) of BGL-ASP are identified based on the impact created on biological activity, pharmacokinetic/pharmacodynamic (PK/PD), immunogenicity and safety. The CQAs of insulin aspart are related to product structure, purity and functionality and are characterised using a series of state-of-the-art orthogonal analytical tools. The primary protein sequence, the secondary, tertiary and quaternary structure are found to be highly similar for BGL-ASP and reference product. The product related impurities of insulin aspart and the assay content are determined using high performance liquid chromatography (HPLC) based analysis and is similar for BGL-ASP and reference insulin aspart sourced from United States of America (US), Europe Union (EU) and India. The safety, efficacy and immunogenicity of BGL-ASP is also found to be comparable with reference product and is confirmed through the clinical trials conducted as recommended by International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) and European Medicines Agency (EMA) guidelines. The data encompassed in this study demonstrates that reference insulin aspart and BGL-ASP are highly similar in terms of structural, physicochemical, and biological properties, thus confirming its safety and efficacy for usage as potential alternative economical medicinal treatment for diabetes mellitus.
Accelerating computer vision-based human identification through the integration of deep learning-based age estimation from 2 to 89 years
Authors: Heinrich Andreas 
Published: February 2024

AbstractComputer Vision (CV)-based human identification using orthopantomograms (OPGs) has the potential to identify unknown deceased individuals by comparing postmortem OPGs with a comprehensive antemortem CV database. However, the growing size of the CV database leads to longer processing times. This study aims to develop a standardized and reliable Convolutional Neural Network (CNN) for age estimation using OPGs and integrate it into the CV-based human identification process. The CNN was trained on 50,000 OPGs, each labeled with ages ranging from 2 to 89 years. Testing included three postmortem OPGs, 10,779 antemortem OPGs, and an additional set of 70 OPGs within the context of CV-based human identification. Integrating the CNN for age estimation into CV-based human identification process resulted in a substantial reduction of up to 96% in processing time for a CV database containing 105,251 entries. Age estimation accuracy varied between postmortem and antemortem OPGs, with a mean absolute error (MAE) of 2.76 ± 2.67 years and 3.26 ± 3.06 years across all ages, as well as 3.69 ± 3.14 years for an additional 70 OPGs. In conclusion, the incorporation of a CNN for age estimation in the CV-based human identification process significantly reduces processing time while delivering reliable results.
Pathological investigation of high pathogenicity avian influenza H5N8 in captive houbara bustards (Chlamydotis undulata), the United Arab Emirates 2020
Authors: Crispo Manuela , Muñoz Mar Carrasco , Lacroix Frédéric , Kheyi Mohamed-Reda , Delverdier Maxence , Croville Guillaume , Dirat Malorie , Gaide Nicolas , Guerin Jean Luc , Le Loc’h Guillaume 
Published: February 2024

AbstractAt the end of 2020, an outbreak of HPAI H5N8 was registered in captive African houbara bustards (Chlamydotis undulata) in the United Arab Emirates. In order to better understand the pathobiology of this viral infection in bustards, a comprehensive pathological characterization was performed. A total of six birds were selected for necropsy, histopathology, immunohistochemistry, RNAscope in situ hybridization and RT-qPCR and nanopore sequencing on formalin-fixed and paraffin-embedded (FFPE) tissue blocks. Gross lesions included mottled and/or hemorrhagic pancreas, spleen and liver and fibrinous deposits on air sacs and intestine. Necrotizing pancreatitis, splenitis and concurrent vasculitis, hepatitis and fibrino-heterophilic peritonitis were identified, microscopically. Viral antigens (nucleoprotein) and RNAs (matrix gene) were both detected within necro-inflammatory foci, parenchymal cells, stromal cells and endothelial cells of affected organs, including the myenteric plexus. Molecular analysis of FFPE blocks successfully detected HPAI H5N8, further confirming its involvement in the lesions observed. In conclusion, HPAI H5N8 in African houbara bustards results in hyperacute/acute forms exhibiting marked pantropism, endotheliotropism and neurotropism. In addition, our findings support the use of FFPE tissues for molecular studies of poorly characterized pathogens in exotic and endangered species, when availability of samples is limited.
Botulinum toxin-A effects on pain, somatosensory and psychosocial features of patients with refractory masticatory myofascial pain: a randomized double-blind clinical trial
Authors: De la Torre Canales Giancarlo , Poluha Rodrigo Lorenzi , Bonjardim Leonardo Rigoldi , Ernberg Malin , Conti Paulo César Rodrigues 
Published: February 2024

AbstractThe antinociceptive effect of BoNT-A have been well documented in animal studies; however, results of few but well-designed randomized placebo-controlled clinical trials about BoNT-A efficacy in masticatory myofascial pain (MFP) are inconsistent. Therefore, the present randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of BoNT-A in patients with refractory MFP. Twenty-eight patients with pain reduction of less than 30% despite conservative treatment and with an average pain intensity of > 50 mm on the visual analogue scale (VAS) participated. Patients were randomly assigned to receive a total of 80 U of BoNT-A or saline solution (SS) injected into the masseter and anterior temporalis muscles. Pain intensity (VAS), quantitative sensory testing (QST), conditioned pain modulation (CPM), and psychosocial status were examined. Follow-up was performed at 1 and 6 months. For repeated-measure comparisons between evaluation times, Friedman test with Bonferroni correction was used for pain and somatosensory variables and the Wilcoxon test for the psychosocial variables. The Mann–Whitney test was used for all comparisons between groups. The BoNT-A group had a significant decrease in pain intensity at follow-ups compared with the SS group (p < 0.001). QST assessment revealed higher pressure pain threshold values in the masseter muscle for BoNT-A group compared to SS (p < 0.03) at all follow-ups. No differences were found for mechanical pain threshold and wind-up ratio values (p > 0.05) in the entire study. The BoNT-A group presented the most efficient CPM effect (p < 0.03) only at the 1 month follow-up in the masseter muscle. There was a significant time effect for BoNT-A in all psychosocial variables (p < 0.05) and a drug effect in the Central Sensitization Inventory (p < 0.01), Pittsburgh Sleep Quality Index (p < 0.004), and Healthy Survey 36 (p < 0.05) at 6 months follow-up. The study demonstrates that a single injection-session of BoNT-A has positive effects on the hall pain spectrum of patients with refractory masticatory myofascial pain.
Machine learning and radiomics for segmentation and classification of adnexal masses on ultrasound
Authors: Barcroft Jennifer F. , Linton-Reid Kristofer , Landolfo Chiara , Al-Memar Maya , Parker Nina , Kyriacou Chris , Munaretto Maria , Fantauzzi Martina , Cooper Nina , Yazbek Joseph , Bharwani Nishat , Lee Sa Ra , Kim Ju Hee , Timmerman Dirk , Posma Joram , Savelli Luca , Saso Srdjan , Aboagye Eric O. , Bourne Tom 
Published: February 2024

AbstractUltrasound-based models exist to support the classification of adnexal masses but are subjective and rely upon ultrasound expertise. We aimed to develop an end-to-end machine learning (ML) model capable of automating the classification of adnexal masses. In this retrospective study, transvaginal ultrasound scan images with linked diagnoses (ultrasound subjective assessment or histology) were extracted and segmented from Imperial College Healthcare, UK (ICH development dataset;n = 577 masses; 1444 images) and Morgagni-Pierantoni Hospital, Italy (MPH external dataset;n = 184 masses; 476 images). A segmentation and classification model was developed using convolutional neural networks and traditional radiomics features. Dice surface coefficient (DICE) was used to measure segmentation performance and area under the ROC curve (AUC), F1-score and recall for classification performance. The ICH and MPH datasets had a median age of 45 (IQR 35–60) and 48 (IQR 38–57) years old and consisted of 23.1% and 31.5% malignant cases, respectively. The best segmentation model achieved a DICE score of 0.85 ± 0.01, 0.88 ± 0.01 and 0.85 ± 0.01 in the ICH training, ICH validation and MPH test sets. The best classification model achieved a recall of 1.00 and F1-score of 0.88 (AUC:0.93), 0.94 (AUC:0.89) and 0.83 (AUC:0.90) in the ICH training, ICH validation and MPH test sets, respectively. We have developed an end-to-end radiomics-based model capable of adnexal mass segmentation and classification, with a comparable predictive performance (AUC 0.90) to the published performance of expert subjective assessment (gold standard), and current risk models. Further prospective evaluation of the classification performance of this ML model against existing methods is required.
Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock
Authors: Nelson Nina , Relógio Angela 
Published: February 2024

AbstractGlioblastoma is one of the most lethal cancers with current therapeutic options lacking major successes. This underlines the necessity to understand glioblastoma biology on other levels and use these learnings for the development of new therapeutic concepts. Mounting evidence in the field of circadian medicine points to a tight interplay between disturbances of the circadian system and glioblastoma progression. The circadian clock, an internal biological mechanism governing numerous physiological processes across a 24-h cycle, also plays a pivotal role in regulationg key cellular functions, including DNA repair, cell cycle progression, and apoptosis. These processes are integral to tumour development and response to therapy. Disruptions in circadian rhythms can influence tumour growth, invasion, and response to treatment in glioblastoma patients. In this review, we explore the robust association between the circadian clock, and cancer hallmarks within the context of glioblastoma. We further discuss the impact of the circadian clock on eight cancer hallmarks shown previously to link the molecular clock to different cancers, and summarize the putative role of clock proteins in circadian rhythm disturbances and chronotherapy in glioblastoma. By unravelling the molecular mechanisms behind the intricate connections between the circadian clock and glioblastoma progression, researchers can pave the way for the identification of potential therapeutic targets, the development of innovative treatment strategies and personalized medicine approaches. In conclusion, this review underscores the significant influence of the circadian clock on the advancement and understanding of future therapies in glioblastoma, ultimately leading to enhanced outcomes for glioblastoma patients.
Longitudinal monitoring of the mouse brain reveals heterogenous network trajectories during aging
Authors: Özalay Özgün , Mediavilla Tomas , Giacobbo Bruno Lima , Pedersen Robin , Marcellino Daniel , Orädd Greger , Rieckmann Anna , Sultan Fahad 
Published: February 2024

AbstractThe human aging brain is characterized by changes in network efficiency that are currently best captured through longitudinal resting-state functional MRI (rs-fMRI). These studies however are challenging due to the long human lifespan. Here we show that the mouse animal model with a much shorter lifespan allows us to follow the functional network organization over most of the animal’s adult lifetime. We used a longitudinal study of the functional connectivity of different brain regions with rs-fMRI under anesthesia. Our analysis uncovers network modules similar to those reported in younger mice and in humans (i.e., prefrontal/default mode network (DMN), somatomotor and somatosensory networks). Statistical analysis reveals different patterns of network reorganization during aging. Female mice showed a pattern akin to human aging, with de-differentiation of the connectome, mainly due to increases in connectivity of the prefrontal/DMN cortical networks to other modules. Our male cohorts revealed heterogenous aging patterns with only one group confirming the de- differentiation, while the majority showed an increase in connectivity of the somatomotor cortex to the Nucleus accumbens. In summary, in line with human work, our analysis in mice supports the concept of de-differentiation in the aging mammalian brain and reveals additional trajectories in aging mice networks.
Anxious about rejection, avoidant of neglect: Infant marmosets tune their attachment based on individual caregiver’s parenting style
Authors: Yano-Nashimoto Saori , Truzzi Anna , Shinozuka Kazutaka , Murayama Ayako Y. , Kurachi Takuma , Moriya-Ito Keiko , Tokuno Hironobu , Miyazawa Eri , Esposito Gianluca , Okano Hideyuki , Nakamura Katsuki , Saito Atsuko , Kuroda Kumi O. 
Published: February 2024

AbstractChildren’s secure attachment with their primary caregivers is crucial for physical, cognitive, and emotional maturation. Yet, the causal links between specific parenting behaviors and infant attachment patterns are not fully understood. Here we report infant attachment in New World monkeys common marmosets, characterized by shared infant care among parents and older siblings and complex vocal communications. By integrating natural variations in parenting styles and subsecond-scale microanalyses of dyadic vocal and physical interactions, we demonstrate that marmoset infants signal their needs through context-dependent call use and selective approaches toward familiar caregivers. The infant attachment behaviors are tuned to each caregiver’s parenting style; infants use negative calls when carried by rejecting caregivers and selectively avoid neglectful and rejecting caregivers. Family-deprived infants fail to develop such adaptive uses of attachment behaviors. With these similarities with humans, marmosets offer a promising model for investigating the biological mechanisms of attachment security.
BECLIN1 is essential for intestinal homeostasis involving autophagy-independent mechanisms through its function in endocytic trafficking
Authors: Tran Sharon , Juliani Juliani , Harris Tiffany J. , Evangelista Marco , Ratcliffe Julian , Ellis Sarah L. , Baloyan David , Reehorst Camilla M. , Nightingale Rebecca , Luk Ian Y. , Jenkins Laura J. , Ghilas Sonia , Yakou Marina H. , Inguanti Chantelle , Johnson Chad , Buchert Michael , Lee James C. , De Cruz Peter , Duszyc Kinga , Gleeson Paul A. , Kile Benjamin T. , Mielke Lisa A. , Yap Alpha S. , Mariadason John M. , Fairlie W. Douglas , Lee Erinna F. 
Published: February 2024

AbstractAutophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show intestinal epithelium-specific BECLIN1 deletion in adult mice leads to rapid fatal enteritis with compromised gut barrier integrity, highlighting its intrinsic critical role in gut maintenance. BECLIN1-deficient intestinal epithelial cells exhibit extensive apoptosis, impaired autophagy, and stressed endoplasmic reticulum and mitochondria. Remaining absorptive enterocytes and secretory cells display morphological abnormalities. Deletion of the autophagy regulator, ATG7, fails to elicit similar effects, suggesting additional novel autophagy-independent functions of BECLIN1 distinct from ATG7. Indeed, organoids derived from BECLIN1 KO mice show E-CADHERIN mislocalisation associated with abnormalities in the endocytic trafficking pathway. This provides a mechanism linking endocytic trafficking mediated by BECLIN1 and loss of intestinal barrier integrity. Our findings establish an indispensable role of BECLIN1 in maintaining mammalian intestinal homeostasis and uncover its involvement in endocytic trafficking in this process. Hence, this study has important implications for our understanding of intestinal pathophysiology.
Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism
Authors: De Solis Alain J. , Del Río-Martín Almudena , Radermacher Jan , Chen Weiyi , Steuernagel Lukas , Bauder Corinna A. , Eggersmann Fynn R. , Morgan Donald A. , Cremer Anna-Lena , Sué Michael , Germer Maximilian , Kukat Christian , Vollmar Stefan , Backes Heiko , Rahmouni Kamal , Kloppenburg Peter , Brüning Jens C. 
Published: February 2024

AbstractAgouti-related peptide (AgRP)-expressing and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combine non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons for comparing metabolic responses in male and female mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. We show that food intake is regulated by the additive effect of AgRP neuron activation and POMC neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated-versus-simultaneous regulation of AgRP and POMC neurons. We identify a neurocircuit engaging Npy1R-expressing neurons in the paraventricular nucleus of the hypothalamus, where activated AgRP neurons and inhibited POMC neurons cooperate to promote food consumption and activate Th+ neurons in the nucleus tractus solitarii. Collectively, these results unveil how food intake is precisely regulated by the simultaneous bidirectional interplay between AgRP and POMC neurocircuits.