bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel role for phospholamban in the thalamic reticular nucleus
Authors: Klocke Benjamin , Britzolaki Aikaterini , Saurine Joseph , Ott Hayden , Krone Kylie , Bahamonde Kiara , Thelen Connor , Tzimas Christos , Sanoudou Despina , Kranias Evangelia G. , Pitychoutis Pothitos M. 
Published: March 2024

AbstractThe thalamic reticular nucleus (TRN) is a brain region that influences vital neurobehavioral processes, including executive functioning and the generation of sleep rhythms. TRN dysfunction underlies hyperactivity, attention deficits, and sleep disturbances observed across various neurodevelopmental disorders. A specialized sarco-endoplasmic reticulum calcium (Ca2+) ATPase 2 (SERCA2)-dependent Ca2+ signaling network operates in the dendrites of TRN neurons to regulate their bursting activity. Phospholamban (PLN) is a prominent regulator of SERCA2 with an established role in myocardial Ca2+-cycling. Our findings suggest that the role of PLN extends beyond the cardiovascular system to impact brain function. Specifically, we found PLN to be expressed in TRN neurons of the adult mouse brain, and utilized global constitutive and innovative conditional genetic knockout mouse models in concert with electroencephalography (EEG)-based somnography and the 5-choice serial reaction time task (5-CSRTT) to investigate the role of PLN in sleep and executive functioning, two complex behaviors that map onto thalamic reticular circuits. The results of the present study indicate that perturbed PLN function in the TRN results in aberrant TRN-dependent phenotypes in mice (i.e., hyperactivity, impulsivity and sleep deficits) and support a novel role for PLN as a critical regulator of SERCA2 in the TRN neurocircuitry.
Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma
Authors: Nejo Takahide , Wang Lin , Leung Kevin K. , Wang Albert , Lakshmanachetty Senthilnath , Gallus Marco , Kwok Darwin W. , Hong Chibo , Chen Lee H. , Carrera Diego A. , Zhang Michael Y. , Stevers Nicholas O. , Maldonado Gabriella C. , Yamamichi Akane , Watchmaker Payal B. , Naik Akul , Shai Anny , Phillips Joanna J. , Chang Susan M. , Wiita Arun P. , Wells James A. , Costello Joseph F. , Diaz Aaron A. , Okada Hideho 
Published: March 2024

AbstractDespite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.
Tumor-infiltrating immune cells and survival in head and neck squamous cell carcinoma: a retrospective computational study
Authors: Zhang Lei , Wang Wei-Quan , Chen Jun-Hong , Feng Jia , Liao Ya-Zhou , Zou You , Liu Rong 
Published: March 2024

AbstractThe immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.
Novel electrochemical platform based on C3N4-graphene composite for the detection of neuron-specific enolase as a biomarker for lung cancer
Authors: Junping Zhang , Zheng Wei , ZhengFang Tang , Yue L. I. Ji , PengHang An , Mingli Zhang , Hongzhi An 
Published: March 2024

AbstractLung cancer remains the leading cause of cancer mortality worldwide. Small cell lung cancer (SCLC) accounts for 10–15% of cases and has an overall 5-years survival rate of only 15%. Neuron-specific enolase (NSE) has been identified as a useful biomarker for early SCLC diagnosis and therapeutic monitoring. This work reports an electrochemical immunosensing platform based on a graphene-graphitic carbon nitride (g-C3N4) nanocomposite for ultrasensitive NSE detection. The g-C3N4 nanosheets and graphene nanosheets were synthesized via liquid exfoliation and integrated through self-assembly to form the nanocomposite. This nanocomposite was used to modify screen-printed carbon electrodes followed by covalent immobilization of anti-NSE antibodies. The unique properties of the graphene-g-C3N4 composite facilitated efficient antibody loading while also enhancing electron transfer efficiency and electrochemical response. Systematic optimization of experimental parameters was performed. The immunosensor exhibited a wide linear detection range of 10 pg/mL to 100 ng/mL and low limit of detection of 3 pg/mL for NSE along with excellent selectivity against interferences. Real serum matrix analysis validated the applicability of the developed platform for sensitive and accurate NSE quantifica-tion at clinically relevant levels. This novel graphene-g-C3N4 nanocomposite based electro-chemical immunoassay demonstrates great promise for early diagnosis of SCLC.
Mathematical formulation and computation of the dynamics of blood flow, heat and mass transfer during MRI scanning
Authors: Mwapinga Annord 
Published: March 2024

AbstractComputational modeling of arterial blood flow, heat and mass transfer during MRI scanning is studied. The flow is assumed to be unsteady, in-compressible, and asymmetric. Mathematical formulation considers the presence of stenosis, joule heating viscous dissipation and chemical reaction. The explicit finite difference scheme is used to numerically solve the model equations. The MATLAB software was used to plot the graphical results. The study reveals that, during MRI scanning, both radial and axial velocities diminish with increase in the strength of magnetic fields. Besides, the study found that, Eckert number and Hartman number enhance the blood’s temperature and the same, diminishes with increase in Prandtl and Reynolds numbers. Concentration profile is observed to decline with increase in chemical reaction parameter, Schmidt number and Reynolds number. Soret number on the other hand, is observed to positively influence the concentration.
Lesion-conditioning of synthetic MRI-derived subtraction-MIPs of the breast using a latent diffusion model
Authors: Kapsner Lorenz A. , Folle Lukas , Hadler Dominique , Eberle Jessica , Balbach Eva L. , Liebert Andrzej , Ganslandt Thomas , Wenkel Evelyn , Ohlmeyer Sabine , Uder Michael , Bickelhaupt Sebastian 
Published: March 2024

AbstractThe purpose of this feasibility study is to investigate if latent diffusion models (LDMs) are capable to generate contrast enhanced (CE) MRI-derived subtraction maximum intensity projections (MIPs) of the breast, which are conditioned by lesions. We trained an LDM with n = 2832 CE-MIPs of breast MRI examinations of n = 1966 patients (median age: 50 years) acquired between the years 2015 and 2020. The LDM was subsequently conditioned with n = 756 segmented lesions from n = 407 examinations, indicating their location and BI-RADS scores. By applying the LDM, synthetic images were generated from the segmentations of an independent validation dataset. Lesions, anatomical correctness, and realistic impression of synthetic and real MIP images were further assessed in a multi-rater study with five independent raters, each evaluating n = 204 MIPs (50% real/50% synthetic images). The detection of synthetic MIPs by the raters was akin to random guessing with an AUC of 0.58. Interrater reliability of the lesion assessment was high both for real (Kendall’s W = 0.77) and synthetic images (W = 0.85). A higher AUC was observed for the detection of suspicious lesions (BI-RADS $$\ge $$
≥
4) in synthetic MIPs (0.88 vs. 0.77; p = 0.051). Our results show that LDMs can generate lesion-conditioned MRI-derived CE subtraction MIPs of the breast, however, they also indicate that the LDM tended to generate rather typical or ‘textbook representations’ of lesions.
The impact of rainfall on the sea surface salinity: a mesocosm study
Authors: Gassen Lisa , Esters Leonie , Ribas-Ribas Mariana , Wurl Oliver 
Published: March 2024

AbstractSea surface salinity may serve as a tracer for freshwater fluxes because it is linked to evaporation and precipitation that force the freshwater balance of the ocean’s surface. The relationship between freshwater fluxes and salinity anomalies in the upper few centimeters remains widely unknown. In a mechanistic approach, we investigated how these anomalies develop by conducting experiments with artificial rain over a large basin. We measured conductivity and temperature at different depths and rain characteristics (intensity, rain temperature, droplet sizes, and velocities). In the absence of turbulence, the rain causes a strong salinity change of up to 6.02 g kg$$^{-1}$$

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in 0–4 cm depth. At the highest rain intensity of 56 mm h$$^{-1}$$

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, salinity changed thrice as fast as at an intensity of 18 mm h$$^{-1}$$

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. At the sea surface microlayer (first millimeter of the surface) the anomalies are always highest and reached a maximum of 14.18 g kg$$^{-1}$$

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. With mechanical mixing, salinity changes were less pronounced (maximum SML salinity anomaly: 6.17 g kg$$^{-1}$$

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), and freshwater was mixed fast with the existing seawater body. In general, our study shows that freshwater remains in the upper few centimeters, and even with induced turbulence, are not mixed below 16 cm.
Pulpotomy for teeth with irreversible pulpitis in immature permanent teeth: a retrospective case series study
Authors: Zhang Na , Kang Qian , Cheng Yuzhao 
Published: March 2024

AbstractTo evaluate the success of pulpotomy in treating immature permanent teeth with irreversible pulpitis. This case series included patients with irreversible pulpitis admitted to the Department of Oral Medicine at the author’s Hospital between 2015 and 2020. The pulpotomies were carried out by clinicians with > 5 years of working experience. The follow-up findings and radiographic images were reviewed by two attending dentists. This study included 49 teeth from 48 children (25 boys and 23 girls). The follow-up was 23.3 ± 6.8 months (from 12 to 40 months). The success rate of pulpotomy was 85.7% (42/49). Pulpotomy failed in seven teeth (14.3%). The treatment success rate for traumatic crown fracture was lower than for dental caries and dens evaginatus (P < 0.001). There were no significant differences in the success rate of the pulp-capping agent, tooth root developmental phase, and pulpotomy method (all P > 0.05). Pulpotomy might be successfully used to treat immature permanent teeth with irreversible pulpitis in young patients mainly caused by caries and a fractured tubercle of dens evaginatus.
Anti-oral cancer properties of potential probiotic lactobacilli isolated from traditional milk, cheese, and yogurt
Authors: Nami Yousef , Tavallaei Omid , Kiani Amir , Moazami Nesa , Samari Mahya , Derakhshankhah Hossein , Jaymand Mehdi , Haghshenas Babak 
Published: March 2024

AbstractThis study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33’s protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients.
Protein kinase C activity modulates nuclear Lamin A/C dynamics in HeLa cells
Authors: Wesley Chase C. , North Dallin V. , Levy Daniel L. 
Published: March 2024

AbstractThe nuclear lamina serves important functions in the nucleus, providing structural support to the nuclear envelope and contributing to chromatin organization. The primary proteins that constitute the lamina are nuclear lamins whose functions are impacted by post-translational modifications, including phosphorylation by protein kinase C (PKC). While PKC-mediated lamin phosphorylation is important for nuclear envelope breakdown during mitosis, less is known about interphase roles for PKC in regulating nuclear structure. Here we show that overexpression of PKC ß, but not PKC α, increases the Lamin A/C mobile fraction in the nuclear envelope in HeLa cells without changing the overall structure of Lamin A/C and Lamin B1 within the nuclear lamina. Conversely, knockdown of PKC ß, but not PKC α, reduces the Lamin A/C mobile fraction. Thus, we demonstrate an isoform-specific role for PKC in regulating interphase Lamin A/C dynamics outside of mitosis.
A large cross sectional study on diaper utilization and beneficial role in outdoor activity and emotions among incontinence elderly people
Authors: Zhang Yunwei , Fang Dawei , Luo Yashuang , Wang Changying , Wan Lingshan , Cao Yifan , Xin Hongyun , Ding Hansheng 
Published: March 2024

AbstractThis study was designed based on a cross-sectional investigation conducted Shanghai, China. Demographic characteristics, diaper utilization, Activities of Daily Living (ADL) and emotion were collected by Unified Needs Assessment Form for Elderly Care Questionnaire. Cognition function was assessed by Mini-mental State Examination (MMSE) scale. Multivariate logistic regression was used for statistical analysis. The diaper utilization rate was 31.2%. Female, higher level of education, poorer ADL and cognition, more severe incontinence and financial dependence on others were facilitating factors for diaper usage (P < 0.05). The possibility of using diaper differed according to the intimacy of caregivers. Among incontinent individuals with relatively good ADL and cognition level, diaper utilization can significantly decrease the risk of going out only once a month (OR: 2.63 vs 4.05), and going out less than once a month (OR: 5.32 vs 6.53). Incontinence people who going out at least once a week had a lower risk of some negative emotion. Significantly, diaper utilization further decreased this risk. In conclusion, for incontinence elderly people with relatively independent ability, proper use of diaper may improve the frequency of outdoor activity and emotion. Nevertheless, diaper utilization should be decided based on elderly people’s own will.
Mitochondrial variants of complex I genes associated with leprosy clinical subtypes
Authors: de Souza Felipe Gouvea , Silva Caio S. , de Araújo Gilderlanio S. , Santana-da-Silva Mayara N. , Gobbo Angélica Rita , da Silva Moisés Batista , Pinto Pablo , da Costa Patrícia Fagundes , Salgado Claudio Guedes , Ribeiro-dos-Santos Ândrea , Cavalcante Giovanna C. 
Published: March 2024

AbstractLeprosy is a chronic bacterial infection mainly caused by Mycobacterium leprae that primarily affects skin and peripheral nerves. Due to its ability to absorb carbon from the host cell, the bacillus became dependent on energy production, mainly through oxidative phosphorylation. In fact, variations in genes of Complex I of oxidative phosphorylation encoded by mtDNA have been associated with several diseases in humans, including bacterial infections, which are possible influencers in the host response to leprosy. Here, we investigated the presence of variants in the mtDNA genes encoding Complex I regarding leprosy, as well as the analysis of their pathogenicity in the studied cohort. We found an association of 74 mitochondrial variants with either of the polar forms, Pole T (Borderline Tuberculoid) or Pole L (Borderline Lepromatous and Lepromatous) of leprosy. Notably, six variants were exclusively found in both clinical poles of leprosy, including m.4158A>G and m.4248T>C in MT-ND1, m.13650C>A, m.13674T>C, m.12705C>T and m.13263A>G in MT-ND5, of which there are no previous reports in the global literature. Our observations reveal a substantial number of mutations among different groups of leprosy, highlighting a diverse range of consequences associated with mutations in genes across these groups. Furthermore, we suggest that the six specific variants exclusively identified in the case group could potentially play a crucial role in leprosy susceptibility and its clinical differentiation. These variants are believed to contribute to the instability and dysregulation of oxidative phosphorylation during the infection, further emphasizing their significance.
Physical activity and sleep changes among children during the COVID-19 pandemic
Authors: Singh Karnika , Armstrong Sarah C. , Wagner Brooke E. , Counts Julie , Skinner Asheley , Kay Melissa , Li Jennifer S. , Shah Svati , Zucker Nancy , Neshteruk Cody , Story Mary , Suarez Lilianna , Kraus William E. , Zizzi Alexandra R. , Dunn Jessilyn 
Published: March 2024

AbstractDaily routines, including in-person school and extracurricular activities, are important for maintaining healthy physical activity and sleep habits in children. The COVID-19 pandemic significantly disrupted daily routines as in-person school and activities closed to prevent spread of SARS-CoV-2. We aimed to examine and assess differences in objectively measured physical activity levels and sleep patterns from wearable sensors in children with obesity before, during, and after a period of school and extracurricular activity closures associated with the COVID-19 pandemic. We compared average step count and sleep patterns (using the Mann–WhitneyUTest) before and during the pandemic-associated school closures by using data from activity tracker wristbands (Garmin VivoFit3). Data were collected from 94 children (aged 5–17) with obesity, who were enrolled in a randomized controlled trial testing a community-based lifestyle intervention for a duration of 12-months. During the period that in-person school and extracurricular activities were closed due to the COVID-19 pandemic, children with obesity experienced objectively-measured decreases in physical activity, and sleep duration. From March 15, 2020 to March 31, 2021, corresponding with local school closures, average daily step count decreased by 1655 steps. Sleep onset and wake time were delayed by about an hour and 45 min, respectively, while sleep duration decreased by over 12 min as compared with the pre-closure period. Step counts increased with the resumption of in-person activities. These findings provide objective evidence for parents, clinicians, and public health professionals on the importance of in-person daily activities and routines on health behaviors, particularly for children with pre-existing obesity. Trial Registration: Clinical trial registration: NCT03339440
An aligned framework of actively collected and passively monitored clinical outcome assessments (COAs) for measure selection
Authors: Campbell Christine Manta , Webster Courtney , Parisi Megan , Sherafat-Kazemzadeh Roya , Braid Jessica , Switzer Thomas , Alves Fávaro Marcelo , Sassano Caprice , Coravos Andrea 
Published: March 2024

AbstractRegulators increasingly require clinical outcome assessment (COA) data for approval. COAs can be collected via questionnaires or digital health technologies (DHTs), yet no single resource provides a side-by-side comparison of tools that collect complementary or related COA measures. We propose how to align ontologies for actively collected and passively monitored COAs into a single framework to allow for rapid, evidence-based, and fit-for-purpose measure selection.
A signal transmission strategy driven by gap-regulated exonuclease hydrolysis for hierarchical molecular networks
Authors: Liu Xin , Zhang Xun , Cui Shuang , Xu Shujuan , Liu Rongming , Wang Bin , Wei Xiaopeng , Zhang Qiang 
Published: March 2024

AbstractExonucleases serve as efficient tools for signal processing and play an important role in biochemical reactions. Here, we identify the mechanism of cooperative exonuclease hydrolysis, offering a method to regulate the cooperative hydrolysis driven by exonucleases through the modulation of the number of bases in gap region. A signal transmission strategy capable of producing amplified orthogonal DNA signal is proposed to resolve the polarity of signals and byproducts, which provides a solution to overcome the signal attenuation. The gap-regulated mechanism combined with DNA strand displacement (DSD) reduces the unpredictable secondary structures, allowing for the coexistence of similar structures in hierarchical molecular networks. For the application of the strategy, a molecular computing model is constructed to solve the maximum weight clique problems (MWCP). This work enhances for our knowledge of these important enzymes and promises application prospects in molecular computing, signal detection, and nanomachines.