bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot retrospective study of comprehensive nursing care on psychological disorder in colorectal cancer undergoing chemotherapy
Authors: Zhang Zhou-Yi , Wang Rui , Zhang Li , Gu Ming-Li , Guan Xiu-E 
Published: September 2022

Background:
This pilot study retrospectively evaluated the effects of comprehensive nursing care (CNC) on psychological disorders in patients with colorectal cancer (CC) undergoing chemotherapy.

Methods:
This study analyzed 70 eligible patients’ case records of CC undergoing chemotherapy. These records were allocated to a treatment group (n = 35) or a control group (n = 35). All 70 patients in both groups received routine nursing care. In addition, 35 patients in the treatment group also received CNC. The primary outcomes were anxiety, as measured by Self-rating Anxiety Scale, and depression, as assessed by Self-rating Depression Scale. The secondary outcomes were quality of life, as measured by The 36-Item Short Form Health Survey, and adverse events. All outcome data were analyzed before and 3-month after treatment.

Results:
At 3-month after treatment, the patients in the treatment group had better outcomes in the Self-rating Anxiety Scale (P<0.01), Self-rating Depression Scale (P<0.01), and The 36-Item Short Form Health Survey (social function, P = .04; emotional role, P = 0.03) than those in the control group. With regard to safety, no treatment-related adverse events were recorded in either group.

Conclusion:
The findings of this pilot retrospective study showed promising effects of CNC on psychological disorders and quality of life in patients with CC undergoing chemotherapy. However, more high-quality clinical trials are required to confirm these findings.
Mechanism of Astragali Radix for the treatment of osteoarthritis: A study based on network pharmacology and molecular docking
Authors: Shao Yiming , He Jiao , Zhang Xinan , Xie Panpan , Lian Hongkai , Zhang Meng 
Published: September 2022

Osteoarthritis (OA) is a degenerative joint disease caused by many factors. Astragali Radix (Huangqi), a traditional Chinese medicine (TCM), is widely used to treat OA. Although it can inhibit the progression of OA, its pharmacological mechanism is unclear.In this study, we used a network pharmacological approach to determine the mechanism by which Huangqi inhibits the progression of OA. We obtained the active ingredients of Huangqi from the Traditional Chinese Systems Pharmacology database and identified potential targets of these ingredients. Next, we identified the OA-related targets by using the GeneCards and Online Mendelian Inheritance in Man databases. Then, a protein–protein interaction (PPI) network was established based on the overlapping genes between the Huangqi targets and the OA targets, and the interactions were analyzed. Subsequently, the Metascape database was used to perform the Gene Ontology biological functions and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis. Furthermore, selected active ingredients and corresponding targets were investigated through molecular docking.In total, 20 active ingredients and 206 related targets were identified. The results of Gene Ontology enrichment analysis showed that the intersection targets were mainly involved in immune inflammation, proliferation, and apoptosis. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that Huangqi might exert antiosteoarthritis effect mainly through the PI3K–Akt signaling pathway, apoptosis, the mitogen-activated protein kinases signaling pathway, and the p53 signaling pathway. Moreover, the molecular docking results indicated that quercetin and kaempferol exhibited the good binding capacity to transcription factor JUN, tumor necrosis factor, and protein kinase B.In summary, we investigated the therapeutic effects of Huangqi from a systemic perspective. These key targets and pathways provide promising directions for future studies to reveal the exact regulating mechanism of Huangqi against OA.
More than a ligand: PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I interferon pathway
Authors: Hodgins Jonathan J. , Abou-Hamad John , Hagerman Ash , Yakubovich Edward , Tanese de Souza Christiano , Marotel Marie , Buchler Ariel , Fadel Saleh , Park Maria M. , Fong-McMaster Claire , Crupi Mathieu F. , Bell John C. , Harper Mary-Ellen , Rotstein Benjamin H. , Auer Rebecca C. , Vanderhyden Barbara C. , Sabourin Luc A. , Bourgeois-Daigneault Marie-Claude , Cook David P. , Ardolino Michele 
Published: September 2022

ABSTRACTTargeting the PD-1/PD-L1 axis has transformed the field of immune-oncology. While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced infection with oncolytic viruses in vitro and in vivo. Consistently, PD-L1 expression marked tumor explants from cancer patients that were best infected by oncolytic viruses. Mechanistically, PD-L1 suppressed type I interferon by promoting a metabolic shift characterized by enhanced glucose uptake and glycolysis rate. Lactate generated from glycolysis was the key metabolite responsible for inhibiting type I interferon responses and enhancing oncolytic virus infection in PD-L1-expressing cells. In addition to adding mechanistic insight into PD-L1 intrinsic function and showing that PD-L1 has a broader impact on immunity and cancer biology besides acting as a ligand for PD-1, our results will also help guide the numerous efforts currently ongoing to combine PD-L1 antibodies with oncolytic virotherapy in clinical trials.Once sentence summaryPD-L1 promotes oncolytic virus efficacy.
Model discovery to link neural activity to behavioral tasks
Authors: Costabile Jamie D , Balakrishnan Kaarthik A , Schwinn Sina , Haesemeyer Martin 
Published: September 2022

SummaryBrains are not engineered solutions to a well-defined problem but arose through selective pressure acting on random variation. It is therefore unclear how well a model chosen by an experimenter can relate neural activity to experimental conditions. Here we developed “Model identification of neural encoding (MINE).” MINE is an accessible framework using convolutional neural networks (CNN) to discover and characterize a model that relates aspects of tasks to neural activity . Although flexible, CNNs are difficult to interpret. We use Taylor decomposition approaches to understand the discovered model and how it maps task features to activity. We apply MINE to a published cortical dataset as well as experiments designed to probe thermoregulatory circuits in zebrafish. MINE allowed us to characterize neurons according to their receptive field and computational complexity, features which anatomically segregate in the brain. We also identified a new class of neurons that integrate thermosensory and behavioral information which eluded us previously when using traditional clustering and regression-based approaches.
Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage
Authors: Ghasemi David R. , Okonechnikov Konstantin , Rademacher Anne , Tirier Stephan , Maass Kendra K. , Schumacher Hanna , Sundheimer Julia , Statz Britta , Rifaioglu Ahmet S. , Bauer Katharina , Schumacher Sabrina , Bortolomeazzi Michele , Giangaspero Felice , Ernst Kati J. , Saez-Rodriguez Julio , Jones David T. W. , Kawauchi Daisuke , Mallm Jan-Philipp , Rippe Karsten , Korshunov Andrey , Pfister Stefan M. , Pajtler Kristian W. 
Published: September 2022

AbstractMedulloblastoma with extensive nodularity (MBEN) are cerebellar tumors with two histologically distinct compartments and varying disease course. In some children MBEN progresses, while others show spontaneous differentiation into more benign tumors. However, the mechanisms that control the tug-of-war between proliferation and differentiation are not well understood. Here, we dissected this process with a multi-modal single cell transcriptome analysis. We found that the internodular MBEN compartment comprised proliferating early cerebellar granular neuronal precursors (CGNP)-like tumor cells as well as stromal, vascular, and immune cells. In contrast, the nodular compartment consisted of postmitotic, neuronally differentiated MBEN cells. Both compartments were connected through an intermediate cell stage of actively migrating CGNPs. Furthermore, astrocyte-like tumor cells were identified that had branched off the main CGNP developmental trajectory. Cells with an astroglial phenotype were found in close proximity to migrating, late CGNP-like and postmitotic neuronally differentiated cells. Our study reveals how the spatial tissue organization is linked to the developmental trajectory of proliferating tumor cells through a migrating precursor stage into differentiated tumor cells with a more benign phenotype. We anticipate that our framework for integrating single nucleus RNA-sequencing and spatial transcriptomics will help to uncover intercompartmental interactions also in other cancers with varying histology.
In silico evaluation of the role of the long non-coding RNA LINC00092 in thyroid cancer progression ; regulation of the miR-34a-5p/RCAN1 axis
Authors: Morovat Saman , Morovat Pejman , Kamali Mohammad Javad , Teimourian Shahram 
Published: September 2022

AbstractBackgroundAs the most prevalent endocrine cancer, thyroid cancer (TC) accounts for 1.7% of all cancer cases. A significant increase in TC morbidity has been observed over the past three decades. TC diagnosis has been reported to be problematic based on the current approach. As a result, it is imperative to develop molecular biomarkers to improve the accuracy of the diagnosis. An analysis of bioinformatics data was conducted in this study to analyze lncRNAs and their roles as ceRNAs associated with the development and progression of TC.Materials and MethodThe first step in this study was to collect RNA-seq data from the GDC database. Then, DESeq2 was used to analyze differentially expressed lncRNAs (DElncRNAs), miRNAs (DEMIs), and mRNAs (DEGs) between TC patients and healthy subjects. Our study identified DElnc-related miRNAs and miRNA-related genes to develop a lncRNA/miRNA/mRNA axis using online tools and screening. A co-expression analysis was performed to investigate correlations between DElncs and their associated mRNAs. Next, a protein-protein interaction (PPI) network was constructed. Functional enrichment and pathway enrichment were conducted on genes in the PPI network to discover additional biological activities among these molecules. Lastly, a correlation between the expression levels and the infiltration abundance of immune cells was assessed through immune infiltration analysis.ResultsThere were 58 DElncs, 34 DEMIs, and 864 DEGs in thyroid tumor tissue and non-tumor tissue samples. Following validation of our lncRNA results with the intersection of differentially expressed lncRNAs in TCGA and GEPIA2, we selected two downregulated DElncs, including AC007743.1 and LINC00092, as the final research elements. We then performed an interaction analysis to predict lncRNAs-miRNAs and miRNAs-mRNAs interactions, which led to identifying the LINC00092/miR-34a-5p and miR-34a-5p/RCAN1 axis, respectively. There was a correlation between LINC00092 and RCAN1 according to Pearson correlation analysis. To improve our understanding of RCAN1, we developed a PPI network. According to the Immune Infiltration Analysis, RCAN1 expression was positively correlated with CD8+ T cells, macrophages, and neutrophils.ConclusionThe results of this study suggest that LINC00092/miR-34a-5p/RCAN1 axis may have a functional role in the progression of TC. LINC00092 may be used as a promising biomarker for TC prognosis and may be a better diagnostic and therapeutic target.
Characterization of magnetic nanoparticles from the shells of freshwater mussel L fortunei and marine P perna mussels
Authors: Valadão Cardoso Antonio , Carvalho e Souza Clara , Dantas Maria Sylvia , Machado Camila Schults , Fraga Freitas Erico Tadeu , Krohling Alisson Carlos , do Rosário Veronica A Martins , Dias Heinene Luiz G 
Published: September 2022

AbstractThe presence of magnetic nanoparticles in animal species, including humans, has been growing steadily, but none have reported the presence in mollusks apart from the radula of chitons, in 1962. In shells this is the first time. Magnetite (Fe3O4) nanoparticles were extracted (using three distinct and rather simple protocols) from the shells of freshwater Limnoperna fortunei (Dunker 1857) and marine Perna perna (Linnaeus 1758) mussels and were fully physically-chemically characterized. Due to the spatial distribution, the ferrimagnetic particles in the shells are in low concentration and present a superparamagnetic behavior characteristic of materials of nanometric sizes. Transmission electron microscopy (TEM, especially HRTEM) indicated that the 50-100 nm round magnetic particles are in fact aggregates of 5-10 nm nanoparticles. Using analysis TEM techniques on the shell of the L fortunei we have not found any iron oxide particle at the periostracum layer nor in the calcite layer. Nevertheless, roughly round nanoparticle aggregates of iron hydroxy/oxide were found in the nacar layer, the aragonite layer. Being the aragonite layer responsible for more than 97% of the shell of the L fortunei and considering the estimated size of magnetic nanoparticles we could infer that they might be distributed throughout the nacar layer.
Metaplasticity: Dark exposure boosts excitability and visual plasticity in adult human cortex
Authors: Min Seung Hyun , Wang Zili , Chen Mengting , Hu Rongjie , Gong Ling , He Zhifen , Wang Xiaoxiao , Hess Robert F. , Zhou Jiawei 
Published: September 2022

AbstractAn interlude of dark exposure for about one week is known to shift the excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting cortical plasticity across species and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies on humans remains elusive. Here, we use magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60-min dark exposure, and measure binocular combination as a behavioral assay to assess visual plasticity in 18 normally sighted human adults (13 females). To induce neuroplastic changes in the observers, 60-min monocular deprivation was performed, which is known to shift sensory eye balance in favor of the previously deprived eye. We report that prior dark exposure strengthens cortical excitability in V1 and boosts visually plasticity in normal adults. Our findings are surprising, given the fact that the interlude is very brief. We present direct evidence that an environmental manipulation that reduces intracortical inhibition can act as a metaplastic facilitator for visual plasticity in adult humans.
Deletion or inhibition of PTPRO mitigates diet-induced hepatic steatosis and inflammation in obesity
Authors: Shintani Takafumi , Suzuki Ryoko , Takeuchi Yasushi , Shirasawa Takuji , Noda Masaharu 
Published: September 2022

ABSTRACTChronic inflammation plays crucial roles in obesity-induced metabolic diseases. We herein demonstrated that mice lacking the protein tyrosine phosphatase receptor type O (PTPRO) exhibited the hyper-obese phenotype when fed a high-fat/high-sucrose diet. However, Ptpro-KO mice with hyperobesity showed the markedly small accumulation of ectopic fat in the liver, improvements in lipid and glucose homeostasis, and low-grade systemic inflammation associated with low macrophage activation. Expression of protein tyrosine phosphatase 1b (Ptp1b), an enzyme which is known to be implicated in metabolic disorders, was also suppressed in Ptpro-KO mice. The administration of AKB9778, a specific inhibitor of PTPRO, to highly obese ob/ob mice reproduced the phenotypes of Ptpro-KO mice along with the amelioration of inflammation. We revealed that an increase in the phosphorylation of Tyr(117) in vimentin, a component of intermediate filaments, by the inhibition of PTPRO promoted the growth of lipid droplets in adipocytes. The improvement in metabolic conditions with the attenuation of inflammation in Ptpro-KO mice was explained by the low activation of NFκb, a key transcription factor for inflammatory response, in adipose tissue. This is the first study to show that PTPRO is a promising target to ameliorate hepatic steatosis and metabolic disorders.
High-Resolution Magnetization-Transfer Imaging of Post-Mortem Marmoset Brain: Comparisons with Relaxometry and Histology
Authors: Marschner Henrik , Pampel André , Müller Roland , Reimann Katja , Bock Nicolas , Morawski Markus , Geyer Stefan , Möller Harald E. 
Published: September 2022

AbstractCell membranes and macromolecules or paramagnetic compounds interact with water proton spins, which modulates magnetic resonance imaging (MRI) contrast providing information on tissue composition. For a further investigation, quantitative magnetization transfer (qMT) parameters (at 3T), including the ratio of the macromolecular and water proton pools, ℱ, and the exchange-rate constant as well as the (observed) longitudinal and the effective transverse relaxation rates (at 3T and 7T), and respectively, were measured at high spatial resolution (200 μm) in a slice of fixed marmoset brain and compared to histology results obtained with Gallyas’ myelin stain and Perls’ iron stain. and were linearly correlated with the iron content for the entire slice, whereas distinct differences were obtained between gray and white matter for correlations of relaxometry and qMT parameters with myelin content. The combined results suggest that the macromolecular pool interacting with water consists of myelin and (less efficient) non-myelin contributions. Despite strong correlation of ℱ and none of these parameters was uniquely specific to myelination. Due to additional sensitivity to iron stores, and were more sensitive for depicting microstructural differences between cortical layers than ℱ.HighlightsMRI (200μm) is correlated with myelin and iron histology in fixed marmoset brain.Detailed z-spectra are employed for precise magnetization-transfer (MT) measurements.Longitudinal and effective transverse relaxation rates depend linearly on tissue iron.Longitudinal relaxation and MT are not uniquely specific to myelin.Myelin and non-myelin macromolecules impact water relaxation and MT contrast.
Exposure to global change and microplastics elicits an immune response in an endangered coral
Authors: Bove Colleen B. , Greene Katharine , Sugierski Sharla , Kriefall Nicola G. , Huzar Alexa K. , Hughes Annabel M. , Sharp Koty , Fogarty Nicole D. , Davies Sarah W. 
Published: September 2022

ABSTRACTGlobal change is increasing seawater temperatures and decreasing oceanic pH, driving declines of coral reefs globally. Coral ecosystems are also impacted by local stressors, including microplastics, which are ubiquitous on reefs. While the independent effects of these global and local stressors are well-documented, their interactions remain less explored. Here, we examine the independent and combined effects of global change (ocean warming and acidification) and microplastics exposures on gene expression (GE) and microbial community composition in the endangered coral Acropora cervicornis. Nine genotypes were fragmented and maintained in one of four experimental treatments: 1) ambient conditions (ambient seawater, no microplastics; AMB); 2) microplastics treatment (ambient seawater, microplastics; MP); 3) global change conditions (warm and acidic conditions, no microplastics; OAW); and 4) multistressor treatment (warm and acidic conditions with microplastics; OAW+MP) for 22 days, after which corals were sampled for genome-wide GE profiling and ITS and 16S metabarcoding. Overall A. cervicornis GE responses to all treatments were subtle; however, corals in the multistressor treatment exhibited the strongest GE responses, and genes associated with innate immunity were overrepresented in this treatment, according to gene ontology enrichment analyses. 16S analyses revealed stable microbiomes dominated by the bacterial associate Aquarickettsia, suggesting that these A. cervicornis fragments exhibited remarkably low variability in bacterial community composition. Future work should focus on functional differences across microbiomes, especially Aquarickettsia and viruses, in these responses. Overall, results suggest that local stressors present a unique challenge to endangered coral species under global change.
Graded optogenetic activation of the auditory pathway for hearing restoration
Authors: Mittring Artur , Moser Tobias , Huet Antoine 
Published: September 2022

AbstractOptogenetic control of neural activity enables innovative approaches to improve functional restoration of diseased sensory and motor systems. For clinical translation to succeed, optogenetic stimulation needs to closely match the coding properties of the targeted neuronal population and employ suitable emitters at their optimal operation. This requires tailoring of channelrhodopsins, emitters and coding strategies. Here, we provide a framework to parametrize optogenetic neural control and apply it to the auditory pathway that requires high temporal fidelity of stimulation. We used viral gene transfer of the ultrafast targeting-optimized Chronos into spiral ganglion neurons (SGNs) of the cochlea. We characterized the light-evoked response byin vivorecordings from individual SGNs and neurons of the anteroventral cochlear nucleus (AVCN) that detect coincident SGN input. Our results demonstrate that spike probability of SGNs can be gradually dialed by adjusting the width of light pulses of constant intensity, which optimally serves efficient laser diode operation. We identified an effective pulse width of 1.6 ms to maximize information encoding in SGNs. An upper boundary of optical stimulation rates results from robust spike rate adaptation that required a few tens of milliseconds to recover. We developed a semi-stochastic stimulation paradigm to rapidly (within minutes) estimate the transfer function from light to SGNs firing. The semi-stochastic stimulus evoked firing of different statistics allowing to approximate the time constant of neuronal integration in the AVCN. Our data pave the way to design the sound coding strategies of future optical cochlear implants.
An Alpha-helical Lid Guides the Target DNA toward Catalysis in CRISPR-Cas12a
Authors: Saha Aakash , Ahsan Mohd , Arantes Pablo R. , Schmitz Michael , Chanez Christelle , Jinek Martin , Palermo Giulia 
Published: September 2022

AbstractCRISPR-Cas12a is a powerful RNA-guided genome-editing system, also emerging as a robust diagnostic tool that cleaves double-stranded DNA using only the RuvC domain. This opens an overarching question on how the spatially distant DNA target strand (TS) traverses toward the RuvC catalytic core. Here, continuous tens of microsecond-long molecular dynamics and free-energy simulations reveal that an ⍺-helical lid, located within the RuvC domain, plays a pivotal role in the traversal of the TS by anchoring the crRNA:TS hybrid and elegantly guiding the TS toward the RuvC core, as also corroborated by DNA cleavage experiments. In this mechanism, the REC2 domain pushes the crRNA:TS hybrid toward the core of the enzyme, while the Nuc domain aids the bending and accommodation of the TS within the RuvC core by bending inward. Understanding of this cardinal process in the functioning of Cas12a will enrich fundamental knowledge and facilitate further engineering strategies for genome-editing.