bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant peripheral nerve sheath tumor in children: A clinicopathologic and molecular study with parallels to the adult counterpart
Authors: Agaram Narasimhan P. , Wexler Leonard H. , Chi Ping , Antonescu Cristina R. 
Published: November 2022

AbstractMalignant peripheral nerve sheath tumors (MPNST) are aggressive neoplasms, arising either sporadically, in the setting of neurofibromatosis type I (NF1) or post radiation. Most MPNST occur in adults and their pathogenesis is driven by the loss of function mutations in the PRC2 complex, regardless of their clinical presentation. In contrast, pediatric MPNST are rare and their pathogenesis has not been elucidated. In this study, we investigate a large cohort of 64 MPNSTs arising in children and young adults (younger than the age of 20 years) to better define their clinicopathologic and molecular features. Sixteen (25%) cases were investigated by MSK‐IMPACT, a targeted NGS panel of 505 cancer genes. Most patients (80%) were aged 11–20 years. A history of NF1 was established in half of the cases. Mean tumor size was 8.5 cm. The most common locations included the extremities (34%) and abdomen/pelvis (27%). Histologically, 89% of high‐grade MPNST showed conventional features, while the remaining three cases showed a predominant epithelioid phenotype. Heterologous differentiation occurred in 25% of high grade cases, with half showing rhabdomyoblastic differentiation. Tumors arose in a background of a plexiform neurofibroma (16%), neurofibroma (13%), and schwannoma in two cases (3%). Immunohistochemically, H3K27me3 expression was lost in 82% of conventional high‐grade MPNST analyzed, while loss of SMARCB1 expression was seen in one epithelioid MPNST. Genomically, all cases showed more than one genetic abnormality, with 53% showing mutations in EED / SUZ12 genes, and 47% of cases harboring alterations in NF1 and CDKN2A/CDKN2B genes. At the last follow‐up, 30% patients died of disease, 28% were alive with disease and 42% had no evidence of disease. NF1 status did not correlate with overall survival. In conclusion, half of pediatric and young adult MPNST were NF1‐related and showed loss of function alterations in PRC2 complex, NF1, and CDKN2A, similar to the adult counterpart. Thus, H3K27me3 loss of expression may be used in the diagnosis of high grade MPNSTs in children. Moreover, a small subset of pediatric MPNST have an epithelioid morphology with different pathogenesis.
LPAR1 and aberrantly expressed LPAR3 differentially promote the migration and proliferation of malignant peripheral nerve sheath tumor cells
Authors: Doutt Shannon Weber , Longo Jody Fromm , Carroll Steven L. 
Published: November 2022

AbstractSchwann cell‐derived neoplasms known as malignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy and the leading cause of death in individuals with neurofibromatosis Type 1. Using genome‐scale shRNA screens, we have previously found evidence suggesting that lysophosphatidic acid receptors (LPARs) are essential for MPNST proliferation and/or survival. Here, we examine the expression and mutational status of all six LPA receptors in MPNSTs, assess the role that individual LPA receptors play in MPNST physiology and examine their ability to activate key neurofibromin‐regulated signaling cascades. We found that human Schwann cells express LPAR1 and LPAR6, while MPNST cells express predominantly LPAR1 and LPAR3. Whole exome sequencing of 16 MPNST cell lines showed no evidence of mutations in any LPAR genes or ENPP2, a gene encoding a major LPA biosynthetic enzyme. Oleoyl‐LPA, an LPA variant with an unsaturated side chain, promoted MPNST cell proliferation and migration. LPAR1 knockdown ablated the promigratory effect of LPA, while LPAR3 knockdown decreased proliferation. Inhibition of R‐Ras signaling with a doxycycline‐inducible dominant negative (DN) R‐Ras mutant, which inhibits both R‐Ras and R‐Ras2, blocked LPA's promigratory effect. In contrast, DN R‐Ras did not affect migration induced by neuregulin‐1β (NRG1β), suggesting that LPA and NRG1β promote MPNST migration via distinct pathways. LPA‐induced migration was also inhibited by Y27632, an inhibitor of the ROCK1/2 kinases that mediate R‐Ras effects in MPNSTs. Thus, LPAR1 and aberrantly expressed LPAR3 mediate distinct effects in MPNSTs. These receptors and the signaling pathways that they regulate are potentially useful therapeutic targets in MPNSTs.
Predictive effect of pretreatment nutritional risk and GLIM‐defined malnutrition on the nutrition impact symptom clusters in patients with head and neck cancer undergoing radiotherapy
Authors: Wang Yujie , Zhang Lichuan , Zhang Tong , Jin Sanli , Huang Zhou , Zhao Dan , Zheng Baomin , Xiao Shaowen , Gong Liqing , Sun Yan , Lu Qian 
Published: November 2022

AbstractBackgroundEvidence supporting predictive effects of pretreatment nutritional risk and nutritional status on nutrition impact symptom (NIS) clusters during radiotherapy in patients with head and neck cancer (HNC) is insufficient.MethodsAt baseline (T1), we collected severity and interference of NIS (Head and Neck Patient Symptom Checklist), nutritional risk, and nutritional status. During (T2) and at the end of radiotherapy (T3), we re‐evaluated NIS. Symptom clusters were identified by exploratory factor analysis using mean scores of NIS severity at T2 and T3. Predictive effects were explored by generalized estimating equations.ResultsFive hundred thirty‐seven patients were recruited and 334 of them completed. Four clusters were identified; the oropharyngeal symptom cluster was the most severe and had the greatest interference with diet. Patients with pretreatment nutritional risk or malnutrition experienced more severe oropharyngeal symptom cluster.ConclusionsPretreatment nutritional risk or malnutrition could predict the oropharyngeal symptom cluster in patients with HNC undergoing radiotherapy.
Magnetohydrodynamic flow of a micropolar nanofluid in association with Brownian motion and thermophoresis: Irreversibility analysis
Authors: Almeida Felicita , Gireesha Bijjanal Jayanna , Venkatesh Puttaswamy 
Published: November 2022

AbstractThis investigation was carried out with the purpose of presenting the flow of micropolar fluid flowing in the microchannel placed parallel to the ground. The prime aim of the work was to study the behavior of micropolar fluid and the response of the microrotation component when the two significant mechanisms namely Brownian movement and thermophoresis are accounted for, as these effects are mainly concerned with the motion of the particles of nano‐dimensions. For the flow of micropolar, we account for the extra kinematics variables combined with the classical continuum mechanics namely microinertia moment tensor and gyration tensor. Magnetic effect and suction/injection of the fluid through the channel walls are also facilitated. The influence on the fluid concentration due to the presence of activation energy was accounted in the present examination. On considering all of these effects, equations are carefully modeled and the solution was attained with the aid of Runge–Kutta Fehlberg 4–5th order method using a shooting scheme. The results have deciphered that the presence of material parameter elevates the microrotation component on the upper half of the channel and depletes it at the lower half. The microinertia parameter shows the opposite behavior of the material parameter. Brownian motion parameter is found to enhance the thermal profile and concentration profile. Lesser entropy was generated when the material parameter was high.
Interleukin‐23 receptor defines T helper 1‐like regulatory T cells in oral squamous cell carcinoma
Authors: Li Wei , An Ning , Wang Mingwei , Liu Xiguo , Mei Zhidan 
Published: November 2022

AbstractBackgroundThe immune responses play significant roles in the onset, progression, and outcome of oral squamous cell carcinoma (OSCC). CD4+ regulatory T cells (Tregs) significantly impact tumor immunity. However, their role in OSCC development remains elusive.MethodsIn a carcinogen‐induced mouse OSCC model, interleukin‐23 receptor (IL‐23R) expression on Tregs and Treg function were determined by flow cytometry. IL‐23R overexpression in Tregs was achieved by lentiviral infection, followed by evaluation of the expression of Forkhead box P3 (Foxp3), T‐bet, retineic‐acid‐receptor‐related orphan nuclear receptor gamma t, and cytokines by flow cytometry. Adoptive transfer assays were applied to analyze the function of IL‐23R−overexpressing Tregs in vivo. The cellular sources of IL‐23 were also determined by flow cytometry.ResultsIL‐23R− Tregs and IL‐23R+ Tregs were found in the tongues but not spleens of OSCC‐bearing mice. IL‐23R+ Tregs expressed lower Foxp3 but higher T‐bet than IL‐23R− Tregs. IL‐23R− Tregs produced abundant IL‐10 and transforming growth factor (TGF)‐β, while IL‐23R+ Tregs produced lower IL‐10 and TGF‐β but remarkably higher interferon (IFN)‐γ. Furthermore, IL‐23R+ Tregs possessed more phosphorylated signal transducer and activator of transcription (STAT3) and STAT4 than IL‐23R− Tregs. IL‐23R+ Tregs were less immunosuppressive than IL‐23R− Tregs, as evidenced by weaker inhibition of activated conventional T cells. IL‐23R overexpression in splenic Tregs remarkably reduced the expression of IL‐10 and TGF‐β but increased IFN‐γ expression when Tregs were adoptively transferred into OSCC‐bearing mice. In the OSCC microenvironment, macrophages, dendritic cells, and malignant OSCC cells produced IL‐23 which might modulate the function of IL‐23R+ Tregs.ConclusionsThis study unveils Treg heterogeneity, thus deepening the understanding of Treg biology and tumor immunity in OSCC.
MicroRNAs target the PI3K/Akt/p53 and the Sirt1/Nrf2 signaling pathways in doxorubicin‐induced cardiotoxicity
Authors: Yarmohammadi Fatemeh , Ebrahimian Zainab , Karimi Gholamreza 
Published: November 2022

AbstractDoxorubicin (DOX) is used as a chemotherapeutic agent in the treatment of solid tumors. Irreversible cardiotoxicity is the major limitation in the clinical use of DOX. Several microRNAs (miRNAs) with diversified functions are identified that participate in exacerbating or suppressing DOX‐induced cardiac damage. The miRNAs are small noncoding regulatory RNAs that modify the expression of the native genes. Studies have demonstrated that miRNAs by modifying the expression of proteins such as PTEN, Akt, and survivin can affect DOX‐induced cardiac apoptosis. Moreover, miRNAs can modulate cardiac oxidative stress in DOX treatment through the posttranscriptional regulation of Sirt1, p66shc, and Nrf2 expressions. This manuscript has reviewed the regulation of the PI3K/Akt/p53 and the Sirt1/Nrf2 pathways by miRNAs in DOX‐induced cardiotoxicity.
Hyperphosphatasia with mental retardation syndrome 3: Cerebrospinal fluid abnormalities and correction with pyridoxine and Folinic acid
Authors: Messina Martina , Manea Emanuela , Cullup Thomas , Tuschl Karin , Batzios Spyros 
Published: November 2022

AbstractGlycosylphosphatidylinositol anchored proteins (GPI‐APs) represent a class of molecules attached to the external leaflet of the plasma membrane by the GPI anchor where they play important roles in numerous cellular processes including neurogenesis, cell adhesion, immune response and signalling. Within the group of GPI anchor defects, six present with the clinical phenotype of Hyperphosphatasia with Mental Retardation Syndrome (HPMRS, Mabry Syndrome) characterized by moderate to severe intellectual disability, dysmorphic features, hypotonia, seizures and persistent hyperphosphatasia. We report the case of a 5‐year‐old female with global developmental delay associated with precocious puberty and persistently raised plasma alkaline phosphatase. Targeted next generation sequencing analysis of the HPMRS genes identified novel compound heterozygous variants in the PGAP2 gene (c.103del p.(Leu35Serfs*90)and c.134A > Gp.(His45Arg)) consistent with the diagnosis of HPMRS type 3. Cerebrospinal fluid (CSF) neurotransmitter analysis showed low levels of pyridoxal phosphate and 5‐methyltetrahydrofolate and raised homovanillic acid. Supplementation with pyridoxine and folinic acid led to normalization of biochemical abnormalities. The patient continues to make developmental progress with significant improvement in speech and fine motor skills. Our reported case expands the clinical spectrum of HPMRS3 in which multisystem involvement is being increasingly recognized. Furthermore, it shows that miss‐targeting GPI‐APs and the effect on normal cellular function could provide a physiopathologic explanation for the CSF biochemical abnormalities with management implications for a group of disorders that currently has no treatment that can lead possibly to improved clinical outcomes.
A possible relationship between Changma and tropical cyclone genesis frequency in the western North Pacific linked to the North Atlantic Oscillation
Authors: Choi JaeWon , Moon Il‐Ju , Khim Boo‐Keun 
Published: November 2022

AbstractThis study analysed the relationship between Changma and tropical cyclone (TC) genesis in the western North Pacific (WNP). The correlations between Changma onset, withdrawal, and duration in Jeju and the southern and central regions of Korea and TC genesis frequencies in June, July, and June–July in the WNP were analysed. The results showed that Changma duration in the southern region and June–July TC genesis frequency exhibited the highest negative correlation. To investigate the mechanism underlying the correlations, the differences in large‐scale environments between the 14 years with the longest Changma duration and the 14 years with the shortest Changma duration were analysed. For 850‐hPa stream flows, anomalous anticyclones are found in most WNP regions, while anomalous cyclones are located in the East Asian mid‐latitude region. In the long Changma duration years, the WNP subtropical high was strengthened in the north–south and east–west directions, the monsoon trough was weakened, and anomalous downward flows are formed at the latitudinal (longitudinal) band of 10°–27°N (100°–180°E) where TCs mainly occur. All these environments provide unfavourable conditions for TCs to occur. The difference in sea surface temperature revealed triple anomaly patterns, such as warm, cold, and warm, in the north–south direction in the North Atlantic. This spatial distribution was similar to the negative North Atlantic Oscillation (NAO) pattern. From the analysis of 500‐hPa stream flow, we confirmed that the NAO acts as a bridge connecting the TC and Changma in the WNP.
Time series analysis for droughts characteristics response to propagation
Authors: Faiz Muhammad Abrar , Zhang Yongqiang , Tian Xiaoqiang , Zhang Xuanze , Ma Ning , Aryal Santosh , Naz Farah 
Published: November 2022

AbstractUnderstanding and exploring hydrological (H) or soil moisture (SM) drought due to meteorological (M) drought under changing climate is crucial for drought early warning. Previously, different methods were used to calculate drought propagation from one state (M to another [H or SM]). However, each method has its pros and cons and thus cannot describe appropriate propagation attributes. In this study, a time series analysis is carried out to explore the propagation process in the Yellow River Basin (YRB) and Hai River Basin (HRB) of China. Standardized Streamflow Index (SSI), Standardized SM Index (SSMI), and Standardized Precipitation Index (SPI) 1‐month time series were calculated using streamflow, satellite‐based SM, and precipitation from 1979 to 2016. The time series framework identifies the average drought propagation as 3.4–8.3 months (M–H) and 2.3–5 months (M–SM) in YRB, while 2.8–7.7 months (M–H) and 2.3–8.5 months (M–SM) in HRB. Cross‐wavelet analysis indicated that periodic characteristics of M drought are responsible for these droughts. Overall, the findings of this study may help to minimize the drought hazards posed by M droughts.
Minimally invasive gingival phenotype modification in gingival recession associated with a non‐carious cervical lesion using the root plastique technique: A quasi‐experimental one‐group pretest‐posttest study
Authors: Romano Luigi , Paolantonio Michele , De Ninis Paolo , Saleh Muhammad H. A. , Sinjari Bruna , Xhajanka Edit , Femminella Beatrice , Wang Hom‐lay , Ravidá Andrea 
Published: November 2022

AbstractBackgroundThis study introduces the root plastique technique (RPT), the aim of which is to modify the gingival phenotype of sites with gingival recessions (GRs) associated with non‐carious cervical lesions (NCCLs) prior to surgical treatment.MethodsRPT was performed in 22 subjects with 53 RT1 A/B + GRs. Changes in keratinized tissue thickness (KTT), keratinized tissue width (KTW), relative gingival recession (RGR), relative clinical attachment level (RCAL), and probing pocket depth (PPD) were measured at baseline (T0) and 2 months (T1) after the procedure was performed. All analyses were performed by means of hierarchical models.ResultsThe study revealed statistically significant changes (P < 0.01) in KTT (0.45 ± 0.04 mm), RGR (0.80 ± 0.13 mm), KTW (0.67 ± 0.07 mm), and RCAL (‐0.72 ± 0.16 mm). No changes in PPD (P > 0.05) were observed. Regression analyses of KTT increase and RGR reduction at T0 showed statistically significant correlation between the two variables (P < 0.05). All the teeth with a KTT of <0.8 mm at T0 (N = 14) reached or surpassed this threshold at T1.ConclusionRPT increases KTT and KTW. In most of the sites, a reduction in GR was also achieved.
Hawaiian waterbird movement across a developed landscape
Authors: Paxton Eben H. , Paxton Kristina L. , Kawasaki Martha T. , Gorresen P. Marcos , van Rees Charles B. , Underwood Jared G. 
Published: November 2022

AbstractA key component for biologists managing mobile species is understanding where and when a species occurs at different locations and scaling management to fit the spatial and temporal patterns of movement. We established an automated radio‐telemetry tracking network to document multi‐year movement in 2016–2018 of 3 endangered waterbirds among wetlands on Oʻahu, Hawaiʻi, USA: ʻalae ʻula or Hawaiian gallinule (gallinule; Gallinula galeata sandvicensis), ʻalae keʻokeʻo or Hawaiian coot (coot; Fulica alai), and aeʻo or Hawaiian stilt (stilt; Himantopus mexicanus knudseni), each with different ecological requirements. There were marked differences in the movement propensity of the species, with no movement among sites detected in gallinules, 31% of coots moving among wetlands, and very high levels of daily movement in stilts. A network analysis revealed strong evidence for fidelity among individual stilts to specific wetlands, indicating different groups of wetlands supported different birds. There was also strong evidence for patterns in daily and seasonal movement patterns of stilts. Our work indicates the importance of each wetland to the waterbirds they support, as each individual had strong fidelity to a single wetland. In addition, for Hawaiian coots and stilts, which were documented moving among multiple wetlands, a network of wetlands may be key for long‐term persistence of these endangered species, and coordinated regional management of waterbirds as a shared resource could provide greater benefits to waterbirds than independent management of each wetland.
Exploring CMMN applicability to knowledge‐intensive process modeling: An empirical evaluation by modelers
Authors: Routis Ioannis , Bardaki Cleopatra , Nikolaidou Mara , Dede Georgia , Anagnostopoulos Dimosthenis 
Published: November 2022

AbstractKnowledge‐intensive processes (KiPs) have emerged characterizing tasks that are data‐driven, change dynamically and depend on the knowledge and experience of knowledge workers. Case Management Model and Notation (CMMN) language was introduced for modeling unstructured, agile human‐centric processes. As the available Business Process Modeling (BPM) methods and practices are not adequate for modeling KiPs, this paper presents an empirical study of the applicability of CMMN to modeling KiPs. After experienced modelers designed the models of three KiPs scenarios utilizing CMMN, their perceptions were collected assessing the support of CMMN to the KiPs characteristics. Specifically, the modelers assessed the support of the newly introduced CMMN notation elements to the KiPs characteristics. Three of them, that is, knowledge‐driven, unpredictable, and goal‐oriented, were highlighted as the ones that get the greater support by CMMN when it comes to modeling KiPs; the participating modelers suggested that the applicability of CMMN to modeling KiPs is mostly reinforced by the Sentries element. Considering that in a knowledge‐driven economy, organizations are called to transform their way of thinking and manage KiPs, we value the modelers' opinions since they shall apply such practices in the future. This research is a first step to assess whether CMMN may be a “fit” for modeling KiPs. When considering the potential of CMMN for KiPs modeling, the perceptions of such real CMMN users are also first indications of the CMMN future in terms of application.
Temporal variation in ecological and evolutionary contributions to phytoplankton functional shifts
Authors: Hattich Giannina S. I. , Listmann Luisa , Havenhand Jonathan , Reusch Thorsten B. H. , Matthiessen Birte 
Published: November 2022

AbstractCommunities and their functioning are jointly shaped by ecological and evolutionary processes that manifest in diversity shifts of their component species and genotypes. How both processes contribute to community functional change over time is rarely studied. We here repeatedly quantified eco‐evolutionary contributions to CO2‐driven total abundance and mean cell size changes after short‐, mid‐, and longer‐term (80, 168, and > 168 d, respectively) in experimental phytoplankton communities. While the CO2‐driven changes in total abundance and mean size in the short‐ and mid‐term could be predominantly attributed to ecological shifts, the relative contribution of evolution increased. Over the longer‐term, the CO2‐effect and underlying eco‐evolutionary changes disappeared, while total abundance increased, and mean size decreased significantly independently of CO2. The latter could be presumably attributed to CO2‐independent genotype selection which fed back to species composition. In conclusion, ecological changes largely dominated the regulation of environmentally driven phytoplankton functional shifts at first. However, evolutionary changes gained importance with time, and can ultimately feedback on species composition, and thus must be considered when predicting phytoplankton change.