bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid-phase ASEM imaging of cellular and structural details in cartilage and bone formed during endochondral ossification: Keap1-deficient osteomalacia
Authors: Sakai Eiko , Sato Mari , Memtily Nassirhadjy , Tsukuba Takayuki , Sato Chikara 
Published: March 2021

AbstractChondrogenesis and angiogenesis drive endochondral ossification. Using the atmospheric scanning electron microscopy (ASEM) without decalcification and dehydration, we directly imaged angiogenesis-driven ossification at different developmental stages shortly after aldehyde fixation, using aqueous radical scavenger glucose solution to preserve water-rich structures. An embryonic day 15.5 mouse femur was fixed and stained with phosphotungstic acid (PTA), and blood vessel penetration into the hypertrophic chondrocyte zone was visualised. We observed a novel envelope between the perichondrium and proliferating chondrocytes, which was lined with spindle-shaped cells that could be borderline chondrocytes. At postnatal day (P)1, trabecular and cortical bone mineralisation was imaged without staining. Additional PTA staining visualised surrounding soft tissues; filamentous connections between osteoblast-like cells and osteocytes in cortical bone were interpreted as the osteocytic lacunar-canalicular system. By P10, resorption pits had formed on the tibial trabecular bone surface. The applicability of ASEM for pathological analysis was addressed using knockout mice of Keap1, an oxidative-stress sensor. In Keap1−/− femurs, we observed impaired calcification and angiogenesis of epiphyseal cartilage, suggesting impaired bone development. Overall, the quick ASEM method we developed revealed mineralisation and new structures in wet bone tissue at EM resolution and can be used to study mineralisation-associated phenomena of any hydrated tissue.
Factors associated with prominent vessel sign on susceptibility-weighted imaging in acute ischemic stroke
Authors: Jiang Hai-fei , Zhang Yi-qun , Pang Jiang-xia , Shao Pei-ning , Qiu Han-cheng , Liu Ao-fei , Li Chen , Jin Min , Man Feng-yuan , Jiang Wei-jian 
Published: March 2021

AbstractThe prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) is not displayed in all cases of acute ischemia. We aimed to investigate the factors associated with the presence of PVS in stroke patients. Consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission. Associated factors for the presence of PVS were analyzed using univariate analyses and multivariable logistic regression analyses. A total of 218 patients were enrolled. The occurrence rate of PVS was 55.5%. Univariate analyses showed significant differences between PVS-positive group and PVS-negative group in age, history of coronary heart disease, baseline NIHSS scores, total cholesterol, hemoglobin, anterior circulation infarct, large vessel occlusion, and cardioembolism. Multivariable logistic regression analyses revealed that the independent factors associated with PVS were anterior circulation infarct (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.5–53.3), large vessel occlusion (OR 123.3; 95% CI 33.7–451.5), and cardioembolism (OR 5.6; 95% CI 2.1–15.3). Anterior circulation infarct, large vessel occlusion, and cardioembolism are independently associated with the presence of PVS on SWI.
Determination of metabolic activity in planktonic and biofilm cells of Mycoplasma fermentans and Mycoplasma pneumoniae by nuclear magnetic resonance
Authors: Awadh Ammar A. , Le Gresley Adam , Forster-Wilkins Gary , Kelly Alison F. , Fielder Mark D. 
Published: March 2021

AbstractMycoplasmas are fastidious microorganisms, typically characterised by their restricted metabolism and minimalist genome. Although there is reported evidence that some mycoplasmas can develop biofilms little is known about any differences in metabolism in these organisms between the growth states. A systematic metabolomics approach may help clarify differences associated between planktonic and biofilm associated mycoplasmas. In the current study, the metabolomics of two different mycoplasmas of clinical importance (Mycoplasma pneumoniaeandMycoplasma fermentans) were examined using a novel approach involving nuclear magnetic resonance spectroscopy and principle component analysis. Characterisation of metabolic changes was facilitated through the generation of high-density metabolite data and diffusion-ordered spectroscopy that provided the size and structural information of the molecules under examination. This enabled the discrimination between biofilms and planktonic states for the metabolomic profiles of both organisms. This work identified clear biofilm/planktonic differences in metabolite composition for both clinical mycoplasmas and the outcomes serve to establish a baseline understanding of the changes in metabolism observed in these pathogens in their different growth states. This may offer insight into how these organisms are capable of exploiting and persisting in different niches and so facilitate their survival in the clinical setting.
Temporal variation and potential origins of atmospheric speciated mercury at a remote island in South China Sea based on two-year field measurement data
Authors: Yeh Ming-Jie , Yuan Chung-Shin , Hung Kuo-Ning , Ie Iau-Ren , Lee Cheng-En , Chiang Kuan-Chen , Soong Ker-Yea 
Published: March 2021

AbstractThis study explored the temporal variation, gas-particle partition, and potential origins of atmospheric speciated mercury at a remote island in the South China Sea. Two-year data of three mercury species was measured at the Taiping Island. Air masses were clustered into five transport routes (A-E) to resolve the potential origins of atmospheric mercury. Field measurement showed that the concentration of gaseous elemental mercury (GEM) (1.33 ± 0.52 ng/m3) was close to the GEM background level of Northern Hemisphere, while those of GOM and PHg were 13.39 ± 3.58 and 94.33 ± 30.25 pg/m3, respectively. Both regular and intensive samplings concluded a consistent trend of higher mercury level in winter and spring than that in summer and fall. GEM dominated atmospheric mercury in all seasons (86.2–98.5%), while the highest partition of particle-bound mercury (PHg) was observed in winter (13.8%). The highest GEM concentrations were observed for Route A originating from central China and western Taiwan Island, and followed by Routes D and E from the Philippines, Malaysia, and Indonesia, while the lowest concentrations of GEM were observed for Routes B and C originating from North China, Korea, and Japan. Most importantly, high correlation of GEM versus levoglucosan and K+ in PM2.5 (r = 0.764 and 0.758, p < 0.01) confirmed that GEM was mainly emitted from biomass burning sources at the surrounding countries.
Variations in stability revealed by temporal asymmetries in contraction of phase space flow
Authors: Williams Zachary C , McNamara Dylan E 
Published: March 2021

AbstractEmpirical diagnosis of stability has received considerable attention, often focused on variance metrics for early warning signals of abrupt system change or delicate techniques measuring Lyapunov spectra. The theoretical foundation for the popular early warning signal approach has been limited to relatively simple system changes such as bifurcating fixed points where variability is extrinsic to the steady state. We offer a novel measurement of stability that applies in wide ranging systems that contain variability in both internal steady state dynamics and in response to external perturbations. Utilizing connections between stability, dissipation, and phase space flow, we show that stability correlates with temporal asymmetry in a measure of phase space flow contraction. Our method is general as it reveals stability variation independent of assumptions about the nature of system variability or attractor shape. After showing efficacy in a variety of model systems, we apply our technique for measuring stability to monthly returns of the S&P 500 index in the time periods surrounding the global stock market crash of October 1987. Market stability is shown to be higher in the several years preceding and subsequent to the 1987 market crash. We anticipate our technique will have wide applicability in climate, ecological, financial, and social systems where stability is a pressing concern.
Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
Authors: Lochrin Sarah E. , Turkbey Baris , Gasmi Billel , Schmidt Keith , Strope Jonathan D. , Chau Cindy H. , Sissung Tristan M. , Price Douglas K. , Cordes Lisa , Markolovic Suzana , Wood Bradford J. , Pinto Peter A. , McKinney Yolanda L. , Shih Joanna H. , Levy Elliot , Madan Ravi , Dahut William , Choyke Peter L. , Merino Maria , Figg William D. 
Published: March 2021

AbstractOATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate disodium to image prostate cancer and to track its utility as a biomarker. A single center open-label non-randomized pilot study recruited men with (1) localized, and (2) metastatic castration resistant prostate cancer (mCRPC). Gadoxetate disodium-enhanced MRI was performed at four timepoints post-injection. The Wilcoxon signed rank test was used to compare MRI contrast enhancement ratio (CER) pre-injection and post-injection. OATP1B3 expression was evaluated via immunohistochemistry (IHC) and a pharmacogenomic analysis of OATP1B3, NCTP and OATP1B1 was conducted. The mCRPC subgroup (n = 9) demonstrated significant enhancement compared to pre-contrast images at 20-, 40- and 60-min timepoints (p < 0.0078). The localized cancer subgroup (n = 11) demonstrated earlier enhancement compared to the mCRPC group, but no retention over time (p > 0.05). OATP1B3 expression on IHC trended higher contrast enhancement between 20–40 min (p ≤ 0.064) and was associated with contrast enhancement at 60 min (p = 0.0422). OATP1B1 haplotype, with N130D and V174A substitutions, impacted enhancement at 40–60 min (p ≤ 0.038). mCRPC lesions demonstrate enhancement after injection of gadoxetate disodium on MRI and retention over 60 min. As inter-individual variability in OATP1B3 expression and function has both predictive and prognostic significance, gadoxetate disodium has potential as a biomarker in prostate cancer.
Electromyographic activation patterns during swallowing in older adults
Authors: Ko Jin Young , Kim Hayoung , Jang Joonyoung , Lee Jun Chang , Ryu Ju Seok 
Published: March 2021

AbstractAge-related weakness due to atrophy and fatty infiltration in oropharyngeal muscles may be related to dysphagia in older adults. However, little is known about changes in the oropharyngeal muscle activation pattern in older adults. This was a prospective and experimental study. Forty healthy participants (20 older [> 60 years] and 20 young [< 60 years] adults) were enrolled. Six channel surface electrodes were placed over the bilateral suprahyoid (SH), bilateral retrohyoid (RH), thyrohyoid (TH), and sternothyroid (StH) muscles. Electromyography signals were then recorded twice for each patient during swallowing of 2 cc of water, 5 cc of water, and 5 cc of a highly viscous fluid. Latency, duration, and peak amplitude were measured. The activation patterns were the same, in the order of SH, TH, and StH, in both groups. The muscle activation patterns were classified as type I and II; the type I pattern was characterized by a monophasic shape, and the type II comprised a pre-reflex phase and a main phase. The oropharyngeal muscles and SH muscles were found to develop a pre-reflex phase specifically with increasing volume and viscosity of the swallowed fluid. Type I showed a different response to the highly viscous fluid in the older group compared to that in the younger group. However, type II showed concordant changes in the groups. Therefore, healthy older people were found to compensate for swallowing with a pre-reflex phase of muscle activation in response to increased liquid volume and viscosity, to adjust for age-related muscle weakness.
Multi-factor mediated functional modules identify novel classification of ulcerative colitis and functional gene panel
Authors: Lai Lijie , Li Hanyang , Feng Qi , Shen Jun , Ran Zhihua 
Published: March 2021

AbstractUlcerative colitis is a chronic, idiopathic, and inflammatory disease of the rectal and colonic mucosa, the behavior of which is of heterogeneity in individuals. Here, we explored the multifactor-mediated functional modules associated with ulcerative colitis classification in the whole genome. Datasets downloaded from the GEO database were used to identify differentially expressed genes between ulcerative colitis patients and healthy individuals initially, followed by acquisition of the remaining ulcerative colitis -related genes from the OMIM and STRING databases. The results identified 914 ulcerative colitis-related genes, of which 60 were differentially expressed genes obtained from GEO datasets. Through weighted co-expression network analysis of ulcerative colitis-related genes, four modules were obtained, three of which were related to ulcerative colitis. Following interactions between microRNA, long noncoding RNA, transcription factors, and module hub genes were predicted and used to construct ulcerative colitis multifactor networks. Additionally, we performed consensus clustering of the ulcerative colitis samples. The results revealed that ulcerative colitis could be divided into four subtypes, with six hub genes identified as potential biomarkers for classification. These findings offer novel insights into ulcerative colitis and a basis for disease classification of ulcerative colitis.
CYP2D6-inhibiting drugs and risk of fall injuries after newly initiated antidepressant and antipsychotic therapy in a Swedish, register-based case-crossover study
Authors: Dahl Marja-Liisa , Leander Karin , Vikström Max , Frumerie Clara , Nordenmalm Sofia , Möller Jette , Söderberg-Löfdal Karin 
Published: March 2021

AbstractDrug-drug interactions have been shown to affect the risk of fall injuries when opioids are used concomitantly with drugs inhibiting the cytochrome P450 2D6 (CYP2D6) enzyme in a previous pharmacoepidemiological study. The aim of this study was to determine whether CYP2D6-inhibiting drugs reinforce the risk of fall injuries when used concomitantly with antidepressants or antipsychotics. We identified all 252,704 adults with a first fall injury leading to hospitalisation from the National Patient Register in Sweden 2006–2013. Data on dispensed drugs was linked from the Swedish Prescribed Drug Register. We applied a case-crossover design to analyse newly dispensed (28 days preceding the fall injury, preceded by a 12-week washout period) antidepressants and antipsychotics, respectively, in relation to risk of a fall injury and according to concomitant use of CYP2D6-inhibiting drugs. Newly dispensed drugs were assessed correspondingly in a control period of equal length, 28 days prior to the 12-week washout period. Overall, the risk of fall injury was increased after newly initiated antidepressant and antipsychotic treatment. For antidepressants, concomitant CYP2D6 inhibitor use further elevated the risk estimates compared to non-use, most pronounced for the groups selective serotonin reuptake inhibitors (sertraline excluded) [OR = 1.47 (95% CI 1.19–1.80) vs. OR = 1.19 (95% CI 1.13–1.26)], and tricyclic antidepressants [OR = 1.71 (95% CI 1.17–2.51) vs. 1.27 (95% CI 1.11–1.47)] as well as for sertraline [OR = 1.61 (95% CI 1.05–2.38) vs. 1.12 (95% CI 1.00–1.26)]. For antipsychotics, the risk of fall injury was not altered by concomitant use of CYP2D6-inhibiting drugs. In conclusion, concomitant use of CYP2D6 inhibiting drugs tends to further increase the risk of fall injury in newly initiated antidepressant treatment, but not in antipsychotic treatment.
A multifaceted approach to understanding bat community response to disturbance in a seasonally dry tropical forest
Authors: Valle Darwin , Griffith Daniel M. , Jara-Guerrero Andrea , Armijos-Ojeda Diego , Espinosa Carlos I. 
Published: March 2021

AbstractGiven widespread habitat degradation and loss, reliable indicators are needed that provide a comprehensive assessment of community response to anthropogenic disturbance. The family Phyllostomidae (Order Chiroptera) has frequently been the focus of research evaluating bats’ response to habitat disturbance in seasonally dry tropical forests (SDTFs). However, few studies compare this family to the larger bat assemblage to assess its efficacy as a bioindicator. We compared community and species-specific attributes of understory phyllostomid and all understory bat species: (1) along a gradient of habitat disturbance within a human-modified SDTF landscape; and (2) between forest and riparian habitats within each disturbance level. We captured 290 individuals belonging to 13 species and 4 families. Phyllostomid species exhibited greater sensitivity to disturbance than the understory bat community as a whole based on richness and beta diversity. Both groups were more sensitive to disturbance in forest than riparian habitat, but phyllostomid species were more likely to be lost from highly disturbed forest habitat. The two dominant species declined in abundance with disturbance but variation in body condition was species-specific. These results suggest that Phyllostomidae are more effective indicators of human disturbance in SDTF than the understory bat community as a whole and evaluation of bats’ response to disturbance is best accomplished with a multifaceted approach.
Pentagalloyl glucose inhibits TNF‐α‐activated CXCL1/GRO-α expression and induces apoptosis‐related genes in triple-negative breast cancer cells
Authors: Mendonca Patricia , Alghamdi Sumaih , Messeha Samia , Soliman Karam F. A. 
Published: March 2021

AbstractIn triple-negative breast cancer (TNBC), the tumor microenvironment is associated with increased proliferation, suppressing apoptotic mechanisms, an altered immune response, and drug resistance. The current investigation was designed to examine the natural compound pentagalloyl glucose (PGG) effects on TNF-α activated TNBC cell lines, MDA-MB-231 and MDA-MB-468. The results obtained showed that PGG reduced the expression of the cytokine GRO-α/CXCL1. PGG also inhibited IƙBKE and MAPK1 genes and the protein expression of IƙBKE and MAPK, indicating that GRO-α downregulation is possibly through NFƙB and MAPK signaling pathway. PGG also inhibited cell proliferation in both cell lines. Moreover, PGG induced apoptosis, modulating caspases, and TNF superfamily receptor genes. It also augmented mRNA of receptors DR4 and DR5 expression, which binds to TNF-related apoptosis-induced ligand, a potent and specific stimulator of apoptosis in tumors. Remarkably, PGG induced a 154-fold increase in TNF expression in MDA-MB-468 compared to a 14.6-fold increase in MDA-MB-231 cells. These findings indicate PGG anti-cancer ability in inhibiting tumor cell proliferation and GRO-α release and inducing apoptosis by increasing TNF and TNF family receptors' expression. Thus, PGG use may be recommended as an adjunct therapy for TNBC to increase chemotherapy effectiveness and prevent cancer progression.
Antioxidants, lysosomes and elements status during the life cycle of sea trout Salmo trutta m. trutta L.
Authors: Kurhaluk Natalia , Tkachenko Halyna 
Published: March 2021

AbstractThe aim of our study was to elucidate the effects of both development stages (parr, smolt, adult, spawner), and kelt as a survival form and sex (male, female) on the functional stability of the lysosomal complex, biomarkers of oxidative stress, and element contents in the muscle tissue of the sea trout (Salmo truttam.truttaL.) sampled in the Pomerania region (northern Poland). We have evaluated the maximal activities of lysosomal enzymes (alanyl aminopeptidase, leucyl aminopeptidase, β-N-acetylglucosaminidase, and acid phosphatase), lipid peroxidation level, and protein carbonyl derivatives as indices of muscle tissue degradation. The relationship between lysosomal activity and oxidative stress biomarkers estimated by the lipid peroxidation level and protein carbonyl derivatives was also assessed, as well as the relationships between element levels and oxidative stress biomarkers. Trends of the main effects (i.e., the development stages and sex alone, the interaction of the sex and development stage simultaneously) on oxidative stress biomarkers, lysosomal functioning, and element contents in the muscle tissue were evaluated. The study has shown sex-related relationships between the pro- and antioxidant balance and the tissue type in the adult stage as well as modifications in the lysosomal functioning induced by long-term environmental stress associated with changing the habitats from freshwater to seawater and intense migrations. The highest level of toxic products generated in oxidative reactions and oxidative modification of proteins was noted in both the spawner stage and the kelt form. The holistic model of analysis of all parameters of antioxidant defense in all development stages and sex demonstrated the following dependencies for the level of lipid peroxidation, oxidative modification of proteins, lysosomal activities, and element contents: TBARS > OMP KD > OMP AD > TAC, AcP > NAG > LAP > AAP and Cu > Fe > Ca > Mn > Zn > Mg, respectively.
Targeted therapy of human leukemia xenografts in immunodeficient zebrafish
Authors: Somasagara Ranganatha R. , Huang Xiaoyan , Xu Chunyu , Haider Jamil , Serody Jonathan S. , Armistead Paul M. , Leung TinChung 
Published: March 2021

AbstractPersonalized medicine holds tremendous promise for improving safety and efficacy of drug therapies by optimizing treatment regimens. Rapidly developed patient-derived xenografts (pdx) could be a helpful tool for analyzing the effect of drugs against an individual’s tumor by growing the tumor in an immunodeficient animal. Severe combined immunodeficiency (SCID) mice enable efficient in vivo expansion of vital tumor cells and generation of personalized xenografts. However, they are not amenable to large-scale rapid screening, which is critical in identifying new compounds from large compound libraries. The development of a zebrafish model suitable for pdx could facilitate large-scale screening of drugs targeted against specific malignancies. Here, we describe a novel strategy for establishing a zebrafish model for drug testing in leukemia xenografts. We used chronic myelogenous leukemia and acute myeloid leukemia for xenotransplantation into SCID zebrafish to evaluate drug screening protocols. We showed the in vivo efficacy of the ABL inhibitor imatinib, MEK inhibitor U0126, cytarabine, azacitidine and arsenic trioxide. We performed corresponding in vitro studies, demonstrating that combination of MEK- and FLT3-inhibitors exhibit an enhanced effect in vitro. We further evaluated the feasibility of zebrafish for transplantation of primary human hematopoietic cells that can survive at 15 day-post-fertilization. Our results provide critical insights to guide development of high-throughput platforms for evaluating leukemia.