bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase, and ethanolamide metabolism with Alzheimer’s disease
Authors: Borkowski Kamil , Pedersen Theresa L. , Seyfried Nicholas T. , Lah James J. , Levey Allan I. , Hales Chadwick M. , Dammer Eric B. , Blach Colette , Louie Gregory , Kaddurah-Daouk Rima , Newman John W. ,   Alzheimer’s Disease Metabolomics Consortium
Published: September 2021

Abstract
Background
Alzheimer’s disease, cardiovascular disease, and other cardiometabolic disorders may share inflammatory origins. Lipid mediators, including oxylipins, endocannabinoids, bile acids, and steroids, regulate inflammation, energy metabolism, and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. Here, we describe the analysis of plasma and cerebrospinal fluid lipid mediators in a case–control comparison of ~150 individuals with Alzheimer’s disease and ~135 healthy controls, to investigate this knowledge gap.

Methods
Lipid mediators were measured using targeted quantitative mass spectrometry. Data were analyzed using the analysis of covariates, adjusting for sex, age, and ethnicity. Partial least square discriminant analysis identified plasma and cerebrospinal fluid lipid mediator discriminates of Alzheimer’s disease. Alzheimer’s disease predictive models were constructed using machine learning combined with stepwise logistic regression.

Results
In both plasma and cerebrospinal fluid, individuals with Alzheimer’s disease had elevated cytochrome P450/soluble epoxide hydrolase pathway components and decreased fatty acid ethanolamides compared to healthy controls. Circulating metabolites of soluble epoxide hydrolase and ethanolamides provide Alzheimer’s disease predictors with areas under receiver operator characteristic curves ranging from 0.82 to 0.92 for cerebrospinal fluid and plasma metabolites, respectively.

Conclusions
Previous studies report Alzheimer’s disease-associated soluble epoxide hydrolase upregulation in the brain and that endocannabinoid metabolism provides an adaptive response to neuroinflammation. This study supports the involvement of P450-dependent and endocannabinoid metabolism in Alzheimer’s disease. The results further suggest that combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease.
A new classification of congenital abnormalities of UPVS: sonographic appearances, screening strategy and clinical significance
Authors: Qin Yue , Wen Huaxuan , Liang Meiling , Luo Dandan , Zeng Qing , Liao Yimei , Zhang Mengyu , Ding Yan , Wen Xin , Tan Ying , Yuan Ying , Li Shengli 
Published: September 2021

AbstractThe umbilical–portal venous system (UPVS) plays an important role in embryonic development, as well as a significant blood circulation system to ensure the normal blood supply of fetal heart and brain and other vital organs. Congenital anomalies of UPVS contain many subtypes with a broad spectrum of manifestations and prognoses. Furthermore, because of fetal small lumen of UPVS, the sonographic evaluation remains difficult in utero. Appreciation of normal embryology and anatomy of UPVS is essential to an understanding of sonographic characteristics of anomalies of UPVS and fetal sequential changes. Through reviewing previous references and our experience with congenital abnormalities of UPVS, a new comprehensive classification is proposed. The new classification identifies three types of congenital abnormalities of UPVS based on morphological abnormalities and shunts. The embryology and etiology, sonographic, clinical and prognostic characteristics of each subtype of the new classification are described in detail. Knowledge of congenital abnormalities of UPVS can give sonographers a clue and aid prenatal sonographic diagnosis. The purpose of this article is to help the sonographers to understand the new classification of congenital abnormalities of UPVS, master the sonographic characteristics of each subtype and prenatal ultrasonographic screening strategy, and guide subsequent appropriate counseling and management.
Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females
Authors: Sárközy Márta , Márványkövi Fanni Magdolna , Szűcs Gergő , Kovács Zsuzsanna Z. A. , Szabó Márton R. , Gáspár Renáta , Siska Andrea , Kővári Bence , Cserni Gábor , Földesi Imre , Csont Tamás 
Published: September 2021

Abstract
Background
Uremic cardiomyopathy is a common cardiovascular complication of chronic kidney disease (CKD) characterized by left ventricular hypertrophy (LVH) and fibrosis enhancing the susceptibility of the heart to acute myocardial infarction. In the early stages of CKD, approximately 60% of patients are women. We aimed to investigate the influence of sex on the severity of uremic cardiomyopathy and the infarct size-limiting effect of ischemic preconditioning (IPRE) in experimental CKD.

Methods
CKD was induced by 5/6 nephrectomy in 9-week-old male and female Wistar rats. Two months later, serum and urine laboratory parameters were measured to verify the development of CKD. Transthoracic echocardiography was performed to assess cardiac function and morphology. Cardiomyocyte hypertrophy and fibrosis were measured by histology. Left ventricular expression of A- and B-type natriuretic peptides (ANP and BNP) were measured by qRT-PCR and circulating BNP level was measured by ELISA. In a subgroup of animals, hearts were perfused according to Langendorff and were subjected to 35 min global ischemia and 120 min reperfusion with or without IPRE (3 × 5 min I/R cycles applied before index ischemia). Then infarct size or phosphorylated and total forms of proteins related to the cardioprotective RISK (AKT, ERK1,2) and SAFE (STAT3) pathways were measured by Western blot.

Results
The severity of CKD was similar in males and females. However, CKD males developed more severe LVH compared to females as assessed by echocardiography. Histology revealed cardiac fibrosis only in males in CKD. LV ANP expression was significantly increased due to CKD in both sexes, however, LV BNP and circulating BNP levels failed to significantly increase in CKD. In both sexes, IPRE significantly decreased the infarct size in both the sham-operated and CKD groups. IPRE significantly increased the phospho-STAT3/STAT3 ratio in sham-operated but not in CKD animals in both sexes. There were no significant differences in phospho-AKT/AKT and phospho-ERK1,2/ERK1,2 ratios between the groups.

Conclusion
The infarct size-limiting effect of IPRE was preserved in both sexes in CKD despite the more severe uremic cardiomyopathy in male CKD rats. Further research is needed to identify crucial molecular mechanisms in the cardioprotective effect of IPRE in CKD.
A novel read methodology to evaluate the optimal dose of 68Ga-satoreotide trizoxetan as a PET imaging agent in patients with gastroenteropancreatic neuroendocrine tumours: a phase II clinical trial
Authors: Miller Colin G. , Grønbæk Henning , Virgolini Irene , Kjaer Andreas , Terve Pierre , Bahri Shadfar , Iversen Peter , Svirydenka Hanna , Rohban Thomas , McEwan Sandy 
Published: September 2021

Abstract
Background
68Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist exhibiting higher tumour-to-background ratios and sensitivity compared to 68Ga-DOTATOC. This randomised, 2 × 3 factorial, phase II study aimed to confirm the optimal peptide mass and radioactivity ranges for 68Ga-satoreotide trizoxetan, using binary visual reading. To that end, 24 patients with metastatic gastroenteropancreatic neuroendocrine tumours received 5–20 µg of 68Ga-satoreotide trizoxetan on day 1 of the study and 30–45 µg on day 16–22, with one of three gallium-68 radioactivity ranges (40–80, 100–140, or 160–200 MBq) per visit. Two 68Ga-satoreotide trizoxetan PET/CT scans were acquired from each patient post-injection, and were scored by experienced independent blinded readers using a binary system (0 for non-optimal image quality and 1 for optimal image quality). For each patient pair of 68Ga-satoreotide trizoxetan scans, one or both images could score 1.

Results
Total image quality score for 68Ga-satoreotide trizoxetan PET scans was lower in the 40–80 MBq radioactivity range (56.3%) compared to 100–140 MBq (90.6%) and 160–200 MBq (81.3%). Both qualitative and semi-quantitative analysis showed that peptide mass (5–20 or 30–45 µg) did not influence 68Ga-satoreotide trizoxetan imaging. There was only one reading where readers diverged on scoring; one reader preferred one image because of higher lesion conspicuity, and the other reader preferred the alternative image because of the ability to identify more lesions.

Conclusions
Binary visual reading, which was associated with a low inter-reader variability, has further supported that the optimal administered radioactivity of 68Ga-satoreotide trizoxetan was 100–200 MBq with a peptide mass up to 50 µg.
Trial registration ClinicalTrials.gov, NCT03220217. Registered 18 July 2017, https://clinicaltrials.gov/ct2/show/NCT03220217
EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases
Authors: Aarntzen Erik H. J. G. , Noriega-Álvarez Edel , Artiko Vera , Dias André H. , Gheysens Olivier , Glaudemans Andor W. J. M. , Lauri Chiara , Treglia Giorgio , van den Wyngaert Tim , van Leeuwen Fijs W. B. , Terry Samantha Y. A. 
Published: September 2021

AbstractInflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.
The metabolic parameters based on volume in PET/CT are associated with clinicopathological N stage of colorectal cancer and can predict prognosis
Authors: Kido Hidenori , Kato Shunsuke , Funahashi Kimihiko , Shibuya Kazutoshi , Sasaki Yousuke , Urita Yoshihisa , Hori Masaaki , Mizumura Sunao 
Published: September 2021

Abstract
Background
A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test.

Result
The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage.

Conclusion
Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.
Recursion formulas for certain quadruple hypergeometric functions
Authors: Younis Jihad , Verma Ashish , Aydi Hassen , Nisar Kottakkaran Sooppy , Alsamir Habes 
Published: September 2021

AbstractA remarkably large number of hypergeometric (and generalized) functions and a variety of their extensions have been presented and investigated in the literature by many authors. In this paper, we introduce five new hypergeometric functions in four variables and then establish several recursion formulas for these new functions. Some interesting particular cases and consequences of the main results are also considered.
Pharmacokinetic herb-drug interactions between Aidi injection and doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma
Authors: Lu Yuan , Pan Jie , Zhu Xiaoqing , Zhang Shuai , Liu Chunhua , Sun Jia , Li Yueting , Chen Siying , Huang Jing , Cao Chuang , Wang Yonglin , Li Yongjun , Liu Ting 
Published: September 2021

AbstractBackgroundAidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC.MethodsExperimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).ResultsPreadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI.ConclusionsIncreased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy
Authors: Wang Zhuo , Zhao Tingting , Zhang Shihui , Wang Junkai , Chen Yunyun , Zhao Hongzhou , Yang Yaxin , Shi Songlin , Chen Qiang , Liu Kuancan 
Published: September 2021

AbstractWnt signaling was initially recognized to be vital for tissue development and homeostasis maintenance. Further studies revealed that this pathway is also important for tumorigenesis and progression. Abnormal expression of signaling components through gene mutation or epigenetic regulation is closely associated with tumor progression and poor prognosis in several tissues. Additionally, Wnt signaling also influences the tumor microenvironment and immune response. Some strategies and drugs have been proposed to target this pathway, such as blocking receptors/ligands, targeting intracellular molecules, beta-catenin/TCF4 complex and its downstream target genes, or tumor microenvironment and immune response. Here we discuss the roles of these components in Wnt signaling pathway in tumorigenesis and cancer progression, the underlying mechanisms that is responsible for the activation of Wnt signaling, and a series of drugs targeting the Wnt pathway provide multiple therapeutic values. Although some of these drugs exhibit exciting anti-cancer effect, clinical trials and systematic evaluation should be strictly performed along with multiple-omics technology.
The influence of light and relative humidity on the formation of epsomite in cadmium yellow and French ultramarine modern oil paints
Authors: Harrison Jessie , Lee Judith , Ormsby Bronwyn , Payne David J. 
Published: September 2021

Abstract
The effect of relative humidity (RH) and light on the development of epsomite (MgSO4·7H2O) in Winsor & Newton cadmium yellow (CY) and French ultramarine (FU) artists’ oil colour paints was investigated. Tube paint samples were aged for 12 weeks at either 50% or 75% RH, under ambient light (200 ± 1 lx), elevated light (11,807 ± 328 lx), and near-dark conditions. Aged paint samples were characterised using light microscopy (LM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Results indicated that ageing at 75% RH in elevated light conditions, promoted the formation of hydrated magnesium sulphate (MgSO4·6–7H2O) crystals on the surface of both paints. The formation of sodium sulphate (Na2SO4) as a degradation product of French ultramarine oil paints after ageing at 75% RH in elevated light conditions is described. The formation of magnesium sulphate crystals in the absence of elevated SO2 is a new finding. For both cadmium yellow and French ultramarine oil paints, the pigments present are a likely source of sulphur, enabling the formation of sulphate salts, i.e., cadmium sulphide (CdS) yellow, and the sulphur radical anions (S3
−) present in ultramarine pigment. Sulphur-containing impurities arising from pigment manufacture are an additional possibility. It was previously theorised that epsomite formation in water-sensitive twentieth century oil paintings resulted from exposure to the elevated atmospheric sulphur dioxide (SO2) levels of the 1950s–1970s. This study demonstrates that hydromagnesite-containing cadmium yellow and French ultramarine oil paints of any period may be vulnerable to water-soluble sulphate salts formation and that this process is promoted by exposure to light and high (75%) RH environments. The formation of sulphate salts as a degradation product is known to contribute toward the development of water sensitivity of modern oil paintings which can pose significant challenges to conservation. Therefore this study highlights the importance of minimising exposure to light and raised relative humidity for paintings containing such CY and FU oil paint passages, to help slow down these types of degradation phenomena which have implications for preservation.
Cumulative deviation of a subpopulation from the full population
Authors: Tygert Mark 
Published: September 2021

AbstractAssessing equity in treatment of a subpopulation often involves assigning numerical “scores” to all individuals in the full population such that similar individuals get similar scores; matching via propensity scores or appropriate covariates is common, for example. Given such scores, individuals with similar scores may or may not attain similar outcomes independent of the individuals’ memberships in the subpopulation. The traditional graphical methods for visualizing inequities are known as “reliability diagrams” or “calibrations plots,” which bin the scores into a partition of all possible values, and for each bin plot both the average outcomes for only individuals in the subpopulation as well as the average outcomes for all individuals; comparing the graph for the subpopulation with that for the full population gives some sense of how the averages for the subpopulation deviate from the averages for the full population. Unfortunately, real data sets contain only finitely many observations, limiting the usable resolution of the bins, and so the conventional methods can obscure important variations due to the binning. Fortunately, plotting cumulative deviation of the subpopulation from the full population as proposed in this paper sidesteps the problematic coarse binning. The cumulative plots encode subpopulation deviation directly as the slopes of secant lines for the graphs. Slope is easy to perceive even when the constant offsets of the secant lines are irrelevant. The cumulative approach avoids binning that smooths over deviations of the subpopulation from the full population. Such cumulative aggregation furnishes both high-resolution graphical methods and simple scalar summary statistics (analogous to those of Kuiper and of Kolmogorov and Smirnov used in statistical significance testing for comparing probability distributions).
Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital
Authors: Adachi Koichiro , Sugitani Yuki , Unita Ryo , Yoshida Kosuke , Beppu Satoru , Terashima Mariko , Fujii Masaya , Shimizu Makiko , Yamazaki Hiroshi 
Published: September 2021

Abstract
Background
Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic.

Case presentation
A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of 100 tablets of loxoprofen (6000 mg) as a suicide attempt was emergently admitted to Kyoto Medical Center. On arrival, the patient was suffering disorders of consciousness. His plasma concentrations of loxoprofen and its reduced trans-alcohol metabolite were 52 and 24 μg/mL, 3.7 and 2.3 μg/mL, 0.81 and 0.54 μg/mL, and 0.015 and 0.011 μg/mL, respectively, at 4, 26, 50, and 121 h after the oral overdose. The observed apparent terminal elimination half-life of loxoprofen during days 1 and 2 of hospitalization was in the range 6–12 h, which is several times longer than the reported normal value. This finding implied nonlinearity of loxoprofen pharmacokinetics over the current 100-fold dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic (PBPK) model founded on data from a normal dose of 60 mg. The reasons for the delayed eliminations from plasma of loxoprofen and its trans-alcohol metabolite in this case are uncertain, but slight renal impairment (low eGFR values) developed on the second and third hospital days and could be a causal factor.

Conclusions
Because the patient’s level of consciousness had gradually improved, he was discharged on the fourth day of hospitalization. The virtual plasma exposures of loxoprofen and its reduced trans-alcohol metabolite estimated using the current simplified PBPK model were lower than the measured values in the overdose case. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide in cases of loxoprofen overdose.