bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Analysis of the Pharmacological Effects of Alcoholic Components in Maotai
Authors: Zhou Wei , Chen Ziyi , Bao Hui , Zhang Guohao , Liu Zhigang 
Published: June 2019

AbstractMaotai liquor is one of the most famous traditional Chinese distilled liquor enjoyed by many people all over the world for its unique production method, impressive liquor quality, and soy sauce‐like and roasted aroma style. It is known that aroma characteristics of liquor mainly depend on the aroma compounds. Alcohols as one of the most important categories of aroma components have been determined in Maotai liquor. However, the systemic analysis of alcoholic compounds in liquor is limited, especially the active alcoholic components and their pharmacological effects. Therefore, in this study, a systemic analysis method was proposed by combining in silico absorption, distribution, metabolism, and excretion (ADME) evaluation, target fishing, network pharmacology technology, pathway analysis, and experimental verification to interpret the pharmacological mechanism of alcoholic compounds in Maotai liquor. Finally, 15 compounds with favorable pharmacokinetic profiles were screened through in silico ADME models. Thirty‐eight related targets of these active compounds were identified by target prediction method. The network pharmacology and pathway analysis were developed to clarify the pharmacological effect of alcoholic compounds in Maotai liquor at the system and pathway level. Moreover, the key active compounds were validated by in vitro experiments that verified the effectiveness of our methods. Our study provides a novel approach to systematically analyze the pharmacological effect of alcoholic compounds in Maotai liquor, which would be beneficial for promoting the in‐depth study of various liquors.Practical ApplicationMaotai liquor is popularly enjoyed in the world for a very long time. However, the systemic analysis of compounds in liquor is limited. Our systematic analysis approach was developed to explore the bioactive ingredients and their related target proteins as well as the pharmacological effects of Maotai liquor. This will provide a new method to understand the pharmacological mechanisms of compounds in various liquors at the systems level, so as to promote the development of liquors and to increase the public awareness of science about alcohol consumption.
Efficacy and safety of iguratimod plus corticosteroid as bridge therapy in treating mild IgG4‐related diseases: A prospective clinical trial
Authors: Zhang Panpan , Gong Yiyi , Liu Zheng , Liu Yanying , Lin Wei , Li Jieqiong , Wang Mu , Liu Xiaowei , Fei Yunyun , Chen Hua , Peng Linyi , Li Jing , Zhou Jiaxin , Shi Qun , Zhang Xuan , Shen Min , Zeng Xiaofeng , Zhang Fengchun , Li Yongzhe , Zhao Yan , Zhang Wen 
Published: June 2019

AbstractAimThe purpose of this study is to evaluate the therapeutic efficacy and safety of iguratimod plus corticosteroid as bridge therapy in the treatment of mild immunoglobulin G4‐related disease (IgG4‐RD).MethodsNewly diagnosed IgG4‐RD patients, without internal organ involvement were enrolled. Patients were given one dose of diprospan, intramuscular injection, and iguratimod, 25 mg, twice daily, for 24 weeks and were followed up at 0, 12 and 24 weeks. Follow‐up indexes included IgG4‐RD responder index (IgG4‐RD RI), serology and imaging, plasma cytokines and adverse drug effect. Flow cytometry was performed for T, B cell subsets and plasma was collected for liquid chromatography mass spectrometry (LC‐MS)‐based metabolomic profiling and data processing.ResultsThirty patients were enrolled. At week 24, 9 (30.0%) patients achieved complete response, 17 (56.7%) patients with partial response, and 4 (13.3%) patients had no response to treatment. IgG4‐RD RI, serum IgG and IgG4 levels decreased significantly at weeks 12 and 24 after treatment, as well as CD3+ CD8+ T cells, plasmablast/plasma cells and memory B cells. The LC‐MS based plasma metabolomic profiles revealed significant changes between untreated patients and healthy donors, which became much similar to normal states after treatment.ConclusionIguratimod plus corticosteroid as bridge therapy is effective for the treatment of mild IgG4‐RD, it can improve the clinical symptoms, reduce serum IgG and IgG4 levels, especially plasmablasts/plasma cells and memory B cells. In addition, the metabolite profiling became similar to normal controls after treatment.
Body mass index associates with disease relapse in patients with giant cell arteritis
Authors: Matsumoto Kotaro , Kaneko Yuko , Takeuchi Tsutomu 
Published: June 2019

AbstractObjectiveTo identify risk factors associated with disease relapse in giant cell arteritis (GCA).MethodsWe reviewed data from 30 consecutive, newly diagnosed patients with GCA. The patients were divided according to relapse or non‐relapse status, and their baseline characteristics were compared.ResultsAmong the 30 patients, 8 relapsed at a median of 28 weeks from GCA diagnosis. Patients with relapse were male‐dominant (male: 88% vs female: 41%, P = 0.02) and showed a higher body mass index (BMI, 23 kg/m2 vs 19 kg/m2, P < 0.01) than non‐relapse patients. Patients with BMI ≥ 21 kg/m2 showed a significantly higher relapse rate than those with BMI < 21 kg/m2 during the 100‐week follow‐up (46% vs 0%, log‐rank test, P < 0.01).ConclusionHigher BMI may be associated with relapse in patients with GCA.
Follicle‐stimulating hormone promotes renal tubulointerstitial fibrosis in aging women via the AKT/GSK‐3β/β‐catenin pathway
Authors: Zhang Kun , Kuang Lin , Xia Fangzhen , Chen Yi , Zhang Wen , Zhai Hualing , Wang Chiyu , Wang Ningjian , Lu Yingli 
Published: June 2019

AbstractEstrogen withdrawal in aging women contributes to the progression of chronic kidney disease (CKD). However, the effect of high circulating follicle‐stimulating hormone (FSH) levels on renal dysfunction remains unknown. In this study, blood samples from 3,055 postmenopausal women were collected and tested, which showed that there was a strong negative correlation between eGFR and FSH levels (p < 0.001), independent of LH, testosterone, and estradiol. Functional FSHR was detected in renal tubular epithelial cells. In vivo, high circulating FSH levels promoted a phenotype of tubulointerstitial fibrosis, characterized by increases in 24‐hr urine protein/creatinine ratio, serum Cr, serum BUN, and ECM deposition. Similar results obtained from cultured HK‐2 cells showed that FSH increased the transcriptional and protein expression of profibrotic mediators (collagen IV, fibronectin, and PAI‐1). This promotion of fibrosis by FSH occurred through the activation of AKT/GSK‐3β/β‐catenin pathway, which could be attenuated by silencing FSHR by siRNA or by LY294002 or MK2206. In addition, FSH‐stimulated HK‐2 cells secreted IL‐8, which promoted macrophage migration to exacerbate tubulointerstitial fibrosis. These results revealed a previously unknown effect of FSH on kidney injury, which may offer a critical insight into the development of CKD in aging postmenopausal women.
Post‐traumatic erosive dermatosis of the scalp: A hypergranulated variant
Authors: Sechi Andrea , Piraccini Bianca Maria , Alessandrini Aurora , Patrizi Annalisa , Tabanelli Michela , Sacchelli Lidia , Misciali Cosimo , Savoia Francesco 
Published: June 2019

AbstractErosive pustular dermatosis of the scalp is a slowly progressive chronic inflammatory disease that predominantly affects elderly male patients with marked actinic damage. The clinical evolution consists firstly of keratotic and erosive plaques surmounted by yellow‐brown crusts and non‐follicular pustules; later, the active crusting lesions regress in number and the scarring process causes diffuse cutaneous thinning and loss of hair follicles. However, manifestations may be atypical, leading to frequent misdiagnosis. We present a case series of post‐traumatic erosive pustular dermatosis on the scalp of 4 elderly patients. The characterising feature was the presence of erosion consisting of abundant hypergranulation tissue, with an almost total lack of crusts and pustules. Dermoscopy showed a unique pattern of stretched and dilated linear, telangiectatic and polymorphous on‐focus vessels, milky‐red areas and white scarring areas. This clinical entity is rarely reported in the literature. The majority of reported cases were located on the legs.
Letter: programmed cell death protein‐1 (PD‐1)‐targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real‐world cohort—more questions than answers. Authors’ reply
Authors: Scheiner Bernhard , Pinter Matthias 
Published: June 2019

Linked ContentThis article is linked to Scheiner and Kung and Wang papers. To view these articles, visit https://doi.org/10.1111/apt.15245 and https://doi.org/10.1111/apt.15322.
Retracted: Sinomenine exerts antitumour effect in gastric cancer cells via enhancement of miR‐204 expression
Authors: Yuan Haifeng , Zhang Jinghua , Li Fuli , Li Wei , Wang Haichao 
Published: June 2019

AbstractGastric carcinoma (GC) is a pernicious neoplasm with high morbidity and mortality. Sinomenine (SIN) has long been exploited to heal rheumatoid arthritis. Recently, SIN has been discovered to exert the antitumour functions in diverse cancers. However, the impacts of SIN on GC remain indistinct. We attempted to expose the antitumour effect of SIN on GC. MKN45 and SGC‐7901 cells were administered with SIN for 24 hours, cell viability, proliferation, apoptosis, migration, invasion and the associated proteins in the above processes were examined via exploiting CCK‐8, BrdU, flow cytometry, Transwell and Western blot. MiR‐204 expression in GC tumour tissues, different GC cell lines and SIN‐stimulated GC cells was investigated by executing RT‐qPCR. The above cell biological processes were reassessed after transfection with miR‐204 inhibitor. The latent mechanisms were probed by examining AMPK and Wnt/β‐catenin pathways. We found that SIN memorably repressed cell proliferation, evoked apoptosis and affected CyclinD1, Bcl‐2, Bax and cleaved‐caspase‐3 expression in MKN45 and SGC‐7901 cells. Cell migration, invasion and expression of MMP‐9 and Vimentin were all restrained by SIN stimulation. The increase of miR‐204 was discovered in GC tissues and SIN‐treated MKN45 and SGC‐7901 cells. But suppression of miR‐204 was observed in AGS, MKN28, MKN45 and SGC‐7901 cells. Suppression of miR‐204 overturned the inhibitory functions of SIN in MKN45 and SGC‐7901 cells. Besides, SIN prohibited AMPK and Wnt/β‐catenin pathways via enhancement of miR‐204. In conclusion, these findings suggested that SIN exerted the antitumour activity in GC cells by hindering AMPK and Wnt/β‐catenin pathways via enhancement of miR‐204.
Germline gene editing and the precautionary principle
Authors: Koplin Julian J. , Gyngell Christopher , Savulescu Julian 
Published: June 2019

AbstractThe precautionary principle aims to influence decision‐making in contexts where some activity poses uncertain but potentially grave threats. This perfectly describes the controversy surrounding germline gene editing. This article considers whether the precautionary principle should influence how we weigh the risks and benefits of human germline interventions, focusing especially on the possible threats to the health of future generations. We distinguish between several existing forms of the precautionary principle, assess their plausibility and consider their implications for the ethics of germline modification. We also offer a novel form of the precautionary principle: the sufficientarian precautionary principle. Some plausible versions of the precautionary principle recommend placing somewhat greater weight on avoiding threats to future generations than on achieving short‐term benefits. However, no plausible versions of the precautionary principle entail that we should outright reject the use germline gene editing in human reproduction and some, such as the sufficientarian version, might endorse its use.
Negative CD19 expression is associated with inferior relapse‐free survival in children with RUNX1‐RUNX1T1–positive acute myeloid leukaemia: results from the Japanese Paediatric Leukaemia/Lymphoma Study Group AML‐05 study
Authors: Sakamoto Kenichi , Shiba Norio , Deguchi Takao , Kiyokawa Nobutaka , Hashii Yoshiko , Moriya‐Saito Akiko , Tomizawa Daisuke , Taga Takashi , Adachi Soichi , Horibe Keizo , Imamura Toshihiko 
Published: June 2019

SummaryWe performed a retrospective analysis of leukaemic surface antigen expression and genomic data from a total of 100 RUNX1‐RUNX1T1–positive paediatric acute myeloid leukaemia (AML) patients enrolled in the Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) AML‐05 protocol to determine risk factors for relapse. In univariate analysis, the KIT exon 17 mutation (n = 21) and CD19 negativity (n = 59) were significant risk factors for relapse (P = 0·01). In multivariate analysis, CD19 negativity was the sole significant risk factor for relapse (hazard ratio, 3·09; 95% confidence interval, 1·26–7·59; P < 0·01), suggesting that biological differences between CD19‐positive and CD19‐negative RUNX1‐RUNX1T1 AML patients should be investigated.
To understand the incomprehensible: A qualitative study of parents' challenges after child removal and their experiences with support services
Authors: Syrstad Ellen , Slettebø Tor 
Published: June 2019

AbstractThis article elucidates the challenges parents face when they lose the care of their children and their experiences of family counselling as a support service in Norway. A qualitative study following five mothers and one father whose children were in care was conducted through two focus groups and six individual interviews. The study found that the parents struggled to understand why their children had been placed in care and felt disempowered by the Child Protection Services (CPS). This situation led to complicated relationships with the CPS. We drew upon positioning theory and Goffman's theories about stigma and identity in this study, and these theories are explicitly used in discussing our analytic results. The study reveals the challenges encountered by CPS due to their dual role: On the one hand, they remove the children, and on the other, they offer support. The parents in this study also received assistance from the Family Counselling Services. Important results of this study are the parents' experiences of the two systems and, in particular, the different positions the systems seemed to place them in.
Reunification of looked‐after children with their birth parents in the United Kingdom: A literature review and thematic synthesis
Authors: Carlson Lyndsey , Hutton Stephanie , Priest Helena , Melia Yvonne 
Published: June 2019

AbstractBackgroundReunification of looked‐after children with their birth parents is the most common route to permanency for looked‐after children in the United Kingdom. Previous research evidence, mainly from American studies, suggests numerous factors that contribute to successful reunification outcomes (Biehal, 2007). Less is known about the current evidence base for reunification practice in the United Kingdom.ObjectiveThis review aimed to identify, appraise, and synthesize published literature concerned with the reunification of looked‐after children with their birth parents in the United Kingdom.MethodsA systematic search of the literature identified eight peer‐reviewed studies conducted between 2005 and 2017 exploring reunification practice in the United Kingdom. Studies were critically appraised and thematically synthesized according to the Thomas and Harden (2008) approach.ResultsEight articles met eligibility criteria. Descriptive themes were support, case management, oscillation, parenting, and reoccurrence of abuse. Analytic themes were lack of guidance and risks associated with return.ConclusionsA pattern of oscillation between home and care was common for many looked‐after children, and remaining in care produced relatively better outcomes. Difficulties arise when comparing studies on reunification, due to methodological variation. Further research is needed to explore the views of reunited children themselves.
FLNC pathogenic variants in patients with cardiomyopathies: Prevalence and genotype‐phenotype correlations
Authors: Ader Flavie , De Groote Pascal , Réant Patricia , Rooryck‐Thambo Caroline , Dupin‐Deguine Delphine , Rambaud Caroline , Khraiche Diala , Perret Claire , Pruny Jean François , Mathieu‐Dramard Michèle , Gérard Marion , Troadec Yann , Gouya Laurent , Jeunemaitre Xavier , Van Maldergem Lionel , Hagège Albert , Villard Eric , Charron Philippe , Richard Pascale 
Published: June 2019

AbstractPathogenic variants in FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes. Our aim was to estimate the prevalence of FLNC pathogenic variants in subtypes of cardiomyopathies and to study the relations between phenotype and genotype. DNAs from a cohort of 1150 unrelated index‐patients with isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non‐compactions) have been sequenced on a custom panel of 51 cardiomyopathy disease‐causing genes. An FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1% to 8% depending on the cardiomyopathy subtype. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in‐frame indel variants were found in other phenotypes. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (P = .01). This work reported the first observation of a left ventricular non‐compaction associated with a unique probably causal variant in FLNC which highlights the role of FLNC in cardiomyopathies. A correlation between the nature of the variant and the cardiomyopathy subtype was observed as well as with SCD risk.
Accuracy and reliability of qualitative echocardiography assessment of right ventricular size and function in neonates
Authors: Smith Aisling , Purna Jyothsna R. , Castaldo Michael P. , Ibarra‐Rios Daniel , Giesinger Regan E. , Rios Danielle R. , Weisz Dany E. , Jain Amish , EL‐Khuffash Afif F. , McNamara Patrick J. 
Published: June 2019

AbstractBackgroundSubjective assessment of right ventricular (RV) function by neonatal echocardiography lacks validation. Incorrect diagnostic assignment in patients with suspected pulmonary hypertension (PH) may lead to unnecessary treatment or missed treatment opportunities.MethodsSix evaluators (experts [n = 3], novice [n = 3]) were asked to independently rate RV characteristics (global function, dilation, and septal flattening) based on standardized echocardiography images. We randomly selected 60 infants, ≥35 weeks gestation at birth, of whom 30 were clinically unwell with acute pulmonary hypertension (aPH) and 30 were healthy controls. aPH was defined by echocardiography presence of right‐left shunting across transitional shunts or elevated right ventricular systolic pressure as estimated by the magnitude of the regurgitant jet across the tricuspid valve with impaired oxygenation. Inter‐rater comparative evaluation within groups and between groups was performed using Kappa statistics.ResultsGlobal agreement between evaluators for subjective assessment of RV function (0.3 [0.03], P < 0.001), size (0.14 [0.02], P < 0.001), and septal flattening (0.2 [0.02], P < 0.001) was uniformly poor. Agreement in RV function assessment was marginally better for both expert (0.32 [0.08], P < 0.001 vs 0.13 [0.081], and P < 0.001) and novice (0.4 [0.08], P < 0.001 vs 0.06 [0.07], and P < 0.001) evaluators. Overall, the diagnosis of aPH vs control was misclassified in 18% of cases.ConclusionThis study demonstrated significant variability in qualitative assessment of RV size and function by trained evaluators, regardless of level of expertise attained. The reliability of objective measures of RV hemodynamics requires prospective evaluation.
mRNA expression profile of bronchoalveolar lavage fluid cells from patients with idiopathic pulmonary fibrosis and sarcoidosis
Authors: Paplińska‐Goryca Magdalena , Goryca Krzysztof , Misiukiewicz‐Stępień Paulina , Nejman‐Gryz Patrycja , Proboszcz Małgorzata , Górska Katarzyna , Maskey‐Warzęchowska Marta , Krenke Rafał 
Published: June 2019

AbstractBackgroundSarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the fibrotic changes in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular analysis of BALf cells from IPF and sarcoidosis patients.MethodsTranscriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real‐time PCR in 32 samples (11 IPF and 21 sarcoidosis).ResultsThe number of genes differentially expressed between IPF and sarcoidosis groups was 4832 (13359 probesets). Cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis.ConclusionsAnalysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells. The most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.