bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Pregnancy Exposure to Rare Earth Elements and Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study
Authors: Xu Xiangrong , Wang Yuanyuan , Han Na , Yang Xiangming , Ji Yuelong , Liu Jue , Jin Chuyao , Lin Lizi , Zhou Shuang , Luo Shusheng , Bao Heling , Liu Zheng , Wang Bin , Yan Lailai , Wang Hai-Jun , Ma Xu 
Published: December 2021

ObjectiveThe extensive use of rare earth elements (REEs) in many technologies was found to have effects on human health, but the association between early pregnancy exposure to REEs and gestational diabetes mellitus (GDM) is still unknown.MethodsThis nested case-control study involved 200 pregnant women with GDM and 200 healthy pregnant women from the Peking University Birth Cohort in Tongzhou. We examined the serum concentrations of 14 REEs during early pregnancy and analyzed their associations with the risk of GDM.ResultsWhen the elements were considered individually in the logistic regression model, no significant associations were found between REEs and GDM, after adjusting for confounding variables (P &gt; 0.05). In weighted quantile sum (WQS) regression, each quartile decrease in the mixture index for REEs resulted in a 1.67-fold (95% CI: 1.12-2.49) increased risk of GDM. Neodymium (Nd), Praseodymium (Pr), and Lanthanum (La) were the most important contributors in the mixture.ConclusionThe study findings indicated that early pregnancy exposure to lower levels of REE mixture was associated with an increased risk of GDM, and Nd, Pr, and La exhibited the strongest effects in the mixture.
Survival of Patients With Idiopathic Inflammatory Myopathies in Slovenia
Authors: Hočevar Alojzija , Viršček Andrej , Krošel Monika , Gradišnik Suzana , Rotar Žiga , Tomšič Matija , Holc Iztok 
Published: December 2021

Background: Idiopathic inflammatory myopathies (IIMs) are rare systemic diseases associated with significant morbidity and mortality. The aim of our study was to estimate for the first time the survival of IIM patients in Slovenia.Methods: We included IIM patients diagnosed between January 2005 and December 2020 and followed at two secondary/tertiary rheumatology centers in the country. To study survival/mortality the censor date of April 14 2021 was set. Kaplan–Meier analysis and standardized mortality ratio (SMR) were plotted using data of age and sex matched Slovenian population as a reference. Cox proportional hazards regression analysis was used to study prognostic factors for IIM mortality.Results: During the 16-year observation period, we identified 217 new IIM patients. During follow up 65 (30.0%) patients died. In the first year following IIM diagnosis the SMR was nearly 7-fold higher compared to the matched general population [SMR 6.88 (95%CI 4.41–10.24)] and remained higher also during the following 4 years. However, when excluding IIM patients with cancer, the survival outcome was, except in the first year after IIM diagnosis [SMR 5.55 (95%CI 3.10–9.15)], comparable to matched general population. In addition to cancer [HR 3.71 (95% CI 2.18–6.04)], cardiac involvement [HR 2.18 (95% CI 1.07–4.45)], fever [HR 2.13 (95% CI 1.13–4.03)], and older age [HR 1.07 (95% CI 1.04–1.09)] were extracted as prognostic factors associated with death.Conclusion: The survival of patients with IIM patients was substantially worse compared to matched general population. Cancer was the leading cause of death in our cohort.
The Cold Hand Sign in Multiple System Atrophy: Frequency-Associated Factors and Its Impact on Survival
Authors: Cao Bei , Liang Yan , Zhang Ling-Yu , Hou Yan-Bing , Ou Ru-Wei , Wei Qian-qian , Shang Huifang 
Published: December 2021

Background: Few studies have focused on the cold hand sign (CHS), a red flag symptom, in multiple system atrophy (MSA).Objective: This study aimed to investigate the frequency and correlative factors of CHS in patients with MSA and the impact of its early occurrence on the survival of these patients.Methods: A total of 483 patients with MSA were enrolled in this study, and the motor and non-motor symptoms between patients with MSA with and without CHS were compared. Moreover, patients with disease duration ≤ 3 years at baseline were followed, and the association between CHS and survival of patients with MSA was examined.Results: The frequencies of CHS in patients with MSA were 20, 15.4, and 25.3% in MSA, MSA-parkinsonian subtype (MSA-P), and MSA-cerebellar subtype (MSA-C), respectively. Higher Unified Multiple System Atrophy Rating Scale (UMSARS) scores and higher Non-Motor Symptom Scale (NMSS) scores at baseline were associated with CHS in MSA. CHS was associated with shorter survival after adjusting for baseline diagnosis subtype, age at onset, sex, orthostatic hypotension, disease duration, autonomic onset, UMSARS total score, and NMSS score (p = 0.001; HR = 3.701; 95% CI = 1.765–7.760).Conclusion: CHS is not rare in patients with MSA. Greater disease severity and more severe non-motor symptoms were associated with CHS in patients with MSA. Patients with early occurrence of CHS had a poor prognosis.
Butylphthalide Combined With Conventional Treatment Attenuates MMP-9 Levels and Increases VEGF Levels in Patients With Stroke: A Prospective Cohort Study
Authors: Xiong Yingqiong , Liu Juanjuan , Xu Yang , Xie Shu , Zhou Xinhua , Cheng Shaomin 
Published: December 2021

Background and Purpose: Butylphtalide increases the vascular endothelial growth factor (VEGF) and decreases matrix metalloproteinase (MMP)-9 in animal models of stroke and might be of use in the management of stroke. To explore whether butylphthalide combined with conventional treatment can change the levels of MMP-9 and VEGF and the National Institutes of Health Stroke Scale (NIHSS) scores of patients with stroke.Methods: This was a prospective cohort study involving inpatients admitted to the Jiangxi Provincial People's Hospital (January–June 2019) due to acute cerebral infarction. The patients received conventional treatments with or without butylphthalide. The changes in the NIHSS scores were compared between groups. Plasma MMP-9 and VEGF were measured by enzyme-linked immunosorbent assay.Results: A total of 24 patients were included in the conventional treatment group and 46 in the butylphthalide group. The butylphthalide group showed lower MMP-9 (130 ± 59 vs. 188 ± 65, p = 0.001) and higher VEGF (441 ± 121 vs. 378 ± 70, p = 0.034) levels on day 6 compared with the conventional treatment group. The changes in MMP-9 and VEGF were significant, starting on day 3 in the butylphthalide group but on day 6 in the conventional treatment group. There were no differences between the two groups in the NIHSS scores at admission and at discharge (p &gt; 0.05). The overall response rate was higher in the butylphthalide group compared with the conventional treatment group (63.0 vs. 37.5%, p = 0.042).Conclusion: Butylphthalide combined with conventional treatment can decrease MMP-9 levels and increase VEGF levels. The patients showed the reduced NIHSS scores, possibly suggesting some improvement in prognosis after stroke. Still, the conclusions need to be confirmed in a larger sample and in different etiological subtypes of stroke.
Hypoxia-Induced Intracellular and Extracellular Heat Shock Protein gp96 Increases Paclitaxel-Resistance and Facilitates Immune Evasion in Breast Cancer
Authors: Tian Tian , Han Jiguang , Huang Jian , Li Shangziyan , Pang Hui 
Published: December 2021

BackgroundsHypoxia contributes to cancer progression, drug resistance and immune evasion in various cancers, including breast cancer (BC), but the molecular mechanisms have not been fully studied. Thus, the present study aimed to investigate this issue.MethodsThe paclitaxel-sensitive BC (PS-BC) cells were administered with continuous low-dose paclitaxel treatment to establish paclitaxel-resistant BC (PR-BC) cells. Exosomes were isolated/purified by using the commercial kit, which were observed by Transmission electron microscopy (TEM). Cell viability was measured by MTT assay, cell apoptosis was determined by flow cytometer (FCM). Gene expressions were respectively measured by Real-Time qPCR, Western Blot and immunofluorescence staining assay. The peripheral mononuclear cells (PBMCs) derived CD8+ T cells were obtained and co-cultured with gp96-containing exosomes, and cell proliferation was evaluated by EdU assay. ELISA was employed to measure cytokine secretion in CD8+ T cells’ supernatants.ResultsHSP gp96 was significantly upregulated in the cancer tissues and plasma exosomes collected from BC patients with paclitaxel-resistant properties. Also, continuous low-dose paclitaxel treatment increased gp96 levels in the descendent PR-BC cells and their exosomes, in contrast with the parental PS-BC cells. Upregulation of gp96 increased paclitaxel-resistance in PS-BC cells via degrading p53, while gp96 silence sensitized PR-BC cells to paclitaxel treatments. Moreover, PR-BC derived gp96 exosomes promoted paclitaxel-resistance in PS-BC cells and induced pyroptotic cell death in the CD8+ T cells isolated from human peripheral blood mononuclear cells (pPBMCs). Furthermore, we noticed that hypoxia promoted gp96 generation and secretion through upregulating hypoxia-inducible factor 1 (HIF-1), and hypoxia increased paclitaxel-resistance and accelerated epithelial-mesenchymal transition (EMT) in PS-BC cells.ConclusionsHypoxia induced upregulation of intracellular and extracellular gp96, which further degraded p53 to increase paclitaxel-sensitivity in BC cells and activated cell pyroptosis in CD8+ T cells to impair immune surveillance.
Increased Risk of Asthma and Allergic Rhinitis in Patients With a Past History of Kawasaki Disease: A Systematic Review and Meta-Analyses
Authors: Lei Wei-Te , Hsu Chih-Wei , Chen Po-Cheng , Tseng Ping-Tao , Kuo Ho-Chang , Guo Mindy Ming-Huey , Tu Yu-Kang , Lin Pao-Yen , Kao Yu-Hsuan , Chang Ling-Sai 
Published: December 2021

Background: Allergic diseases are frequently observed in children with Kawasaki disease (KD). However, the evidence supporting the association between KD and allergies has been conflicting. The objective of the current study is to examine the association between KD and allergic diseases.Methods: We conducted an electronic search using PubMed, Embase, and the Cochrane through 24 July 2021. The inclusion criteria consisted of studies that examined the prevalence of allergic diseases in children with a previous diagnosis of KD and in a comparison group. We pooled studies by using a random effects model. The effects of KD on the subsequent risk of allergic diseases were expressed as odds ratio (OR) with 95% confidence intervals (CI).Results: We included a total of four studies that assessed the effect of KD on asthma, allergic rhinitis, and atopic dermatitis vs. non-KD children (KD individuals for asthma, four studies, n = 8,474; allergic rhinitis, four studies, n = 8,474; atopic dermatitis, three studies, n = 8,330). The overall prevalence of asthma, allergic rhinitis, and atopic dermatitis was 9.12, 27.63, and 6.55% among patients with previous KD. The meta-analysis showed a significantly increased risk of asthma (OR:1.437, CI: 1.067–1.937) and allergic rhinitis (OR: 1.726, CI: 1.291–2.307) in patients with KD, compared with the control groups. However, patients with KD did not have a significantly different level of risk of atopic dermatitis (OR: 1.243, 95% CI: 0.857–1.802).Conclusion: This meta-analysis supports that individuals with KD are more likely to have asthma and allergic rhinitis compared to controls.
mTORC1 Signaling Pathway Mediates Chronic Stress-Induced Synapse Loss in the Hippocampus
Authors: Luo Yu-Fei , Ye Xiao-Xia , Fang Ying-Zhao , Li Meng-Die , Xia Zhi-Xuan , Liu Jian-Min , Lin Xiao-Shan , Huang Zhen , Zhu Xiao-Qian , Huang Jun-Jie , Tan Dong-Lin , Zhang Yu-Fei , Liu Hai-Ping , Zhou Jun , Shen Zu-Cheng 
Published: December 2021

Background: The mechanistic target of rapamycin complex 1 (mTORC1) signaling has served as a promising target for therapeutic intervention of major depressive disorder (MDD), but the mTORC1 signaling underlying MDD has not been well elucidated. In the present study, we investigated whether mTORC1 signaling pathway mediates synapse loss induced by chronic stress in the hippocampus.Methods: Chronic restraint stress-induced depression-like behaviors were tested by behavior tests (sucrose preference test, forced swim test and tail suspension test). Synaptic proteins and alternations of phosphorylation levels of mTORC1 signaling-associated molecules were measured using Western blotting. In addition, mRNA changes of immediate early genes (IEGs) and glutamate receptors were measured by RT-PCR. Rapamycin was used to explore the role of mTORC1 signaling in the antidepressant effects of fluoxetine.Results: After successfully establishing the chronic restraint stress paradigm, we observed that the mRNA levels of some IEGs were significantly changed, indicating the activation of neurons and protein synthesis alterations. Then, there was a significant downregulation of glutamate receptors and postsynaptic density protein 95 at protein and mRNA levels. Additionally, synaptic fractionation assay revealed that chronic stress induced synapse loss in the dorsal and ventral hippocampus. Furthermore, these effects were associated with the mTORC1 signaling pathway-mediated protein synthesis, and subsequently the phosphorylation of associated downstream signaling targets was reduced after chronic stress. Finally, we found that intracerebroventricular infusion of rapamycin simulated depression-like behavior and also blocked the antidepressant effects of fluoxetine.Conclusion: Overall, our study suggests that mTORC1 signaling pathway plays a critical role in mediating synapse loss induced by chronic stress, and has part in the behavioral effects of antidepressant treatment.
Associations Between High Plasma Methylxanthine Levels, Sleep Disorders and Polygenic Risk Scores of Caffeine Consumption or Sleep Duration in a Swiss Psychiatric Cohort
Authors: Laaboub Nermine , Gholam Mehdi , Sibailly Guibet , Sjaarda Jennifer , Delacrétaz Aurélie , Dubath Céline , Grosu Claire , Piras Marianna , Ansermot Nicolas , Crettol Severine , Vandenberghe Frederik , Grandjean Carole , Gamma Franziska , Bochud Murielle , von Gunten Armin , Plessen Kerstin Jessica , Conus Philippe , Eap Chin B. 
Published: December 2021

Objective: We first sought to examine the relationship between plasma levels of methylxanthines (caffeine and its metabolites) and sleep disorders, and secondarily between polygenic risk scores (PRS) of caffeine consumption or sleep duration with methylxanthine plasma levels and/or sleep disorders in a psychiatric cohort.Methods: Plasma levels of methylxanthines were quantified by ultra-high performance liquid chromatography/tandem mass spectrometry. In inpatients, sleep disorder diagnosis was defined using ICD-10 “F51.0,” sedative drug intake before bedtime, or hospital discharge letters, while a subgroup of sedative drugs was used for outpatients. The PRS of coffee consumption and sleep duration were constructed using publicly available GWAS results from the UKBiobank.Results: 1,747 observations (1,060 patients) were included (50.3% of observations with sleep disorders). Multivariate analyses adjusted for age, sex, body mass index, setting of care and psychiatric diagnoses showed that patients in the highest decile of plasma levels of methylxanthines had more than double the risk for sleep disorders compared to the lowest decile (OR = 2.13, p = 0.004). PRS of caffeine consumption was associated with plasma levels of caffeine, paraxanthine, theophylline and with their sum (β = 0.1; 0.11; 0.09; and 0.1, pcorrected = 0.01; 0.02; 0.02; and 0.01, respectively) but not with sleep disorders. A trend was found between the PRS of sleep duration and paraxanthine levels (β = 0.13, pcorrected = 0.09).Discussion: Very high caffeine consumption is associated with sleep disorders in psychiatric in- and outpatients. Future prospective studies should aim to determine the benefit of reducing caffeine consumption in high caffeine-consuming patients suffering from sleep disorders.
Improved Production of Streptomyces sp. FA1 Xylanase in a Dual-Plasmid Pichia pastoris System
Authors: Xia Wei , Hu Mengkai , Pan Yang , Wu Dan , Wu Jing 
Published: December 2021

Methanol is considered as a potential hazard in the methanol-induced yeast expression of food-related enzymes. To increase the production efficiency of recombinant proteins in Pichia pastoris without methanol induction, a novel dual-plasmid system was constructed, for the first time, by a combining the strategies of genomic integration and episomal expression. To obtain a high copy number of the target gene, the autonomously replicating sequence derived from Kluyveromyces lactis (PARS) was used to construct episomal vectors carrying the constitutive promoters PGAP and PGCW14. In addition, an integrative vector carrying the PGCW14 promoter was constructed by replacing the PGAP promoter sequence with a partial PGCW14 promoter. Next, using xylanase XynA from Streptomyces sp. FA1 as the model enzyme, recombination strains were transformed with different combinations of integrating and episomal vectors that were constructed to investigate the changes in the protein yield. Results in shake flasks indicated that the highest enzyme yield was achieved when integrated PGAP and episomal PGCW14 were simultaneously transformed into the host strain. Meanwhile, the copy number of xynA increased from 1.14 ± 0.46 to 3.06 ± 0.35. The yield of XynA was successfully increased to 3925 U·mL−1 after 102 h of fermentation in a 3.6 L fermenter, which was 16.7-fold and 2.86-fold of the yields that were previously reported for the constitutive expression and methanol-induced expression of the identical protein, respectively. Furthermore, the high-cell-density fermentation period was shortened from 132 h to 102 h compared to that of methanol-induced system. Since the risk of methanol toxicity is removed, this novel expression system would be suitable for the production of proteins related to the food and pharmaceutical industries.
On some problems of public policy to combat poverty and income inequality
Authors: Kutepova N. 
Published: December 2021

. The article examines how in modern Russia since the beginning of the 90s of the last century, poverty has formed as a mass phenomenon, reveals the specific features of this phenomenon, which can be called “new poverty”, as well as some new factors contributing to the replenishment of marginalized layers. It shows how the poverty of workers affects the quality of the country's labor potential, what tasks in these conditions face social policy. Purpose of work: to identify why overcoming poverty currently remains largely an unresolved problem that threatens the country's economic security.
It is concluded that the methods used to assess poverty and inequality do not fully assess the extent and nature of the phenomenon under study, that it is not this fate for centuries, but is largely man-made, and the social policy of the state can be a factor in the marginalization of the population. It is proved that the depreciation of labor is not a factor of competitiveness, but a factor in the destruction of labor potential and brain drain. Therefore, the main thing in solving the problem of poverty is to ensure decent income from work.
Reflexo de dilatação pupilar e a mensuração da dor no paciente anestesiado: revisão de literatura
Authors: Brait Ana Beatriz Foleto , Reis Bruna Alvim , Lemos Bruno Denardi , Fernandes Isabela de Jesus , Rocha Bruno Ambrósio da , Prandini Mirto Nelso 
Published: December 2021

Introdução. A validação da presença de dor em pacientes sob anestesia geral permanece um desafio. A correta mensuração da sedoanalgesia pode proporcionar o uso de doses mínimas para ser atingido, evitando-se subdosagens ou superdosagens. Estudos recentes têm correlacionado a pupilometria com o nível de dor no paciente não comunicativo. Objetivos. Por meio de uma revisão bibliográfica, procuramos correlacionar a pupilometria e o reflexo de dilatação pupilar na monitorização da analgesia, no paciente sedado e não comunicativo, sob o uso de opioides e hipnóticos, bem como comparar a pupilometria com o uso de parâmetros vitais como frequência cardíaca, uso do índice de analgesia e nocicepção e o BIS. Método. Foi realizada uma revisão bibliográfica na plataforma “PubMed”, em inglês, espanhol e português, entre o período de 1996 a 2020. A busca nas bases mencionadas resultou em 38 artigos. Resultados. Verificou-se que a pupilometria apresentou dados mais confiáveis na avaliação da nocicepção quando comparada com frequência cardíaca e pressão arterial, porém ainda há dificuldade de padronização de aplicação. A pupilometria mede diversos componentes: amplitude máxima, latência, velocidade de dilatação e contração, e tamanho máximo e mínimo. Quando avaliados os sinais vitais como frequência cardíaca e pressão arterial a pupilometria tem se mostrado um melhor preditor de analgesia, tornando-se um melhor indicador para a titulação, quando utilizados remifentanil ou propofol. Conclusões. A avaliação do reflexo de dilatação pupilar permite a mensuração da reatividade do sistema nervoso autônomo ao estímulo da dor, podendo proporcionar tratamento individualizado e com maior segurança.
Muros, dominación y resistencia. La autodeterminación de los pueblos en Palestina y al-Masriq
Authors: Viciconto Jorge Omar 
Published: December 2021

Los muros se convierten en elementos válidos para visualizar los alcances de la globalización y sus contradicciones. El construido por Israel en Cisjordania, en perjuicio de Palestina, posibilita analizar conflictos históricos con implicancias a escalas locales, regionales y globales. En este artículo, a través del caso mencionado, examinamos las resistencias de los pueblos que luchan por su autodeterminación y la dominación que ejercen sobre ellos los estados nacionales insertos dentro de intereses geopolíticos. Los muros son tecnologías de control y disciplinamiento que regulan el adentro y el afuera, imponen intervenciones arbitrarias y construyen legitimidad mediante mecanismos de otrificación. Se constituyen en sofisticadas herramientas del biopoder estatal que con el desarrollo de la necropolítica llegan al límite de justificar la limpieza étnica y el exterminio, ante la llamativa ausencia en las agendas diplomáticas de aquello denominado “comunidad internacional”.