bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations Between Maternal Thyroid Function and Birth Outcomes in Chinese Mother-Child Dyads: A Retrospective Cohort Study
Authors: Chen Geng-Dong , Pang Ting-Ting , Lu Xia-Fen , Li Peng-Sheng , Zhou Zi-Xing , Ye Shao-Xin , Yang Jie , Shen Xiu-Yin , Lin Dong-Xin , Fan Da-Zhi , Lu De-Mei , Liu Zheng-Ping
Published: February 2021

Objective

Although research suggests a close association between maternal thyroid function and birth outcomes, no clear conclusion has been reached. We aimed to explore this potential association in a retrospective cohort study.

Methods

This study included 8985 mother–child dyads. The maternal serum free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab) concentrations and birth outcome data were reviewed from medical records. Subjects with TPO Ab concentrations of >34 and ≤34 IU/ml were classified into the TPO Ab positivity (+) and TPO Ab negativity (−) groups, respectively.

Results

Compared with subjects in the normal group (0.1 ≤ TSH < 2.5 mIU/L and TPO Ab−), those with TSH concentrations of 2.5–4.0 mIU/L and TPO Ab− had a 0.65-fold lower risk of low birth weight (LBW). In contrast, those with TSH concentrations of >4.0 mIU/L, regardless of the TPO Ab status, had a 2.01-fold increased risk of LBW. Subclinical hypothyroidism, regardless of the TPO Ab status, was associated with a 1.94-fold higher risk of LBW when compared with that in subjects with euthyroidism and TPO Ab−. No other significant associations were observed.

Conclusion

A maternal TSH concentration of 2.5–4.0 mIU/L was associated with a lower risk of LBW when combined with TPO Ab−, whereas subjects with a TSH concentration of >4.0 mIU/L had an increased risk of LBW. Subclinical hypothyroidism appears to be associated with a higher risk of LBW.
Strontium Is Released Rapidly From Agricultural Lime–Implications for Provenance and Migration Studies
Authors: Andreasen Rasmus , Thomsen Erik
Published: February 2021

The use of strontium isotopes in pre-historic mobility studies requires accurate isoscapes for evaluating whether pre-historic individuals are local to the areas in which they were buried or not. Isoscapes are often based on modern-day samples, commonly surface waters. There is, however, growing evidence that modern-day farming has a significant impact on the strontium isotopic composition of surface waters and farmed soils, mainly due to the use of agricultural lime for soil improvement. In this paper, we investigate the fate of strontium from agricultural lime in an experimentally-manipulated field in central Jutland, Denmark. Agricultural limestone was added to this field at very high rates in 2012 and 2013 to investigate CO2 storage in soils. Strontium was first measured from the site in 2014. In 2019 we reevaluated strontium concentrations and found that 80–100% of the strontium from the agricultural lime had leached out of the organic-rich topsoil, and likely seeped into the underlying groundwater and nearby surface waters. In both the sandy soils of the liming test site and farmed soils and heathland in the adjacent area, Sr exhibits a degree of mobility similar to that of calcium, which is in agreement with data for other soil types and what is predicted by the size of its hydrated ions. Strontium isotopic compositions of unfarmed heathland samples show much higher 87Sr/86Sr ratios, and so are not influenced by carbonates, suggesting that the limestone 87Sr/86Sr signature seen in the farmland and in streams and rivers in contact with this comes from agricultural lime, and not from natural carbonate relicts occasionally found in the area. This suggests that the 87Sr/86Sr signatures of the area were higher in pre-historic times, and that an isoscape map based on samples from modern-day farmland is inappropriate for application to provenance and mobility studies of pre-historic people. Thus, it is critical that the possible impact of farming is evaluated when conducting provenance and mobility studies, especially in areas with Sr-poor soils and where agricultural lime is used for soil improvement. Overlooking this can result in significant overestimation of the degree of pre-historic mobility.
Using Genomics to Link Populations of an Invasive Species to Its Potential Sources
Authors: Resh Carlee A. , Galaska Matthew P. , Benesh Kasey C. , Gardner Jonathan P. A. , Wei Kai-Jian , Yan Ruo-Jin , Mahon Andrew R.
Published: February 2021

The introduction and subsequent range expansion of the Northern snakehead (Channa argus: Channidae, Anabantiformes) is one of a growing number of problematic biological invasions in the United States. This harmful aquatic invasive species is a predatory freshwater fish native to northeastern Asia that, following deliberate introduction, has established itself in multiple water basins in the eastern United States, as well as expanding its range into the Midwest. Previous work assessed the population structure and estimated the long-term effective population sizes of the populations present in the United States, but the source of the initial introduction(s) to the U.S. remains unidentified. Building on earlier work, we used whole genome scans (2b-RAD genomic sequencing) to analyze single nucleotide polymorphisms (SNPs) from C. argus to screen the genomes of these invasive fish from United States waters and from three sites in their native range in China. We recovered 2,822 SNP loci from genomic DNA extracted from 164 fish sampled from the eastern United States and Arkansas (Mississippi River basin), plus 30 fish sampled from three regions of the Yangtze River basin in China (n = 10 individuals per basin). Our results provide evidence supporting the Yangtze River basin in China, specifically the Bohu and/or Liangzi lakes, is a likely source of the C. argus introductions in multiple regions of the U.S., including the Lower Hudson River basin, Upper Hudson River basin and Philadelphia (Lower Delaware River basin). This information, in conjunction with additional sampling from the native range, will help to determine the source(s) of introduction for the other U.S. populations. Additionally, this work will provide valuable information for management to help prevent and manage future introductions into United States waterways, as well as aid in the development of more targeted strategies to regulate established populations and inhibit further spread.
Complement Factor I Mutation May Contribute to Development of Thrombotic Microangiopathy in Lupus Nephritis
Authors: Tseng Min-Hua , Fan Wen-Lang , Liu Hsuan , Yang Chia-Yu , Ding Jhao-Jhuang , Lee Hwei-Jen , Huang Shih-Ming , Lin Shih-Hua , Huang Jing-Long
Published: February 2021

Objective:Renal thrombotic microangiopathy (TMA) is associated with complement overactivation and poor outcome in patients with lupus nephritis (LN). The role of genetic makeup of complement system in these patients remains to be elucidated.

Methods:The clinical and laboratory characteristics of 100 patients with LN during 2010–2017 were retrospectively analyzed. LN patients with renal TMA and condition-matched LN patients without renal TMA were studied. Twenty normal subjects were also enrolled for comparison. Whole exome sequence followed by Sanger sequence was used in our study cohort.

Results:Eight patients with renal TMA and eight condition-matched patients were enrolled from 100 LN patients with mean age 11.2 ± 2.0 years. Compared with condition-matched LN patients without renal TMA, LN patients with renal TMA exhibited statistically higher serum urea. Although most patients with renal TMA responded to plasma exchange, they had significantly higher relapse rate of nephritis, lower remission rate, and higher risk of end-stage renal disease and mortality. Compared with patients without renal TMA and normal subjects, those with renal TMA had significantly lower serum complement factor H (CFH) and plasma ADAMTS13 activity. Molecular analysis of all 100 patients with LN uncovered that three patients with renal TMA harbored mutations, two missense and non-sense, onCFIandCFHR2. The non-sense mutation, E302X, onCFImay impair its interaction C3b/CFH complex by loss of the heavy chain of complement factor I on simulation model.

Conclusion:In addition to low serum CFH level and plasma ADAMTS13 activity, defects in genes responsible for complement regulatory proteins may contribute to the development of renal TMA in patients with LN.
The Role of Gut Microbiota in Chronic Itch-Evoked Novel Object Recognition-Related Cognitive Dysfunction in Mice
Authors: Li Yujuan , Zhang Wencui , Sun Tainning , Liu Baowen , Manyande Anne , Xu Weiguo , Xiang Hong-Bing
Published: February 2021

The high incidence of patients with chronic itch highlights the importance of fundamental research. Recent advances in the interface of gut microbiota have shed new light into exploring this phenomenon. However, it is unknown whether gut microbiota plays a role in chronic itch in rodents with or without cognitive dysfunction. In this study, the role of gut microbiota in diphenylcyclopropenone (DCP)-evoked chronic itch was investigated in mice and hierarchical cluster analysis of novel object recognition test (ORT) results were used to classify DCP-evoked itch model in mice with or without cognitive dysfunction (CD)-like phenotype and 16S ribosomal RNA (rRNA) gene sequencing was used to compare gut bacterial composition between CD (Susceptible) and Non-CD phenotypes (Unsusceptible) in chronic itch mice. Results showed that the microbiota composition was significantly altered by DCP-evoked chronic itch and chronic itch induced novel object recognition-related CD. However, abnormal gut microbiota composition induced by chronic itch may not be correlated with novel object recognition-related CD.
Activated Hepatic Stellate Cells Induce Infiltration and Formation of CD163+ Macrophages via CCL2/CCR2 Pathway
Authors: Xi Sujuan , Zheng Xiaoyan , Li Xiangyong , Jiang Yuming , Wu Yuankai , Gong Jiao , Jie Yusheng , Li Zhanyi , Cao Jing , Sha Liuping , Zhang Min , Chong Yutian
Published: February 2021

Background: Activated hepatic stellate cells (aHSCs) regulate the function of immune cells during liver fibrosis. As major innate cells in the liver, macrophages have inducible plasticity. Nevertheless, the mechanisms through which aHSCs regulate macrophages' phenotype and function during liver fibrosis and cirrhosis remain unclear. In this study, we examined the immunoregulatory function of aHSCs during liver fibrosis and explored their role in regulating macrophage phenotype and function.

Methods: A total of 96 patients with different stages of chronic hepatitis B-related liver fibrosis were recruited in the study. Metavir score system was used to evaluate the degree of fibrosis. The expression of hepatic CCL2 and M2 phenotype macrophage marker CD163 were detected by immunohistochemistry, and the relationship among hepatic CD163, CCL2, and fibrosis scores were also explored. In the in vitro model, the aHSCs isolated from human liver tissues and THP-1-derived M0-type macrophages (M0MΦ) were co-cultured to observe whether and how aHSCs regulate the phenotype and function of macrophages. To explore whether CCL2/CCR2 axis has a crucial role in macrophage phenotypic changes during liver fibrosis, we treated the M0MΦ with recombinant human CCL2 or its specific receptor antagonist INCB-3284. Furthermore, we used LX2 and TGF-β-activated LX2 to mimic the different activation statuses of aHSCs to further confirm our results.

Results: In patients, the infiltration of M2 macrophages increased during the progression of liver fibrosis. Intriguingly, as a key molecule for aHSC chemotactic macrophage aggregation, CCL2 markedly up-regulated the expression of CD163 and CD206 on the macrophages, which was further confirmed by adding the CCR2 antagonist (INCB 3284) into the cell culture system. In addition, the TGF-β stimulated LX2 further confirmed that aHSCs up-regulate the expression of CD163 and CD206 on macrophages. LX2 stimulated with TGF-β could produce more CCL2 and up-regulate other M2 phenotype macrophage-specific markers, including IL-10, ARG-1, and CCR2 besides CD163 and CD206 at the gene level, indicating that the different activation status of aHSCs might affect the final phenotype and function of macrophages.

Conclusions: The expression of the M2 macrophage marker increases during liver fibrosis progression and is associated with fibrosis severity. AHSCs can recruit macrophages through the CCL2/CCR2 pathway and induce M2 phenotypic transformation.
sEMG: A Window Into Muscle Work, but Not Easy to Teach and Delicate to Practice—A Perspective on the Difficult Path to a Clinical Tool
Authors: Martin Bernard J. , Acosta-Sojo Yadrianna
Published: February 2021

Surface electromyography (sEMG) may not be a simple 1,2,3 (muscle, electrodes, signal)-step operation. Lists of sEMG characteristics and applications have been extensively published. All point out the noise mimicking perniciousness of the sEMG signal. This has resulted in ever more complex manipulations to interpret muscle functioning and sometimes gobbledygook. Hence, as for all delicate but powerful tools, sEMG presents challenges in terms of precision, knowledge, and training. The theory is usually reviewed in courses concerning sensorimotor systems, motor control, biomechanics, ergonomics, etc., but application requires creativity, training, and practice. Software has been developed to navigate the essence extraction (step 4); however, each software requires some parametrization, which returns back to the theory of sEMG and signal processing. Students majoring in Ergonomics or Biomedical Engineering briefly learn about the sEMG method but may not necessarily receive extensive training in the laboratory. Ergonomics applications range from a simple estimation of the muscle load to understanding the sense of effort and sensorimotor asymmetries. In other words, it requires time and the basics of multiple disciplines to acquire the necessary knowledge and skills to perform these studies. As an example, sEMG measurements of left/right limb asymmetries in muscle responses to vibration-induced activity of proprioceptive receptors, which vary with gender, provide insight into the functioning of sensorimotor systems. Beyond its potential clinical benefits, this example also shows that lack of testing time and lack of practitioner's sufficient knowledge are barriers to the utilization of sEMG as a clinical tool.
Autonomic Characteristics of Sudden Unexpected Death in Epilepsy in Children—A Systematic Review of Studies and Their Relevance to the Management of Epilepsy in Rett Syndrome
Authors: Singh Jatinder , Lanzarini Evamaria , Santosh Paramala
Published: February 2021

Aim: To systematically identify and critically appraise studies that investigate the autonomic characteristics of Sudden Unexpected Death in Epilepsy (SUDEP) in the pediatric population. We also wanted to explore how this information would be relevant to the management of epilepsy in patients with Rett Syndrome.

Method: Using PRISMA guidelines, a systematic review of PubMed, Scopus, Cochrane, PsycINFO, Embase, and Web of Science databases was performed to identify eligible studies. After extracting data from the included studies, a thematic analysis was undertaken to identify emerging themes. A quality appraisal was also done to assess the quality of the included studies.

Results: The systematic search revealed 41 records, and 15 full-text articles on the autonomic characteristics of SUDEP in children were included in the final analysis. Following thematic analysis, three themes were identified (I) modulation in sympathovagal tone, (II) pre- and post-ictal autonomic changes, and (III) other markers of autonomic dysregulation in children with epilepsy. Modulation in sympathovagal tone emerged as the theme with the highest frequency followed by pre- and post-ictal autonomic changes. While the themes provide additional insight into the management of epilepsy in the Rett Syndrome population, the quality of evidence concerning the autonomic characteristics of SUDEP in the pediatric population was low and underscores the importance of much needed research in this area.

Conclusion: The mechanism of SUDEP in the pediatric population is complex and involves an interplay between several components of the autonomic nervous system. While direct clinical inferences regarding pediatric SUDEP could not be made, the thematic analysis does suggest that in vulnerable populations such as Rett Syndrome, where there is already a pervasive autonomic dysregulation, pro-active surveillance of the autonomic profile in this patient group would be useful to better manage epilepsy and reduce the SUDEP risk.
Early Mobilization After Stroke: Do Clinical Practice Guidelines Support Clinicians' Decision-Making?
Authors: Rethnam Venesha , Hayward Kathryn S. , Bernhardt Julie , Churilov Leonid
Published: February 2021

Importance: Early mobilization, out-of-bed activity, is a component of acute stroke unit care; however, stroke patient heterogeneity requires complex decision-making. Clinically credible and applicable CPGs are needed to support and optimize the delivery of care. In this study, we are specifically exploring the role of clinical practice guidelines to support individual patient-level decision-making by stroke clinicians about early mobilization post-stroke.

Methods: Our study uses a novel, two-pronged approach. (1) A review of CPGs containing recommendations for early mobilization practices published after 2015 was appraised using purposely selected items from the Appraisal of Guidelines Research and Evaluation–Recommendations Excellence (AGREE-REX) tool relevant to decision-making for clinicians. (2) A cross-sectional study involving semi-structured interviews with Australian expert stroke clinicians representing content experts and CPG target users. Every CPG was independently assessed against the AGREE-REX standard by two reviewers. Expert stroke clinicians, invited via email, were recruited between June 2019 to March 2020.The main outcomes from the review was the proportion of criteria addressed for each AGREE-REX item by individual and all CPG(s). The main cross-sectional outcomes were the distributions of stroke clinicians' responses about the utility of CPGs, specific areas of uncertainty in early mobilization decision-making, and suggested parameters for inclusion in future early mobilization CPGs.

Results: In 18 identified CPGs, many did not adequately address the “Evidence” and “Applicability to Patients” AGREE-REX items. Out of 30 expert stroke clinicians (11 physicians [37%], 11 physiotherapists [37%], 8 nurses [26%]; median [IQR] years of experience, 14 [10–25]), 47% found current CPGs “too broad or vague,” while 40% rely on individual clinical judgement and interpretation of the evidence to select an evidence-based choice of action. The areas of uncertainty in decision-making revealed four key suggestions: (1) more granular descriptions of patient and stroke characteristics for appropriate tailoring of decisions, (2) clear statements about when clinical flexibility is appropriate, (3) detailed description of the intervention dose, and (4) physical assessment criteria including safety parameters.

Conclusions: The lack of specificity, clinical applicability, and adaptability of current CPGs to effectively respond to the heterogeneous clinical stroke context has provided a clear direction for improvement.
Examination of the Prefrontal Cortex Hemodynamic Responses to the Fist-Edge-Palm Task in Naïve Subjects Using Functional Near-Infrared Spectroscopy
Authors: Kobayashi Satoshi , Iwama Yudai , Nishimaru Hiroshi , Matsumoto Jumpei , Setogawa Tsuyoshi , Ono Taketoshi , Nishijo Hisao
Published: February 2021

The Fist-Edge-Palm (FEP) task, a manual hand task, has been used to detect frontal dysfunctions in clinical situations: its performance failures are observed in various prefrontal cortex (PFC)-related disorders, including schizophrenia. However, previous imaging studies reported that the performance of the FEP task activated motor-related areas, but not the PFC. Here, we aimed to investigate the relationships between the performance of the FEP task and PFC functions. Hemodynamic activity in the PFC, including the dorsolateral PFC (area 46) and frontal pole (area 10), was recorded. Healthy young subjects performed the FEP task as well as a palm tapping (PT) task (control task) three times. The subjects also completed a Wisconsin Card Sorting Test (WCST) and Schizotypal Personality Scale (STA) questionnaire. We found that hemodynamic activity (Oxy-Hb) in the PFC increased in the first trial of the FEP task but decreased considerably in the second and third trials compared to the PT task. The number of performance errors in the FEP task also decreased in the second and third trials. Error reduction (i.e., learning) in the FEP task between the first and second trials was negatively correlated with schizotypal trait and the number of perseveration errors in the WCST. Furthermore, changes in the PFC hemodynamic activity between the first and second trials were positively correlated with error reduction in the FEP task between the first and second trials, and negatively correlated with the number of perseveration errors in the WCST. These results suggest that learning in the FEP task requires PFC activation, which is negatively associated with perseveration errors in the WCST. The results further suggest that the FEP task, in conjunction with near-infrared spectroscopy, may be useful as a diagnostic method for various disorders with PFC dysfunction.
Modeling Circadian Phototransduction: Retinal Neurophysiology and Neuroanatomy
Authors: Rea Mark S. , Nagare Rohan , Figueiro Mariana G.
Published: February 2021

The retina is a complex, but well-organized neural structure that converts optical radiation into neural signals that convey photic information to a wide variety of brain structures. The present paper is concerned with the neural circuits underlying phototransduction for the central pacemaker of the human circadian system. The proposed neural framework adheres to orthodox retinal neuroanatomy and neurophysiology. Several postulated mechanisms are also offered to account for the high threshold and for the subadditive response to polychromatic light exhibited by the human circadian phototransduction circuit. A companion paper, modeling circadian phototransduction: Quantitative predictions of psychophysical data, provides a computational model for predicting psychophysical data associated with nocturnal melatonin suppression while staying within the constraints of the neurophysiology and neuroanatomy offered here.
Cyfip1 Regulates SynGAP1 at Hippocampal Synapses
Authors: Sahasrabudhe Abhishek , Begum Fatema , Guevara Christopher A. , Morrison Chenel , Hsiao Kuangfu , Kezunovic Nebojsa , Bozdagi-Gunal Ozlem , Benson Deanna L.
Published: February 2021

In humans, copy number variations inCYFIP1appear to have sweeping physiological and structural consequences in the brain, either producing or altering the severity of intellectual disability, autism, and schizophrenia. Independently,SynGAP1haploinsufficiency produces intellectual disability and, frequently, autism. Cyfip1 inhibits protein translation and promotes actin polymerization, and SynGAP1 is a synaptically localized Ras/Rap GAP. While these proteins are clearly distinct, studies investigating their functions in mice have shown that each regulates the maturation of synapses in the hippocampus and haploinsufficiency for either produces an exaggerated form of mGluR-dependent long-term depression, suggesting that some signaling pathways converge. In this study, we examined howCyfip1haploinsufficiency impacts SynGAP1 levels and localization, as well as potential sites for mechanistic interaction in mouse hippocampus. The data show that synaptic, but not total, levels of SynGAP1 inCyfip1+/–mice were abnormally low during early postnatal development and in adults. This may be in response to a shift in the balance of kinases that activate SynGAP1 as levels of Cdk5 were reduced and those of activated CaMKII were maintained inCyfip1+/–mice compared to wild-type mice. Alternatively, this could reflect altered actin dynamics as Rac1 activity inCyfip1+/–hippocampus was boosted significantly compared to wild-type mice, and levels of synaptic F-actin were generally enhanced due in part to an increase in the activity of the WAVE regulatory complex. Decreased synaptic SynGAP1 coupled with a CaMKII-mediated bias toward Rap1 inactivation at synapses is also consistent with increased levels of synaptic GluA2, increased AMPA receptor-mediated responses to stimulation, and increased levels of synaptic mGluR1/5 compared to wild-type mice. Collectively, our data suggest that Cyfip1 regulates SynGAP1 and the two proteins work coordinately at synapses to appropriately direct actin polymerization and GAP activity.
Characterization of Algae Dietary Supplements Using Antioxidative Potential, Elemental Composition, and Stable Isotopes Approach
Authors: Kejžar Jan , Jagodic Hudobivnik Marta , Nečemer Marijan , Ogrinc Nives , Masten Rutar Jasmina , Poklar Ulrih Nataša
Published: February 2021

Dietary supplements based on algae, known for their nutritional value and bioactive properties, are popular products among consumers today. While commercial algal products are regarded safe by numerous studies, information about the production and origin of such products is scarce. In addition, dietary supplements are not as strictly regulated as food and medicinal drugs. We characterized different algal products (kelps: Laminariales,Spirulinaspp.,Chlorellaspp., andAphanizomenon flos-aquae), obtained on Slovenian market, based on their elemental composition (X-ray fluorescence, inductively coupled plasma–mass spectrometry), antioxidative potential [DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, total phenolic content], and stable isotope values [carbon (C), nitrogen (N), and sulfur (S); elemental analyzer isotope ratio mass spectrometry (EA-IRMS) method]. Antioxidative potential is consistent among products of the same type, withA. flos-aquaesamples having 4.4 times higher antioxidative potential compared toChlorellaspp. and 2.7 times higher compared toSpirulinaspp. Levels of toxic trace elements (arsenic, cadmium, mercury, and lead) are below the maximum allowed values and as such do not pose risk to consumers' health. Samples ofSpirulinaspp. have relatively high δ15N (7.4 ‰ ± 4.4‰) values, which indicate use of organic nitrogen sources in certain samples. Likewise, different elemental composition and isotopic ratios of stable elements (C, N, and S) for the samples withSpirulinaspp. orChlorellaspp. are the consequence of using different nutrient sources and algae-growing techniques. Statistical analysis (principal component analysis) has confirmed that all testedA. flos-aquaesamples originate from the same source, supposedly Klamath Lake (Oregon, USA). HawaiianSpirulina pacificacan also be differentiated from all the other samples because of its characteristically high metal content (iron, manganese, zinc, cobalt, nickel, vanadium).Chlorellaspp. andSpirulinaspp. require further analyses with larger number of samples, as differentiation is not possible based on results of this study.
Oral Realgar-Indigo Naturalis Formula Plus Retinoic Acid for Acute Promyelocytic Leukemia
Authors: Lou Yinjun , Ma Yafang , Jin Jie , Zhu Honghu
Published: February 2021

Treatment paradigm of acute promyelocytic leukemia (APL) is by no mean the most remarkable story of cancer therapy. Recently, the advent of oral arsenic formulations (oral-arsenic trioxide and Realgar-Indigo Naturalis formula (RIF)) based regimens may provide a therapeutic advance by curing APL with two oral agents. Indeed, the oral RIF plus all-trans-retinoic acid (ATRA) without chemotherapy display highly efficacy in patients with APL. The safety profile of RIF plus ATRA make possible to treat APL patients in a home-based manner during postremission therapy. To our knowledge, RIF was the first commercially available oral arsenic agent approved in China. The RIF plus ATRA regimens are becoming a preferred frontline care for APL in China. In this review, we will discuss the history, current evidences and challengers of RIF-based strategies in APL. More and more APL patients may enjoy a cure with a normal quality-of-life after induction in the near future.
The Potential Roles of Exosomal miR-214 in Bone Metastasis of Lung Adenocarcinoma
Authors: Zhang Jian , Wu Jiangmei
Published: February 2021

Bone metastasis is closely related to the alterations of bone microenvironment. In this article, we hypothesize that exosomes may be involved in the “vicious circle” by transferring miR-214. miR-214 is highly expressed in lung adenocarcinoma, and is closely related to the degree of lung cancer progression. As a key regulator of bone homeostasis, miR-214 promotes osteoclast differentiation and mediates intercellular communication between osteoclasts and osteoblasts via the way of exosomal miRNA. Therefore, it is highly probable that exosomal miR-214 derived from lung adenocarcinoma may disrupt bone homeostasis by enhancing bone resorption. Exosomal miR-214 can be released by lung adenocarcinoma cells, enters peripheral circulation, and is taken up by osteoclasts, consequently stimulating osteoclast differentiation. The enhanced bone resorption alters the bone microenvironment by releasing multiple cytokines and growth factors favoring cancer cells. The circulating cancer cells migrate to bone, proliferate, and colonize, resulting in the formation of metastasis. Furthermore, osteoclasts derived exosomal miR-214 may in turn contribute to cancer progression. In this way, the exosomal miR-214 from osteoclasts and lung adenocarcinoma cells mediates the positive interaction between bone resorption and bone metastasis. The levels of exosomal miR-214 in the peripheral circulation may help predict the risk of bone metastasis. The exosomal miR-214 may be a potential therapeutic target for both prevention and treatment of bone metastasis in patients with lung adenocarcinoma.
In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method
Authors: Tang Congrong , Niu Xiaohui , Shi Lu , Zhu Huidan , Lin Guanyang , Xu Ren-ai
Published: February 2021

In the current research experiment, a sensitive, precise and rapid bioanalytical approach involving the detection of fedratinib concentrations in rat plasma by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique was optimized and established, and it was employed to describe the changes of fedratinib concentrations after oral treatment with various antifungal drugs (isavuconazole, posaconazole, fluconazole and itraconazole). An Acquity UPLC BEH reverse-phase C18 column (2.1 mm × 50 mm, 1.7 μm) was used for chromatographic separation of fedratinib and bosutinib (as internal standard (IS) in our study) under a linear gradient elution of the mobile phase, which was composed of solution A (acetonitrile) and solution B (water with 0.1% formic acid), along with 0.40 ml/min flow rate. The analyte and internal standard were measured with electrospray ion source in positive ion mode on a XEVO TQS triple quadrupole tandem mass spectrometer. The newly developed UPLC-MS/MS assay displayed enough linearity within the concentration range of 0.5–500 ng/ml for calibration curve. The intra- and inter-day of precision and accuracy were evaluated and validated to meet the requirements for the guidelines of bioanalytical assay. In addition, the findings of matrix effect, recovery, and stability were all within the acceptable limits. The new UPLC-MS/MS method was also successfully applied to characterize the pharmacokinetic changes of fedratinib in rats in the present of different antifungal drugs (such as isavuconazole, posaconazole, fluconazole and itraconazole). It turned out that fluconazole resulted in a prominent inhibitory effect on fedratinib metabolism in rats, followed by treatment with itraconazole and isavuconazole. Therefore, the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors may occur.
The Hemodynamic Mechanism of FFR-Guided Coronary Artery Bypass Grafting
Authors: Li Bao , Mao Boyan , Feng Yue , Liu Jincheng , Zhao Zhou , Duan Mengyao , Liu Youjun
Published: February 2021

Clinically, fractional flow reserve (FFR)-guided coronary artery bypass grafting (CABG) is more effective than CABG guided by coronary angiography alone. However, no scholars have explained the mechanism from the perspective of hemodynamics. Two patients were clinically selected; their angiography showed 70% coronary stenosis, and the FFRs were 0.7 (patient 1) and 0.95 (patient 2). The FFR non-invasive computational model of the two patients was constructed by a 0–3D coupled multiscaled model, in order to verify that the model can accurately calculate the FFR results. Virtual bypass surgery was performed on these two stenoses, and a CABG multiscaled model was constructed. The flow rate of the graft and the stenosis coronary artery, as well as the wall shear stress (WSS) and the oscillatory shear index (OSI) in the graft were calculated. The non-invasive calculation results of FFR are 0.67 and 0.91, which are close to the clinical results, which proves that our model is accurate. According to the CABG model, the flow ratios of the stenosis coronary artery to the graft of patient 1 and patient 2 were 0.12 and 0.42, respectively. The time-average wall shear stress (TAWSS) results of patient 1 and patient 2 grafts were 2.09 and 2.16 Pa, respectively, and WSS showed uniform distribution on the grafts. The OSI results of patients 1 and 2 grafts were 0.0375 and 0.1264, respectively, and a significantly high OSI region appeared at the anastomosis of patient 2. The FFR value of the stenosis should be considered when performing bypass surgery. When the stenosis of high FFR values is grafted, a high OSI region is created at the graft, especially at the anastomosis. In the long term, this can cause anastomotic blockage and graft failure.
Blueberry Polyphenol Extracts Enhance the Intestinal Antioxidant Capacity in Weaned Rats by Modulating the Nrf2–Keap1 Signal Pathway
Authors: Zhao Fangfang , Yan Shen , Tian Mengliang
Published: February 2021

Weaning causes the generation of excessive reactive oxygen species in the body, which could lead to oxidative stress. Polyphenols, for which blueberries are an important dietary source, are known for various health benefits including antioxidant properties. Here, we sought to elucidate the effects of blueberry polyphenol extracts (BPE) on intestinal antioxidant capacity and possible underlying mechanisms in weaned rats. Ninety-six rats were assigned to two groups and fed either a standard diet or a standard diet supplemented with BPE (200 mg/kg). The results showed that BPE supplementation increased (P < 0.05) catalase and superoxide dismutase activities and decreased (P < 0.05) interleukin-1 and interferon-γ contents in the jejunum and ileum. The abundances of mammalian target of rapamycin, ribosomal p70 S6 kinase and eukaryotic initiation factor 4E-binding protein 1 mRNA were elevated in the jejunum and ileum (P < 0.05) after BPE supplementation. Additionally, BPE supplementation decreased (P < 0.05) Kelch-like ECH-associated protein 1 (Keap1) gene transcription and enhanced (P < 0.05) NF-E2-related factor 2 (Nrf2) gene transcription in the jejunum and ileum. According to our results, BPE-induced protective effects against oxidative stress appear through the promotion of the jejunal and ileal antioxidant defense system in weaned rats, which was associated with the Nrf2–Keap1 signaling pathway.
Georgian Grapevine Cultivars: Ancient Biodiversity for Future Viticulture
Authors: Sargolzaei Maryam , Rustioni Laura , Cola Gabriele , Ricciardi Valentina , Bianco Piero A. , Maghradze David , Failla Osvaldo , Quaglino Fabio , Toffolatti Silvia L. , De Lorenzis Gabriella
Published: February 2021

Grapevine (Vitis vinifera) is one of the most widely cultivated plant species of agricultural interest, and is extensively appreciated for its fruits and the wines made from its fruits. Considering the high socio-economic impact of the wine sector all over the world, in recent years, there has been an increase in work aiming to investigate the biodiversity of grapevine germplasm available for breeding programs. Various studies have shed light on the genetic diversity characterizing the germplasm from the cradle ofV. viniferadomestication in Georgia (South Caucasus). Georgian germplasm is placed in a distinct cluster from the European one and possesses a rich diversity for many different traits, including eno-carpological and phenological traits; resistance to pathogens, such as oomycetes and phytoplasmas; resistance to abiotic stresses, such as sunburn. The aim of this review is to assess the potential of Georgian cultivars as a source of useful traits for breeding programs. The unique genetic and phenotypic aspects of Georgian germplasm were unraveled, to better understand the diversity and quality of the genetic resources available to viticulturists, as valuable resources for the coming climate change scenario.
Ambidexterity in Social Capital, Dynamic Capability, and SMEs’ Performance: Quadratic Effect of Dynamic Capability and Moderating Role of Market Orientation
Authors: Zhou Luanping , Peng Michael Yao-Ping , Shao Lijin , Yen Hsin-Yi , Lin Ku-Ho , Anser Muhammad Khalid
Published: February 2021

The importance of organizational ambidexterity was stressed in different fields of management. This study was using a distinct method to measure the differences in the degree of ambidexterity to bridge the gap with the previous studies and to provide more insights in the successful management of exploitation and exploration. This study surveyed Taiwanese small and medium-sized enterprises (SMEs) to test the hypotheses. We issued 1000 questionnaires in total and received 234 valid ones. Results indicate exploitative and explorative capabilities exerting non-linear effect on performance. Likewise, ambidexterity and its interaction with market orientation have positive influence on firm performance. This study used structural equation modeling to analyze data, as this approach is known to be particularly advantageous for the exploratory nature of this study. We also used hierarchical regression analysis to test interaction and moderating effects. The study contributes to the literature in two ways. First, we offer a clearer understanding of the complete concept of social capital, including inter-firm and intra-firm social capital, and how contributes to improving and extending existing exploitative capabilities. Second, this study outlines how market orientation can have different effects on an ambidextrous strategy that is adopted to improve Taiwanese SMEs performance.
The University as a Source of Social Capital in Chile
Authors: Labra Pascale , Vargas Miguel , Céspedes Cristián
Published: February 2021

This paper investigates the structure and composition of the social network formed on the campus of the Faculty of Economics and Business of Diego Portales University, Chile, exposing a series of characteristics that are aligned with similar research in the field of networks. We use a model of social networks formation in order to understand socioeconomic and academic factors that predict the formation of friendship between two students. Specifically, we test empirically our model, using students' administrative information. Of special interest is the impact of the length of stay of the students in the university, with which we refer to the years completed in the degree course, in the probability of establishing friendship ties where being socioeconomically different is a condition. The mechanism behind a result like this is the sense of belongingness that being part of the same institution may induce amongst students. By means of counterfactual simulations we found evidence in favor that passing through the university increases the probability of forming friendship networks, which can mean a kind of social capital, thus reducing socioeconomic segregation from the Chilean school system. Given the importance of this finding, we believe that policies that increase the sense of belongingness such as cultural events, leaderships programs, and community should be implemented on university campuses.
Agreement of Ultra-Short-Term Heart Rate Variability Recordings During Overseas Training Camps in Under-20 National Futsal Players
Authors: Chen Yung-Sheng , Pagaduan Jeffrey C. , Bezerra Pedro , Crowley-McHattan Zachary J. , Kuo Cheng-Deng , Clemente Filipe Manuel
Published: February 2021

Background: Monitoring the daily change in resting heart rate variability (HRV) can provide information regarding training adaptation and recovery status of the autonomic nervous system (ANS) during training camps. However, it remains unclear whether postural stabilization is essential for valid and reliable ultra-short-term (HRVUST) recordings in short-term overseas training camps.

Design: Observational and longitudinal study.

Purpose: This study aimed to investigate ultra-short-term heart rate variability recordings under stabilization or post-stabilization periods in four overseas training camps.

Participant: Twenty-seven U-20 male national team futsal players voluntarily participated in this study.

Method: Resting HRV was evaluated for 10 min during the early morning of each training camp. The natural logarithm of the root mean square of successive normal-to-normal interval differences (LnRMSSD) was used for comparisons. Time segments of HRV were divided into two periods with three measures within each: (1) the first 30-s (1st_30 s LnRMSSD), the first 60-s (1st_60 s LnRMSSD), and the 5-min standard (1st_5 min LnRMSSD) during stabilization; (2) the first 30-s (2nd_30 s LnRMSSD), the first 60-s (2nd_60 s LnRMSSD), and the 5-min standard (2nd_5 min LnRMSSD) after stabilization.

Result: The results demonstrated trivial to small ES (−0.03; 0.46), very large to nearly perfect ICC (0.76; 0.98), and narrow range of SEM (0.06; 0.31) when all time segments of HRVUST were compared to the 1st_5 min and 2nd_5 min HRV. Furthermore, the magnitude of the correlation coefficients ranged from very high to nearly perfect for all the time segments (r = 0.83; 0.97). The HRVUST posted excellent agreement in all time segments (bias = −0.05; 0.12) with/without postural stabilization. Trivial to small levels of effect size in all time segments of LnRMSSDmean (0.02; 0.41 ES) and LnRMSSDcv (−0.49; −0.02 ES) across overseas training camps was identified.

Conclusion: The first 30 or 60-s LnRMSSD recordings can be used to evaluate daily cardiac-autonomic function during overseas training camps in futsal players. The process for stabilization seems to be unnecessary for measuring the morning resting LnRMSSD in overseas training camps among young adult futsal players.
Assessment of the Quality of Life in Parents of Children With ADHD: Validation of the Multicultural Quality of Life Index in Norwegian Pediatric Mental Health Settings
Authors: Mundal Ingunn , Laake Petter , Mezzich Juan , Bjørkly Stål K. , Lara-Cabrera Mariela Loreto
Published: February 2021

Background: The brief generic Multicultural Quality of Life Index (MQLI) is a culturally informed self-report 10-item questionnaire used to measure health-related quality of life (QoL). QoL is an important outcome measure in guiding healthcare and is held as a substantial parameter to evaluate the effectiveness of healthcare. Attention Deficit Hyperactivity Disorder (ADHD) in children might negatively influence the parents’ QoL. Having a validated questionnaire to measure QoL for this population will therefore be a vital first step in guiding healthcare for parents of children with ADHD. We aimed to examine the reliability and validity of the Norwegian version of the MQLI in a sample of parents of children with ADHD.

Methods: In a cross-sectional study, 128 parents of children with ADHD were recruited from four outpatient clinics within the Child and Adolescents Mental Health Services (CAMHS) in Norway. They completed the MQLI along with an alternative well-being scale, the Five-item World Health Organization Well-being Index (WHO-5), and a form including demographic variables. Reliability and validity of the MQLI were examined. We conducted a factor analysis and calculated internal consistency and the correlation between the MQLI and the WHO-5.

Results: Factor analysis of the parents reported MQLI yielded a one-factor solution. For the MQLI, Cronbach’s alpha was 0.73. The correlation between the two measures of MQLI and WHO-5 was high (r = 0.84), reflecting convergent validity since the association between the two measures was strong.

Conclusion: Results from this study support the reliability and validity of the Norwegian version of the MQLI for assessment of quality of life in parents of children with ADHD with good psychometric properties. Study findings support the use of the questionnaire in CAMHS.
Cannabis Use and Mental Illness: Understanding Circuit Dysfunction Through Preclinical Models
Authors: Jenkins Bryan W. , Khokhar Jibran Y.
Published: February 2021

Patients with a serious mental illness often use cannabis at higher rates than the general population and are also often diagnosed with cannabis use disorder. Clinical studies reveal a strong association between the psychoactive effects of cannabis and the symptoms of serious mental illnesses. Although some studies purport that cannabis may treat mental illnesses, others have highlighted the negative consequences of use for patients with a mental illness and for otherwise healthy users. As epidemiological and clinical studies are unable to directly infer causality or examine neurobiology through circuit manipulation, preclinical animal models remain a valuable resource for examining the causal effects of cannabis. This is especially true considering the diversity of constituents in the cannabis plant contributing to its effects. In this mini-review, we provide an updated perspective on the preclinical evidence of shared neurobiological mechanisms underpinning the dual diagnosis of cannabis use disorder and a serious mental illness. We present studies of cannabinoid exposure in otherwise healthy rodents, as well as rodent models of schizophrenia, depression, and bipolar disorder, and the resulting impact on electrophysiological indices of neural circuit activity. We propose a consolidated neural circuit-based understanding of the preclinical evidence to generate new hypotheses and identify novel therapeutic targets.