bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-Archean granitic rocks: contrasting petrogenetic processes and tectonic environments
Authors: Janoušek Vojtěch , Bonin Bernard , Collins William J. , Farina Federico , Bowden Peter
Published: December 2019

Granitic rocks represent a ubiquitous component of upper continental crust but their origin remains highly controversial. This controversy stems from the fact that the granites may result from fractionation of mantle-derived basaltic magmas or partial melting of different crustal protoliths at contrasting pressure–temperature conditions, either water-fluxed or fluid-absent. Consequently, many different mechanisms have been proposed to explain the compositional variability of granites ranging from whole igneous suites down to mineral scale. This Special Publication presents an overview of the state of the art and envisages future avenues towards a better understanding of granite petrogenesis.
Gestures as Intrinsic Creativity Support
Authors: Liao Jingxian , Wang Hao-Chuan
Published: December 2019

Interpersonal communication is essential to group creativity tasks, such as group brainstorming. However, what's easily overlooked in supporting group creativity is the potential use of nonverbal behavior in communication. When people communicate verbally (e.g., discussing a topic through conversation), they may also co-produce hand movements along with verbal contents as part of the communication process. Going beyond using external interventions for creativity gain, we examine the potential to facilitate worker's in-conversation gesture use as an intrinsic mechanism for bolstering group creativity. In this paper, we aim to gain a deeper understanding of the usage and function of hand gestures in computer-mediated group brainstorming. Through a laboratory study, we verified that metaphoric gestures, or producing spatial cues with hands to convey intended concepts, can best influence self's and partner's idea generation. Also, the positive effect of metaphoric gesture is independent of media richness of communication medium (e.g., whether there's visibility or not). The results help to fill in the knowledge gap regarding how gesture use may relate to group creativity, and reveal the potential viability of shaping metaphoric gesture use as an intrinsic creativity support.
Relationship of a thinned medial layer to the attenuated contractile response in atherosclerotic coronary arteries
Authors: Nakamura Takamitsu , Horikoshi Takeo , Kugiyama Kiyotaka
Published: December 2019

Coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis. This study aimed to clarify the relationship between thickness of the medial layer and the contractile response to acetylcholine (ACh) in coronary artery using optical coherence tomography (OCT). The OCT and the vasomotor response to ACh in the left anterior descending coronary artery were assessed in 32 patients with previous myocardial infarction. The intimal and medial layer areas were measured by planimetric analysis of the OCT images. The coronary contractile response to ACh had a positive linear relationship with medial area ( r = 0.61, P < 0.001). In contrast, the relationship between the coronary contractile response to ACh and intimal area was described by an inverted U-shaped curve that was fitted to a quadratic regression model ( R2 = 0.35, P = 0.002, y-axis, contraction; x-axis, intimal area). The contractile response increased as the intimal layer thickened up to the inflection point; thereafter, the contractile response declined. The relationship between medial area and intimal area was also described by an inverted U-shaped curve that was fitted to a quadratic regression model ( R2 = 0.41, P < 0.01, y-axis, medial area; x-axis, intimal area). The medial area increased as the intimal area thickened up to the inflection point; thereafter, the medial area thinned. In conclusion, the thinned medial layer was associated with the attenuated contractile response in a coronary artery with greater atherosclerosis.

NEW & NOTEWORTHY This is the first clinical study to show the relationship between the contractile response and the thickness of medial smooth muscle layer in coronary artery of patients with previous myocardial infarction using OCT. The contractile response to acetylcholine was attenuated, and medial layer area was thinned in coronary artery with greater atherosclerosis compared with those in coronary artery with mild or moderate atherosclerosis. The coronary contractile response was positively correlated with thickness of the medial layer in coronary arteries with either mild or greater atherosclerosis. Thus, coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis, which could be related to the thinned medial layer.
Antenatal sildenafil citrate treatment increases offspring blood pressure in the placental-specificIgf2knockout mouse model of FGR
Authors: Renshall L. J. , Cottrell E. C. , Cowley E. , Sibley C. P. , Baker P. N. , Thorstensen E. B. , Greenwood S. L. , Wareing M. , Dilworth M. R.
Published: December 2019

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring ( P < 0.05) and reduced glucose sensitivity in both WT ( P < 0.01) and P0 ( P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life.

NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.
Effect of Microwave or Ultrasound Irradiation in the Extraction from Feather Keratin
Authors: Rodríguez-Clavel Isis S. , Paredes-Carrera Silvia P. , Flores-Valle Sergio O. , Paz-García Eri J. , Sánchez-Ochoa Jesús C. , Pérez-Gutiérrez Rosa M.
Published: December 2019

The extraction of feather keratin biopolymer structures was studied using chicken feathers as a biomass material by the cold acid hydrolysis reaction; the recrystallization stage was performed using microwave or ultrasound irradiation, and conduction heating was used as a reference. The microwave or ultrasound irradiation modified the texture and the morphology of the obtained materials, and they can be controlled depending on the time exposure and the power of the irradiation; this has high relevance in the design of new materials to obtain nanostructures depending on the specific application. It was found that the microwave irradiation promotes the growth of the beta sheet over the alpha helix, and in the case of ultrasound irradiation, the growth is reversed being similar to the conduction heating; the porosity properties remain invariant, modifying the particle sizes depending on the exposure time and power of irradiation. Therefore, the feather keratin biopolymer, when modified by microwaves and ultrasound in the recrystallization stage, is a fibrous protein that has good mechanical, structural, morphological, and thermal properties with potential applications such as development of biocompatible materials with cellular interaction and in catalysis as catalytic and enzymatic support to mention just a few.
Berberine Ameliorates Doxorubicin-Induced Cardiotoxicity via a SIRT1/p66Shc-Mediated Pathway
Authors: Wu Yan-Zhao , Zhang Lan , Wu Zi-Xiao , Shan Tong-tong , Xiong Chen
Published: December 2019

Doxorubicin- (DOX-) induced cardiotoxicity is associated with oxidative stress and cardiomyocyte apoptosis. The adaptor protein p66Shc regulates the cellular redox status and determines cell susceptibility to apoptosis. This study is aimed at investigating the involvement of sirtuin 1- (SIRT1-) mediated p66Shc inhibition in DOX-induced redox signalling and exploring the possible protective mechanisms of berberine (Ber) against DOX-triggered cardiac injury in rats and a cultured H9c2 cell line. Our results showed that the Ber pretreatment markedly increased CAT, SOD, and GSH-PX activities, decreased the levels of MDA, and improved the electrocardiogram and histopathological changes in the myocardium in DOX-treated rats (in vivo). Furthermore, Ber significantly ameliorated the DOX-induced oxidative insult and mitochondrial damage by adjusting the levels of intracellular ROS, ΔΨm, and [Ca2+]m in H9c2 cells (in vitro). Importantly, the Ber pretreatment increased SIRT1 expression following DOX exposure but downregulated p66Shc. Consistent with the results demonstrating the SIRT1-mediated inhibition of p66Shc expression, the Ber pretreatment inhibited DOX-triggered cardiomyocyte apoptosis and mitochondrial dysfunction. After exposing H9c2 cells to DOX, the increased SIRT1 expression induced by Ber was abrogated by a SIRT1-specific inhibitor (EX527) or the use of siRNA against SIRT1. Accordingly, SIRT1 inhibition significantly abrogated the suppression of p66Shc expression and protection of Ber against DOX-induced oxidative stress and apoptosis. These results suggest that Ber protects the heart from DOX injury through SIRT1-mediated p66Shc suppression, offering a novel mechanism responsible for the protection of Ber against DOX-induced cardiomyopathy.
A Novel Biomarker Based on miRNA to Predict the Prognosis of Muscle-Invasive Bladder Urothelial Carcinoma
Authors: Feng Yueyi , Feng Qingting , Xu Lingkai , Jiang Yiqing , Meng Fang , Shu Xiaochen
Published: December 2019

Muscle-invasive bladder urothelial carcinoma (MIBC) is characteristic of high mortality and high recurrence. Distinguishing the prognostic risk of MIBC at the molecular level of miRNA expression is rarely performed and thus of great significance for the management and treatment of MIBC in clinics. Adaptive lasso Cox’s proportional hazards model was used to explore the relationship between differential expression miRNAs (DEmiRNAs) and MIBC survival. Furthermore, we evaluated the epithelial-mesenchymal transition (EMT) score and immune infiltration abundance by exploring EMT signature genes and TIMER database, respectively. A total of 8 DEmiRNAs were detected to be associated with the survival rate of MIBC by using the lasso Cox algorithm. Through the linear combination of these 8 DEmiRNAs, we constructed a calculated marker, which could be used to distinguish the prognosis risk in both TCGA dataset (HR = 2.03, 95% CI = (1.47, 2.83)) and independent validation dataset (HR = 7.74, 95% CI = (1.05, 56.93)). Meanwhile, the constructed marker had reasonably high predictive values of the AUC (area under the curve) in the TCGA dataset and validation dataset being 0.73 and 0.63, respectively. In addition, we observed that the expression values of let-7c, miR-100, and miR-145 were associated with EMT score and the abundance of macrophage in tumor tissue as well. This newly identified risk score signature based on the combination of 8 miRNAs could significantly predict the prognostic risk of MIBC and might provide insight into immunotherapy and targeted therapy of MIBC.
Segmented Linear Regression Modelling of Time-Series of Binary Variables in Healthcare
Authors: Valsamis Epaminondas Markos , Husband Henry , Chan Gareth Ka-Wai
Published: December 2019

Introduction. In healthcare, change is usually detected by statistical techniques comparing outcomes before and after an intervention. A common problem faced by researchers is distinguishing change due to secular trends from change due to an intervention. Interrupted time-series analysis has been shown to be effective in describing trends in retrospective time-series and in detecting change, but methods are often biased towards the point of the intervention. Binary outcomes are typically modelled by logistic regression where the log-odds of the binary event is expressed as a function of covariates such as time, making model parameters difficult to interpret. The aim of this study was to present a technique that directly models the probability of binary events to describe change patterns using linear sections. Methods. We describe a modelling method that fits progressively more complex linear sections to the time-series of binary variables. Model fitting uses maximum likelihood optimisation and models are compared for goodness of fit using Akaike’s Information Criterion. The best model describes the most likely change scenario. We applied this modelling technique to evaluate hip fracture patient mortality rate for a total of 2777 patients over a 6-year period, before and after the introduction of a dedicated hip fracture unit (HFU) at a Level 1, Major Trauma Centre. Results. The proposed modelling technique revealed time-dependent trends that explained how the implementation of the HFU influenced mortality rate in patients sustaining proximal femoral fragility fractures. The technique allowed modelling of the entire time-series without bias to the point of intervention. Modelling the binary variable of interest directly, as opposed to a transformed variable, improved the interpretability of the results. Conclusion. The proposed segmented linear regression modelling technique using maximum likelihood estimation can be employed to effectively detect trends in time-series of binary variables in retrospective studies.
Interplay between the Adaptive Immune System and Insulin Resistance in Weight Loss Induced by Bariatric Surgery
Authors: Villarreal-Calderón José Romeo , Cuéllar Ricardo X. , Ramos-González Martín R. , Rubio-Infante Nestor , Castillo Elena C. , Elizondo-Montemayor Leticia , García-Rivas Gerardo
Published: December 2019

Low-grade chronic inflammation plays a pivotal role among other pathophysiological mechanisms involved in obesity. Innate and adaptive immune cells undergo systemic proinflammatory polarization that gives rise to an increased secretion of proinflammatory cytokines, which in turn leads to insulin resistance. Bariatric surgery is currently the most effective treatment for obesity, as it brings on significant weight loss, glucose metabolism improvement, and a decrease in systemic inflammation biomarkers. After bariatric surgery, several changes have been reported to occur in adaptive immunity, including reduction in CD4+ and CD8+ T cell counts, a decrease in the Th1/Th2 ratio, an increase in B regulatory cells, and reduction in proinflammatory cytokine secretion. Overall, there seems to be a major shift in several lymphocyte populations from a proinflammatory to an anti-inflammatory phenotype. Furthermore, increased antioxidant activity and reduced lipid and DNA oxidation products have been reported after bariatric surgery in circulating mononuclear cells. This paper highlights the shift in the adaptive immune system in response to weight loss and improved insulin sensitivity, as well as the interplay between immunological and metabolic adaptations as a result of bariatric surgery. Finally, based on data from research, we propose several mechanisms such as changes in adaptive immune cell phenotypes and their by-products, recruitment in adipose tissue, reduced oxidative stress, and modification in metabolic substrate availability as drivers to reduce low-grade chronic inflammation after bariatric surgery in severe obesity.
Serum Autofluorescence and Biochemical Markers in Athlete’s Response to Strength Effort in Normobaric Hypoxia: A Preliminary Study
Authors: Drzazga Zofia , Schisler Izabela , Poprzęcki Stanisław , Michnik Anna , Czuba Miłosz
Published: December 2019

The human organism has the ability to adapt to hypoxia conditions. Training in hypoxia is used in sport to improve the efficiency of athletes; however, type of training affects the direction and scope of this process. Therefore, in this study, the usefulness of serum fluorescence spectroscopy to study the assessment of athlete’s response to strength effort in hypoxia is considered in comparison with biochemical assay. Six resistance-trained male subjects took part in a research experiment. They performed barbell squats in simulated normobaric hypoxic conditions with deficiency of oxygen 11.3%, 13% 14.3% compared to 21% in normoxic conditions. Fluorescence intensity of tyrosine revealed high sensitivity on strength effort whereas tryptophan was more dependent on high altitude. Changes in emission in the visible region are associated with altering cell metabolism dependent on high altitude as well as strength training and endurance training. Significant changes in serum fluorescence intensity with relatively weak modifications in biochemical assay at 3000 m above sea level (ASL) were observed. Training at 5000 m ASL caused changes in fluorescence parameters towards the normobaric specific values, and pronounced decreases of lactate level and kinase creatine activity were observed. Such modifications of fluorescence and biochemical assay indicate increased adaptation of the organism to effort in oxygen-deficient conditions at 5000 m ASL, unlike 3000 m ASL. Fluorescence spectroscopy study of serum accompanied by biochemical assay can contribute to the understanding of metabolic regulation and the physiological response to hypoxia. The results of serum autofluorescence during various concepts of altitude training may be a useful method to analyze individual response to acute and chronic hypoxia. An endogenous tryptophan could be exploited as intrinsic biomarker in autofluorescence studies. However, these issues require further research.
Multiplicative Zagreb Indices of Molecular Graphs
Authors: Zhang Xiujun , Awais H. M. , Javaid M. , Siddiqui Muhammad Kamran
Published: December 2019

Mathematical modeling with the help of numerical coding of graphs has been used in the different fields of science, especially in chemistry for the studies of the molecular structures. It also plays a vital role in the study of the quantitative structure activities relationship (QSAR) and quantitative structure properties relationship (QSPR) models. Todeshine et al. (2010) and Eliasi et al. (2012) defined two different versions of the 1st multiplicative Zagreb index as ∏Γ=∏p∈VΓdΓp2 and ∏1Γ=∏pq∈EΓdΓp+dΓq, respectively. In the same paper of Todeshine, they also defined the 2nd multiplicative Zagreb index as ∏2Γ=∏pq∈EΓdΓp×dΓq. Recently, Liu et al. [IEEE Access; 7(2019); 105479–-105488] defined the generalized subdivision-related operations of graphs and obtained the generalized F-sum graphs using these operations. They also computed the first and second Zagreb indices of the newly defined generalized F-sum graphs. In this paper, we extend this study and compute the upper bonds of the first multiplicative Zagreb and second multiplicative Zagreb indices of the generalized F-sum graphs. At the end, some particular results as applications of the obtained results for alkane are also included.
Cathepsin B pH-Dependent Activity Is Involved in Lysosomal Dysregulation in Atrophic Age-Related Macular Degeneration
Authors: Voisin Audrey , Monville Christelle , Plancheron Alexandra , Béré Emile , Gaillard Afsaneh , Leveziel Nicolas
Published: December 2019

Age-related macular degeneration (AMD) is characterized by retinal pigment epithelial (RPE) cell dysfunction beginning at early stages of the disease. The lack of an appropriate in vitro model is a major limitation in understanding the mechanisms leading to the occurrence of AMD. This study compared human-induced pluripotent stem cell- (hiPSC-) RPE cells derived from atrophic AMD patients (77 y/o±7) to hiPSC-RPE cells derived from healthy elderly individuals with no drusen or pigmentary alteration (62.5 y/o±17.5). Control and AMD hiPSC-RPE cell lines were characterized by immunofluorescence, flow cytometry, and electronic microscopy. The toxicity level of iron after Fe-NTA treatment was evaluated by an MTT test and by the detection of dichloro-dihydro-fluorescein diacetate. Twelve hiPSC-RPE cell lines (6 AMD and 6 controls) were used for the experiment. Under basal conditions, all hiPSC-RPE cells expressed a phenotypic profile of senescent cells with rounded mitochondria at passage 2. However, the treatment with Fe-NTA induced higher reactive oxygen species production and cell death in hiPSC-RPE AMD cells than in hiPSC-RPE Control cells. Interestingly, functional analysis showed differences in lysosomal activity between the two populations. Indeed, Cathepsin B activity was higher in hiPSC-RPE AMD cells compared to hiPSC-RPE Control cells in basal condition and link to a pH more acidic in this cell population. Moreover, oxidative stress exposure leads to an increase of Cathepsin D immature form levels in both populations, but in a higher proportion in hiPSC-RPE AMD cells. These findings could demonstrate that hiPSC-RPE AMD cells have a typical disease phenotype compared to hiPSC-RPE Control cells.
Inhibition of Triggering Receptor Expressed on Myeloid Cell-1 Alleviates Acute Gouty Inflammation
Authors: He Yonglong , Yang Qibin , Wang Xiuxiu , Jia Aimin , Xie Wenguang , Zhou Jingguo
Published: December 2019

Gout is a prevalent form of aseptic inflammation caused by the deposition of monosodium urate (MSU) crystals in joints or tissues. Triggering receptor expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on innate immune cells including granulocytes, monocytes, and macrophages. TREM-1 serves as a link between innate immunity and adaptive immunity, playing a crucial role in regulating inflammation and immune response. The purpose of this study was to investigate the potential role of TREM-1 in THP-1 cells and peripheral blood mononuclear cells (PBMCs) from patients with gouty arthritis (GA). In the current study, we found that the mRNA and protein levels of TREM-1 increased in PBMCs from GA patients and soluble TREM-1 in plasma as well. In addition, an increased level of TREM-1 was observed in THP-1 treated with monosodium urate (MSU) in vitro, along with upregulation of proinflammatory cytokines. Moreover, upon specific inhibition of TREM-1, Toll-like receptor 4 (TLR-4), and myeloid differentiation factor 88 (MyD88), the levels of MyD88 and proinflammatory cytokines were decreased after MSU challenge in THP-1 cells. Interestingly, inhibition of TLR-4 could enhance the effect of TREM-1 inhibitor in MSU-induced inflammation. Taken together, our findings suggested that TREM-1 could accelerate MSU-induced acute inflammation. Inhibition of TREM-1 may provide a new strategy for alleviating acute gouty inflammation.
Diabetes Is Associated with Musculoskeletal Pain, Osteoarthritis, Osteoporosis, and Rheumatoid Arthritis
Authors: Rehling Thomas , Bjørkman Anne-Sofie Dam , Andersen Marie Borring , Ekholm Ola , Molsted Stig
Published: December 2019

Aim. To investigate the associations between diabetes and musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis. Methods. Self-reported data were provided by the nationwide Danish National Health Survey 2013. Inclusion criteria were age≥40 years and known diabetes status. The exposure variable was diabetes, and the outcome variables included musculoskeletal pain during the last 14 days in three body sites (back/lower back, limbs, and shoulder/neck), osteoarthritis, osteoporosis, and rheumatoid arthritis. Logistic regression analyses adjusted for age, gender, BMI, education, marital status, and physical activity were performed. Results. 9,238 participants with diabetes were 65.6±11.0 (mean±SD) years old; 55.6% were males. 99,980 participants without diabetes were 59.2±11.8 years old; 46.7% were males. Diabetes was associated with back/lower back pain (OR 1.2 (CI 95% 1.1-1.2), p<0.001), pain in the limbs (1.4 (1.3-1.4), p<0.001), shoulder/neck pain (1.2 (1.1-1.3), p<0.001), osteoarthritis (1.3 (1.2-1.4), p<0.001), osteoporosis (1.2 (1.1-1.4), p=0.010), and rheumatoid arthritis (1.6 (1.4-1.7), p<0.001). In participants with diabetes, physical activity was associated with reduced pain (e.g., back/lower back pain (0.7 (0.6-0.7), p<0.001)). Conclusion. Diabetes was associated with elevated odds of having musculoskeletal pain. Diabetes was also associated with elevated odds of having osteoarthritis, osteoporosis, and rheumatoid arthritis. The most frequent disease in individuals with diabetes was osteoarthritis. The reported pain may have negative impacts on the level of physical activity. Health-care professionals should remember to inform patients with diabetes that musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis are not contraindications to exercise training.
CD8+γδ T Cells Are More Frequent in CMV Seropositive Bone Marrow Grafts and Display Phenotype of an Adaptive Immune Response
Authors: Gaballa Ahmed , Arruda Lucas C. M. , Rådestad Emelie , Uhlin Michael
Published: December 2019

The role of gamma delta (γδ) T cells in human cytomegalovirus (HCMV) immune surveillance has been the focus of research interest for years. Recent reports have shown a substantial clonal proliferation of γδ T cells in response to HCMV, shedding light on the adaptive immune response of γδ T cells. Nevertheless, most efforts have focused on Vδ2negγδ T cell subset while less attention has been given to investigate other less common γδ T cell subsets. In this regard, a distinct subpopulation of γδ T cells that expresses the CD8 coreceptor (CD8+γδ T cells) has not been thoroughly explored. Whether it is implicated in HCMV response and its ability to generate adaptive response has not been thoroughly investigated. In this study, we combined flow cytometry and immune sequencing of the TCR γ-chain (TRG) to analyze in-depth bone marrow (BM) graft γδ T cells from CMV seropositive (CMV+) and CMV seronegative (CMV-) donors. We showed that the frequency of CD8+γδ T cells was significantly higher in CMV+ grafts compared to CMV- grafts (P<0.001). Further characterization revealed that CD8+γδ T cells from CMV+ grafts express Vγ9- and preferentially differentiated from a naive to terminal effector memory phenotype (CD27low/-CD45RO-). In line with these findings, TRG immune sequencing revealed clonal focusing and reduced usage of the Vγ9/JP gene segment in a CMV+ graft. Furthermore, CD8+γδ T cells showed an enhanced response to TCR/CD3 and cytokine stimulation in contrast to CD8-γδ T cells. We conclude that γδ T cells in BM grafts are reshaped by donor CMV serostatus and highlight the potential adaptive role of CD8+γδ T cells in HCMV immune response.
Famine Exposure in Early Life and Risk of Metabolic Syndrome in Adulthood: Comparisons of Different Metabolic Syndrome Definitions
Authors: Ning Feng , Ren Jie , Song Xin , Zhang Dong , Liu Li , Zhang Lei , Sun Jianping , Zhang Dongfeng , Pang Zengchang , Qiao Qing , Diabetes Prevention Program on behalf of Qingdao
Published: December 2019

This study examined the association between famine exposure in early life and the risk of metabolic syndrome (MetS) in adulthood during the 1959–1961 Chinese Famine. Two cross-sectional surveys involving randomly selected Chinese adults aged 35–74 years in the Qingdao area were conducted. A total of 9,588 individuals were grouped into four birth cohorts of unexposed (born between January 1, 1962, and December 31, 1975), fetal-exposed (born between January 1, 1959, and December 31, 1961), childhood-exposed (born between January 1, 1949, and December 31, 1958), and adolescence/adult-exposed cohorts (born between January 1, 1931, and December 31, 1948). We assessed the prevalence rate of MetS in relation to famine exposure according to three definitions of MetS by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF), and China Diabetes Society (CDS). According to the CDS criterion, the prevalence rates of MetS were 17.8%, 25.7%, 31.1%, and 45.3% in the unexposed, fetal-, childhood-, and adolescence/adult-exposed cohorts, respectively (P<0.001). For the CDS criteria, compared with individuals without famine exposure, odds ratios (95% confidence interval) for MetS were 1.36 (1.02–1.81), 1.36 (1.06–1.75), and 1.60 (1.06–2.41) in women and 1.10 (0.79–1.53), 1.07 (0.79–1.42), and 1.21 (0.74–1.99) in men who were exposed in the fetal, childhood, and adolescence/adult periods, respectively, after adjustment for age, study cohorts, residential areas, education levels, income levels, current smoking, and current drinking. The same trend was observed in fetal and childhood exposure for the NCEP-ATP III and IDF definitions, except for a marginal effect in adolescence/adult exposure. Sensitivity analysis revealed that the odds ratios for MetS prevalence for the CDS definition were 1.37 (1.03–1.82), 1.40 (1.09–1.79), and 1.58 (1.04–2.40) among fetal, childhood, and adolescence/adult exposure in rural areas, respectively. The CDS definition is superior to the other definitions for determining the association between famine exposure and MetS with respect to early life. Famine exposure in early life is associated with an increased risk of MetS in later life, especially in women. Early-life malnutrition and later life overnutrition were critical in determining adulthood metabolic disorders.
Adsorption of COD in Coking Wastewater on Nitric Acid-Modified Blue Coke Activated Carbon
Authors: Jiang Xu , Lan Xinzhe , Song Yonghui , Xing Xiangdong
Published: December 2019

The blue coke activated carbon (BAC) modified by nitric acid at different concentrations was used as an adsorbent to remove COD from coking wastewater. Characterization of BAC was performed using N2adsorption/desorption techniques, scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and Boehm titration. The results showed the Brunner–Emmet–Teller (BET) specific surface area and iodine value of BAC became higher after modification, and the adsorption capacity of BAC for coking wastewater was effectively improved with nitric acid modification. The optimal nitric acid concentration for modification was 3 mol/L (BAC-N3), which had more acid functional group contents than unmodified. The chemical oxygen demand (COD) removal rate was to reach 77.05% when 4 g BAC-N3 was added into 50 mL coking wastewater in 120 min with a shaking speed of 100 rpm at 25°C. Langmuir model could better describe equilibrium adsorption data by BAC-N3, and the kinetic study showed that the adsorption process was best fitted by the pseudo-second-order kinetic model.
Suspected Brugada Phenocopy Secondary to Coronary Slow Flow
Authors: Shim Alicia , Seecheran Rajeev , Seecheran Valmiki , Persad Sangeeta , Sreenivasan Shiva , Henry Ronald , Seecheran Naveen Anand
Published: December 2019

Brugada syndrome (BrS) is a genetic condition that accentuates the risk of potentially lethal ventricular arrhythmias and sudden cardiac death (SCD) in a structurally normal heart. The Brugada electrocardiographic pattern may manifest separately from the syndrome—this clinical scenario has been described as Brugada phenocopy (BrP). Many etiologies of BrP have been reported, but it has not yet been reported as a result of coronary slow flow (CSF) phenomenon. This case report highlights a suspected coronary slow flow-associated Brugada type 1 electrocardiographic pattern, which subsequently normalized following the institution of guideline-directed medical therapy for acute coronary syndrome.
A Traditional Clinic Chinese Medicine Prescription Qu-Zhuo-Tong-Bi (QZTB) Alleviates Gouty Arthritis in Model Rats
Authors: Lv Huiqing , Chen Jianzhi , Liu Fenfen , Jin Yan , Xu Zhenghao , Wen Chengping , Yu Jie
Published: December 2019

Qu-Zhuo-Tong-Bi (QZTB) is an empirical traditional Chinese medicine prescription for treating acute gouty arthritis clinically without serious adverse effects in mainland China. However, the biochemical mechanism underlying the therapeutic action produced by QZTB treatment against acute gouty arthritis and the effect on recurrent attack remain unknown. In this study, we investigated the anti-inflammatory and analgesic effects of QZTB on acute gouty arthritis and the recurrent attack in rats, as well as the underlying mechanisms. The gouty arthritis model was established by intra-articular injection of monosodium urate (MSU) crystal suspension (2 mg/50 μL) into the right ankle joint of Sprague Dawley (SD) male rats. QZTB (500 mg/kg) and the positive control drug meloxicam were administrated by gavages twice a day for 7 days before, or 3 days after, first MSU injection in different experiments, respectively. The analgesic effects were evaluated by pain-like behaviors and hind paw mechanical withdrawal threshold testing. The anti-inflammatory activities were evaluated by ankle swelling measurement, histologic examination, NLRP3 inflammasome, and inflammatory cytokine expression. Western blot and quantitative real-time PCR were used to detect the protein and mRNA expressions of NLRP3. IL-1β and TNF-α level in the blood serum were detected by enzyme-linked immunosorbent assay (ELISA). QZTB can suppress ankle swelling and synovial inflammation in the MSU-induced gouty arthritis rat model. QZTB alleviated the acute attack and prevented the recurrent attack of gouty arthritis. In addition, QZTB treatment significantly decreased both mRNA and protein levels of NLRP3, as well as the production of IL-1 and TNF-α in the ankle joint of model rats. Taken together, these results suggest that QZTB may be a promising herbal formula for the prevention and treatment of gouty arthritis in humans.
Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus
Authors: Cherney David Z.I. , Repetto Enrico , Wheeler David C. , Arnold Suzanne V. , MacLachlan Sharon , Hunt Philip R. , Chen Hungta , Vora Jiten , Kosiborod Mikhail
Published: December 2019

Background: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. Methods: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. Results: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. Conclusion: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies.
Vitamin D and Neurotrophin Levels and Their Impact on the Symptoms of Schizophrenia
Authors: Peitl Vjekoslav , Silić Ante , Orlović Ivona , Vidrih Branka , Crnković Danijel , Karlović Dalibor
Published: December 2019

Introduction: Vitamin D is involved in brain development and functioning, as well as in regulation of neurotrophic factors. Changes in the expression of those factors are possibly responsible for morphologic abnormalities and symptoms in patients suffering from schizophrenia. Objective: The main goal of this research was to investigate the interrelationship between vitamin D, nerve growth factors (NGF, brain-derived neurotrophic factor [BDNF], and neuregulin-1 [NRG1]), and schizophrenia symptom domains. Methods: This research included 97 inpatients diagnosed with schizophrenia. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Blood samples were taken in order to analyze concentrations of vitamin D, BDNF, NRG1, and NGF growth factors. The obtained results were used in a multiple regression analysis. Results: The vitamin D concentration positively affected the concentration of NRG1 (F = 8.583, p = 0.005) but not the concentration of other investigated growth factors (BDNF and NGF). The clinical characteristics and symptom domains of schizophrenia seemed to be unaffected by the concentrations of vitamin D, BDNF, and NGF, while the NRG1 concentration significantly affected positive symptom domains of schizophrenia (F = 4.927, p = 0.030). Conclusion: The vitamin D concentration positively affected NRG1 levels but not schizophrenia symptomatology as measured by PANSS. The as­sociation between the two could be intermediated via NRG1.
The Use of Ziziphus spina-christi Extract in Treating Erlotinib (Tarceva®) Associated Rash: A Case Report
Authors: Alzahrani Ali M. , Alzahrani Asma A. , Alsharm Abdullah A.
Published: December 2019

The most common side effect for cancer patients using epidermal growth factor receptor inhibitors (EGFRI) is the development of an itchy papulopustular rash. In severe cases, the patients are forced to stop taking the medications, hence affecting treatment outcomes. We herein report a case of a 50-year-old patient who developed a papulopustular rash after starting erlotinib. He treated himself with Ziziphus spina-christi leaves which is a plant well known for its anti-inflammatory and antibacterial properties in the middle east. We hypothesize that the anti-inflammatory, soothing, and antibacterial activity of the Ziziphus tree might actually represent a possible better treatment of the rash than available treatments, particularly in patients on EGFR blockers, and hence improve treatment outcomes.
TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle
Authors: Zhou Xinyu , Park Ki Ho , Yamazaki Daiju , Lin Pei-hui , Nishi Miyuki , Ma Zhiwei , Qiu Liming , Murayama Takashi , Zou Xiaoqin , Takeshima Hiroshi , Zhou Jingsong , Ma Jianjie
Published: December 2019

Rationale:

Trimeric intracellular cation (TRIC)-A and B are distributed to endoplasmic reticulum/sarcoplasmic reticulum intracellular Ca
2+
stores. The crystal structure of TRIC has been determined, confirming the homotrimeric structure of a potassium channel. While the pore architectures of TRIC-A and TRIC-B are conserved, the carboxyl-terminal tail (CTT) domains of TRIC-A and TRIC-B are different from each other. Aside from its recognized role as a counterion channel that participates in excitation-contraction coupling of striated muscles, the physiological function of TRIC-A in heart physiology and disease has remained largely unexplored.

Objective:

In cardiomyocytes, spontaneous Ca
2+
waves, triggered by store overload–induced Ca
2+
release mediated by the RyR
2
(type 2 ryanodine receptor), develop extrasystolic contractions often associated with arrhythmic events. Here, we test the hypothesis that TRIC-A is a physiological component of RyR
2
-mediated Ca
2+
release machinery that directly modulates store overload–induced Ca
2+
release activity via CTT.

Methods and Results:

We show that cardiomyocytes derived from the TRIC-A
−/−
(TRIC-A knockout) mice display dysregulated Ca
2+
movement across sarcoplasmic reticulum. Biochemical studies demonstrate a direct interaction between CTT-A and RyR
2
. Modeling and docking studies reveal potential sites on RyR
2
that show differential interactions with CTT-A and CTT-B. In HEK293 (human embryonic kidney) cells with stable expression of RyR
2
, transient expression of TRIC-A, but not TRIC-B, leads to apparent suppression of spontaneous Ca
2+
oscillations. Ca
2+
measurements using the cytosolic indicator Fura-2 and the endoplasmic reticulum luminal store indicator D1ER suggest that TRIC-A enhances Ca
2+
leak across the endoplasmic reticulum by directly targeting RyR
2
to modulate store overload–induced Ca
2+
release. Moreover, synthetic CTT-A peptide facilitates RyR
2
activity in lipid bilayer reconstitution system, enhances Ca
2+
sparks in permeabilized TRIC-A
−/−
cardiomyocytes, and induces intracellular Ca
2+
release after microinjection into isolated cardiomyocytes, whereas such effects were not observed with the CTT-B peptide. In response to isoproterenol stimulation, the TRIC-A
−/−
mice display irregular ECG and develop more fibrosis than the WT (wild type) littermates.

Conclusions:

In addition to the ion-conducting function, TRIC-A functions as an accessory protein of RyR
2
to modulate sarcoplasmic reticulum Ca
2+
handling in cardiac muscle.
Revision of the shell-carrying crab genus Conchoecetes Stimpson, 1858 (Crustacea: Brachyura: Dromiidae)
Authors: McLAY COLIN L. , NARUSE TOHRU
Published: December 2019

The genus Conchoecetes Stimpson, 1858, has long been considered to include three species: C. artificiosus (Fabricius, 1798), C. andamanicus Alcock, 1900, and C. intermedius Lewinsohn, 1984. The type species, C. artificiosus, has been assumed to be widely distributed throughout the Indo-West Pacific and a fourth species, C. conchifera (Haswell, 1882), from Australia, has been regarded as a synonym. The enigmatic and long overlooked “Caphyra pectenicola Adams, in Belcher, 1848” is shown to be a species of Conchoecetes occurring in Java, Singapore and the Gulf of Thailand. We review the status of these species, establish C. conchifera as a valid species, and describe five new species: C. atlas n. sp., C avikele n. sp., C. chanty n. sp., C. investigator n. sp. and C. pembawa n. sp. In this revision we recognize 10 valid species in Conchoecetes. They are distributed from Southern Africa, across the Indian Ocean to Australia and northwards to China. Formerly considered to be cosmopolitan, C. artificiosus is restricted to India, Sri Lanka Pakistan, as well as the Persian Gulf and Madagascar, while C. intermedius, first discovered near Madagascar, is shown to be the most widespread species occurring from Africa to China.
Bicorniphontodes (Copepoda: Harpacticoida: Laophontodinae Lang, 1944): a new genus with description of a new species from the Napoleon Reef, Gulf of Aqaba, Red Sea, Egypt
Authors: GEORGE KAI HORST , GEORGE KAI HORST , GLATZEL THOMAS , SCHRÖDER KATHARINA
Published: December 2019

Findings of a new representative of the Laophontodinae Lang, 1944 (Copepoda, Harpacticoida) from the Napoleon Reef (Gulf of Aqaba, Red Sea, Egypt) provided new insights into the systematics of the type genus Laophontodes T. Scott, 1894. Bicorniphontodes clarae gen. et sp. nov., which is described in the present contribution, shares exclusively six derived characters with Laophontodes bicornis A. Scott, 1896, L. horstgeorgei George & Gheerardyn, 2015, and partly with L. hamatus (Thomson, 1883), and L. ornatus Krishnaswamy, 1957: (1) cephalothorax medio-laterally with triangular extensions and (2) postero-laterally with paired cuticular processes, (3) free body somites except telson dorsally with hyaline frills ending in rounded lappets, (4) furcal setae I and II displaced subapically, (5) antennar allobasis lacking abexopodal seta on endopodal half, (6) outer spines of the last segment of swimming legs 2 and 3 unipinnate and comb-like, with the pinnae being extremely long and set widely apart. Thus, the named species are excluded from Laophontodes and united together with B. clarae gen. et sp. nov. in Bicorniphontodes gen. nov. as Bicorniphontodes bicornis comb. nov., B. hamatus comb. nov., B. horstgeorgei comb. nov., and B. ornatus comb. nov.. Beside the description of B. clarae gen. et sp. nov., a detailed phylogenetic discussion regarding the systematic relationships of the named species and the justification of the erection of Bicorniphontodes gen. nov. is given, including its distribution in the world’s oceans. A key to species is also provided.
Does Language Determine Our World’s Borders? The Deaf Beyond the Pale
Authors: Szpilman Magdalena
Published: December 2019

Does Language Determine Our World’s Borders? The Deaf Beyond the PaleThe limits of our language are the limits of our worldLudwig Wittgenstein“If not in words, how did she organize her thoughts?,” asks contemporary American writer André Aciman thinking of his deaf mother. In other words, how did she organize her world – one could ask, since even if not consciously, it is often assumed that “the limits of our language are the limits of our world.” Taking Ludwig Wittgenstein’s well-known dictum as a starting point, I would like to present an interdisciplinary approach to the subject, set on the border of comparative literature, linguistics, and medicine. In my paper, using the works of Plato (Cratylus), Denis Diderot (Paradox of Acting), Étienne Bonnot de Condillac (Philosophical Writings of Etienne Bonnot Abbé de Condillac), Oliver Sacks (Seeing Voices: A Journey into the World of the Deaf), and others, I focus on how people perceive the borders (limits) of our world through the prism of language. Is language just a prosthesis, a grafted limb one can live without? Do hands speak more intimately than words? Or maybe deafness is more of a disability than blindness? Is hearing essential for creating memory, allowing comparison, judgment and association of ideas? From a medical point of view, it is impossible to develop speech without hearing. So how does not hearing and therefore not speaking limit our world? Does it at all? Czy język określa granice naszego świata? Głusi poza nawiasemGranice naszego języka są granicami naszego świata.(Ludwig Wittgenstein)Jeśli nie w słowach, jak organizowała swoje myśli? – pyta współczesny amerykański pisarz André Acimana w eseju o swoje głuchej matce. Innymi słowy, można zapytać - jak organizowała swój świat - bo nawet nieświadomie wierzymy, że: granice naszego języka są granicami naszego świata. Biorąc za punkt wyjścia słynne powiedzenie Ludwiga Wittgensteina oraz wykorzystując dzieła Platona (Kratylos), Denisa Diderota (Paradoks o aktorze), Étienne’a Bonnota de Condillaca (Traktat o wrażeniach zmysłowych), Olivera Sacksa (Zobaczyć głos) i innych, analizuję postrzeganie granic świata przez pryzmat języka, w ujęciu interdyscyplinarnym, z pogranicza literatury porównawczej, językoznawstwa i medycyny. Czy język to tylko proteza, bez której można żyć? Czy ręce mówią dokładniej niż słowa? A może bycie głuchym to niepełnosprawność znacznie bardziej ograniczająca niż bycie niewidomym? Czy słyszenie jest naprawdę ważne, ponieważ odgrywa kluczową rolę w tworzeniu pamięci, umożliwiając porównywanie, ocenianie i tworzenie skojarzeń? Słyszenie, z medycznego punktu widzenia, jest niezbędne do wykształcenia mowy. Jak zatem niesłyszenie, a zatem niemówienie ogranicza nasz świat? Czy ogranicza?