bluuebunny/crossref_metadata_2025 huggingface dataset:
Proximate Composition, Antinutritional Content, Microbial Load, and Sensory Acceptability of Noodles Formulated from Moringa (Moringa oleifera) Leaf Powder and Wheat Flour Blend
Authors: Zula Aemiro Tadesse , Ayele Dagem Alemayehu , Egigayhu Woinshet Abera
Published: April 2021

Background. Noodle products are popular throughout the world, and they can be prepared from cereal like wheat, maize, and rice. Nowadays, healthy and nutritious product requirement has been increasing. Thus, research on the nutrition-rich but neglected crop is becoming visible nowadays to ensure global food security and to satisfy the nutritional need. Research indicated that moringa tree leaf powder has good nutritional value, but it is not yet customized and properly consumed. Method. The study is aimed at developing noodles from wheat flour and moringa leaf powder and evaluating proximate composition, antinutritional content (phytate and tannin), microbial load (total plate count and yeast and mold count), and sensory acceptability. The experiment contains four treatments and one control. The data from proximate composition, antinutritional content, microbial load, and sensory acceptability were subjected to SAS version 9 software. A complete randomized design was used to analyze the proximate composition, antinutritional content, and microbial load data, and a randomized complete block design was used to analyze the acceptability test. Result. The study revealed that in the noodles formulated from 80% durum wheat flour and 20% of moringa leaf powder, the ash, protein, fat, fiber, gross energy, phytate, and tannin content were increased by 39.39%, 10.86%, 153%, 42.2%, 3.43%, 39.83%, and 329.78%, respectively, as compared with noodles made from 100% durum wheat flour. However, moisture, total bacteria count, and yeast and mold count were decreased by 28.71%, 45.52%, and 55.93%, respectively. Similarly, the study also revealed that the acceptability test of noodles was decreased as moringa leaf powder concentration is increased. Conclusion. In conclusion, besides the good nutritional profile and antimicrobial capacity, moringa has antinutritional content and influences the sensory acceptability of products. Therefore, limiting the moringa leaf powder concentration is needed during the development of products using moringa leaf powder.
Field Deployment of a Mobile Biosafety Laboratory Reveals the Co-Circulation of Dengue Viruses Serotype 1 and Serotype 2 in Louga City, Senegal, 2017
Authors: Dieng Idrissa , Diarra Maryam , Diagne Moussa Moïse , Faye Martin , Dior Ndione Marie Henriette , Ba Yamar , Diop Mamadou , Ndiaye El Hadji , Marinho de Andrade Zanotto Paolo , Diop Boly , Ndiaye Mamadou , Bousso Abdoulaye , Dia Ndongo , Diallo Mawlouth , Barry Aliou , Fall Gamou , Loucoubar Cheikh , Sall Amadou Alpha , Faye Ousmane , Faye Oumar
Published: April 2021

Dengue virus (DENV) is the most prevalent arboviral threat worldwide. This virus belonging to genus Flavivirus, Flaviviridae family, is responsible for a wide spectrum of clinical manifestations, ranging from asymptomatic or mild febrile illness (dengue fever) to life-threatening infections (severe dengue). Many sporadic cases and outbreaks have occurred in Senegal since 1970. Nevertheless, this article describes a field investigation of suspected dengue cases, between 05 September 2017 and 17 December 2017 made possible by the deployment of a Mobile Biosafety Laboratory (MBS-Lab). Overall, 960 human sera were collected and tested in the field for the presence of viral RNA by real-time RT-PCR. Serotyping, sequencing of complete E gene, and phylogenetic analysis were also performed. Out of 960 suspected cases, 131 were confirmed dengue cases. The majority of confirmed cases were from Louga community. Serotyping revealed two serotypes, Dengue 1 (100/104; 96, 15%) and Dengue 2 (04/104; 3, 84%). Phylogenetic analysis of the sequences obtained indicated that the Dengue 1 strain was closely related to strains isolated, respectively, in Singapore (Asia) in 2013 (KX380803.1) outbreak and it cocirculated with a Dengue 2 strain closely related to strains from a Burkina Faso dengue outbreak in 2016 (KY62776.1). Our results showed the co-circulation of two dengue virus serotypes during a single outbreak in a short time period. This co-circulation highlighted the need to improve surveillance in order to prevent future potential severe dengue cases through antibody-dependent enhancement (ADE). Interestingly, it also proved the reliability and usefulness of the MBS-Lab for expedient outbreak response at the point of need, which allows early cases management.
Dynamic Behaviors of a Two‐Degree‐of‐Freedom Impact Oscillator with Two‐Sided Constraints
Authors: Li Songtao , Li Qunhong , Meng Zhongchuan
Published: April 2021

The dynamic model of a vibroimpact system subjected to harmonic excitation with symmetric elastic constraints is investigated with analytical and numerical methods. The codimension‐one bifurcation diagrams with respect to frequency of the excitation are obtained by means of the continuation technique, and the different types of bifurcations are detected, such as grazing bifurcation, saddle‐node bifurcation, and period‐doubling bifurcation, which predicts the complexity of the system considered. Based on the grazing phenomenon obtained, the zero‐time‐discontinuity mapping is extended from the single constraint system presented in the literature to the two‐sided elastic constraint system discussed in this paper. The Poincare mapping of double grazing periodic motion is derived, and this compound mapping is applied to obtain the existence conditions of codimension‐two grazing bifurcation point of the system. According to the deduced theoretical result, the grazing curve and the codimension‐two grazing bifurcation points are validated by numerical simulation. Finally, various types of periodic‐impact motions near the codimension‐two grazing bifurcation point are illustrated through the unfolding diagram and phase diagrams.
Clinical Characteristics, Management, and Natural History of Chronic Inducible Urticaria in a Pediatric Cohort
Authors: Miles Laura May , Gabrielli Sofianne , Le Michelle , Netchiporouk Elena , Baum Sharon , Greenberger Shoshana , Ensina Luis F. , Jafarian Fatemeh , Zhang Xun , Ben-Shoshan Moshe
Published: April 2021

Background: Some forms of chronic urticaria (CU) can be specifically attributed to a response to a definite trigger, referred to as chronic inducible urticaria (CIndU). We aimed to assess the demographics, clinical characteristics, comorbidities, natural history, and management of pediatric patients with CIndU. Methods: Over a 6-year period, children presenting to the allergy clinic at the Montreal Children’s Hospital (MCH) with CIndU were prospectively recruited. CU was defined as the presence of wheals and/or angioedema, occurring for at least 6 weeks. A standardized diagnostic test was used to establish the presence of a specific form of urticaria. Resolution was defined as the absence of hives for 1 year without treatment. Results: Sixty-four patients presented with CIndU, of which 51.6% were male, with a median age of 12.5 (interquartile range 7.3, 15.9) years. Cold CU and cholinergic CU were the most common subtypes (60.3 and 41.3%, respectively). Basophil counts were undetectable in 48.4% of the cases, and C-reactive protein levels were elevated in 7.8% of patients. Of all cases, 71.4% were controlled with second-generation antihistamines. The resolution rate was of 45.3% (95% confidence interval 33.1–57.5%), based on per-protocol population within the 6-year course of the study. Resolution was more likely in patients who presented with well-controlled urticaria control test scores and elevated CD63 counts and in those suffering from thyroid comorbidity. Conclusion: The natural history of CIndU resolution in pediatric patients was relatively low and was associated with elevated CD63 levels, as well as thyroid comorbidity.
Relationship between Immunophenotype and Clinicopathological Findings for Superficial Nonampullary Duodenal Epithelial Tumor
Authors: Fukusada Shigeki , Shimura Takaya , Iwasaki Hiroyasu , Okuda Yusuke , Katano Takahito , Nishigaki Ruriko , Ozeki Takanori , Kitagawa Mika , Nishie Hirotada , Tanaka Mamoru , Ozeki Keiji , Kubota Eiji , Tanida Satoshi , Kataoka Hiromi
Published: April 2021

Introduction: The natural history and prognosis of superficial nonampullary duodenal epithelial tumors (SNADETs) remain uncertain. We elucidated the relationship between immunophenotype and clinicopathological features. Materials and Methods: A total of 98 SNADETs were divided into 3 groups according to immunohistochemical findings: gastric phenotype (G type), gastrointestinal phenotype (GI type), and intestinal phenotype (I type). Cellular dysplasia was divided into low-grade dysplasia and high-grade dysplasia/adenocarcinoma (≥HGD). White opaque substance (WOS) deposition was categorized into diffuse WOS, partial WOS, and no WOS, based on endoscopic findings. Results: Of the 98 SNADETs, 4 lesions (4.1%) were G type, 32 lesions (32.7%) were GI type, and 62 lesions (63.2%) were I type. All G-type SNADETs were located in the oral side of the papilla including the bulb, and the rate of bulbar lesions was significantly higher in the G type than in the GI and I types (p = 0.004). The most frequent type of WOS was no WOS (4/4, 100%) for G type, partial WOS (19/32, 59.4%) for GI type, and diffuse WOS (34/62, 54.8%) for I type (p < 0.001), and loss of intestinal character was significantly correlated with WOS deficiency. GI/I-type SNADETs with partial or no WOS and G-type SNADETs were associated with ≥HGD. Additionally, the frequency of ≥HGD lesion was significantly higher in the CD10-negative group than in the CD10-positive group (57.1 vs. 19.8%, p = 0.043). Conclusion: Pathological intestinal character was correlated with the presence of WOS, and CD10 loss was associated with malignant potential of SNADETs.
Risk Factors for Olfactory and Gustatory Dysfunctions in Patients with SARS-CoV-2 Infection
Authors: Galluzzi Francesca , Rossi Veronica , Bosetti Cristina , Garavello Werner
Published: April 2021

Introduction: Smell and taste loss are characteristic symptoms of SARS-CoV-2 infection. The aim of this study is to investigate the prevalence and risk factors associated with olfactory and gustatory dysfunctions in coronavirus disease (COVID-19) patients. Methods: We conducted an observational, retrospective study on 376 patients with documented SARS-CoV-2 infection admitted to the San Gerardo Hospital in Monza, Italy, from March to July 2020. All patients answered a phone questionnaire providing information on age, sex, smoking status, and clinical characteristics. Adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated through logistic regression models including relevant covariates. Results: The prevalence of olfactory and gustatory dysfunctions in COVID-19 patients was 33.5 and 35.6%, respectively. Olfactory dysfunctions were significantly directly associated with current smoking and history of allergy, the multivariable ORs being 6.53 (95% CI 1.16–36.86) for current smokers versus never smokers, and 1.89 (95% CI 1.05–3.39) for those with an allergy compared to those without any allergy. Respiratory allergy in particular was significantly associated with olfactory dysfunctions (multivariable OR 2.30, 95% CI 1.02–5.17). Significant inverse associations were observed for patients aged 60 years or more (multivariable OR 0.33, 95% CI 0.19–0.57) and hospitalization (multivariable OR 0.22, 95% CI 0.06–0.89). Considering gustatory dysfunctions, after allowance of other variables a significant direct association was found for respiratory allergies (OR 2.24, 95% CI 1.03–4.86), and an inverse association was found only for hospitalization (OR 0.21, 95% CI 0.06–0.76). Conclusion: Our study indicates that current smoking and history of allergy (particularly respiratory) significantly increase the risk for smell loss in COVID-19 patients; the latter is also significantly associated to taste loss. Hospitalization has an inverse association with the risk of olfactory and gustatory dysfunctions, suggesting that these may be symptoms characteristics of less severe SARS-CoV-2 infection.
Interleukin-6 in Amniotic Fluid: A Reliable Marker for Adverse Outcomes in Women in Preterm Labor and Intact Membranes
Authors: Leaños-Miranda Alfredo , Nolasco-Leaños Ana Graciela , Carrillo-Juárez Reyes Ismael , Molina-Pérez Carlos José , Isordia-Salas Irma , Ramírez-Valenzuela Karla Leticia
Published: April 2021

Introduction: Amniotic fluid (AF) interleukin-6 (IL-6) concentration has been associated to preterm delivery and perinatal morbidity and mortality in women with preterm labor and intact membranes. Nevertheless, the clinical significance of this biomarker of intra-amniotic inflammation (IAI) is still unclear due in part to the paucity of large studies. Methods: AF IL-6 concentrations were determined in 452 consecutive women with preterm labor and intact membranes, categorized into 3 groups: 302 without IAI (IL-6 of <2.6 ng/mL), 64 with mild IAI (IL-6 of 2.6–11.2 ng/mL), and 86 with severe IAI (IL-6 of ≥11.3 ng/mL). Results: The severe IAI group had a short pregnancy duration from amniocentesis to delivery (median 3 days) than in without IAI group (median 45 days); meanwhile, the mild IAI group had a latency that was intermediate to the severe and without IAI groups (median 9.5 days). As compared to women without IAI, women with mild and severe IAI had higher rates of preterm delivery at both <34 and <37 weeks of gestation and perinatal morbidity and mortality. Furthermore, the risk of various individual adverse outcomes (short latency from amniocentesis to delivery [at ≤3 days, ≤7 days, and ≤14 days], preterm delivery at both <34 and <37 weeks of gestation, histologic chorioamnionitis, respiratory distress syndrome, and congenital sepsis) was higher in women with severe IAI (OR ≥ 2.8), compared with women without IAI. Conclusions: AF IL-6 concentrations appear to be suitable marker to assess the degree of IAI and are associated with increased risk of adverse outcomes.
Pathogenesis of Higher Blood Pressure and Worse Renal Function in Salt-Sensitive Hypertension
Authors: Chu Yuguang , Zhou Yan , Lu Shihua , Lu Feng , Hu Yuanhui
Published: April 2021

Background: The underlying pathogenesis of patients with salt-sensitive hypertension expressing higher blood pressure and severer renal damage remains uncertain. Methods: We recruited 329 subjects, 131 in salt-sensitive (SS) group, 148 in nonsalt-sensitive (NSS) group, and 50 healthy people in normal group and tested their renal function, 24-h ambulatory blood pressure, and growth factor series. Results: The SS group showed worse renal function with lower estimated glomerular filtration rate and higher urinary microalbumin, α-microglobulin, urinary protein Cr ratio, and urinary immunoglobulin. Most indicators in 24-h ambulatory blood pressure of the SS group were significantly enhanced than the NSS group, indicating their higher blood pressure. The significantly elevated growth factors in the SS group were AR, BMP-5, EG-VEGF, GH, HGF, IGFBP-2, IGFBP-3, IGFBP-6, MCSFR, NT-4, PDGF-AA, SCF, SCFR, VEGFR2, VEGFR3, and VEGF-D, compared to other 2 groups or one of them. PI3K-AKT pathway was activated in the SS group. Conclusions: Differences in growth factors and pathways may account for the manifestations of the SS group. Activated PI3K-AKT pathway with higher IGFBP-3 and GH can lead to renal damage. Higher MCSFR in the SS group indicates that high blood pressure and severe kidney damage may be associated with the activation of the immune system. EG-VEGF, VEGFR2, VEGFR3, and VEGF-D can also explain the elevated blood pressure due to the dilated lymphatic system which drains excess sodium and water back into circulation. The SS group presented higher AR and HGF which may worsen renal function by regulating cell proliferation and tumor formation. However, due to the potential low awareness rate of hypertension at the very beginning, we cannot ensure the exact occurrence order of blood pressure, renal damage, and salt sensitivity. Therefore, further studies which can track data from the onset of hypertension are needed.
Probe-Based Confocal Laser Endomicroscopy and Barrett’s Esophagus: Just a Scientific Toy or Significant Improvement in Diagnosis?
Authors: Vranić Luka , Nadarević Tin , Štimac Davor
Published: April 2021

Background: Barrett’s esophagus (BE) requires surveillance to identify potential neoplasia at an early stage. The standard surveillance regimen includes random 4-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding, and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents a real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1,000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patients. The main advantages would be real-time diagnosis and decision-making, greater diagnostic accuracy, and evaluation of larger area compared to random biopsies. Clinical pCLE studies in the esophagus show high diagnostic accuracy, and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key Messages: Despite promising results, its role in routine use in patients with BE remains questionable primarily due to lack of well-organized double-blind randomized trials.
Loss of TIMP4 (Tissue Inhibitor of Metalloproteinase 4) Promotes Atherosclerotic Plaque Deposition in the Abdominal Aorta Despite Suppressed Plasma Cholesterol Levels
Authors: Hu Mei , Jana Sayantan , Kilic Tolga , Wang Faqi , Shen Mengcheng , Winkelaar Gerrit , Oudit Gavin Y. , Rayner Katey , Zhang Da-wei , Kassiri Zamaneh
Published: April 2021

Objective:

Atherosclerosis is accumulation of lipids and extracellular matrix in the arterial wall. TIMPs (tissue inhibitor of metalloproteinases) can impact plaque deposition by regulating ECM (extracellular matrix) turnover. TIMP4 also influences lipid metabolism and smooth muscle cell (SMC) proliferation. We investigated the role of TIMP4 in atherosclerosis.

Approach and Results:

Mice lacking low-density lipoprotein receptor (
Ldlr
−/−
) and
Timp4
(
Timp4
−/−
/
Ldlr
−/−
) were fed high-fat diet (HFD) or regular laboratory diet. After 3 or 6 months, HFD-fed male and female
Timp4
−/−
/
Ldlr
−/−
mice exhibited higher plaque density in the abdominal aorta (but not in aortic valves, arch, thoracic aorta) compared with
Ldlr
−/−
mice. Although plasma lipid and cholesterol levels were lower in
Timp4
−/−
/
Ldlr
−/−
-HFD, cholesterol content in the abdominal aorta was higher along with elevated inflammatory cytokines, MMP (matrix metalloproteinase) activities, CD68
+
/calponin
+
macrophage-like SMCs in
Timp4
−/−
/
Ldlr
−/−
-HFD compared with
Ldlr
−/−
-HFD mice. In vitro, oxidized LDL (low-density lipoprotein) markedly increased CD68 expression, reduced SMC markers, increased lipid uptake, and reduced cholesterol efflux protein ABCA1 (ATP-binding cassette transporter A1) in
Timp4
−/−
/
Ldlr
−/−
compared with
Ldlr
−/−
primary SMCs from abdominal, but not thoracic aorta. TIMP4 expression in the abdominal aorta (in vivo) and its corresponding SMCs (in vitro) was ≈2-fold higher than in the thoracic aorta and SMCs; TIMP4 levels decreased following HFD.
Timp4
-deficiency in bone marrow–derived macrophages did not alter their foam cell formation capacity.

Conclusions:

TIMP4 protects against plaque deposition in the abdominal aorta independent of plasma cholesterol levels. TIMP4 prevents proteolytic degradation of ABCA1 in SMCs, hindering cholesterol accumulation and transdifferentiation to macrophage-like foam cells, representing a novel negative regulator of atherosclerosis.
Role of the Peroxisome Proliferator Activated Receptors in Hypertension
Authors: Fang Shi , Livergood M. Christine , Nakagawa Pablo , Wu Jing , Sigmund Curt D.
Published: April 2021

Nuclear receptors represent a large family of ligand-activated transcription factors which sense the physiological environment and make long-term adaptations by mediating changes in gene expression. In this review, we will first discuss the fundamental mechanisms by which nuclear receptors mediate their transcriptional responses. We will focus on the PPAR (peroxisome proliferator-activated receptor) family of adopted orphan receptors paying special attention to PPARγ, the isoform with the most compelling evidence as an important regulator of arterial blood pressure. We will review genetic data showing that rare mutations in PPARγ cause severe hypertension and clinical trial data which show that PPARγ activators have beneficial effects on blood pressure. We will detail the tissue- and cell-specific molecular mechanisms by which PPARs in the brain, kidney, vasculature, and immune system modulate blood pressure and related phenotypes, such as endothelial function. Finally, we will discuss the role of placental PPARs in preeclampsia, a life threatening form of hypertension during pregnancy. We will close with a viewpoint on future research directions and implications for developing novel therapies.
The Gut Microbiome in Hypertension
Authors: Avery Ellen G. , Bartolomaeus Hendrik , Maifeld Andras , Marko Lajos , Wiig Helge , Wilck Nicola , Rosshart Stephan P. , Forslund Sofia K. , Müller Dominik N.
Published: April 2021

The pathogenesis of hypertension is known to involve a diverse range of contributing factors including genetic, environmental, hormonal, hemodynamic and inflammatory forces, to name a few. There is mounting evidence to suggest that the gut microbiome plays an important role in the development and pathogenesis of hypertension. The gastrointestinal tract, which houses the largest compartment of immune cells in the body, represents the intersection of the environment and the host. Accordingly, lifestyle factors shape and are modulated by the microbiome, modifying the risk for hypertensive disease. One well-studied example is the consumption of dietary fibers, which leads to the production of short-chain fatty acids and can contribute to the expansion of anti-inflammatory immune cells, consequently protecting against the progression of hypertension. Dietary interventions such as fasting have also been shown to impact hypertension via the microbiome. Studying the microbiome in hypertensive disease presents a variety of unique challenges to the use of traditional model systems. Integrating microbiome considerations into preclinical research is crucial, and novel strategies to account for reciprocal host-microbiome interactions, such as the wildling mouse model, may provide new opportunities for translation. The intricacies of the role of the microbiome in hypertensive disease is a matter of ongoing research, and there are several technical considerations which should be accounted for moving forward. In this review we provide insights into the host-microbiome interaction and summarize the evidence of its importance in the regulation of blood pressure. Additionally, we provide recommendations for ongoing and future research, such that important insights from the microbiome field at large can be readily integrated in the context of hypertension.
Guideline-Driven Management of Hypertension
Authors: Carey Robert M. , Wright Jackson T. , Taler Sandra J. , Whelton Paul K.
Published: April 2021

Several important findings bearing on the prevention, detection, and management of hypertension have been reported since publication of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. This review summarizes and places in context the results of relevant observational studies, randomized clinical trials, and meta-analyses published between January 2018 and March 2021. Topics covered include blood pressure measurement, patient evaluation for secondary hypertension, cardiovascular disease risk assessment and blood pressure threshold for drug therapy, lifestyle and pharmacological management, treatment target blood pressure goal, management of hypertension in older adults, diabetes, chronic kidney disease, resistant hypertension, and optimization of care using patient, provider, and health system approaches. Presenting new information in each of these areas has the potential to increase hypertension awareness, treatment, and control which remain essential for the prevention of cardiovascular disease and mortality in the future.
Increased Reactive Oxygen Species–Mediated Ca
2+
/Calmodulin-Dependent Protein Kinase II Activation Contributes to Calcium Handling Abnormalities and Impaired Contraction in Barth Syndrome
Authors: Liu Xujie , Wang Suya , Guo Xiaoling , Li Yifei , Ogurlu Roza , Lu Fujian , Prondzynski Maksymilian , de la Serna Buzon Sofia , Ma Qing , Zhang Donghui , Wang Gang , Cotton Justin , Guo Yuxuan , Xiao Ling , Milan David J. , Xu Yang , Schlame Michael , Bezzerides Vassilios J. , Pu William T.
Published: April 2021

Background:

Mutations in tafazzin (
TAZ
), a gene required for biogenesis of cardiolipin, the signature phospholipid of the inner mitochondrial membrane, causes Barth syndrome (BTHS). Cardiomyopathy and risk of sudden cardiac death are prominent features of BTHS, but the mechanisms by which impaired cardiolipin biogenesis causes cardiac muscle weakness and arrhythmia are poorly understood.

Methods:

We performed in vivo electrophysiology to define arrhythmia vulnerability in cardiac-specific
TAZ
knockout mice. Using cardiomyocytes derived from human induced pluripotent stem cells and cardiac-specific
TAZ
knockout mice as model systems, we investigated the effect of
TAZ
inactivation on Ca
2+
handling. Through genome editing and pharmacology, we defined a molecular link between
TAZ
mutation and abnormal Ca
2+
handling and contractility.

Results:

A subset of mice with cardiac-specific
TAZ
inactivation developed arrhythmias, including bidirectional ventricular tachycardia, atrial tachycardia, and complete atrioventricular block. Compared with wild-type controls, BTHS-induced pluripotent stem cell–derived cardiomyocytes had increased diastolic Ca
2+
and decreased Ca
2+
transient amplitude. BTHS-induced pluripotent stem cell–derived cardiomyocytes had higher levels of mitochondrial and cellular reactive oxygen species than wild-type controls, which activated CaMKII (Ca
2+
/calmodulin-dependent protein kinase II). Activated CaMKII phosphorylated the RYR2 (ryanodine receptor 2) on serine 2814, increasing Ca
2+
leak through RYR2. Inhibition of this reactive oxygen species–CaMKII–RYR2 pathway through pharmacological inhibitors or genome editing normalized aberrant Ca
2+
handling in BTHS-induced pluripotent stem cell–derived cardiomyocytes and improved their contractile function. Murine
Taz
knockout cardiomyocytes also exhibited elevated diastolic Ca
2+
and decreased Ca
2+
transient amplitude. These abnormalities were ameliorated by Ca
2+
/calmodulin-dependent protein kinase II or reactive oxygen species inhibition.

Conclusions:

This study identified a molecular pathway that links
TAZ
mutation with abnormal Ca
2+
handling and decreased cardiomyocyte contractility. This pathway may offer therapeutic opportunities to treat BTHS and potentially other diseases with elevated mitochondrial reactive oxygen species production.
Can the World Be Redeemed? Geʾulah versus Pidyon: Toward a Mundane, Non-Eschatological Approach to Redemption
Authors: Cooper Julie E.
Published: April 2021

In this essay, I juxtapose two conceptions of redemption, as expressed by the Hebrew terms geʾulah and pidyon. I contend that today, the non-eschatological conception of redemption that animates the term pidyon is more politically salient than traditional cautions against geʾulah-inspired apocalypticism. Indeed, restoring the more mundane understanding of redemption suggested by pidyon – as release from inherited narratives and obligations – may help us break the stalemate that has descended upon Israeli politics.
Can vermicompost and biochar control Meloidogyne javanica on eggplant?
Authors: Ebrahimi Mohsen , Mousavi Amir , Souri Mohammad Kazem , Sahebani Navazolah
Published: April 2021

The root-knot nematode, Meloidogyne javanica, is the most damaging species of plant-parasitic nematodes in eggplant cultivation in Iran. We studied the effect of pistachio and date palm biochars, vermicompost and a mixture of each of these biochars with vermicompost on M. javanica. To investigate the effect of these organic materials on survival, hatching and attraction of the second-stage juvenile (J2) towards the root, bioassays were performed in the laboratory using extracts of organic material. Vermicompost extract increased J2 mortality and decreased hatching and the number of J2 attracted to the eggplant roots. However, either type of biochar alone or mixed with vermicompost did not cause J2 mortality, nor did they inhibit hatching and attraction of J2 towards the root. To determine the effect of organic matter on J2 invasion and reproduction, pot experiments were performed in a completely randomised design with four replications in the glasshouse. Vermicompost reduced the number of J2 that penetrated the roots, number of egg masses and the final population of M. javanica eggs and J2. The suppressing effect of vermicompost might be attributed to the release of toxic compounds such as ammonium and improved soil nutrient and plant growth, leading to plants more tolerant to nematode damage. Pistachio and date biochars alone or combined with vermicompost had no adverse effect on the nematode reproduction compared to non-treated soil. Both types of biochar reduced the suppressing effect of vermicompost, most probably due to the absorbance of suppressive compounds in vermicompost by the high surface area of the biochar.
Singing to the Wind
Authors: Provenza Antonietta
Published: April 2021

This paper focuses on a passage of Himerius’ Oration 47 (Simon. fr. 251 Poltera = 535 PMG + p. 157 SLG), where Simonides is cited for a song that leads a ship with favourable winds, and on a passage in Plutarch’s Quaestiones Convivales (722b–c) quoting a Simonidean fragment (17 Poltera = 595 PMG) on the propagation of sounds through still air. I argue that they both can be linked with the Argonautic myth of Orpheus. In fact, the former might have some connections with the myth of Oreithyia and Boreas, parents of Zetes and Kalaïs, involved in the Argonautic expedition; moreover, it has some similarities with a fragment from Euripides’ Hypsipyle (752g Kannicht) representing Orpheus on the Argo. The latter fragment, in its turn, seems to refer to Orpheus’ encounter with the Sirens, and to presuppose common assumptions that were later examined and better developed by Aristotle and his school.
“Melodias Visuais, Poesias Musicais: Antiguidade Sonoras”
Authors: Cerqueira Fábio Vergara , Santos Amanda Basilio
Published: April 2021

This report deals with the activities carried out at the XX Jornada de História Antiga [XX Ancient History Conference], promoted by LECA (Laboratory of Studies on Ancient Ceramics) and held at UFPEL (Universidade Federal de Pelotas, Brasil); the conference was devoted to ancient Greek and Roman music, with a multidisciplinary approach. Here we present its aims, a description of the meeting, and some of the outcomes which resulted from the event.
Trump and Muslims: A Critical Discourse Analysis of Islamophobic Rhetoric in Donald Trump’s Selected Tweets
Authors: Khan Mohsin Hassan , Qazalbash Farwa , Adnan Hamedi Mohd , Yaqin Lalu Nurul , Khuhro Rashid Ali
Published: April 2021

The emergence of Donald Trump as an anti-Muslim-Islam presidential candidate and victory over Hillary Clinton is an issue of debate and division in the United States’ political sphere. Many commentators and political pundits criticize Trump for his disparaging rhetoric on Twitter and present him as an example of how Twitter can be an effective tool for the construction and extension of political polarization. The current study analyzes the selected tweets by Donald Trump posted on Twitter to unmask how he uses language to construct Islamophobic discourse structures and attempts to form his ideological structures along with. The researchers hypothesize that Islamophobia is a marked feature of Trump’s political career realized by specific rhetorical and discursive devices. Therefore, the study purposively takes 40 most controversial tweets of Donald Trump against Islam and Muslims and carried out a critical discourse analysis with the help of macro-strategies of the discourse given by Wodak and Meyer and van Dijk’s referential strategies of political discourse. The findings reveal that Trump uses language rhetorically to exclude people of different ethnic identities, especially Muslims, through demagogic language to create a difference of “us” vs. “them” and making in this way “America Great Again”.
Value-at-Risk Analysis for Measuring Stochastic Volatility of Stock Returns: Using GARCH-Based Dynamic Conditional Correlation Model
Authors: Afzal Fahim , Haiying Pan , Afzal Farman , Mahmood Asif , Ikram Amir
Published: April 2021

To assess the time-varying dynamics in value-at-risk (VaR) estimation, this study has employed an integrated approach of dynamic conditional correlation (DCC) and generalized autoregressive conditional heteroscedasticity (GARCH) models on daily stock return of the emerging markets. A daily log-returns of three leading indices such as KSE100, KSE30, and KSE-ALL from Pakistan Stock Exchange and SSE180, SSE50 and SSE-Composite from Shanghai Stock Exchange during the period of 2009–2019 are used in DCC-GARCH modeling. Joint DCC parametric results of stock indices show that even in the highly volatile stock markets, the bivariate time-varying DCC model provides better performance than traditional VaR models. Thus, the parametric results in the DCC-GRACH model indicate the effectiveness of the model in the dynamic stock markets. This study is helpful to the stockbrokers and investors to understand the actual behavior of stocks in dynamic markets. Subsequently, the results can also provide better insights into forecasting VaR while considering the combined correlational effect of all stocks.
Higher throughput drug screening for rare respiratory diseases: readthrough therapy in primary ciliary dyskinesia
Authors: Lee Dani Do Hyang , Cardinale Daniela , Nigro Ersilia , Butler Colin R. , Rutman Andrew , Fassad Mahmoud R. , Hirst Robert A. , Moulding Dale , Agrotis Alexander , Forsythe Elisabeth , Peckham Daniel , Robson Evie , Smith Claire M. , Somavarapu Satyanarayana , Beales Philip L. , Hart Stephen L. , Janes Sam M. , Mitchison Hannah M. , Ketteler Robin , Hynds Robert E. , O'Callaghan Christopher
Published: April 2021

Background

Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies followed by ciliated differentiation at the air–liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique's broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that can be expanded from such biopsies.

Methods

We describe an immunofluorescence screening method, enabled by extensive expansion of basal cells from PCD patients and the directed differentiation of these cells into ciliated epithelium in miniaturised 96-well transwell format ALI cultures. As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia), in this case caused by a homozygous nonsense mutation in the MCIDAS gene.

Results

Initial analyses of ciliary ultrastructure, beat pattern and beat frequency in the 96-well transwell format ALI cultures indicate that a range of different PCD defects can be retained in these cultures. The screening system in our proof-of-principal investigation allowed drugs that induce translational readthrough to be evaluated alone or in combination with nonsense-mediated decay inhibitors. We observed restoration of basal body formation but not the generation of cilia in the patient's nasal epithelial cells in vitro.

Conclusion

Our study provides a platform for higher throughput analyses of airway epithelia that is applicable in a range of settings and suggests novel avenues for drug evaluation and development in PCD caused by nonsense mutations.
Dietary intake of vitamin A, lung function and incident asthma in childhood
Authors: Talaei Mohammad , Hughes David A. , Mahmoud Osama , Emmett Pauline M. , Granell Raquel , Guerra Stefano , Shaheen Seif O.
Published: April 2021

Background

Longitudinal epidemiological data are scarce on the relationship between dietary intake of vitamin A and respiratory outcomes in childhood. We investigated whether a higher intake of preformed vitamin A or pro-vitamin β-carotene in mid-childhood is associated with higher lung function and with asthma risk in adolescence.

Methods

In the Avon Longitudinal Study of Parents and Children, dietary intakes of preformed vitamin A and β-carotene equivalents were estimated by food frequency questionnaire at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and forced expiratory flow at 25–75% of FVC (FEF25–75%) were measured at 15.5 years and transformed to z-scores. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years.

Results

In multivariable adjusted models, a higher intake of preformed vitamin A was associated with higher lung function and a lower risk of incident asthma: comparing topversusbottom quartiles of intake, regression coefficients for FEV1and FEF25–75%were 0.21 (95% CI 0.05–0.38; ptrend=0.008) and 0.18 (95% CI 0.03–0.32; ptrend=0.02), respectively; odds ratios for FEV1/FVC below the lower limit of normal and incident asthma were 0.49 (95% CI 0.27–0.90; ptrend=0.04) and 0.68 (95% CI 0.47–0.99; ptrend=0.07), respectively. In contrast, there was no evidence for association with β-carotene. We also found some evidence for modification of the associations between preformed vitamin A intake and lung function byBCMO1,NCOR2andSCGB1A1gene polymorphisms.

Conclusion

A higher intake of preformed vitamin A, but not β-carotene, in mid-childhood is associated with higher subsequent lung function and lower risk of fixed airflow limitation and incident asthma.
Lung ultrasound assessment for pneumothorax following transbronchial lung cryobiopsy
Authors: Laursen Christian B. , Pietersen Pia I. , Jacobsen Niels , Falster Casper , Juul Amanda D. , Davidsen Jesper R.
Published: April 2021

Background

Iatrogenic pneumothorax is a common and clinically important transbronchial cryobiopsy (TBCB) complication. A study was conducted to assess the diagnostic accuracy and clinical impact of immediate post-procedure lung ultrasound for diagnosing iatrogenic pneumothorax in patients suspected of interstitial lung disease (ILD) undergoing TBCB.

Study design and methods

In patients undergoing TBCB due to suspected ILD, lung ultrasound of the anterior surface of the chest was performed immediately after the TBCB procedure prior to extubation. Presence of lung point was used as a definite sign of pneumothorax. Chest radiography was routinely performed 2 h after TBCB and was used as the reference standard.

Results

A total of 141 consecutive patients were included. Post-procedure lung ultrasound identified definite pneumothorax in five patients (3.6%, 95% confidence interval (CI) 1.5–8.3%). Chest radiography at 2 h identified 19 patients (13.5%, 95% CI 8.7–20.2%) with pneumothorax following TBCB. The diagnostic accuracy of lung ultrasound for diagnosing pneumothorax was as follows: sensitivity: 21.1% (95% CI 6.1–45.6%), specificity: 99.2% (95% CI 95.5–100.0%), positive predictive value (PPV): 80.0% (95% CI 28.4–99.5%) and negative predictive value (NPV): 89.0% (95% CI 82.5–93.7%). Post-procedure lung ultrasound had a clinical impact in five patients (3.6%, 95% CI 1.5–8.3), of which four had a pleural drain inserted prior to extubation and one underwent prolonged observation prior to extubation.

Interpretation

Lung ultrasound performed immediately following TBCB has a clinical impact by identifying patients with pneumothorax in need of immediate treatment prior to extubation and by monitoring pneumothorax size in the operating room. Supplementary imaging prior to patient discharge is still needed however, as the majority of pneumothoraxes develop later in the post-procedure period.
Relationship between miR-378c and YY1 expression in patients with gastric cancer and the clinicopathological features
Authors: Zhang Lei , Zou Lei , Sun Peng
Published: April 2021

Background

The purpose of this study was to explore the clinical value of miR-378c and its target gene YY1 in gastric cancer.

Methods

The TCGA database was employed to analyse miR-378c expression in gastric cancer. qRT-PCR was applied to identify miR-378c and YY1 in tissues and serum of patients suffering from gastric cancer. The association of miR-378c with the clinical data of patients with gastric cancer was analysed. Receiver operating characteristics (ROC) curve analysis was used to determine the diagnostic value of miR-378c and YY1 in gastric cancer, and analyse the relationship between miR-378c and YY1 and patients’ survival. Pearson’s test was applied to determine the association between miR-378c and YY1 in tissue and serum of patients. Dual-Luciferase Reporter assay was employed to examine the targeting association between miR-378c and YY1. Finally, independent prognostic factors was determined in patients with gastric cancer using Cox regression analysis.

Results

In the TCGA database, miR-378c was weakly expressed in gastric cancer. Overall, patients with low expression had a lower survival rate. The expression of miR-378c decreased and the expression of YY1 increased in cancer tissues and serum of tumour patients. In patients with low expression of miR-378c the tumour size was ≥ 5 cm. Low differentiation, high TNM staging and lymph node invasion rate increased significantly, but the 5-year survival rate decreased in the patients. miR-378c and YY1 had better diagnostic value in gastric cancer. TargetScan, miRDB, starBase and miRTarBase predicted that YY1 was a potential gene of miR-378c, and the Dual-Luciferase Reporter assay revealed that there was a targeting relationship between the two, which was proved by correlation analysis. Multivariate Cox analysis revealed that differentiation, TNM staging and miR-378c were independent prognostic factors for patients.

Conclusions

MiR-378c is weakly expressed in gastric cancer patients and may be considered as a promising diagnostic and prognostic indicator for gastric cancer.
A high-density genetic map construction and sex-related loci identification in Chinese Giant salamander
Authors: Hu Qiaomu , Liu Yang , Liao Xiaolin , Tian Haifeng , Ji Xiangshan , Zhu Jiajie , Xiao Hanbing
Published: April 2021

Background

The Chinese giant salamanderAndrias davidianusis an important amphibian species in China because of its increasing economic value, protection status and special evolutionary position from aquatic to terrestrial animal. Its large genome presents challenges to genetic research. Genetic linkage mapping is an important tool for genome assembly and determination of phenotype-related loci.

Results

In this study, we constructed a high-density genetic linkage map using ddRAD sequencing technology to obtain SNP genotyping data of members from an full-sib family which sex had been determined. A total of 10,896 markers were grouped and oriented into 30 linkage groups, representing 30 chromosomes ofA. davidianus. The genetic length of LGs ranged from 17.61 cM (LG30) to 280.81 cM (LG1), with a mean inter-locus distance ranging from 0.11(LG3) to 0.48 cM (LG26). The total genetic map length was 2643.10 cM with an average inter-locus distance of 0.24 cM. Three sex-related loci and four sex-related markers were found on LG6 and LG23, respectively.

Conclusion

We constructed the first High-density genetic linkage map and identified three sex-related loci in the Chinese giant salamander. Current results are expected to be a useful tool for future genomic studies aiming at the marker-assisted breeding of the species.
Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer
Authors: Zheng Sheng , Zhang Zizhen , Ding Ning , Sun Jiawei , Lin Yifeng , Chen Jingyu , Zhong Jing , Shao Liming , Lin Zhenghua , Xue Meng
Published: April 2021

Introduction

Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC).

Methods

mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively.

Results

Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation.

Conclusions

We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.