bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Gene Expression Programming to Evaluate Strength Characteristics of Hydrated-Lime-Activated Rice Husk Ash-Treated Expansive Soil
Authors: Onyelowe Kennedy C. , Jalal Fazal E. , Onyia Michael E. , Onuoha Ifeanyichukwu C. , Alaneme George U.
Published: April 2021

Gene expression programming has been applied in this work to predict the California bearing ratio (CBR), unconfined compressive strength (UCS), and resistance value (R value or Rvalue) of expansive soil treated with an improved composites of rice husk ash. Pavement foundations suffer failures due to poor design and construction, poor materials handling and utilization, and management lapses. The evolution of sustainable green materials and optimization and soft computing techniques have been deployed to improve on the deficiencies being suffered in the abovementioned areas of design and construction engineering. In this work, expansive soil classified as A-7-6 group soil was treated with hydrated-lime activated rice husk ash (HARHA) in an incremental proportion to produce 121 datasets, which were used to predict the behavior of the soil’s strength parameters utilizing the mutative and evolutionary algorithms of GEP. The input parameters were HARHA, liquid limit (

w

L

), (plastic limit

w

P

, plasticity index

I

P

, optimum moisture content (

w

OMC

), clay activity (AC), and (maximum dry density (δmax) while CBR, UCS, and R value were the output parameters. A multiple linear regression (MLR) was also conducted on the datasets in addition to GEP to serve as a check mechanism. At the end of the computing and iterations, MLR and GEP optimization methods proposed three equations corresponding to the output parameters of the work. The responses validation on the predicted models shows a good correlation above 0.9 and a great performance index. The predicted models’ performance has shown that GEP soft computing has predicted models that can be used in the design of CBR, UCS, and R value for soils being used as foundation materials and being treated with admixtures as a binding component.
Reinforcement Number of a Graph with respect to Half-Domination
Authors: Muhiuddin G. , Sridharan N. , Al-Kadi D. , Amutha S. , Elnair M. E.
Published: April 2021

In this paper, we introduce the concept of reinforcement number with respect to half-domination and initiate a study on this parameter. Furthermore, we obtain various upper bounds for this parameter. AMS subject classification: 05C38, 05C40, 05C69.
The Prevalence of Malaria among Children in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Tegegne Yalewayker , Worede Abebaw , Derso Adane , Ambachew Sintayehu
Published: April 2021

Background. Malaria is one of the most public health important and life-threatening parasitic infections caused by the protozoan parasite. Since children are immunologically naive to the malaria parasite, they are the main vulnerable groups. During malaria infection, they might have a complication of anemia, cerebral malaria, coma, respiratory distress, and a decrease in cognitive and behavioral improvement. Therefore, this review was aimed at determining the pooled prevalence of malaria among children in Ethiopia. Methods. The current systematic review and meta-analysis were conducted based on the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guideline. Electronic bibliographic databases such as Google Scholar, PubMed, and Science Direct were used for searching relevant literature. Besides, the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used for critical appraisal of studies. Using the STATA 14 software, the pooled Meta logistic regression was computed to present the pooled prevalence with a 95% confidence interval (CI). Result. The overall estimated pooled prevalence of malaria among children in Ethiopia was 9.07 (95% CI: 6.32, 11.82). Subgroup analysis based on malaria signs and symptoms showed that the pooled prevalence of malaria among asymptomatic and symptomatic children was 6.67% (95% CI: 0.36, 12.98) and 27.17% (95% CI: 18.59, 35.76), respectively. Conclusion. The findings revealed a high prevalence of malaria among children in Ethiopia. As a result, still there is a need of improving and rechecking the existing malaria prevention and control measures of the country.
Anti-Inflammatory and Anti-Vascular Leakage Effects by Combination of Centella asiatica and Vitis vinifera L. Leaf Extracts
Authors: Seo Myung-Gi , Jo Min-Jeong , Hong Nam In , Kim Min Jung , Shim Kyu Suk , Shin Eunju , Lee Jeong Jun , Park Sang-Joon
Published: April 2021

Venous insufficiency results from several factors responsible for the progression of inflammation and oxidative damage of veins. Recently, natural extracts have been proposed for the treatment of venous insufficiency, but their efficacies have not been fully elucidated. In the present study, we evaluate the combinatorial effects on anti-inflammatory and anti-vascular leakage potential of mixed compositions containing different proportions of Centella asiatica extract (CE) and Vitis vinifera L. leaf extract (VVE) using an inflammation model of lipopolysaccharide- (LPS-) stimulated RAW264.7 cells and various vascular permeability models in mice (acetic-acid-induced peritoneal vascular model, mustard-oil-stimulated ear vascular model, and carrageenan-induced paw edema model). Pretreatment of CE and VVE in a 1 : 3 combination dose dependently inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) through downregulation of the nuclear factor-κB (NF-κB) pathway in LPS-stimulated RAW264.7 macrophages. In vascular permeability-related mouse models, pretreatment with the CE-VVE 1 : 3 combination significantly reduced the permeability of peritoneal or ear veins caused by acetic acid and mustard oil, respectively. Furthermore, pretreatment of the CE-VVE 1 : 3 combination ameliorated inflammation and edema of the hind paw caused by carrageenan injection. Thus, the combination of CE and VVE showed significant anti-inflammatory qualities and anti-vascular leakage effects. These findings indicate that an optimal combination of CE and VVE may have a more synergistic effect than that of CE or VVE alone as a putative agent against vascular incompetence.
Efficacy and Safety of a Combination of Shenmai Injection plus Chemotherapy for the Treatment of Lung Cancer: A Meta-Analysis
Authors: Qin Guo-wei , Xu Tong-tong , Lv Xiang-wei , Jiang Shi-min , Zhang Ke-jia , Xu Ming , Fu Lu , Wu Qi , Zhou Yao
Published: April 2021

Objective. To perform a systematic evaluation of the efficacy and safety of combined treatment of Shenmai injection and chemotherapy for lung cancer. Methods. A literature search for randomized controlled trials (RCTs) describing the treatment of lung cancer by Shenmai injection and chemotherapy or chemotherapy alone was performed using the PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Value In Paper (VIP), China BioMed, and Wanfang databases. The databases were searched for entries published before September 1, 2019. Results. Thirty-seven RCTs, comprising a total of 2808 cases, were included in the present meta-analysis. Of these, 1428 cases were treated by Shenmai injection plus chemotherapy, and 1380 cases were treated only by chemotherapy. The results of meta-analysis showed that the combined treatment (Shenmai injection plus chemotherapy) increased the short-term efficacy of treatment (relative risk [RR] = 1.183, 95% confidence interval [CI] = 1.043–1.343,

P
<
0.01

) and improved patients’ quality of life (RR = 1.514, 95%CI = 1.211–1.891,

P
<
0.01

) compared with chemotherapy alone. With regard to the adverse effects, the combined treatment markedly reduced the incidence of white blood cell (WBC) reduction (RR = 0.846, 95%CI = 0.760–0.941,

P
<
0.01

), platelet reduction (RR = 0.462, 95% CI = 0.330–0.649,

P
<
0.01

), and hemoglobin reduction (RR = 0.462, 95% CI = 0.330–0.649,

P
<
0.01

) and alleviated drug-induced liver injury (RR = 0.677, 95%CI = 0.463–0.990,

P
<
0.05

). However, it did not offer a significant protective effect (RR = 0.725, 95%CI = 0.358–1.468,

P
<
0.05

). The effect of the combined treatment on the occurrence of vomiting was considerable (RR = 0.889, 95%CI = 0.794–0.996,

P
<
0.05

), and the combined treatment markedly increased the immunity of patients with lung cancer. Conclusion. The combined treatment of Shenmai injection plus chemotherapy enhanced the short-term efficacy of chemotherapy, improved the patient quality of life, alleviated the adverse effects of chemotherapeutics, and increased the patient immunity. These results should be confirmed by large-scale, high-quality RCTs.
Behavior of SD-OCT Detectable Hyperreflective Foci in Diabetic Macular Edema Patients after Therapy with Anti-VEGF Agents and Dexamethasone Implants
Authors: Rübsam Anne , Wernecke Laura , Rau Saskia , Pohlmann Dominika , Müller Bert , Zeitz Oliver , Joussen Antonia M.
Published: April 2021

Purpose. Diabetic macular edema (DME) is the most common cause of blindness in the working-age population. Spectral-domain optical coherence tomography (SD-OCT) allows detection and monitoring of the edema and a detailed analysis of the retinal structure. Hyperreflective foci (HF) are small, circumscribed lesions on OCT, and their origin is yet to be determined. Our study was aimed to shed light on HF pathophysiology, by analyzing their number and location in DME patients at baseline and after therapy. Methods. A prospective, observational study on 59 eyes of 51 DME patients who were treated with antivascular endothelial growth factor (VEGF) therapy (VEGF group,

n
=
40

eyes) or dexamethasone implant (DEX group,

n
=
19

). HF and hard exudates (HE) were discriminated by their appearance on fundus photographs and their size on OCT. Quantity and location of HF and HE were analyzed at baseline and after therapy. Results. DME decreased in 75% of patients in the VEGF (455.5 μm vs. 380.8 μm,

p
=
0.02

) and in 95% of patients in the DEX group (471.6 μm vs. 381.9 μm,

p
=
0.007

). The number of foci decreased in 62.5% of patients after anti-VEGF (130.6 vs. 111.1,

p
=
0.07

) and in 68% of patients after dexamethasone injection ((123.4 vs. 94.9,

p
=
0.02

) 5.1). A subgroup of 15% of eyes, all treated with anti-VEGF, showed accumulation of larger HF in outer retinal layers to visible HE during DME resolution, whereas smaller HF, found in all retinal layers, remained unchanged. There was a trend towards a dynamic shift of the foci from inner to outer retinal layers. Conclusion. The dynamic rearrangement of the small HF and their slightly greater reduction after anti-inflammatory therapy suggest inflammatory cells as their origin, whereas larger HF in the outer retinal layers correspond to microexudates. Furthermore, we found a more favourable outcome in patients with HF after treatment with dexamethasone implants compared to anti-VEGF agents.
Use of α-Lactalbumin and Caseinoglycomacropeptide as Biopeptide Precursors and as Functional Additives in Milk Beverages Fermented by L. helveticus
Authors: Skrzypczak Katarzyna , Fornal Emilia , Domagała Dorota , Gustaw Waldemar , Jabłońska-Ryś Ewa , Sławińska Aneta , Radzki Wojciech , Kononiuk Anna , Waśko Adam
Published: April 2021

The objective of this investigation was to verify whether biologically active peptides (BAPs) could be obtained from water solutions of α-lactalbumin (α-la) and caseinoglycomacropeptide (CGMP) through an application of the new Lactobacillus helveticus strains. Also, the aim of this research was to determine the influence of addition of the analyzed protein preparations to milk subjected to fermentation by tested bacterial strains on the physicochemical properties of obtained milk beverages. The results indicate that CGMP is a more preferable source for the production of BAPs by the test bacteria than α-la. The antihypertensive and ACE inhibitory effects were the most widespread bioactivities among the detected BAPs. α-la containing fermented milk beverages had higher values of springiness, gumminess, chewiness, and resilience than analogous products containing CGMP, while CGMP-supplemented fermented products exhibited higher values of the hardness parameter. The highest values of hardness (

0.416
±
0.05

 N) were recorded for beverages fermented by DSMZ containing the addition of CGMP, while the lowest value of this parameter (

0.186
±
0.06

 N) was noted for products containing α-la and fermented by B734. Moreover, CGMP-containing fermented products were characterized by a generally higher value of the proteolysis index (PI) than analogous variants containing α-la. The use of analyzed strains and the selected protein preparations has a positive effect on the texture of fermented milk beverages and might contribute to an increase in the health-promoting potential of such products.
Inhibition of the FACT Complex Targets Aberrant Hedgehog Signaling and Overcomes Resistance to Smoothened Antagonists
Authors: Mo Jialin , Liu Fang , Sun Xi , Huang Hongting , Tan Kezhe , Zhao Xiaojing , Li Rui , Jiang Wenyan , Sui Yi , Chen Xiaosong , Shen Kunwei , Zhang Liye , Ma Jie , Zhao Kewen , Tang Yujie
Published: April 2021

Hedgehog signaling is aberrantly activated in hematologic malignancies and solid tumors, and targeting it is a promising therapeutic strategy against these cancers. Resistance to clinically available hedgehog-targeted Smoothened inhibitor (SMOi) drugs has become a critical issue in hedgehog-driven cancer treatment. Our previous studies identified inhibition of BET and CDK7 as two epigenetic/transcriptional-targeted therapeutic strategies for overcoming SMOi resistance, providing a promising direction for anti-hedgehog drug development. To uncover additional strategies for inhibiting aberrant hedgehog activity, here we performed CRISPR-Cas9 screening with an single-guide RNA library targeting epigenetic and transcriptional modulators in hedgehog-driven medulloblastoma cells, combined with tumor dataset analyses. Structure specific recognition protein 1 (SSRP1), a subunit of facilitates chromatin transcription (FACT) complex, was identified as a hedgehog-induced essential oncogene and therapeutic target in hedgehog-driven cancer. The FACT inhibitor CBL0137, which has entered clinical trials for cancer, effectively suppressed in vitro and in vivo growth of multiple SMOi-responsive and SMOi-resistant hedgehog-driven cancer models. Mechanistically, CBL0137 exerted anti-hedgehog activity by targeting transcription of GLI1 and GLI2, which are core transcription factors of the hedgehog pathway. SSRP1 bound the promoter regions of GLI1 and GLI2, while CBL0137 treatment substantially disrupted these interactions. Moreover, CBL0137 synergized with BET or CDK7 inhibitors to antagonize aberrant hedgehog pathway and growth of hedgehog-driven cancer models. Taken together, these results identify FACT inhibition as a promising epigenetic/transcriptional-targeted therapeutic strategy for treating hedgehog-driven cancers and overcoming SMOi resistance.

Significance:

This study identifies FACT inhibition as an anti-hedgehog therapeutic strategy for overcoming resistance to Smoothened inhibitors and provides preclinical support for initiating clinical trials of FACT-targeted drug CBL0137 against hedgehog-driven cancers.
Recruitment of KMT2C/MLL3 to DNA Damage Sites Mediates DNA Damage Responses and Regulates PARP Inhibitor Sensitivity in Cancer
Authors: Chang Antao , Liu Liang , Ashby Justin M. , Wu Dan , Chen Yanan , O'Neill Stacey S. , Huang Shan , Wang Juan , Wang Guanwen , Cheng Dongmei , Tan Xiaoming , Petty W.J. , Pasche Boris C. , Xiang Rong , Zhang Wei , Sun Peiqing
Published: April 2021

When recruited to promoters, histone 3 lysine 4 (H3K4) methyltransferases KMT2 (KMT2A-D) activate transcription by opening chromatin through H3K4 methylation. Here, we report that KMT2 mutations occur frequently in non–small cell lung cancer (NSCLC) and are associated with high mutation loads and poor survival. KMT2C regulated DNA damage responses (DDR) through direct recruitment to DNA damage sites by Ago2 and small noncoding DNA damage response RNA, where it mediates H3K4 methylation, chromatin relaxation, secondary recruitment of DDR factors, and amplification of DDR signals along chromatin. Furthermore, by disrupting homologous recombination (HR)–mediated DNA repair, KMT2C/D mutations sensitized NSCLC to Poly(ADP-ribose) polymerase inhibitors (PARPi), whose efficacy is unclear in NSCLC due to low BRCA1/2 mutation rates. These results demonstrate a novel, transcription-independent role of KMT2C in DDR and identify high-frequency KMT2C/D mutations as much-needed biomarkers for PARPi therapies in NSCLC and other cancers with infrequent BRCA1/2 mutations.

Significance:

This study uncovers a critical role for KMT2C in DDR via direct recruitment to DNA damage sites, identifying high-frequency KMT2C/D mutations as biomarkers for response to PARP inhibition in cancer.
Molecular Subtypes of Pancreatic Cancer: A Proteomics Approach
Authors: Thakur Ravi , Singh Pankaj K.
Published: April 2021

Through molecular subtyping, therapeutic vulnerabilities can be exploited for developing personalized medicine. The real utility of molecular subtyping lies in the clinical translation for disease characterization. Proteomic methods with defined marker sets hold great promise for improving therapy outcomes by improving the speed of predictions for devising treatment strategies.

See related article by Son et al., p. 3370
Interleukin-4 Receptor Inhibition Targeting Metastasis Independent of Macrophages
Authors: Cleary Megan M. , Bharathy Narendra , Abraham Jinu , Kim Jin-Ah , Rudzinski Erin R. , Michalek Joel E. , Keller Charles
Published: April 2021

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma occurring in children and carries a dismal prognosis when metastatic disease is detected. Our previous work has suggested the cytokine receptor IL4Rα may play a role in contributing to metastasis in the alveolar subtype of rhabdomyosarcoma (aRMS), and thus could present a therapeutic target. The IL4 signaling axis has been characterized in various adult cancers as well; however, pediatric trials often follow similar adult trials and the role of the IL4Rα receptor has not been explored in the context of a mediator of metastasis in adult disease. Here, we demonstrate that the impact of IL4Rα blockade in an orthotopic allograft model of aRMS is not mediated by a macrophage response. We further examine the effect of IL4 blockade in adult colon, breast, and prostate cancers and find that inhibition of IL4Rα signaling modulates in vitro cell viability of HCT-116 colon carcinoma cells; however, this finding did not translate to an autocrine-related in vivo difference in tumor burden or lung metastasis. Our results suggest that if humanized IL4 mouse host strains are not available (or not ideal due to the need for immunosuppressing the host innate immune response for xenograft systems), then genetically-engineered mice and mouse allograft studies may be the best indicator of therapeutic targeting efficacy.
Primary Dwarfism, Microcephaly, and Chorioretinopathy due to a PLK4 Mutation in Two Siblings
Authors: Martín-Rivada Álvaro , Pozo-Román Jesús , Güemes María , Ortiz-Cabrera Nelmar Valentina , Pérez-Jurado Luis A. , Argente Jesús
Published: April 2021

Introduction: Primary autosomal recessive microcephalies (MCPHs) are characterized by primary dwarfism with MCPH and may present delayed psychomotor development and visual impairment. Biallelic loss of function variants in the PLK4 gene, which encodes the polo-like kinase 4 protein involved in centriole biogenesis, has been recently identified in several patients with MCPH and various ethnic backgrounds. Case Presentation: Here, we describe 2 siblings of different sex from Equatorial Guinea harboring a homozygous frameshift mutation in PLK4 (c.1299_1303del, p.Phe433Leufs*6). A Seckel syndrome spectrum phenotype was present in both siblings, with short stature, severe MCPH, reduced brain volume, and distinctive facial features. They also presented severe intellectual disability, lissencephaly/pachygyria, subependymal heterotopia, and ophthalmological impairment. One of them suffered from deafness, and scoliosis was observed in the other. Discussion/Conclusion: Biallelic variants in PLK4 lead to a syndrome where severe short stature, MCPH, and cognitive impairment are constant features. However, ocular, skeletal, and other neurological manifestations can vary upon the same genetic basis.
Evaluation of the Anxiety Level of Mothers of Children with Epilepsy during the COVID-19 Pandemic Period
Authors: Celik Halil , Acikel Sadettin Burak , Ozdemir Fatih Mehmet Akif , Aksoy Erhan , Oztoprak Ulkuhan , Cucu Ergin , Kucur Ozge , Ceylan Nesrin , Yuksel Deniz
Published: April 2021

Background and Aim: Although anyone can be affected by the COVID-19 pandemic, it may cause additional concern for people with chronic conditions. Epilepsy is the most common neurological disease in childhood and adolescence. The aim of this study was to determine anxiety levels among the mothers of children under follow-up for epilepsy in our clinic during the COVID-19 pandemic. Methods: The study group consisted of the mothers of epilepsy patients who were under follow-up in the pediatric neurology outpatient clinic of the tertiary care center and were scheduled for a routine examination during the COVID-19 pandemic. The mothers’ anxiety levels according to the Beck Anxiety Inventory and their opinions about COVID-19 in relation to their child were assessed and compared based on whether the mother/patient attended their appointments in person and whether the child had frequent or infrequent seizures. Results: There was no statistically significant difference in anxiety level between the mothers of 64 children with epilepsy who attended their appointment during the pandemic and those of the mothers of 52 who did not attend their appointment. However, the mothers of children with frequent seizures had significantly higher anxiety levels. Conclusion: Anxiety level of mothers whose children have frequent seizures was significantly higher compared to mothers whose children have infrequent seizures. It is important to be aware about this point and using telemedicine approach in suitable population and postpone routine outpatient follow-up appointments as much as possible.
IgA Nephropathy: “The Times They Are a-Changin”
Authors: Glassock Richard J.
Published: April 2021

Background: Primary IgA Nephropathy (IgA N) is a very common and often progressive glomerular disease. At present, the diagnosis of IgA N is totally dependent on kidney biopsy, but the prospect for a future diagnosis by means of a “liquid” biopsy is promising. A great deal is now understood regarding its diverse clinical and pathological features as well as its epidemiology, genetics, prognosis, and pathogenesis. Treatment approaches are now on increasingly solid evidence-based grounds, but many uncertainties continue to be devil the field. Better means of categorization of patients into a hierarchy of progression risk at the time of diagnosis will undoubtedly refine and personalize treatment decisions. Summary: The panorama of treatment strategies is undergoing a rapid transformation, largely due to an increase in large randomized clinical trials testing available agents and novel therapeutic classes. It is anticipated that the combination of better prognostic tools and new strategies for treatment of IgA N will alter the landscape of therapeutic algorithms for patients with IgA N. Key Messages: This review seeks to describe some of the evolutionary changes in the approach to treatment of IgA N, to place them in the context of current management, and to identify knowledge gaps that need to be addressed.
Oral Candidiasis and COVID-19 in Users of Removable Dentures: Is Special Oral Care Needed?
Authors: Jerônimo Laura Silva , Esteves Lima Rafael Paschoal , Suzuki Thaís Yumi Umeda , Discacciati José Augusto César , Bhering Cláudia Lopes Brilhante
Published: April 2021

Elderly patients with systemic disorders and immunocompromised patients seem to have a higher risk of developing morbidity from COVID-19. Candida albicans (C. albicans) is a potentially dangerous pathogen for these patients, especially for denture wearers with prosthetic stomatitis who require mechanical ventilation. C. albicans infection, the main candidiasis infection associated with denture wear, can complicate COVID-19 and increase the associated morbidity and mortality. Therefore, early diagnosis of C. albicans infection in COVID-19 patients is important to establish more effective antifungal treatment methods and prophylaxis strategies. Hospitalized COVID-19 patients should undergo an oral examination to assess their oral health, and those with poor oral health should receive the appropriate care and monitoring.
Taxes to Unhealthy Food and Beverages and Oral Health in Mexico: An Observational Study
Authors: Hernández-F Mauricio , Cantoral Alejandra , Colchero M. Arantxa
Published: April 2021

In January 2014, taxes on sugar-sweetened beverages and nonessential energy-dense food were implemented in Mexico to discourage the consumption of these products. Published evaluations have shown reductions in purchases of taxed food and beverages associated with the implementation of this fiscal policy. Although there are some studies on the impact on health based on simulation studies, no evaluations with empirical data on changes in oral health have been published. We used administrative records and data from an epidemiological surveillance system to estimate changes in (1) outpatient visits related to dental caries; (2) having experienced dental caries: Decayed, Missing and Filled Teeth (DMFT) >0 for permanent dentition or dmft >0 for primary dentition (dmft); (3) number of teeth with caries experience (DMFT and dmft), (4) cases with DMFT >0 or dmft >0, and (5) the series of mean DMFT or dmft, associated with the taxes. We estimated probit and negative binomial models for outcomes at individual level, and interrupted time series analysis for population-level outcomes. The implementation of the taxes was associated with negative changes in the trends of outpatient visits, as well as for cases with DMFT >0, dmft >0 and mean DMFT. Taxes were also associated with a lower probability of having experienced dental caries and with a lower number of teeth with caries experience in the samples studied. Our results suggest positive impacts of the implementation of taxes on unhealthy food and beverages in the oral health of Mexicans, which are the first health benefits observed, and add to the health benefits predicted by modeling studies.
Extensive Extraneural Metastases of Cerebral Glioblastoma in a Pediatric Patient: An Extreme Case Report and Comprehensive Review of the Literature
Authors: Oktay Kadir , Yildirim Dogu Cihan , Acikalin Arbil , Ozsoy Kerem Mazhar , Cetinalp Nuri Eralp , Erman Tahsin
Published: April 2021

Introduction: Extraneural metastases of glioblastoma are very rare clinical entities, especially in pediatric patients. Because of their rarity, they can be confused with other pathological processes. Case Presentation: We report a case of 16-year-old boy with extensive extraneural metastases of glioblastoma. Lung, liver, cervical lymph nodes, skin, and bone metastases were detected in the patient. Conclusion: We describe the presentation, evaluation, and diagnosis of this rare condition with regard to pertinent literature.
Prevalence and Sociodemographic Determinants of Substance Use in Turkey
Authors: Ünübol Hüseyin , Hızlı Sayar Gökben
Published: April 2021

Background: Substance use disorder is a serious public health problem. It is essential to know who is prone to substance use in order to adopt appropriate measures. Objectives: This study aims to determine the use prevalence ratios of substance use (tobacco, alcohol, cannabis, cocaine, synthetic cannabinoids, ecstasy, and others) in a large-scale sample of a general population. It also intends to examine related sociodemographic factors. Methods: This study is based on a cross-sectional survey conducted with a nationally representative sample of 24,494 individuals in face-to-face interviews conducted by a trained team of 125 clinical psychologists. Results: Lifetime prevalence of single substance use and polysubstance use are 4.5 and 2.6%, respectively (nicotine and alcohol excluded). Age, gender, education level, and marital status are important sociodemographic determinants for other substance use. Similarly, smoking and alcohol consumption are important determinants for other substance use. The multinomial regression analysis results showed that compared with adults aged 39 years and older, early-emerging adults (aged 18–23 years), late-emerging adults (aged 24–29 years), and young adults (aged 30–39 years) are more likely to turn to single substance use and polysubstance use. Conclusion: Tobacco, alcohol, and other substance use are serious health concerns in Turkey. Sociodemographic status is an important determinant of several aspects of tobacco, alcohol, and other substance use and, therefore, should be examined thoroughly to be able to develop effective protective and preventive strategies.
Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy
Authors: Coellar Juan D. , Long Jianyin , Danesh Farhad R.
Published: April 2021

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main functions and mechanisms of actions of lncRNAs, and their promise as therapeutic targets in kidney diseases, emphasizing on the role of some of the best-characterized lncRNAs implicated in the pathogenesis and progression of diabetic nephropathy.
Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes
Authors: Mesirca Pietro , Nakao Shu , Nissen Sarah Dalgas , Forte Gabriella , Anderson Cali , Trussell Tariq , Li Jue , Cox Charlotte , Zi Min , Logantha Sunil , Yaar Sana , Cartensen Helena , Bidaud Isabelle , Stuart Luke , Soattin Luca , Morris Gwilym M. , da Costa Martins Paula A. , Cartwright Elizabeth J. , Oceandy Delvac , Mangoni Matteo E. , Jespersen Thomas , Buhl Rikke , Dobrzynski Halina , Boyett Mark R. , D’Souza Alicia
Published: April 2021

Rationale:

Athletes present with atrioventricular node dysfunction manifesting as atrioventricular block. This can necessitate electronic pacemaker implantation, known to be more frequent in athletes with a long training history.

Objective:

Atrioventricular block in athletes is attributed to high vagal tone. Here, we investigated the alternative hypothesis that electrical remodeling of the atrioventricular node is responsible.

Methods and Results:

Radiotelemetry ECG data and atrioventricular node biopsies were collected in sedentary and trained Standardbred racehorses, a large-animal model of the athlete’s heart. Trained horses presented with longer PR intervals (that persisted under complete autonomic block) versus sedentary horses, concomitant with reduced expression of key ion channels involved in atrioventricular node conduction: L-type Ca
2+
channel subunit Ca
V
1.2 and HCN4 (hyperpolarization-activated cyclic nucleotide-gated channel 4). Atrioventricular node electrophysiology was explored further in mice; prolongation of the PR interval (in vivo and ex vivo), Wenckebach cycle length, and atrioventricular node refractory period were observed in mice trained by swimming versus sedentary mice. Transcriptional profiling in laser-capture microdissected atrioventricular node revealed striking reduction in pacemaking ion channels in trained mice, translating into protein downregulation of Ca
V
1.2 and HCN4. Correspondingly, patch-clamp recordings in isolated atrioventricular node myocytes demonstrated a training-induced reduction in
I

Ca,
L

and
I
f
density that likely contributed to the observed lower frequency of action potential firing in trained cohorts. MicroRNA (miR) profiling and in vitro studies revealed miR-211-5p and miR-432 as direct regulators of Ca
V
1.2 and HCN4. In vivo miRs suppression or detraining restored training-induced PR prolongation and ion channel remodeling.

Conclusions:

Training-induced atrioventricular node dysfunction is underscored by likely miR-mediated transcriptional remodeling that translates into reduced current density of key ionic currents involved in impulse generation and conduction. We conclude that electrical remodeling is a key mechanism underlying atrioventricular block in athletes.
Cardiac‐Specific Deletion of Orai3 Leads to Severe Dilated Cardiomyopathy and Heart Failure in Mice
Authors: Gammons Jesse , Trebak Mohamed , Mancarella Salvatore
Published: April 2021

Background

Orai3 is a mammalian‐specific member of the Orai family (Orai1‒3) and a component of the store‐operated Ca
2+
entry channels. There is little understanding of the role of Orai channels in cardiomyocytes, and its role in cardiac function remains unexplored. Thus, we developed mice lacking Orai1 and Orai3 to address their role in cardiac homeostasis.

Methods and Results

We generated constitutive and inducible cardiomyocyte‐specific Orai3 knockout (Orai3
cKO
) mice. Constitutive Orai3‐loss led to ventricular dysfunction progressing to dilated cardiomyopathy and heart failure. Orai3
cKO
mice subjected to pressure overload developed a fulminant dilated cardiomyopathy with rapid heart failure onset, characterized by interstitial fibrosis and apoptosis. Ultrastructural analysis of Orai3‐deficient cardiomyocytes showed abnormal M‐ and Z‐line morphology. The greater density of condensed mitochondria in Orai3‐deficient cardiomyocytes was associated with the upregulation of DRP1 (dynamin‐related protein 1). Cardiomyocytes isolated from Orai3
cKO
mice exhibited profoundly altered myocardial Ca
2+
cycling and changes in the expression of critical proteins involved in the Ca
2+
clearance mechanisms. Upregulation of TRPC6 (transient receptor potential canonical type 6) channels was associated with upregulation of the RCAN1 (regulator of calcineurin 1), indicating the activation of the calcineurin signaling pathway in Orai3
cKO
mice. A more dramatic cardiac phenotype emerged when Orai3 was removed in adult mice using a tamoxifen‐inducible Orai3
cKO
mouse. The removal of Orai1 from adult cardiomyocytes did not change the phenotype of tamoxifen‐inducible Orai3
cKO
mice.

Conclusions

Our results identify a critical role for Orai3 in the heart. We provide evidence that Orai3‐mediated Ca
2+
signaling is required for maintaining sarcomere integrity and proper mitochondrial function in adult mammalian cardiomyocytes.
Assessment of antinuclear antibodies (ANA): National recommendations on behalf of the Croatian society of medical biochemistry and laboratory medicine
Authors: Tešija Kuna Andrea , Đerek Lovorka , Drvar Vedrana , Kozmar Ana , Gugo Katarina
Published: April 2021

Antinuclear antibodies (ANA) represent a family of autoantibodies targeting ubiquitous cellular constituents and are a hallmark of systemic inflammatory autoimmune rheumatic diseases named connective tissue diseases (CTD). The gold standard method for ANA determination is indirect immunofluorescence (IIF) on the human laryngeal epidermoid carcinoma cell line type 2 substrate (HEp-2), but with increasing demand for ANA testing, novel methods eased for automation emerged, which allows testing by staff less experienced in this specific field of laboratory diagnostic. In 2016 The working group (WG) for laboratory diagnostics of autoimmune diseases as part of the Committee for the Scientific Professional Development of the Croatian Society of Medical Biochemistry and Laboratory Medicine (CSMBLM) published the data of a survey regarding general practice in laboratory diagnostics of autoimmune diseases in Croatia. Results indicated high diversity in the performance of autoantibody testing as well as reporting of the results and indicated the need of creating recommendations for the assessment of ANA that would help harmonize diagnostics of systemic autoimmune rheumatic diseases in Croatia. This document encompasses twenty-seven recommendations for ANA testing created concerning indications for ANA testing, preanalytical, analytical, and postanalytical issues, including rational algorithm and quality control assurance. These recommendations are based on the relevant international recommendations and guidelines for the assessment of ANA testing and relevant literature search and should help to harmonize the approach in ANA testing and clarify differences in interpretation of the results obtained using different methods of determination.
On Yang Xingmi’s Bloc—With an Emphasis on Socio-political Setting, Subjugation, and Subordination
Authors: Ng Pak-sheung
Published: April 2021

The disintegration of Tang central authority and the resultant spawning of local strongmen (tuhao 土豪) shaped the socio-political nature of Yang Xingmi’s 楊行密 (852–905) bloc. Generally speaking, blocs founded by tuhao had generally been characterized by provincialism, but Yang Xingmi managed to avoid excessive reliance on a particular geographical origin. How to handle the challenges posed by recalcitrant meritorious officials was also of major concern to Yang Xingmi, and later Xu Wen 徐溫 (862–927), in the process of consolidating their authority. Thanks to a strong central army, rebellions initiated by ambitious meritorious officials were suppressed. In addition to finding methods for subjugating Yang’s recalcitrant meritorious officials, Xu Wen needed to address challenges posed by local strongmen; this article serves as a case study on the methodology of using genealogical records to examine the dynamics instrumental in shaping local history.
The Prefatory Self: Images of the Author in Traditional Chinese Drama
Authors: Wang Guojun
Published: April 2021

This article considers representations of Chinese opera authors in the prefatory space of their theatrical works. Despite the longstanding tradition of portraiture and drama production in premodern China, existing materials suggest that pictorial depictions of the authors started to appear in play scripts primarily during the Qing dynasty. How are those images related to theatrical works and their authors? Instead of treating authorship as a type of ownership, this article studies the multifaceted nature of authorial images by examining the depiction of the authors’ hairstyles and clothing alongside other content in the front matter of those plays. Situating the phenomenon within the histories of Chinese drama, clothing, and book culture, this article argues that authors increasingly appeared in late imperial Chinese drama in their social roles, moving from the prefatory space to the drama script proper.
Une mise en scène cartographique de la mission
Authors: Vasquez Jean-Michel
Published: April 2021

En 1885, le périodique des Missions Catholiques se lance dans la réalisation de grandes cartes à partir des travaux de missionnaires et portant sur l’ avancée de l’ évangélisation sur tous les continents. “Pour suivre la marche et les progrès de la civilisation”, chaque année jusqu’ en 1915, une carte sera publiée et offerte aux souscripteurs. Ensemble, la trentaine de cartes compose un corpus inégalé sur la représentation des missions catholiques. Simple décoration ou véritable outil de propagande, ces cartes destinées à être affichées et exposées méritent une analyse de leur forme comme de leur contenu. A l’ aide d’ exemples originaux, il s’ agira de montrer quels avantages détient le support cartographique dans un objectif de communication et de mesurer la place qu’ occupent les cartes affichées dans la société française de l’ époque.
Les dioramas
Authors: Girard Max
Published: April 2021

Le but de cet article est d’ étudier l’ utilisation des dioramas missionnaires à l’ exposition coloniale de Paris en 1931. Les dioramas y deviennent les vecteurs les plus utilisés par les missionnaires catholiques pour représenter le contact avec les populations colonisées et leur rôle dans la « mission civilisatrice ». Les différents types de dioramas qui expriment une vision paternaliste des « Autres » sont de moins en moins utilisés à partir de l’ exposition de 1937, car les organisateurs leur préfèrent des vecteurs plus dynamiques comme le cinéma ou les congrès qui montrent l’ universalité et le dynamisme de l’ Eglise.
Diversity and phylogeny of the brown alga Lobophora (Dictyotales, Phaeophyceae) in Singapore
Authors: KWAN VALERIE , YIP ZHI TING , FONG JENNY , HUANG DANWEI
Published: April 2021

The brown macroalgal genus Lobophora (Phaeophyceae: Dictyotaceae) plays an ecologically significant role in many marine ecosystems, but their diversity and taxonomy remain poorly studied. Until 2012, six Lobophora species had been recognised globally based on morphological features. Yet, with more than 100 evolutionary taxonomic units characterised to date, it is now acknowledged that Lobophora comprises many cryptic species and its diversity was vastly underestimated. In light of a growing body of research integrating molecular and morphological data to delimit cryptic species, this study assessed the diversity and phylogeny of Lobophora in Singapore. A combination of molecular data and morphological observations were used to delimit and identify species from 33 specimens collected at eight sites in the southern islands of Singapore. The mitochondrial cox3 and chloroplast psbA genes were amplified and sequenced for phylogenetic analysis. Three formally described species, L. challengeriae, L. lamourouxii, L. pachyventera (comprising two morphotypes), as well as one undescribed putative species, Lobophora sp61, were recovered. These findings replace the record of the Atlantic species L. variegata in Singapore and suggest that there are more species to be discovered in the biodiverse region of Southeast Asia. Precise understanding of Lobophora diversity is critical for ongoing and future work on coral–macroalgal ecological relationships.
A new species of Echidnodella (Asterinales, Lembosiaceae) from Western Ghats of Kerala State, India
Authors: MOHAMED HINA , THOMAS JACOB
Published: April 2021

Black mildews belong to a wide range of leaf inhabiting fungal genera, which causes severe damage to the living leaves, affect photosynthetic efficiency, cause physiological imbalances, and reduces the plants’ aesthetic value. During a survey of foliicolous fungi in Vagamon hills of Kerala state’s Western Ghats region, an endemic medicinal plant Xanthophyllum arnottianum was found infected with an undescribed species of black mildew causing fungal genus Echidnodella.  Their mycelia are non-appressoriate and devoid of hypostroma. Thyriothecia are oval, ellipsoidal, X or Y shaped, elongated producing eight uniseptate brown coloured ascospores in each bitunicate asci. Echidnodella was distinguished from the allied genus Echidnodes in the absence of paraphyses and from the genera Lembosia and Morenoella in the lack of appressoria (haustoria). This new species, Echidnodella vagamonensis is described and illustrated in detail to provide the consolidated account of the species known on this host genus.
A new species of Microvelia Westwood, 1834 (Hemiptera: Heteroptera: Veliidae) from southeastern Brazil
Authors: MAGALHÃES OSÉIAS MARTINS , MACHADO GUSTAVO LISBOA VIEIRA , CARNEIRO MARCO ANTONIO ALVES , MOREIRA FELIPE FERRAZ FIGUEIREDO
Published: April 2021

Microvelia joceliae Magalhães & Moreira, sp. nov. is described and illustrated based on material from Parque Natural Municipal das Andorinhas, Minas Gerais State, in southeastern Brazil. The new species can be distinguished from congeners occurring in the region by the pronotum of the apterous form covering almost the entire thorax dorsally, proepisternum with black denticles, male abdominal segments V–VII ventrally depressed, shape of the asymmetrical parameres, and female abdominal laterotergites reflected over the mediotergites and almost touching over segments V–VII.
A new species of Campyloneura (Hemiptera: Heteroptera: Miridae) from Cameroon with a review of the genus
Authors: KONSTANTINOV FEDOR V.
Published: April 2021

A second species of the previously monotypic plant bug genus Campyloneura, C. joceliae sp. nov. is described based on specimens from Nkolbisson, Cameroon. A key, differential diagnoses, digital habitus images, illustrations of male and female genitalic structures, and scanning micrographs of diagnostic morphological structures are provided for the new species and C. virgula (Herrich-Schaeffer, 1835).
Hypsipyrgias joseliae, a new species of lace bugs (Heteroptera: Tingidae: Tinginae) from New Guinea with a key to species of the genus Hypsipyrgias, and comments on three allied genera Hypsipyrgias Kirkaldy, 1908, Diplocysta Horváth, 1925, and Hypsotingis Drake, 1960
Authors: LIS BARBARA , LIS JERZY A.
Published: April 2021

Hypsipyrgias joseliae sp. n. (Heteroptera: Tingidae: Tinginae) from New Guinea is described, illustrated and compared with its two relatives, namely H. telamonides Kirkaldy, 1908 from Australia, and H. euphues Drake and Ruhoff, 1962 from Lord Howe Island. Key to species of the genus Hypsipyrgias is also provided. Two genera very closely related to Hypsipyrgias Kirkaldy, 1908, namely Hypsotingis Drake, 1960 and Diplocysta Horváth, 1925 are re-diagnosed. Diplocysta globuliformis Hacker, 1928, D. papuana Drake, 1960, D. rustica, Drake, 1960 and D. thaleia Drake and Ruhoff, 1965 are transferred from Diplocysta to Hypsotingis.
Illustrated guide to Pentatominae (Hemiptera: Pentatomidae) species associated with the four main grain crops in Rio Grande do Sul state, Brazil
Authors: BARROS LURDIANA D. , PAIM MARCELO R. , KREIN VERÔNICA , CARABAJAL VICTOR , BRANDÃO MARCELA N. , BERNARDES PAULA DE O. , LINDNER MARIANA F.
Published: April 2021

Several stink bugs in the subfamily Pentatominae are crop pests or have the potential to damage plants of economic importance. In the Brazilian state of Rio Grande do Sul, where agriculture plays a major role in the economy, the knowledge about pest stink bugs is fragmented and, in some instances, outdated. This work provides a summary of Pentatominae species recorded in Rio Grande do Sul feeding on the four most important grain crops for the state, i.e. soybean, rice, maize, and wheat, plus canola, an emerging crop. This survey is enhanced with new records from scientific collections, a short diagnosis for each species, distribution maps, an identification key, and carefully illustrated to allow for species recognition in the field. With this work, we aim to reunite the scattered knowledge of the group in one single revision, and provide a useful tool for identifying the pest stink bugs of Rio Grande do Sul.
Jocezia, a new Carpocorini genus from the Neotropics (Heteroptera: Pentatomidae: Pentatominae)
Authors: DELLAPÉ GIMENA , FUENTES DANIELA
Published: April 2021

Carpocorini is the largest tribe of Pentatominae, containing 127 genera and more than 500 species distributed worldwide. A new genus, Jocezia n. gen., and a new species, Jocezia inusitata n. sp., from Argentina are described and illustrated. The new genus is included in the Hypatropis group, together with the genera Hypatropis, Amauromelpia, Luridocimex and Stysiana, and characterized by the head in lateral view with the mandibular plates in a higher level than clypeus and the absence of parameres. An updated key to the Hypatropis group genera is provided.