bluuebunny/crossref_metadata_2025 huggingface dataset:
Thematic Maps of the Impact of Urbanization and Socioeconomic Factors on the Distribution of the Incidence of Cutaneous Leishmaniasis Cases in Sefrou Province, Central North of Morocco (2007–2011)
Authors: Talbi Fatima Zahra , Nouayti Nordine , El Omari Hajar , Najy Mohamed , Lahouiti Khadija , Fadil Mouhcine , Ech-Chafay Hassan , Lachhab Mohamed , Janati Idrissi Abdellatif , El Ouali Lalami Abdelhakim
Published: July 2020

Background. Leishmaniases are vector-borne diseases with health risks. They cause a big health problem. These parasitic diseases are transmitted by the parasite of the genusLeishmaniathrough sandflies.Objective. The aim of this work is to study the distribution of the incidence of cutaneous leishmaniasis (CL) cases and the impact of urbanization and socioeconomic factors and their effects as leishmaniasis risk factors.Methods. We conducted a retrospective study of CL cases collected at the level of Sefrou Province during the period from 2007 to 2011. The data was collected from registers of the Medical Delegation of Sefrou Province. The socioeconomic data, namely, the poverty rate, the popular density, and the type of environment (urban/rural) of Sefrou Province, were obtained from the High Commission for Planning. Statistical analysis was performed by SPSS software (version 20). The data were registered in a Microsoft Excel 2010 file. Statistical analysis was based on one-way analysis of variance (ANOVA), and then a correlation study was carried out (Pearson correlation). The results were considered significant whenpwas less than 0.05. The database was analyzed by QGIS 2.18, which is open source software.Results. A total of 349 cases of CL were collected at Sefrou Province from 2007 to 2011. A percentage of 49% of the cases come from urban areas, while 51% of the cases come from rural areas. In the statistical analysis, the division of the incidence of CL cases was found to be significantly associated only with urbanization. For the other factors, the number of people or the poverty rate is not taken into account in the incidence dynamics.Conclusion. This study may be useful for the implementation of future adequate measures and controls. Getting rid of leishmaniasis requires a comprehensive approach by acting on the sources of contamination through good continuous surveillance, appropriate management, effective vector control, and awareness-raising strategies.
Development and Application of Fluid-Solid Coupling Similar Materials in Discharge Test of Old Goaf Water
Authors: Li Zhenhua , Ma Mingxiao , Bao Yongsheng
Published: July 2020

To study the evolution law of the discharge pathway for the old goaf water in the Datong mining area, a new fluid-solid coupling similar material was developed based on the fluid-solid coupling similarity theory. In the developed similar material, sand and barite powder were used as aggregate, polyurethane and white portland cement as binder, and water and silicone oil as regulator. The effects of different proportions on mechanical properties and water physical properties of materials were obtained through the experiments. The results show that the strength of the developed material is mainly controlled by cement and polyurethane, the hydrophilicity is affected by silicone oil, and the permeability coefficient is mainly affected by cement and polyurethane. For grouting agent, cement can realize the overall control function, and polyurethane can realize the local control in a certain range. As an ideal fluid-solid coupling similar simulation material, the developed material can simulate rock mass with different permeability and different strength. Besides, this material has been successfully applied to an experimental study on the mechanism of old goaf water discharge in an extra-thick coal seam in the Datong mining area, and the development and evolution characteristics of the old goaf water discharge pathway is obtained. This new kind of fluid-solid coupling similar material is developed based on the fluid-solid coupling similarity theory, which is suitable for revealing the evolution law of discharge pathway for the old golf water in the Datong mining area.
Improvement of Thermal and Mechanical Properties of Vietnam Deproteinized Natural Rubber via Graft Copolymerization with Methyl Methacrylate
Authors: Nguyen Thi Nhan , Duy Hieu Nguyen , Anh Dung Tran , Thi Thuong Nghiem , Nguyen Thu Ha , Van Nam Nguyen , Quang Tung Tran , Huy Tung Nguyen , Thi Thuy Tran
Published: July 2020

In this study, we investigated the improvement of the thermal and mechanical properties of Vietnam deproteinized natural rubber (DPNR) via graft copolymerization of methyl methacrylate (MMA). The graft copolymerization was achieved successfully in latex stage using tert-butyl hydroperoxide (TBHPO) and tetra-ethylenepentamine (TEPA) as radical initiators at 30°C. By grafting with various MMA feeds and initiator concentration of 6.6×10−5 mol/g-rubber, the highest grafting efficiency and conversion were achieved at MMA of 15 wt.% per kg of rubber, 68% and 90%, respectively. The structure of grafted copolymers was characterized by 1H NMR, FTIR-ATR, and GPC, and thermal properties were investigated through DSC and TGA measurements. These showed that graft copolymers were more stable and rigid than DPNR. Storage modulus (G′) of graft copolymer was found to double that of DPNR, which contributed to the formation of graft copolymer. After sulfur vulcanization, the mechanical properties of DPNR-graft-PMMA, such as tensile strength, tear strength, and hardness, were improved significantly. Curing behaviors of the graft copolymers were found to be remarkably better than virgin DPNR.
In Vitro and In Vivo Anti‐Inflammatory Activities of Benjakul: A Potential Medicinal Product from Thai Traditional Medicine
Authors: Kuropakornpong Pranporn , Itharat Arunporn , Panthong Sumalee , Sireeratawong Seewaboon , Ooraikul Buncha
Published: July 2020

Benjakul (BJK) is a Thai traditional remedy consisting of five plants: Piper chaba Hunt., Piper sarmentosum Roxb., Piper interruptum Opiz., Plumbago indica Linn., and Zingiber officinale Roscoe. It is used as a first‐line drug to balance patient’s symptoms before other treatments. BJK ethanolic extract has been reported to show anti‐inflammatory activity through various mediators, e.g., nitric oxide, TNF‐α, IL‐1β, and IL‐6. Therefore, BJK could serve as a potential novel anti‐inflammatory herbal medicine. However, studies on prostaglandin E2 (PGE2), one of the key mediators in acute inflammation, and anti‐inflammation in animal models (in vivo) have not been done. This study investigated the anti‐inflammatory activity of BJK extract and some of its chemical compounds against PGE2 production in murine macrophage (RAW 264.7) cell line and two in vivo models of anti‐inflammatory studies. Ethanolic extract of BJK (BJK[E]) showed high inhibitory activity against PGE2 production with an IC50 value of 5.82 ± 0.10 μg/mL but its water extract (BJK[W]) was inactive. Two chemicals from BJK[E], i.e., plumbagin and myristicin, which served as biological markers, showed strong activity with IC50 values of 0.08 ± 0.01 and 1.80 ± 0.06 μg/mL, respectively. BJK[E] was administered both topically and orally to rats inhibited with inflammation induced by ethyl phenylpropiolate (rat ear edema model) and carrageenan (hind paw edema model). Moreover, the biological activity of BJK extract did not reduce after six‐month storage under accelerated condition (40°C, 75% RH). This indicated its stability and a 24‐month shelf‐life under normal condition. These results supported not only the use of BJK in Thai traditional medicine but also the possibility of further development of phytopharmaceutical products from BJK.
RAD51AP1 Deficiency Reduces Tumor Growth by Targeting Stem Cell Self-Renewal
Authors: Bridges Allison E. , Ramachandran Sabarish , Pathania Rajneesh , Parwal Utkarsh , Lester Adrienne , Rajpurohit Pragya , Morera Daley S. , Patel Nikhil , Singh Nagendra , Korkaya Hasan , Manicassamy Santhakumar , Prasad Puttur D. , Lokeshwar Vinata B. , Lokeshwar Bal L. , Ganapathy Vadivel , Thangaraju Muthusamy
Published: July 2020

RAD51-associated protein 1 (RAD51AP1) plays an integral role in homologous recombination by activating RAD51 recombinase. Homologous recombination is essential for preserving genome integrity and RAD51AP1 is critical for D-loop formation, a key step in homologous recombination. Although RAD51AP1 is involved in maintaining genomic stability, recent studies have shown that RAD51AP1 expression is significantly upregulated in human cancers. However, the functional role of RAD51AP1 in tumor growth and the underlying molecular mechanism(s) by which RAD51AP1 regulates tumorigenesis have not been fully understood. Here, we use Rad51ap1-knockout mice in genetically engineered mouse models of breast cancer to unravel the role of RAD51AP1 in tumor growth and metastasis. RAD51AP1 gene transcript was increased in both luminal estrogen receptor–positive breast cancer and basal triple-negative breast cancer, which is associated with poor prognosis. Conversely, knockdown of RAD51AP1 (RADP51AP1 KD) in breast cancer cell lines reduced tumor growth. Rad51ap1-deficient mice were protected from oncogene-driven spontaneous mouse mammary tumor growth and associated lung metastasis. In vivo, limiting dilution studies provided evidence that Rad51ap1 plays a critical role in breast cancer stem cell (BCSC) self-renewal. RAD51AP1 KD improved chemotherapy and radiotherapy response by inhibiting BCSC self-renewal and associated pluripotency. Overall, our study provides genetic and biochemical evidences that RAD51AP1 is critical for tumor growth and metastasis by increasing BCSC self-renewal and may serve as a novel target for chemotherapy- and radiotherapy-resistant breast cancer.

Significance:

This study provides in vivo evidence that RAD51AP1 plays a critical role in breast cancer growth and metastasis by regulating breast cancer stem cell self-renewal.
The Synthetic Small Molecule FL3 Combats Intestinal Tumorigenesis via Axin1-Mediated Inhibition of Wnt/β-Catenin Signaling
Authors: Jackson Dakota N. , Alula Kibrom M. , Delgado-Deida Yaritza , Tabti Redouane , Turner Kevin , Wang Xuan , Venuprasad K. , Souza Rhonda F. , Désaubry Laurent , Theiss Arianne L.
Published: July 2020

Colorectal cancer exhibits aberrant activation of Wnt/β-catenin signaling. Many inhibitors of the Wnt/β-catenin pathway have been tested for Wnt-dependent cancers including colorectal cancer, but are unsuccessful due to severe adverse reactions. FL3 is a synthetic derivative of natural products called flavaglines, which exhibit anti-inflammatory and cytoprotective properties in intestinal epithelial cells, but has not been previously tested in cell or preclinical models of intestinal tumorigenesis. In vitro studies suggest that flavaglines target prohibitin 1 (PHB1) as a ligand, but this has not been established in the intestine. PHB1 is a highly conserved protein with diverse functions that depend on its posttranslational modifications and subcellular localization. Here, we demonstrate that FL3 combats intestinal tumorigenesis in the azoxymethane-dextran sodium sulfate and ApcMin/+ mouse models and in human colorectal cancer tumor organoids (tumoroids) by inhibiting Wnt/β-catenin signaling via induction of Axin1 expression. FL3 exhibited no change in cell viability in normal intestinal epithelial cells or human matched-normal colonoids. FL3 response was diminished in colorectal cancer cell lines and human colorectal cancer tumoroids harboring a mutation at S45 of β-catenin. PHB1 deficiency in mice or in human colorectal cancer tumoroids abolished FL3-induced expression of Axin1 and drove tumoroid death. In colorectal cancer cells, FL3 treatment blocked phosphorylation of PHB1 at Thr258, resulting in its nuclear translocation and binding to the Axin1 promoter. These results suggest that FL3 inhibits Wnt/β-catenin signaling via PHB1-dependent activation of Axin1. FL3, therefore, represents a novel compound that combats Wnt pathway–dependent cancers, such as colorectal cancer.

Significance:

Targeting of PHB1 by FL3 provides a novel mechanism to combat Wnt-driven cancers, with limited intestinal toxicity.
Progresses Toward Precision Medicine inRET-altered Solid Tumors
Authors: Belli Carmen , Anand Santosh , Gainor Justin F. , Penault-Llorca Frederique , Subbiah Vivek , Drilon Alexander , Andrè Fabrice , Curigliano Giuseppe
Published: July 2020

RET (rearranged during transfection) gene encodes a receptor tyrosine kinase essential for many physiologic functions, but RET aberrations are involved in many pathologies. While RET loss-of-function mutations are associated with congenital disorders like Hirschsprung disease and CAKUT, RET gain-of-function mutations and rearrangements are critical drivers of tumor growth and proliferation in many different cancers. RET-altered (RET+) tumors have been hitherto targeted with multikinase inhibitors (MKI) having anti-RET activities, but they inhibit other kinase targets more potently and show limited clinical activities. The lack of target specificity and consequently increased side effects, responsible for dose reduction and drug discontinuation, are critical limitations of MKIs in the clinics. New selective RET inhibitors, selpercatinib and pralsetinib, are showing promising activities, improved response rates, and more favorable toxicity profiles in early clinical trials. This review critically discusses the oncogenic activation of RET and its role in different kinds of tumors, clinical features of RET+ tumors, clinically actionable genetic RET alterations and their diagnosis, and the available data and results of nonselective and selective targeting of RET.
A Case of Steatocystoma Multiplex in a Psoriatic Patient during Treatment with Anti-IL-12/23
Authors: Marasca Claudio , Megna Matteo , Donnarumma Marianna , Fontanella Giuseppina , Cinelli Eleonora , Fabbrocini Gabriella
Published: July 2020

Steatocystoma multiplex (SM) is an autosomal dominant disorder developing in adolescence or early adult age. The occurrence of multiple asymptomatic cutaneous cysts on the axillae, groin, trunk, and limbs characterizes the disease. SM is associated with a missense mutation in the keratin 17 gene (KRT17), a gene encoding for a type I intermediate filament (keratin 17 [K17]), mainly expressed in the epithelial appendages (hair follicles and sebaceous glands). Here, we report a case of appearance of multiple steatocystomas in a psoriatic patient during ustekinumab treatment, an interleukin (IL)-12/IL-23 inhibitor. Our hypothesis is that ustekinumab could have unmasked a potential genetic predisposition to SM by reducing the expression of interferon-γ and IL-17/IL-22 and consequently acting on the K17 pathway.
Etiology and Management of Acute Metabolic Acidosis: An Update
Authors: Matyukhin Igor , Patschan Susann , Ritter Oliver , Patschan Daniel
Published: July 2020

Background: The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician’s perspective. Summary: We performed a systematic search on PubMed, applying the following search terms: “acute metabolic acidosis,” “lactic acidosis,” “metformin” AND “acidosis,” “unbalanced solutions” AND “acidosis,” “bicarbonate” AND “acidosis” AND “outcome,” “acute metabolic acidosis” AND “management,” and “acute metabolic acidosis” AND “renal replacement therapy (RRT)/dialysis.” The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.
How a Devastating Case of Acanthamoeba Sclerokeratitis Ended up with Serious Systemic Sequelae
Authors: Bataillie Sophie , Van Ginderdeuren Rita , Van Calster Joachim , Foets Beatrijs , Delbeke Heleen
Published: July 2020

A 35-year old soft contact lens wearer with a proven bilateral Acanthamoeba keratitis developed a nodular scleritis. Based on the stepladder approach described by Iovieno et al. [Ophthalmology. 2014 Dec;121(12):2340–7], nonsteroidal anti-inflammatory drugs, methylprednisolone, and later azathioprine were added to the antiamoebic treatment. Unfortunately, there was further deterioration and an endophthalmitis developed. Unbearable pain and concerns of spread to the brain urged an enucleation. Histopathological examination confirmed Acanthamoeba cysts in the cornea, sclera, retina, choroid, and vitreous body. As a side effect of the immunosuppressive treatment, the patient developed myopathy, pulmonary aspergillosis, and an avascular necrosis of the hip. Scleritis is a devastating complication of Acanthamoeba keratitis with a poor prognosis and a high enucleation rate. Acanthamoeba sclerokeratitis is, due to cyst-free biopsies, mostly assigned to an immune-mediated mechanism, justifying the use of immunosuppressive treatment. Scleritis in our case contributed to the extracorneal spread of Acanthamoeba. Our case is the first documented extracorneal spread of Acanthamoeba without previous surgery. Extracorneal spread of Acanthamoeba should be considered, even in the case of false-negative biopsies. We strongly recommend serial sections of the retrieved scleral specimen in case of negative histopathological examination to exclude an infection. Even when an immune-mediated scleritis is suspected, systemic immunosuppressive treatment should always be used with the greatest caution. Awareness of the side effects and monitoring by an experienced physician is mandatory.
Bilateral XEN Gel Stent Implantation in Juvenile-Onset Open-Angle Glaucoma
Authors: Klug Emma , Solá-Del Valle David
Published: July 2020

The purpose of the current case is to report the successful management of juvenile-onset open-angle glaucoma with bilateral XEN Gel Stent (Allegran Inc., Irvine, CA) implantation in a patient first diagnosed during pregnancy with co-existing dysautonomia. Treatment with the XEN Gel Stent provided dramatic reductions in intraocular pressure (IOP), and glaucoma medications sustained up to 23 months postoperatively. The success of this case may suggest that this minimally invasive procedure could be an effective treatment option for younger patients who require substantial reductions in IOP and glaucoma medication burden.
Negative Association between Caloric Intake and Estimated Glomerular Filtration Rate in a Chinese Population: Mediation Models Involving Mitochondrial Function
Authors: Ma Chifa , He Shuli , Li Pingping , Zhang Huabing , Li Wei , Li Yuxiu
Published: July 2020

Background: With the shortening of leukocyte telomere length (LTL) and decrease in the copy number of mitochondrial DNA, mitochondrial dysfunction and oxidative stress are considered important drivers of the aging process. Although previous experimental studies report that caloric intake is associated with age-related renal dysfunction through the changes in mitochondrial function, there are insufficient epidemiological data to establish this association. Objective: We aimed to explore the association between caloric intake and renal function and to investigate whether mitochondrial DNA copy number (mtDNAcn) mediated this association by cross-sectional analysis. Methods: A total of 403 individuals from a Chinese rural cohort (women = 66.50%; mean age = 53.94 ± 10.27 years) with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and with differences in the glucose tolerance status (diabetes, n = 106; prediabetes, n = 125; normal glucose tolerance, n = 172) were included. Dietary data were obtained by a 24-h food recall, and caloric intake was normalized by ideal body weight. The mtDNAcn and LTL were detected using real-time PCR assay. The associations between caloric intake, aging markers, and renal function were analyzed by partial correlation analysis and multiple linear regression analysis. Mediation analysis was applied to examine the role of mtDNAcn in the association between caloric intake and eGFR. Results: Caloric intake was higher while age-adjusted mtDNAcn was lower in individuals with eGFR <90 mL/min/1.73 m2 (n = 140) than in those with eGFR ≥90 mL/min/1.73 m2 (n = 263). After adjusting for multiple factors, linear regression analysis revealed that caloric intake was negatively associated with eGFR and mtDNAcn, while mtDNAcn was positively associated with eGFR. Moreover, mediation analysis indicated that the indirect effect of caloric intake on eGFR through mtDNAcn was significant (β = –0.0505, 95% confidence interval –0.0931 to –0.0190). Conclusions: Caloric intake was negatively associated with eGFR in a Chinese population, and the association was partly mediated by decreased mtDNAcn.
Use of Immunotherapy in Extensive-Stage Small Cell Lung Cancer
Authors: Konala Venu Madhav , Madhira Bhaskar Reddy , Ashraf Sara , Graziano Stephen
Published: July 2020

Lung cancer is a leading cause of cancer death in the United States and around the world. Approximately 13% of lung cancers are small cell lung cancer (SCLC). SCLC is generally classified as a limited-stage and extensive-stage disease depending on the extent of involvement. For patients with the extensive-stage disease, until recently, chemotherapy alone has been the recommended treatment, although radiotherapy could be used in select patients for palliation of symptoms. The standard of care for extensive-stage SCLC is platinum doublet chemotherapy with either cisplatin or carboplatin in combination with etoposide. Even though first-line therapy has an initial response rate of 60–80%, the prognosis is poor, with overall survival of 10–12 months. The only FDA-approved second line of therapy is topotecan, approved both as an intravenous formulation as well as an oral formulation, with response rates of 6–12% in chemorefractory disease and 15–37% in chemosensitive disease. Immunotherapy has recently been approved as a first-line agent in metastatic SCLC in combination with chemotherapy. It is also approved as a third-line agent in metastatic SCLC after the failure of two chemotherapy regimens. The FDA approved four drugs, two of them being PD-1 inhibitors (pembrolizumab, nivolumab), and two of them being PD-L1 inhibitors (atezolizumab and durvalumab) in SCLC. This review article summarizes the significance of immunotherapy in the treatment of extensive-stage SCLC, its side effects, and limitations.
Moving beyond Ordinary Factor Analysis in Studies of Personality and Personality Disorder: A Computational Modeling Perspective
Authors: Haines Nathaniel , Beauchaine Theodore P.
Published: July 2020

Almost all forms of psychopathology, including personality disorders, are arrived at through complex interactions among neurobiological vulnerabilities and environmental risk factors across development. Yet despite increasing recognition of etiological complexity, psychopathology research is still dominated by searches for large main effects causes. This derives in part from reliance on traditional inferential methods, including ordinary factor analysis, regression, ANCOVA, and other techniques that use statistical partialing to isolate unique effects. In principle, some of these methods can accommodate etiological complexity, yet as typically applied they are insensitive to interactive functional dependencies (modulating effects) among etiological influences. Here, we use our developmental model of antisocial and borderline traits to illustrate challenges faced when modeling complex etiological mechanisms of psychopathology. We then consider how computational models, which are rarely used in the personality disorders literature, remedy some of these challenges when combined with hierarchical Bayesian analysis.
Azathioprine for Connective Tissue Disease-Associated Interstitial Lung Disease
Authors: Boerner Eda B. , Cuyas Marta , Theegarten Dirk , Ohshimo Shinichiro , Costabel Ulrich , Bonella Francesco
Published: July 2020

Background: Immunosuppressive therapy still is the standard treatment for patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Objectives: This retrospective study aimed to provide data on the tolerability and efficacy of azathioprine in progressive CTD-ILDs. Methods: A total of 56 patients with CTD-ILD treated with azathioprine between 2003 and 2014 were included in the study. The patients were assessed every 3 months during follow-up. Results: The mean treatment duration was 34 months, with a range of 3–105 months. Fifteen patients (27%) discontinued treatment due to side effects, mostly due to elevated liver enzymes, within the first 3 months. Forty-one patients were treated for longer than 3 months, and 27 of those (66%) had stabilization or improvement of pulmonary function during treatment. In patients who remained stable or improved, the mean FVC was 62 ± 17% predicted (% pred) at initiation of treatment and 65 ± 17% pred at the last follow-up visit (p = 0.036), and the mean DLCO was 38 ± 16% pred at initiation of treatment and 39 ± 17% pred at the last follow-up visit (p = 0.06). Conclusions: Azathioprine can stabilize or improve CTD-ILD. While early drug intolerance is frequent, most patients who have tolerated the drug well achieve long-term stabilization or improvement of lung function.
Intra-Amniotic Sildenafil Treatment Promotes Lung Growth and Attenuates Vascular Remodeling in an Experimental Model of Congenital Diaphragmatic Hernia
Authors: Okolo Frances , Zhang GuangFeng , Rhodes Julie , Gittes George K. , Potoka Douglas A.
Published: July 2020

Background: Defective lung development resulting in lung hypoplasia and an attenuated and hypermuscularized pulmonary vasculature contributes to significant postnatal mortality in congenital diaphragmatic hernia (CDH). We hypothesize that deficient embryonic pulmonary blood flow contributes to defective lung development in CDH, which may therefore be ameliorated via enhancement of embryonic pulmonary blood flow. Methods: The mouse nitrofen model of CDH was utilized to measure embryonic pulmonary blood flow by in utero intracardiac injection of FITC-labeled tomato lectin and color-flow Doppler ultrasound. The effect of prenatal intra-amniotic treatment with sildenafil on survival, lung growth, and vascular morphology in the nitrofen model was determined. Results: Nitrofen-treated embryos exhibited decreased blood flow in the lung periphery compared to controls, and intra-amniotic sildenafil significantly improved embryonic pulmonary blood flow. Similar to nitrofen alone, pups delivered after nitrofen treatment and intra-amniotic injection of dextrose control exhibited respiratory distress and never survived beyond 6 h. Intra-amniotic sildenafil ameliorated respiratory distress in nitrofen-treated pups and improved postnatal survival to 82%. Following intra-amniotic sildenafil treatment at embryonic day (E)10.5, nitrofen-treated P0 lungs were larger with increased left lobe weight, reduced small pulmonary arterial wall muscularization, and increased airway branching complexity compared to controls. Intra-amniotic sildenafil treatment later at E15.5 also resulted in improved survival, lung growth, and attenuation of vascular remodeling in nitrofen-treated embryos. Conclusions: Defective embryonic pulmonary blood flow may contribute to lung maldevelopment in CDH. Enhancement of embryonic pulmonary blood flow via intra-amniotic sildenafil results in lung growth and attenuation of pulmonary vascular remodeling and may have therapeutic potential for CDH.
ПЕРЕХІД ВІД ПЕДІАТРИЧНОЇ МЕДИЧНОЇ ДОПОМОГИ ДО ОРІЄНТОВАНОЇ НА ДОРОСЛИХ СИСТЕМИ ОХОРОНИ ЗДОРОВ’Я: ВИКЛИК ДЛЯ ПАЦІЄНТІВ З ЮВЕНІЛЬНИМ ІДІОПАТИЧНИМ АРТРИТОМ
Authors: Pidkova O. V.
Published: July 2020

У статті подано короткий опис ювенільного ідіопатичного артриту: поширеність, етіологія та необ­хідність цілеспрямованого запланованого переходу підлітків, хворих на ювенільний ідіопатичний артрит, від педіатричної допомоги до орієнтованої на дорослих системи охорони здоров’я.
Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure
Authors: Davidson Michael T. , Grimsrud Paul A. , Lai Ling , Draper James A. , Fisher-Wellman Kelsey H. , Narowski Tara M. , Abraham Dennis M. , Koves Timothy R. , Kelly Daniel P. , Muoio Deborah M.
Published: July 2020

Rationale:

Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse.

Objective:

This study sought to explore the premise that mitochondrial Kac contributes to heart failure by disrupting oxidative metabolism.

Methods and Results:

A DKO (dual knockout) mouse line with deficiencies in CrAT (carnitine acetyltransferase) and Sirt3 (sirtuin 3)—enzymes that oppose Kac by buffering the acetyl group pool and catalyzing lysine deacetylation, respectively—was developed to model extreme mitochondrial Kac in cardiac muscle, as confirmed by quantitative acetyl-proteomics. The resulting impact on mitochondrial bioenergetics was evaluated using a respiratory diagnostics platform that permits comprehensive assessment of mitochondrial function and energy transduction. Susceptibility of DKO mice to heart failure was investigated using transaortic constriction as a model of cardiac pressure overload. The mitochondrial acetyl-lysine landscape of DKO hearts was elevated well beyond that observed in response to pressure overload or Sirt3 deficiency alone. Relative changes in the abundance of specific acetylated lysine peptides measured in DKO versus Sirt3 KO hearts were strongly correlated. A proteomics comparison across multiple settings of hyperacetylation revealed ≈86% overlap between the populations of Kac peptides affected by the DKO manipulation as compared with experimental heart failure. Despite the severity of cardiac Kac in DKO mice relative to other conditions, deep phenotyping of mitochondrial function revealed a surprisingly normal bioenergetics profile. Thus, of the >120 mitochondrial energy fluxes evaluated, including substrate-specific dehydrogenase activities, respiratory responses, redox charge, mitochondrial membrane potential, and electron leak, we found minimal evidence of oxidative insufficiencies. Similarly, DKO hearts were not more vulnerable to dysfunction caused by transaortic constriction–induced pressure overload.

Conclusions:

The findings challenge the premise that hyperacetylation per se threatens metabolic resilience in the myocardium by causing broad-ranging disruption to mitochondrial oxidative machinery.
Coronary Flow Capacity to Identify Stenosis Associated With Coronary Flow Improvement After Revascularization: A Combined Analysis From DEFINE FLOW and IDEAL
Authors: Murai Tadashi , Stegehuis Valérie E. , van de Hoef Tim P. , Wijntjens Gilbert W. M. , Hoshino Masahiro , Kanaji Yoshihisa , Sugiyama Tomoyo , Hamaya Rikuta , Nijjer Sukhjinder S. , de Waard Guus A. , Echavarria‐Pinto Mauro , Knaapen Paul , Meuwissen Martijn , Davies Justin E. , van Royen Niels , Escaned Javier , Siebes Maria , Kirkeeide Richard L. , Gould K. Lance , Johnson Nils P. , Piek Jan J. , Kakuta Tsunekazu
Published: July 2020

Background

Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave‐free ratio, and CFR.

Methods and Results

Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect ‐Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian‐Dutch‐English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed. CFC classified prerevascularization lesions as normal (14), mildly reduced (40), moderately reduced (31), and severely reduced (48). Lesions with larger impairment of CFC showed greater increase in coronary flow and vice versa (median percent increase in coronary flow by revascularization: 4.2%, 25.9%, 50.1%, and 145.5%, respectively;
P
<0.001). Compared with the conventional cutoff values of fractional flow reserve, instantaneous wave‐free ratio, and CFR, an ischemic CFC defined as moderately to severely reduced CFC showed higher diagnostic accuracy with higher specificity to predict a >50% increase in coronary flow after percutaneous coronary intervention. Receiver operating characteristic curve analysis demonstrated that only CFC has a superior predictive efficacy to CFR (
P
<0.05). Multivariate analysis revealed lesions with ischemic CFC to be the independent predictor of a significant coronary flow increase after percutaneous coronary intervention (odds ratio, 10.7; 95% CI, 4.6–24.8;
P
<0.001).

Conclusions

CFC showed significant improvement of identification of lesions that benefit from revascularization compared with CFR with respect to coronary flow increase.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02328820.
Place and Environment in the Ongoing Evolution of Cognitive Neuroscience
Authors: Irwin Louis N. , Irwin Brian A.
Published: July 2020

Cognitive science today increasingly is coming under the influence of embodied, embedded, extended, and enactive perspectives, superimposed on the more traditional cybernetic, computational assumptions of classical cognitive research. Neuroscience has contributed to a greatly enhanced understanding of brain function within the constraints of the traditional cognitive science approach, but interpretations of many of its findings can be enriched by the newer alternative perspectives. Here, we note in particular how these frameworks highlight the cognitive requirements of an animal situated within its particular environment, how the coevolution of an organism's biology and ecology shape its cognitive characteristics, and how the cognitive realm extends beyond the brain of the perceiving animal. We argue that these insights of the embodied cognition paradigm reveal the central role that “place” plays in the cognitive landscape and that cognitive scientists and philosophers alike can gain from paying heed to the importance of a concept of place. We conclude with a discussion of how this concept can be applied with respect to cognitive function, species comparisons, ecologically relevant experimental designs, and how the “hard problem” of consciousness might be approached, among its other implications.
Voluntary Control of Task Selection Does Not Eliminate the Impact of Selection History on Attention
Authors: Henare Dion T. , Kadel Hanna , Schubö Anna
Published: July 2020

The human visual system can only process a fraction of the information present in a typical visual scene, and selection is historically framed as the outcome of bottom–up and top–down control processes. In this study, we evaluated how a third factor, an individual's selection history, interacts with top–down control mechanisms during visual search. Participants in our task were assigned to one of two groups in which they developed a history of either shape or color selection in one task, while searching for a shape singleton in a second task. A voluntary task selection procedure allowed participants to choose which task they would perform on each trial, thereby maximizing their top–down preparation. We recorded EEG throughout and extracted lateralized ERP components that index target selection (NT) and distractor suppression (PD). Our results showed that selection history continued to guide attention during visual search, even when top–down control mechanisms were maximized with voluntary task selection. For participants with a history of color selection, the NT component elicited by a shape target was attenuated when accompanied by a color distractor, and the distractor itself elicited a larger PD component. In addition, task-switching results revealed that participants in the color group had larger, asymmetric switch costs implying increased competition between task sets. Our results support the notion that selection history is a significant factor in attention guidance, orienting the visual system reflexively to objects that contradict an individual's current goals—even when these goals are intrinsically selected and prepared ahead of time.
Erratum: Chauveau, O., Pastori, T., Souza-Chies, T.T. & Eggers, L. (2014) Overlooked diversity in Brazilian Cypella (Iridaceae, Iridoideae): four new taxa from the Río de la Plata grasslands. Phytotaxa 174 (1): 25–42.

Authors: CHAUVEAU OLIVIER , PASTORI TAMARA , SOUZA-CHIES TATIANA T. , EGGERS LILIAN
Published: July 2020

We have noticed an inadvertent error in our article entitled “Overlooked diversity in Brazilian Cypella (Iridaceae: Iridoideae): four new taxa from the Río de la Plata grasslands” (Phytotaxa 174 (1): 25–42).
An Evaluation of Block-Maximum-Based Estimation of Very Long Return Period Precipitation Extremes with a Large Ensemble Climate Simulation
Authors: Ben Alaya M. A. , Zwiers F. , Zhang X.
Published: July 2020

The recurring devastation caused by extreme events underscores the need for reliable estimates of their intensity and frequency. Operational frequency and intensity estimates are very often obtained from generalized extreme value (GEV) distributions fitted to samples of annual maxima. GEV distributed random variables are “max-stable,” meaning that the maximum of a sample of several values drawn from a given GEV distribution is again GEV distributed with the same shape parameter. Long-period return value estimation relies on this property of the distribution. The data to which the models are fitted may not, however, be max-stable. Observational records are generally too short to assess whether max-stability holds in the upper tail of the observations. Large ensemble climate simulations, from which we can obtain very large samples of annual extremes, provide an opportunity to assess whether max-stability holds in a model-simulated climate and to quantify the impact of the lack of max-stability on very long period return-level estimates. We use a recent large ensemble simulation of the North American climate for this purpose. We find that the annual maxima of short-duration precipitation extremes tend not to be max-stable in the simulated climate, as indicated by systematic variation in the estimated shape parameter as block length is increased from 1 to 20 years. We explore how the lack of max-stability affects the estimation of very long period return levels and discuss reasons why short-duration precipitation extremes may not be max-stable.
Sub-Surface Molecular Analysis and Imaging in Turbid Media Using Time-Gated Raman Spectral Multiplexing
Authors: Corden Christopher , Matousek Pavel , Conti Claudia , Notingher Ioan
Published: July 2020

Obtaining molecular information deeper within optically turbid samples is valuable in many applications. However, in many cases this is challenging, in particular when the sample elicits strong laser-induced fluorescence emission. Here, we investigated the use of time-gated and micro-spatially offset Raman spectroscopy (micro-SORS) based on spectral multiplexing detection to obtain sub-surface molecular analysis and imaging for both fluorescing and non-fluorescing samples. The multiplexed spectral detection achieved with a digital micromirror device (DMD) allowed fast acquisition of the time-gated signals to enable three-dimensional Raman mapping (raster scanning in the lateral x,y plane and using time-of-flight calibration for the axial z-direction). Sub-millimeter resolution molecular depth mapping was achieved with dwell times on the order of seconds per pixel. To suppress fluorescence backgrounds and enhance Raman bands, time-gated Raman spectroscopy was combined with micro-SORS to recover Raman signals of red pigments placed behind a layer of optically turbid material. Using a defocusing micro-SORS approach, both fluorescence and Raman signals from the surface layers were further suppressed, which enhanced the Raman signals from the deeper sublayers containing the pigment. These results demonstrate that time-gated Raman spectroscopy based on spectral multiplexed detection, and in combination with micro-SORS, is a powerful technique for sub-surface molecular analysis and imaging, which may find practical applications in medical imaging, cultural heritage, forensics, and industry.
The Influence of Visual-Manual Distractions on Anticipatory Driving
Authors: He Dengbo , Donmez Birsen
Published: July 2020

Objective

The aim of this study is to investigate how anticipatory driving is influenced by distraction.

Background

The anticipation of future events in traffic can allow potential gains in recognition and response times. Anticipatory actions (i.e., control actions in preparation for potential traffic changes) have been found to be more prevalent among experienced drivers in simulator studies when driving was the sole task. Despite the prevalence of visual-manual distractions and their negative effects on road safety, their influence on anticipatory driving has not yet been investigated beyond hazard anticipation.

Methods

A simulator experiment was conducted with 16 experienced and 16 novice drivers. Half of the participants were provided with a self-paced visual-manual secondary task presented on a dashboard display.

Results

More anticipatory actions were observed among experienced drivers; experienced drivers also exhibited more efficient visual scanning behaviors as indicated by higher glance rates toward and percent times looking at cues that facilitate the anticipation of upcoming events. Regardless of experience, those with the secondary task displayed reduced anticipatory actions and paid less attention toward anticipatory cues. However, experienced drivers had lower odds of exhibiting long glances toward the secondary task compared to novices. Further, the inclusion of glance duration on anticipatory cues increased the accuracy of a model predicting anticipatory actions based on on-road glance durations.

Conclusion

The results provide additional evidence to existing literature supporting the role of driving experience and distraction engagement in anticipatory driving.

Application

These findings can guide the design of in-vehicle systems and guide training programs to support anticipatory driving.
Fuzzy comprehensive evaluation of classroom teaching quality of college teachers
Authors: Ma Feixiong , Zhu Zichuan , Zhou Mi , Pan Wen-Tsao
Published: July 2020

At present, some classroom teaching evaluation methods are actually difficult to reasonably and fairly evaluate teachers’ true teaching level and classroom teaching quality. There are many shortcomings and drawbacks. In order to overcome the shortcomings of traditional teaching evaluation and enhance the evaluation effect, this paper combines the current advanced management methods with the merits of traditional evaluation methods, and applies the fuzzy evaluation method to combine qualitative assessment and quantitative assessment. First of all, establish a scientific and reasonable classroom teaching quality assessment index system, determine the standard assessment criteria, and then select and use the fuzzy comprehensive evaluation model to evaluate the classroom teaching quality, thus establishing a complete and effective teaching quality evaluation system.
Recognition Investigation of Community Pharmacists Implementing Good Pharmacy Practice in Korea
Authors: Kim Dae-Won , Lee Beom-Jin
Published: July 2020

This study aimed to verify, for the first time, the need for Good Pharmacy Practice (GPP) regulations as guidelines to provide pharmaceutical care services in community pharmacies in Korea. Statistical analyses were performed with demographic characteristics, institutional factors, and diversity factors of 3 pharmaceutical care services as independent variables and the favorability of GPP implementation as a dependent variable. In assessing the diversity of methods of providing pharmaceutical care services as an indicator of willingness to provide these services, this study understood such diversity as an innovative behavior that represents the efforts and willingness of pharmacists to provide better services. The results of descriptive statistics showed that most pharmacists in community pharmacy recognize that guidelines are necessary to provide better pharmaceutical care services. The statistical correlation analysis results confirmed that a greater need for guidelines was strongly related to higher GPP favorability. The institutional factors had the greatest influence on GPP favorability, rather than diversity factors of pharmaceutical care services, ultimately with the Korean perspectives to equate the GPP with the guidelines for pharmaceutical care services. Our study confirmed that it is a wish and a policy task of community pharmacists in Korea to enact GPP as soon as possible.
Transparency and the efficiency of multi-actor decision-making processes: an empirical analysis of 244 decisions in the European Union
Authors: Brandsma Gijs Jan , Meijer Albert
Published: July 2020

Studies into decision-making suggest the existence of a tension between transparent and efficient decision-making. It is assumed that an increase in transparency leads to a decline in the efficiency of decision-making processes; however, this assumption has not been tested empirically. This study provides a starting point for investigating the complex relationship between transparency and efficiency on a set of 244 European Union legislative processes between 2014 and 2019. It finds that transparency neither speeds up nor slows down decision-making processes, and that the efficiency of the lawmaking process depends on political complexity. Our results call for further systematic research into the causes and consequences of decision-making transparency.

Points for practitioners

In decision-making processes, transparency is widely seen as both a blessing and a curse. On the one hand, it is seen as a virtue that fosters legitimacy and participation; on the other hand, it is said to reduce decisional efficiency. However, our study of 244 European Union legislative processes shows that transparency has no effect on their duration. This calls for a re-appreciation of the effects of transparency in decision-making processes.
The impact of the COVID-19 pandemic on intercountry adoption and international commercial surrogacy
Authors: Fronek Patricia , Rotabi Karen Smith
Published: July 2020

The COVID-19 pandemic has created unprecedented economic, health and social impacts as it has swept the globe. Intercountry adoption and international surrogacy are practices immediately affected, furthering vulnerabilities of children and vulnerable adults. This short report calls attention to heightened risks, raises awareness for practitioners in these fields and asserts the need for caution.