bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats
Authors: Kalange Muhamudu , Nansunga Miriam , Kasozi Keneth Iceland , Kasolo Josephine , Namulema Jackline , Atusiimirwe Jovile Kasande , Ayikobua Emmanuel Tiyo , Ssempijja Fred , Munanura Edson Ireeta , Matama Kevin , Semuyaba Ibrahim , Zirintunda Gerald , Okpanachi Alfred Omachonu 
Published: April 2020

Abstract
Objective
Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of this study was to investigate the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on ulcer induction. Malondialdehyde (MDA), reduced glutathione (GSH) and major histological changes in male Wistar rats following ulcer induction using Indomethacin were investigated. Gastric ulcers were in four groups; Group I was administered Artesunate, group II received Artesunate-Amodiaquine, group III received Artemether-Lumefantrine, and group IV was a positive control (normal saline). Group V was the negative control consisting of healthy rats.

Results
Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate. In addition, levels of MDA were significantly higher in the combination of therapies while levels of GSH were lower in comparison to Artesunate and the negative control. Microscopically, antimalarial combination therapies were associated with severe inflammation and tissue damage than Artesunate in the gastric mucosa showing that antimalarial combination therapies exert their toxic effects through oxidative stress mechanisms, and this leads to cellular damage. Findings in this study demonstrate a need to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.
Thyrotoxic periodic paralysis presenting in an African-American teenage male: case report
Authors: Glass Joshua , Osipoff Jennifer 
Published: April 2020

Abstract
Background
Thyrotoxic periodic paralysis is a rare complication of hyperthyroidism and is associated with hypokalemia and muscle paralysis. This condition is most commonly seen in Asian men.

Case presentation
We report on a 14-year-old African American male with Graves’ disease and intermittent asthma who presented with bilateral leg weakness. The patient demonstrated signs of thyrotoxicosis and laboratory evaluation revealed hypokalemia and hyperthyroidism. Following the administration of potassium supplementation clinical status improved and the patient was discharged home on a high dose of methimazole and propranolol. At a 6-month follow up visit, he was found to be clinically euthyroid and demonstrated no signs of hyperthyroidism or muscle weakness.

Conclusion
Children presenting with weakness and hypokalemia should be investigated for thyroid dysfunction. Correction of hypokalemia improves acute presentation, but the patient will remain at risk for paralysis until euthyroid state is achieved.
Examining the impact of a social skills training program on preschoolers’ social behaviors: a cluster-randomized controlled trial in child care centers
Authors: Larose Marie-Pier , Ouellet-Morin Isabelle , Vergunst Francis , Vitaro Frank , Girard Alain , E. Tremblay Richard , Brendgen Mara , M. Côté Sylvana 
Published: April 2020

Abstract
Background
Preschoolers regularly display disruptive behaviors in child care settings because they have not yet developed the social skills necessary to interact prosocially with others. Disruptive behaviors interfere with daily routines and can lead to conflict with peers and educators. We investigated the impact of a social skills training program led by childcare educators on children’s social behaviors and tested whether the impact varied according to the child’s sex and family socio-economic status.

Methods
Nineteen public Child Care Centers (CCC, n = 361 children) located in low socio-economic neighborhoods of Montreal, Canada, were randomized into one of two conditions: 1) intervention (n = 10 CCC; 185 children) or 2) wait list control (n = 9 CCC; 176 children). Educators rated children’s behaviors (i.e., disruptive and prosocial behaviors) before and after the intervention. Hierarchical linear mixed models were used to account for the nested structure of the data.

Results
At pre-intervention, no differences in disruptive and prosocial behaviors were observed between the experimental conditions. At post-intervention, we found a significant sex by intervention interaction (β intervention by sex = − 1.19, p = 0.04) indicating that girls in the intervention condition exhibited lower levels of disruptive behaviors compared to girls in the control condition (f2 effect size = − 0.15). There was no effect of the intervention for boys.

Conclusions
Girls may benefit more than boys from social skills training offered in the child care context. Studies with larger sample sizes and greater intervention intensity are needed to confirm the results.

Trial registration
Current clinical trial number is ISRCTN84339956 (Retrospectively registered in March 2017). No amendment to initial protocol.
In vitro and in vivo effects of flubendiamide and copper on cyto-genotoxicity, oxidative stress and spleen histology of rats and its modulation by resveratrol, catechin, curcumin and α-tocopherol
Authors: Mandil Rajesh , Prakash Atul , Rahal Anu , Singh S. P. , Sharma Deepak , Kumar Rahul , Garg Satish Kumar 
Published: April 2020

Abstract
Background
Living organisms are frequently exposed to more than one xenobiotic at a time either by ingestion of contaminated food/fodder or due to house-hold practices, occupational hazards or through environment. These xenobiotics interact individually or in combination with biological systems and act as carcinogen or produce other toxic effects including reproductive and degenerative diseases. Present study was aimed to investigate the cyto-genotoxic effects of flubendiamide and copper and ameliorative potential of certain natural phyotconstituent antioxidants.

Method
In vitro cytogenotoxic effects were evaluated by employing battery of assays including Propidium iodide staining, Tunel assay, Micronuclei, DNA fragmentation and Comet assay on isolated splenocytes and their prevention by resveratrol (5 and 10 μM), catechin (10 and 20 μM), curcumin (5 and 10 μM) and α-tocopherol (5, 10 and 20 μM). In vivo study was also undertaken daily oral administration of flubendiamide (200 mg/kg) or copper (33 mg/kg) and both these in combination, and also all these concurrently with of α-tocopherol to Wistar rats for 90 days.

Results
Flubendiamide and copper produced concentration-dependent cytotoxic effects on splenocytes and at median lethal concentrations, flubendiamide (40 μM) and copper (40 μM) respectively produced 71 and 81% nonviable cells, higher number of Tunel+ve apoptotic cells, 7.86 and 9.16% micronucleus and 22.90 and 29.59 comets/100 cells and DNA fragmentation. In vivo study revealed significant (P < 0.05) increase in level of lipid peroxidation (LPO) and decrease in glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities in groups exposed to flubendiamide or copper alone or both these in combination. Histopathological examination of rat spleens revealed depletion of lymphoid tissue, separation of splenocytes and rarification in splenic parenchyma of xenobiotic(s) treated groups.

Conclusion
Flubendiamide and copper induce oxidative stress and produce cytogenotoxic effects along with histoarchitectural changes in spleen. All four tested natural antioxidants (resveratrol, catechin, curcumin and α-tocopherol) reduced flubendiamide and copper-induced cytotoxic effects in rat splenocytes. Rat splenocytes are very sensitive to flubendiamide and copper-induced cytogenotoxicity, therefore, these can be effectively employed for screening of compounds for their cytogenotoxic potential. α-tocopherol was effective in restoring alterations in oxidative stress biomarkers and preventing histoarchitectural lesions in spleen.
Clinical, imaging, and molecular analysis of pediatric pontine tumors lacking characteristic imaging features of DIPG
Authors: Chiang Jason , Diaz Alexander K. , Makepeace Lydia , Li Xiaoyu , Han Yuanyuan , Li Yimei , Klimo Paul , Boop Frederick A. , Baker Suzanne J. , Gajjar Amar , Merchant Thomas E. , Ellison David W. , Broniscer Alberto , Patay Zoltan , Tinkle Christopher L. 
Published: April 2020

AbstractDiffuse intrinsic pontine glioma (DIPG) is most commonly diagnosed based on imaging criteria, with biopsy often reserved for pontine tumors with imaging features not typical for DIPG (atypical DIPG, ‘aDIPG’). The histopathologic and molecular spectra of the clinical entity aDIPG remain to be studied systematically. In this study, thirty-three patients with newly diagnosed pontine-centered tumors with imaging inconsistent with DIPG for whom a pathologic diagnosis was subsequently obtained were included. Neoplasms were characterized by routine histology, immunohistochemistry, interphase fluorescence in situ hybridization, Sanger and next-generation DNA/RNA sequencing, and genome-wide DNA methylome profiling. Clinicopathologic features and survival outcomes were analyzed and compared to those of a contemporary cohort with imaging features consistent with DIPG (typical DIPG, ‘tDIPG’). Blinded retrospective neuroimaging review assessed the consistency of the initial imaging-based diagnosis and correlation with histopathology. WHO grade II-IV infiltrating gliomas were observed in 54.6% of the cases; the remaining were low-grade gliomas/glioneuronal tumors or CNS embryonal tumors. Histone H3 K27M mutation, identified in 36% of the cases, was the major prognostic determinant. H3 K27M–mutant aDIPG and H3 K27M–mutant tDIPG had similar methylome profiles but clustered separately from diffuse midline gliomas of the diencephalon and spinal cord. In the aDIPG cohort, clinicoradiographic features did not differ by H3 status, yet significant differences in clinical and imaging features were observed between aDIPG without H3 K27M mutation and tDIPG. Neuroimaging review revealed discordance between the classification of aDIPG and tDIPG and did not correlate with the histology of glial/glioneuronal tumors or tumor grade. One patient (3.1%) developed persistent neurologic deficits after surgery; there were no surgery-related deaths. Our study demonstrates that surgical sampling of aDIPG is well-tolerated and provides significant diagnostic, therapeutic, and prognostic implications, and that neuroimaging alone is insufficient to distinguish aDIPG from tDIPG. H3 K27M-mutant aDIPG is epigenetically and clinically similar to H3 K27M-mutant tDIPG.
Lipid-coated ZnO nanoparticles synthesis, characterization and cytotoxicity studies in cancer cell
Authors: Cao Dingding , Shu Xugang , Zhu Dandan , Liang Shengli , Hasan Murtaza , Gong Sheng 
Published: April 2020

AbstractZnO nanoparticles are widely used in biological, chemical, and medical fields, but their toxicity impedes their wide application. In this study, pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm) and lipid-coated ZnO NPs (~ 13 nm; ~ 22 nm; ~ 52 nm) with different morphologies were prepared by chemical method and characterized by TEM, XRD, HRTEM, FTIR, and DLS. Our results showed that the lipid-coated ZnO NPs (~ 13 nm; ~ 22 nm; ~ 52 nm) groups improved the colloidal stability, prevented the aggregation and dissolution of nanocrystal particles in the solution, inhibited the dissolution of ZnO NPs into Zn2+cations, and reduced cytotoxicity more efficiently than the pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm). Compared to the lipid-coated ZnO NPs, pristine ZnO NPs (~ 7 nm; ~ 18 nm; ~ 49 nm) could dose-dependently destroy the cells at low concentrations. At the same concentration, ZnO NPs (~ 7 nm) exhibited the highest cytotoxicity. These results could provide a basis for the toxicological study of the nanoparticles and direct future investigations for preventing strong aggregation, reducing the toxic effects of lipid-bilayer and promoting the uptake of nanoparticles by HeLa cells efficiently.
Unsteady shock front waviness in shock-buffet of transonic aircraft
Authors: Apetrei Razvan Marian , Ciobaca Vlad , Curiel-Sosa Jose Luis , Qin Ning 
Published: April 2020

AbstractThe unsteady transonic aerodynamics of a wing-body configuration is investigated by solving the Unsteady Reynolds-averaged Navier-Stokes equations closed with the full Reynolds Stress Model. This work presents the prediction of flow field characteristics during deep shock-buffet penetration of a transport aircraft-representative geometry. Mach number of 0.85, and Reynolds number of 5 million based on the mean chord, are selected to reproduce experimental test conditions that serve as validating datasets. The results obtained give information about both surface and flow field shock-buffet dynamics. An unsteady shock front is observed on the suction side of the wing which gives birth to the so-called buffet cells. Flow field characteristics are dominated by the presence of lambda-shaped shocks and fully separated boundary layer over a significant part of the wing.
Comparison of short-term (saliva) and long-term (hair) cortisol levels in out-patients with melancholic and non-melancholic major depression
Authors: Herane-Vives Andrés , Young Allan H. , Wise Toby , Aguirre Juan , de Angel Valeria , Arnone Danilo , Papadopoulos Andrew , Cleare Anthony J. 
Published: April 2020

Background
Major depressive episodes (MDEs) show diverse cortisol level alterations. Heterogeneity in symptom profiles, symptom severity and cortisol specimens may explain these heterogeneous results. Less severely ill out-patients with a non-melancholic MDE (NM-MDE) may have a variation in the rhythm of cortisol secretion rather than in its concentration.

Method
Cortisol measures were taken (a) over a short-term period (12 h) by measuring daily salivary output using the area under the curve with respect to the ground (AUCg) and (b) over a long-term period (3 months) in hair. Additionally, cortisol reactivity measures in saliva – the cortisol awakening response and the 30 min delta cortisol secretion after awakening (DELTA) – were investigated in 19 patients with a melancholic MDE (M-MDE) and 52 with a NM-MDE, and in 40 matched controls who were recruited from the UK and Chile. Depression severity scores were correlated with different cortisol measures.

Results
The NM-MDE group showed a decreased AUCg in comparison with controls (P = 0.02), but normal cortisol reactivity and long-term cortisol levels. The M-MDE group did not exhibit any significant cortisol alterations nor an association with depression severity scores. Higher Hamilton Rating Scale for Depression score was linked with decreased hair cortisol concentration (HCC, P = 0.05) and higher DELTA (P = 0.04) in NM-MDEs, whereas decreased HCC was the sole alteration associated with out-patients with severe M-MDEs.

Conclusions
The contrasting short- and long-term cortisol output results are compatible with an alteration in the rhythm of cortisol secretion in NM-MDEs. This alteration may consist of large and/or intense episodes of hypercortisolaemia in moderate NM-MDEs and frequent, but brief and sharp early-morning DELTAs in its severe form. These changes may reflect the effects of environmental factors or episodes of nocturnal hypercortisolaemia that were not measured by the short-term samples used in this study.
CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes
Authors: Capello Michela , Fahrmann Johannes F. , Rios Perez Mayrim V. , Vykoukal Jody V. , Irajizad Ehsan , Tripathi Satyendra C. , Roife David , Bantis Leonidas E. , Kang Ya’an , Kundnani Deepali L. , Xu Hanwen , Prakash Laura R. , Long James P. , Katayama Hiroyuki , Fleury Alia , Ferri-Borgogno Sammy , Baluya Dodge L. , Dennison Jennifer B. , Aguilar-Bonavides Clemente , Casabar Julian P. , Celiktas Muge , Do Kim-Anh , Fiehn Oliver , Maitra Anirban , Wang Huamin , Feng Ziding , Chiao Paul J. , Katz Matthew H. , Fleming Jason B. , Hanash Samir M. 
Published: April 2020

PURPOSE The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC. METHODS PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment. RESULTS High CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84; P = .02). High HbA1C levels were associated with longer overall survival in patients who received neoadjuvant FOLFIRINOX treatment ( P = .04). CONCLUSION To our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.
Relevance and Effectiveness of Molecular Tumor Board Recommendations for Patients With Non–Small-Cell Lung Cancer With Rare or Complex Mutational Profiles
Authors: Koopman Bart , van der Wekken Anthonie J. , ter Elst Arja , Hiltermann T. Jeroen N. , Vilacha Juliana F. , Groves Matthew R. , van den Berg Anke , Hiddinga Birgitta I. , Hijmering-Kappelle Lucie B. M. , Stigt Jos A. , Timens Wim , Groen Harry J. M. , Schuuring Ed , van Kempen Léon C. 
Published: April 2020

PURPOSE Molecular tumor boards (MTBs) provide physicians with a treatment recommendation for complex tumor-specific genomic alterations. National and international consensus to reach a recommendation is lacking. In this article, we analyze the effectiveness of an MTB decision-making methodology for patients with non–small-cell lung cancer (NSCLC) with rare or complex mutational profiles as implemented in the University Medical Center Groningen (UMCG). METHODS The UMCG-MTB comprises (pulmonary) oncologists, pathologists, clinical scientists in molecular pathology, and structural biologists. Recommendations are based on reported actionability of variants and molecular interpretation of pathways affected by the variant and supported by molecular modeling. A retrospective analysis of 110 NSCLC cases (representing 106 patients) with suggested treatment of complex genomic alterations and corresponding treatment outcomes for targeted therapy was performed. RESULTS The MTB recommended targeted therapy for 59 of 110 NSCLC cases with complex molecular profiles: 24 within a clinical trial, 15 in accordance with guidelines (on label) and 20 off label. All but 16 recommendations involved patients with an EGFR or ALK mutation. Treatment outcome was analyzed for patients with available follow-up (10 on label and 16 off label). Adherence to the MTB recommendation (21 of 26; 81%) resulted in an objective response rate of 67% (14 of 21), with a median progression-free survival of 6.3 months (interquartile range, 3.2-10.6 months) and an overall survival of 10.4 months (interquartile range, 6.3-14.6 months). CONCLUSION Targeted therapy recommendations resulting from the UMCG-MTB workflow for complex molecular profiles were highly adhered to and resulted in a positive clinical response in the majority of patients with metastatic NSCLC.
Improving inverse Compton sources by avoiding non-linearities
Authors: Terzić B. , Krafft G. A. , Petrillo V. , Drebot I. , Ruijter M. 
Published: April 2020

Abstract
We present a new, more nuanced understanding of non-linear effects in inverse Compton sources. Deleterious non-linear effects can arise even at low laser intensities, a regime previously viewed as linear. After laying out a survey of non-linear phenomena which degrade the effectiveness of inverse Compton sources, we discuss two powerful techniques designed to avoid these non-linearities. Starting with the known technique of non-linear longitudinal chirping of the laser pulse in the high laser field regime, we show that the simple stretching of the laser pulse, while keeping the energy constant, can significantly increase the spectral density of the scattered radiation in many operating regimes. Our numerical simulations show that combining these two techniques avoids detrimental non-linearities and improves the performance of inverse Compton sources over an order of magnitude.