bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor suppressive activities of solvatochromic 3,3′‐azadimethylene dinaphthospiropyran in colon cancer model
Authors: Lagisetty Pallavi , Eeda Venkateswararao , Yadav Vivek R. , Nimmo Susan L. , Subramaniam Dharmalingam , Powell Douglas R. , Awasthi Vibhudutta 
Published: September 2020

AbstractSpiropyrans have been extensively investigated because of their thermo‐ and photochromic characteristics, but their biotherapeutic properties have not been explored much. We report anti‐proliferative properties of a novel 3,3′‐azadimethylene dinaphthospiropyran 11. Dibenzospiropyrans and dinaphthospiropyrans were synthesized by a simple and expedient method using acid‐catalyzed aldol condensation of salicylaldehyde and 2‐hydroxy‐1‐naphthaldehyde, respectively, with cyclic ketones. Together with structural elucidation by 2D NMR and X‐ray crystallography studies, we provide a putative mechanism for their formation. Compound 11 showed solvatochromism and exhibited altered spectral characteristics depending on the pH. In acidic conditions, 11 remains in open form, whereas upon alkalinization it reverts back to closed form. Based on the in vitro anti‐proliferative activity in H441, HCT‐116, MiaPaCa‐2, and Panc‐1 cancer cell lines, 11 was submitted to further investigation. It reduced HCT116 colonosphere formation and demonstrated induction of caspase cascade, suggesting apoptosis. In vitro proliferation assays also suggested that HCl and trifluoroacetate salts of 11 are more effective. Treatment of mice carrying HCT‐116 xenografts with 11 (5 µg/day, intraperitoneal for 3 weeks) suppressed tumor growth by 62%. Overall, the results reveal a new series of structurally complex, but relatively easy to synthesize molecules of which compound 11 represents a lead for anticancer development.
Synthesis, extracorporeal nephrotoxicity, and 3D‐QSAR of andrographolide derivatives
Authors: Gu Lili , Lu Jiaqi , Li Qin , Huang Wenhai , Wu Ningzi , Yu Qingqing , Lu Hong , Zhang Xinyue 
Published: September 2020

AbstractAndrographolide is a traditional Chinese medicine monomer with many pharmacological activities, but has potential nephrotoxicity. Here, we aim to investigate the relationship between modification of andrographolide structure and its nephrotoxicity. Twenty‐three andrographolide derivatives were synthesized, and their structures were confirmed by1H‐NMR and HRMS. Nephrotoxicity of these compounds against human renal tubular epithelial (HK‐2) cells was evaluated using the MTT assay. The results indicated that most of them had significantly reduced nephrotoxicity, especially compoundsIII,V, andIXc, with IC50values of 1,985, 1,300, and 806.9 μmol/L, respectively, which were obviously superior to andrographolide (IC5030.60 μmol/L). However, compoundsIa–If(IC50values < 30 μmol/L), the 14‐OH derivatives of andrographolide, showed higher nephrotoxicity than that of andrographolide. Three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) models of COMFA and COMSIA were established (COMFA:q2 = 0.639,r2 = 0.951; COMSIA:q2 = 0.569,r2 = 0.857). This model allowed proposing five new compounds with lower theoretical nephrotoxicity, which would be worthwhile to synthesize and evaluate. We believe that predicted models will help us to understand the structural modification requirements of andrographolide to reduce the nephrotoxicity, and further investigations will be needed to determine the mechanism involved in the effect of less nephrotoxic compounds.
Modulation of co‐stimulatory signal from CD2–CD58 proteins by a grafted peptide
Authors: Parajuli Pravin , Sable Rushikesh , Shrestha Leeza , Dahal Achyut , Gauthier Ted , Taneja Veena , Jois Seetharama 
Published: September 2020

AbstractPeptides were designed to inhibit the protein–protein interaction of CD2 and CD58 to modulate the immune response. This work involved the design and synthesis of eight different peptides by replacing each amino acid residue in peptide 6 with alanine as well as grafting the peptide to the sunflower trypsin‐inhibitor framework. From the alanine scanning studies, mutation at position 2 of the peptide was shown to result in increased potency to inhibit cell adhesion interactions. The most potent peptide from the alanine scanning was further studied for its detailed three‐dimensional structure and binding to CD58 protein using surface plasmon resonance and flow cytometry. This peptide was used to graft to the sunflower trypsin inhibitor to improve the stability of the peptide. The grafted peptide, SFTI‐a1, was further studied for its potency as well as its thermal, chemical, and enzymatic stability. The grafted peptide exhibited improved activity compared to our previously grafted peptide and was stable against thermal and enzymatic degradation.
Design and biological evaluation of phenyl imidazole analogs as hedgehog signaling pathway inhibitors
Authors: Sun Chiyu , Zhang Ying , Wang Han , Yin Zhengxu , Wu Lingqiong , Huang Yanmiao , Zhang Wenhu , Wang Youbing , Hu Qibo 
Published: September 2020

AbstractThe hedgehog (Hh) signaling pathway is involved in diverse aspects of cellular events. Aberrant activation of Hh signaling pathway drives oncogenic transformation for a wide range of cancers, and it is therefore a promising target in cancer therapy. In the principle of association and ring‐opening, we designed and synthesized a series of Hh signaling pathway inhibitors with phenyl imidazole scaffold, which were biologically evaluated in Gli‐Luc reporter assay. Compound 25 was identified to possess high potency with nanomolar IC50, and moreover, it preserved the inhibition against wild‐type and drug‐resistant Smo‐overexpressing cells. A molecular modeling study of compound 25 expounded its binding mode to Smo receptor, providing a basis for the further structural modification of phenyl imidazole analogs.
Intradermal Phleum pratense allergoid immunotherapy. Double‐blind, randomized, placebo‐controlled trial
Authors: Sola Martínez Francisco Javier , Barranco Jiménez Ruth María , Martín García Cristina , Senent Sánchez Carlos , Blanco Guerra Carlos , Fernández‐Rivas Montserrat , Vega Castro Arantza , Dávila González Ignacio , Carbonell Martínez Antonio , Panizo Bravo Carmen , Gómez Torrijos Elisa , Rodríguez Gil David , Palacios Peláez Ricardo 
Published: September 2020

AbstractBackgroundIn allergology, the intradermal approach is generally used to establish an aetiological diagnosis, with limited experience in specific allergen immunotherapy.ObjectiveTo evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde‐polymerized Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen.MethodsMulticentre, randomized, double‐blind, placebo‐controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of six doses in a weekly interval, of either placebo; 0.03 or 0.06 μg of protein per dose of P pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale.ResultsThe dose of 0.06 μg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded.Conclusion & Clinical RelevanceIntradermal immunotherapy with P pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.
Effect of long‐term glucocorticoid therapy on cardiac functions in children with congenital adrenal hyperplasia
Authors: Amr Nermine Hussein , Mahmoud Rana Abdelhakim Ahmed , Youssef Omneyia , Toaima Nadin Nabil , Elsedfy Heba 
Published: September 2020

AbstractBackgroundGlucocorticoids play an important role in cardiac physiology. Chronic exposure and higher doses may cause adverse effects on the myocardium, especially in young patients receiving long‐term therapy.ObjectiveTo assess cardiac function in children with congenital adrenal hyperplasia (CAH) and its relation to glucocorticoid dose and therapy duration.MethodsForty‐seven patients with CAH due to 21‐hydroxylase deficiency were compared to 47 controls. Patients were subdivided according to treatment duration (Group A: less than 6 years, Group B: more than 6 years). Mean daily glucocorticoid and cumulative glucocorticoid doses were calculated. Echocardiography was performed for patients and controls to evaluate cardiac functions, chamber dimensions and tissue Doppler valvular status.ResultsCompared to controls, patients had cardiac chamber hypertrophy reflected by higher M‐mode dimensions. Patients had lower fractional shortening, defective ventricular relaxation, lower average mitral and tricuspid e´/a´ ratios (e´ early diastolic, a´ late diastolic) as well as s´ (systolic) velocities, higher average mitral E/e ratio and higher left ventricle TDI Tei index (P < .05). Group B had lower average mitral e´/a´ and tricuspid s´ velocities, and higher average mitral E/e ratio (P < .05). Cumulative glucocorticoid dose significantly correlated with different echocardiographic parameters.ConclusionLong‐term glucocorticoid therapy even within the recommended therapeutic range adversely affects cardiac functions in children with 21‐hydroxylase deficiency.
The evolution of the nosology of osteogenesis imperfecta
Authors: Chetty Manogari , Roomaney Imaan Amina , Beighton Peter 
Published: September 2020

AbstractOsteogenesis imperfecta (OI) is a relatively common genetic skeletal disorder with an estimated frequency of 1 in 20 000 worldwide. The manifestations are diverse and although individually rare, the several different forms contribute to the production of a significant number of affected individuals with considerable morbidity and mortality. During the last decade, there have been extensive molecular investigations into the etiology of OI and these advances have direct relevance to the medical management of the disorder, and the purpose of this review is to document the history and evolution of the nosology of OI. The current nosology, based on molecular concepts, which are crucial in the identification of genotype‐phenotype correlations in persons with OI, is also outlined. The successive revisions of the nosology and classification of OI have highlighted the importance of the nomenclature of the condition in order for it to be recognized by clinicians, scientists and patient advocacy groups. In this way, improved counseling of patients and individualized, tailored therapeutic approaches based on the underlying pathophysiology of the individual's type of OI have been facilitated.
Extracellular biofilm matrix leads to microbial dysbiosis and reduces biofilm susceptibility to antimicrobials on titanium biomaterial: An in vitro and in situ study
Authors: Costa Raphael Cavalcante , Souza João Gabriel Silva , Bertolini Martinna , Retamal‐Valdes Belén , Feres Magda , Barão Valentim A. R. 
Published: September 2020

AbstractObjectivesTo test the role of exopolysaccharide (EPS) polymers matrix to modulate the composition/virulence of biofilms growing on titanium (Ti) surfaces, the effect on antibiotic susceptibility, and whether a dual‐targeting therapy approach for disrupted EPS matrix could improve the antimicrobial effect.Materials and MethodsA microcosm biofilm model using human saliva as inoculum was used, and the microbial composition was assessed by checkerboard DNA–DNA hybridization. EPS‐enriched biofilms virulence was tested using fibroblast monolayer. Povidone‐iodine (PI) was used as EPS‐targeting agent followed by amoxicillin + metronidazole antibiotic to reduce bacterial biomass using an in situ model.ResultsAn EPS‐enriched environment, obtained by sucrose exposure, promoted bacterial accumulation and led to a dysbiosis on biofilms, favoring the growth of Streptococcus, Fusobacterium, and Campylobacter species and even strict anaerobic species related to peri‐implant infections, such as Porphyromonas gingivalis and Tannerella forsythia (~3‐fold increase). EPS‐enriched biofilm transitioned from a commensal aerobic to a pathogenic anaerobic profile. EPS increased biofilm virulence promoting higher host cell damage and reduced antimicrobial susceptibility, but the use of a dual‐targeting approach with PI pre‐treatment disrupted EPS matrix scaffold, increasing antibiotic effect on in situ biofilms.ConclusionAltogether, our data provide new insights of how EPS matrix creates an environment that favors putative pathogens growth and shed light to a promising approach that uses matrix disruption as initial step to potentially improve implant‐related infections treatment.
Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study
Authors:   EuroSurg Collaborative
Published: September 2020

AbstractAimAspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery.MethodThis was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis.ResultsA total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56–1.87, P = 0.932).ConclusionIn patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion.
A colorimetric chemosensor for selective detection of copper ions
Authors: Kim Ahran , Chae Ju Byeong , Rha Chang Joo , Kim Cheal 
Published: September 2020

AbstractA water‐applicable hexamethylbenzene (HMB) chemosensor, (E)‐2‐((2‐hydroxy‐3‐methoxybenzylidene)amino)benzamide, displayed a selective colour change from colourless to yellow in the existence of copper ions. The detection limit was computed as 1.57 μmol/L, which is substantially lower than the World Health Organisation guideline (31.5 μmol/L) for copper ions. Probe HMB could also sense and quantify copper ions in real water samples. The coordination mode of HMB to copper ions was demonstrated through Job plot, electrospray ionisation mass spectroscopy and proton nuclear magnetic resonance titration, and was also supported by theoretical studies.
H3 relaxin protects against calcium oxalate crystal‐induced renal inflammatory pyroptosis
Authors: Liu Jiannan , Yang Kelaier , Jin Yinshan , Liu Yadong , Chen Yaodong , Zhang Xiaohui , Yu Shiliang , Song Erlin , Chen Song , Zhang Jingbo , Jing Guanhua , An Ruihua 
Published: September 2020

AbstractObjectivesCalcium oxalate (CaOx) crystals can activate inflammatory cytokines by triggering inflammasomes, which cause damage to the adhered epithelium, a dysfunctional microenvironment and even renal failure. However, a comprehensive and in‐depth understanding of the mechanisms underlying the effects of these crystals on damage and cytokine function in renal tubular epithelial cells (TECs) remains limited and to be explored.Materials and MethodsWe detected the pyroptosis of TECs induced after exposure to CaOx crystals and demonstrated the significance of cytokine activation in the subsequent inflammatory processes through a proteomic study. We then conducted animal and cell experiments to verify relevant mechanisms through morphological, protein, histological and biochemical approaches. Human serum samples were further tested to help explain the pathophysiological mechanism of H3 relaxin.ResultsWe verified that crystal‐induced extracellular adenosine triphosphate (ATP) upregulation via the membrane purinergic 2X7 receptor (P2X7R) promotes ROS generation and thereby activates NLRP3 inflammasome‐mediated interleukin‐1β/18 maturation and gasdermin D cleavage. Human recombinant relaxin‐3 (H3 relaxin) can act on the transmembrane receptor RXFP1 to produce cAMP and subsequently improves crystal‐derived damage via ATP consumption. Additionally, endogenous relaxin‐3 was found to be elevated in patients with renal calculus and can thus serve as a biomarker.ConclusionsOur results provide previously unidentified mechanistic insights into CaOx crystal‐induced inflammatory pyroptotic damage and H3 relaxin‐mediated anti‐inflammatory protection and thus suggest a series of potential therapeutic targets and methods for but not limited to nephrocalcinosis.
Peace in the valley? Qualitative insights on collaborative coexistence from the Wood River Wolf Project
Authors: Martin Jeff Vance 
Published: September 2020

AbstractThreats posed by wild predators to livestock production have too often resulted in human–wildlife conflict, to the detriment of these keystone species and broader biodiversity conservation. Long‐standard practices of lethal control are increasingly seen as costly, controversial, and ineffective, however, with nonlethal alternatives ever more prominent. In addition to assessing these tools' ecological effectiveness, there remains a key role for the social sciences, particularly qualitative research, in identifying obstacles to and opportunities for the long‐term sustainability and scaling up of these coexistence interventions. The Wood River Wolf Project (WRWP), a collaboration among ranchers, environmental organizations, and government agencies in Blaine County, Idaho, has pursued coexistence between gray wolves and domestic sheep since 2008, demonstrating and developing nonlethal techniques and garnering regional and international attention as a model for collaborative coexistence. Yet the Project has also struggled with changing conditions and internal challenges. Investigation of this prominent effort—its history and practices as well as the broader socio‐political and economic context—highlights the challenges of adaptive governance in the face of reduced capacity and hostile legal‐political contexts, while providing important insights for practitioners and policymakers promoting wildlife coexistence in shared landscapes.
Systematic evaluation of therapeutic effects of stem cell transplantation trials for heart diseases in China
Authors: Que Wan‐Cai , Qiu Hong‐Qiang , Chen Hui‐Yun , Wang Shao‐Zhen , Cheng Yu , Liao Lian‐Ming 
Published: September 2020

AbstractBackgroundTo systematically assess the quality of reports of clinical trials of stem cell for heart diseases published in Chinese.MethodsThe quality of reports was assessed according to the CONSORT statement and the Jadad score. The association between the CONSORT scores and the reported therapeutic effects was evaluated.ResultsA total of 36 randomized clinical trials were identified, and 1552 patients were included. The mean CONSORT score was 7.06 (SD = 2.99). The proportion of reports with a Jadad score of 3 was 8.33%. The improvement of left ventricular function, myocardial perfusion area, left ventricular diastolic diameter, and cardiac output decreased with the increase in the CONSORT score.ConclusionsThe percentages of high‐quality reports published in Chinese on stem cell therapy for heart diseases are low. Although stem cell transplantation seems promising for heart diseases, high‐quality studies are needed to verify the conclusions．
Acute coronary syndromes in the peri‐operative period after kidney transplantation in United States
Authors: Goyal Abhinav , Lo Kevin Bryan , Chatterjee Kshitij , Mathew Roy O. , McCullough Peter A. , Bangalore Sripal , Rangaswami Janani 
Published: September 2020

AbstractIntroductionChronic kidney disease is an independent risk factor for cardiovascular disease. Despite careful preoperative evaluation, there is a risk of acute coronary syndromes after kidney transplant.MethodsThe National Inpatient Sample for the years 2004‐2013 was used for this retrospective cohort study. All adult patients undergoing kidney transplantation were identified using the appropriate ICD‐9‐CM codes. Multivariate logistic regression was used to identify predictors of acute coronary syndromes in the peri‐operative period after kidney transplantation.ResultsA total of 147 431 kidney transplants were performed from 2004 through 2013 in the United States. The average peri‐operative in‐hospital mortality was 0.5%. Acute coronary syndrome occurred in 1.3% patients in the peri‐operative period. Half of patients with acute coronary syndromes had pre‐existing coronary artery disease. The strongest predictors of acute coronary syndromes included older age: 45‐64 years. OR 3.28 95% CI (1.85‐5.83), ≥65 years. OR 4.84 (2.59‐9.05), race: African American, OR 0.66 (0.47‐0.93) and pre‐existing coronary artery disease OR 3.83 (2.84‐5.15). The case fatality rates were 16.9% and 5.3% for STEMI and NSTEMI, respectively. The overall mortality for any ACS event was 7.1%.ConclusionAcute coronary syndrome in the immediate peri‐operative period after kidney transplantation is rare but is associated with high rates of mortality.
Comparative cytological and histological assessment of 828 primary soft tissue and bone lesions, and proposal for a system for reporting soft tissue cytopathology
Authors: Köster Jan , Ghanei Iman , Domanski Henryk A. 
Published: September 2020

AbstractIntroductionThe aim of the study was to evaluate the diagnostic utility of fine needle aspiration (FNA) cytology and core needle biopsies (CNBs) in a series of primary soft tissue and bone lesions and to test a possible system for reporting results of FNA cytology of soft tissue lesion.MethodsThis retrospective study encompassed 828 primary soft tissue and bone lesions, analysed with FNA, CNB and/or surgical specimen in order to perform sensitivity/specificity as well as accuracy analyses. The series was then used to test a system for reporting soft tissue cytopathology with six categories and the risk of malignancy in each category was calculated.ResultsWith a malignant diagnosis defined as positive test result, FNA and CNB analysis showed sensitivity of 87% and 94%, respectively, and specificity of 89% and 95%, respectively. FNA and CNB analyses identified the correct histopathological entity of the examined lesion in 55% and 66%, respectively. The risk of malignancy within the tested categories was non‐diagnostic 42%, non‐neoplastic 0%, atypia of unknown significance 46%, neoplasm benign 3%, neoplasm of unknown malignant potential 27%, suspicious for malignancy 72% and malignant 97%.ConclusionFNA cytology is a suitable tool to determine the malignant potential of a sampled soft tissue/bone lesion but is inferior to CNB in defining the correct entity. A standardised reporting system might improve the clinical management of patients with soft tissue tumours examined primarily by FNA cytology.