bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of Antimicrobial Resistance and Limiting Use of Antibiotics by the Application of De-escalation and Streamlining: A Review Update
Authors: Saha Ritu , Uddin Bhuiyan Mohammad Mahtab 
Published: December 2020

De-escalation is a critical component that lies at the center of antimicrobial stewardship programs. It is a clinically effective concept in reducing infection with drug resistant isolates. Although there is significant and serious shortfalls like establishment of the real impact of de-escalation on antimicrobial resistance development; it is now well demonstrated that there is no harm for patients, whether it genuinely improve clinical outcomes. Further studies are needed to establish the most effective tools to implement de-escalation, particularly in terms of providing clear guidelines to clinicians to enable them to be confident in applying this maneuver in our country. It is interesting that this concept of de-escalation is now being explored in different types of infection.
Journal of National Institute of Neurosciences Bangladesh, 2020;6(2): 140-142
Factors influencing short-term effectiveness and efficiency of the care provided by Dutch general practice mental health professionals
Authors: Vennemann Tosca G.R. , Wijnen Ben F.M. , Ringoir Lianne , Kenter Audry , Van Bon-Martens Marja J.H. , Alessie Rob J.M. , Nuyen Jasper 
Published: December 2020

Introduction: This study examined whether factors related to general practice mental health professionals (GP-MHPs), that is, characteristics of the professional, the function, and the care provided, were associated with short-term effectiveness and efficiency of the care provided by GP-MHPs to adults in Dutch general practice.
Methods: A prospective cohort study was conducted among 320 adults with anxiety or depressive symptoms who had an intake consultation with GP-MHPs (n = 64). Effectiveness was measured in terms of change in quality-adjusted life years (QALYs) 3 months after intake; and efficiency in terms of net monetary benefit (NMB) at 3-month follow-up. A range of GP-MHP-related predictors and patient-related confounders was considered.
Results: Patients gained on average 0.022 QALYs at 3-month follow-up. The mean total costs per patient during the 3-month follow-up period (€3,864; 95% confidence interval [CI]: €3,196-€4,731) decreased compared to that during the 3 months before intake (€5,220; 95% CI: €4,639–€5,925), resulting largely from an increase in productivity. Providing mindfulness and/or relaxation exercises was associated with QALY decrement. Having longer work experience as a GP-MHP (≥2 years) and having 10-20 years of work experience as a mental health care professional were negatively associated with NMB. Furthermore, a higher number of homework exercises tended to be related to less efficient care. Finally, being self-employed and being seconded from an organization in which primary care and mental health care organizations collaborate were related to a positive NMB, while being seconded from a mental health organization tended towards such a relationship.
Conclusions: Findings seem to imply that the care provided by GP-MHPs contributes to improving patients’ functioning. Some GP-MHP-related characteristics appear to influence short-term effectiveness and efficiency of the care provided. Further research is needed to confirm and better explain these findings and to examine longer-term effects.
CRISPR/Cas9 como perspectiva de cura para o Diabetes mellitus tipo 1
Authors: Silva Milena Roberta Freire da , Souza Karolayne Silva , Santos Milena Danda Vasconcelos , Leite Kaleen Massari , Silva Jaqueline dos Santos , Silva Diego Canuto Bispo da , Fidelis Kleber Ribeiro , Silva Rodrigo Reges dos Santos , Santos Graziele dos , Silva Renata Pereira Lima da , Nunes Filipe Silva , Brito Leandro Paes de , Oliveira Felicson Leonardo Oliveira , Oliveira Maria Betânia Melo de 
Published: December 2020

Introdução O Diabetes mellitus do tipo 1 (DM1), é considerado uma doença autoimune, crônica, multifatorial, que envolve a destruição progressiva das células β das ilhotas pancreáticas, sendo estas responsáveis pela produção de insulina, resultando assim na perda da produção e secreção da mesma. Estima-se que mais de 30 mil brasileiros sofram desta patologia. Três mecanismos são responsáveis pela destruição destas células: suscetibilidade genética, autoimunidade e fatores ambientais. Neste sentido, o objetivo deste estudo foi realizar um levantamento acerca das principais perspectivais de cura desta doença utilizando o sistema CRISPR/Cas9. Metodologia: Trata-se de uma revisão bibliográfica com buscas nas bases eletrônicas nacionais e internacionais na língua portuguesa e inglesa. Resultados: Visto que esta patologia ainda não possui cura, apenas tratamento, o sistema CRISPR/Cas9 surge como uma terapia promissora, assim como a terapia com células-tronco mensenquimais pluripotentes (MSC), as quais possui a funcionalidade, principalmente, de reparação e sobrevivência de células β das ilhotas pancreáticas, as MSCs possuem a capacidade de modificação do microambiente das áreas de lesão pancreática, anulando a destruição autoimune contra as células β podendo restaurar a normoglicemia do paciente. Conclusão: Tendo em vista que esta é uma patologia de cunho genético, o CRISPR/Cas9 associado a terapia com células mensenquimais pluripotentes vem se mostrando como uma ferramenta versátil e eficaz no tratamento do DM1. No entanto, faz-se necessárias novas pesquisas capazes de induzir estratégias para o melhoramento de alterações genéticas e maior eficiência do efeito terapêutico.
Quality of Italian tomatoes grown with different forms of calcium application
Authors: Andrade Isa Gabriela Vieira de , Souza Gilmário Noberto de , Aires Eduardo Santana , Gomes Ítala Laiane Silva , Rocha Ruy de Carvalho , Figueiredo Neto Acácio , Aragão Carlos Alberto 
Published: December 2020

Tomato is one of the most consumed vegetables in the world. This work aimed to evaluate post-harvest quality of Italian Saladete tomatoes grown in a protected environment, with different ways of calcium application, in the Middle São Francisco Valley. Consisting of five Italian tomato hybrids (Anjico, Gabrielle, Liberty, Ty 2006 and Shanty), and three different ways of calcium application (T0 without application of calcium; T1 application of calcium in the opening flower, and T2 weekly application of calcium in the fruit). Poductivity, average fruit mass, incidence of apical rot, fruit firmness, soluble solids (SS), titratable acidity (AT), and pH, were analized. The experimental design used was a completely randomized block design in a factorial scheme (five cultivars x three ways of calcium application), with three repetition and using two central plants as useful plot for analysis, except for fruit firmness that was carried out in a completely randomized design, using tree fruits per analysis. According to the results obtained, hybrids of Italian saladete tomatoes behaved in a satisfactory manner, therefore it is recommended to cultivate hybrids of Italian saladete tomatoes in the Middle São Francisco Valley, mainly hybrid Anjico. Calcium application way did not interfere with post-harvest attributes.
Color Stability of Flowable Composites in Different Viscosities
Authors: KORKUT Bora , HACIALI Cigdem 
Published: December 2020

Objective: This in vitro study was aimed to evaluate the color stability of resin-based composite materials in different viscosities immersed in various colorant solutions.Methods: 250 composite samples of A2 shades were prepared using two high-viscosity flowable composites (G-aenial Injectable, GC, Tokyo, Japan; Estelite Super Low Flow, Tokuyama Dental, Japan A2 shade), a bulk-fill flowable composite (Filtek Bulk-Fill, 3M, USA), a low-viscosity flowable composite (Filtek Ultimate Flowable, 3M, USA), and a packable composite (Filtek Ultimate, 3M, USA). Samples were polymerized and polished from both sides with a LED curing unit (Valo Grand, Ultradent, Switzerland) and polishing discs (SofLex, 3M, USA). Then divided by test groups (n=10 for each) regarding colorant solutions; coke (CocaCola Company, USA), tea (Yellow Label, Lipton, Rize, Turkey), coffee (Nescafe Classic; Nestle, Switzerland), red wine (Doluca, Öküzgözü, Doluca, İstanbul, Turkey), and physiologic saline as the control solution. Samples were discolored for 144 hours with solutions in an incubator at 37°C, and repolished after discoloration. Color measurements were performed using a clinical spectrophotometer (EasyShade IV, Vita, Germany) and a colorimeter (ShadeStar, Dentsply Sirona, USA). Two-way Anova test and Tukey HSD test were used for statistical analyses.Results: Composite material and colorant solution were considered effective factors for influencing the color change, regarding after discoloration scores (p&lt;0.001, p&lt;0.001, respectively). In addition, colorant solution was found more effective than the type of composite. Filtek Ultimate Flowable presented significantly the highest level of color change among others (p&lt;0.001), for both ‘after discoloration (5,34 ± 3,78b)’ and ‘after repolishing (3,93 ± 2,23b)’ periods. No significant difference in color change was found between Gaenial Injectable, Estelite Super Low Flow, Filtek Bulk Fill Flowable, and Filtek Ultimate, and all showed imperceptible color changes (∆E*&lt;3.7). Red wine solution showed significantly the highest level of color change (8,00 ± 2,08d) among other colorant solutions (p&lt;0.001), and followed by coffee (4,59 ± 1,52c), tea (3,38 ± 1,21b), and coke (1,58 ± 0,99a), respectively. A strong relation was found between the spectrophotometer and colorimeter measurements.Conclusion: Viscosity was considered an effective factor for discoloration of RBCs. Color stability of high viscosity flowable composite materials were found to be good and similar to packable composite. Samples immersed in red wine showed the greatest level of discoloration and followed by coffee, tea, and coke. The repolishing procedure was considered effective for reversing back the surface discoloration of composite materials.
Inhibiting Protein Kinase D Promotes Airway Epithelial Barrier Integrity in Mouse Models of Influenza A Virus Infection
Authors: Veazey Janelle M. , Eliseeva Sophia I , Hillman Sara E. , Stiles Kristie , Smyth Timothy R. , Morrissey Charlotte E. , Tillotson Erika J. , Topham Dave J. , Chapman Timothy J. , Georas Steve N. 
Published: December 2020

RationaleProtein kinase D (PKD) is a serine/threonine kinase family that is involved in a wide array of signaling pathways. Although PKD has been implicated in immune responses, relatively little is known about the function of PKD in the lung or during viral infections.ObjectivesWe investigated the hypothesis that PKD is involved in multiple aspects of host response to viral infection.MethodsThe selective PKD inhibitor CRT0010166 was administered to C57BL/6 mice prior to and during challenge with either inhaled double-stranded RNA or Influenza A Virus. PKD signaling pathways were investigated in human bronchial epithelial cells treated with CRT0010166, double-stranded RNA, and/or infected with Influenza A Virus.MeasurementsTotal protein and albumin accumulation in the bronchoalveolar fluid was used to asses inside/out leak. Clearance of inhaled FITC-dextran out of the airspace was used to assess outside/in leak. Cytokines and neutrophils in bronchoalveolar lavage were assayed with ELISAs and cytospins respectively. Viral RNA level was assessed with RT-PCR and protein level assessed by ELISA.Main ResultsPKD inhibition prevented airway barrier dysfunction and pro-inflammatory cytokine release. Epithelial cells express PKD3, and PKD3 siRNA knock-down inhibited polyI:C induced cytokine production. Lung epithelial-specific deletion of PKD3 (CC10-Cre x PKD3-floxed mice) partially attenuated polyI:C-induced barrier disruption in vivo. Mechanistically, we found that PKD promoted cytokine mRNA transcription, not secretion, likely through activating the transcription factor Sp1. Finally, prophylactic CRT treatment of mice promoted barrier integrity during influenza virus infection and reduced viral burden.ConclusionsInhibiting PKD promotes barrier integrity, limit pathogenic cytokine levels, and restrict Influenza A Virus infection. Therefore, PKD is an attractive target for novel antiviral therapeutics.
Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome
Authors: Augé Hélène , Notarantonio Anne-Béatrice , Morizot Romain , Quinquenel Anne , Fornecker Luc-Matthieu , Hergalant Sébastien , Feugier Pierre , Broséus Julien 
Published: December 2020

IntroductionRichter Syndrome (RS) is defined as the development of an aggressive lymphoma in the context of Chronic Lymphocytic Leukemia (CLL), with a Diffuse Large B-Cell Lymphoma (DLBCL) histology in 95% cases. RS genomic landscape shares only a few features with de novo DLBCLs and is marked by a wide spectrum of cytogenetic abnormalities. Little is known about RS microenvironment. Therapeutic options and efficacy are limited, leading to a 12 months median overall survival. The new targeted treatments usually effective in CLL fail to obtain long-term remissions in RS.MethodsWe reviewed available PubMed literature about RS genomics, PD-1/PD-L1 (Programmed Death 1/Programmed Death Ligand 1) pathway triggering and subsequent new therapeutic options.ResultsData from about 207 patients from four landmark papers were compiled to build an overview of RS genomic lesions and point mutations. A number of these abnormalities may be involved in tumor microenvironment reshaping. T lymphocyte exhaustion through PD-L1 overexpression by tumor cells and subsequent PD-1/PD-L1 pathway triggering is frequently reported in solid cancers. This immune checkpoint inhibitor is also described in B lymphoid malignancies, particularly CLL: PD-1 expression is reported in a subset of prolymphocytes from the CLL lymph node proliferation centers. However, there is only few data about PD-1/PD-L1 pathway in RS. In RS, PD-1 expression is a hallmark of recently described « Regulatory B-cells », which interact with tumor microenvironment by producing inhibiting cytokines such as TGF-β and IL-10, impairing T lymphocytes anti-tumoral function. Based upon the discovery of high PD-1 expression on tumoral B lymphocyte from RS, immune checkpoint blockade therapies such as anti-PD-1 antibodies have been tested on small RS cohorts and provided heterogeneous but encouraging results.ConclusionRS genetic landscape and immune evasion mechanisms are being progressively unraveled. New protocols using targeted treatments such as checkpoint inhibitors as single agents or in combination with immunochemotherapy are currently being evaluated.
Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of the GOODLUPUS Study
Authors: Bourse Chalvon Nellie , Orquevaux Pauline , Giusti Delphine , Gatouillat Gregory , Tabary Thierry , Tonye Libyh Marcelle , Chrusciel Jan , Drame Moustapha , Stockton-Bliard Grace , Amoura Zahir , Arnaud Laurent , Lorenz Hanns-Martin , Blaison Gilles , Bonnotte Bernard , Magy-Bertrand Nadine , Revuz Sabine , Voll Reinhard Edmund , Hinschberger Oliver , Schwarting Andreas , Pham Bach Nga , Martin Thierry , Pennaforte Jean-Loup , Servettaz Amelie 
Published: December 2020

IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or withoutproliferativerenal damage and compared to a healthy control group.MethodologyThis retrospective study was performed on SLE patients’ sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer &gt;6 U/ml).ResultsThe cohort was composed of 100 SLE patients withproliferativeLN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (&gt;10 U/ml) by the automated technique, three sera were found “ambivalent” (&gt;7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.ConclusionAnti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.
FDG-PET Profiles of Extratemporal Metabolism as a Predictor of Surgical Failure in Temporal Lobe Epilepsy
Authors: Tang Yongxiang , Liao Guang , Li Jian , Long Tingting , Li Yulai , Feng Li , Chen Dengming , Tang Beisha , Hu Shuo 
Published: December 2020

Objective: Metabolic abnormality in the extratemporal area on fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is not an uncommon finding in drug-resistant temporal lobe epilepsy (TLE), however the correlation between extratemporal metabolic abnormalities and surgical long-term prognosis has not been fully elucidated. We aim to investigate FDG-PET extratemporal metabolic profiles predictive of failure in surgery for TLE patients.Methods: Eighty-two patients with unilateral TLE (48 female, 34 male; 25.6 ± 10.6 years old; 37 left TLE, 45 right TLE) and 30 healthy age-matched controls were enrolled. Patients were classified either as experiencing seizure-recurrence (SZR, Engel class II through IV) or seizure-free (SZF, Engel class I) at least 1 year after surgery. Regional cerebral metabolism was evaluated by FDG-PET with statistical parametric mapping (SPM12). Abnormal metabolic profiles and patterns on FDG-PET in SZR group were evaluated and compared with those of healthy control and SZF subjects on SPM12. Volume and intensity as well as special brain areas of abnormal metabolism in temporal and extratemporal regions were quantified and visualized.Results: With a median follow-up of 1.5 years, 60% of patients achieved Engel class I (SZF). SZR was associated with left TLE and widespread hypometabolism in FDG-PET visual assessment (both p &lt; 0.05). All patients had hypometabolism in the ipsilateral temporal lobe but SZR was not correlated with volume or intensity of temporal hypometabolism (median, 1,456 vs. 1,040 mm3; p &gt; 0.05). SZR was correlated with extratemporal metabolic abnormalities that differed according to lateralization: in right TLE, SZR exhibited larger volume in extratemporal areas compared to SZF (median, 11,060 vs. 2,112 mm3; p &lt; 0.05). Surgical failure was characterized by Cingulum_Ant_R/L, Frontal_Inf_Orb_R abnormal metabolism in extratemporal regions. In left TLE, SZR presented a larger involvement of extratemporal areas similar to right TLE but with no significant (median, 5,873 vs. 3,464 mm3; p &gt; 0.05), Cingulum_Ant_ R/L, Parietal_Inf_L, Postcentral_L, and Precuneus_R involved metabolic abnormalities were correlated with SZR.Conclusions: Extratemporal metabolic profiles detected by FDG-PET may indicate a prominent cause of TLE surgery failure and should be considered in predictive models for epilepsy surgery. Seizure control after surgery might be improved by investigating extratemporal areas as candidates for resection or neuromodulation.
Potential Mechanisms for Traditional Chinese Medicine in Treating Airway Mucus Hypersecretion Associated With Coronavirus Disease 2019
Authors: Zhang Yuanfeng , Wang Zheyi , Zhang Yue , Tong Hongxuan , Zhang Yiling , Lu Tao 
Published: December 2020

BackgroundThe rapid development of coronavirus disease 2019 (COVID-19) pandemic has become a great threat to global health. Its mortality is associated with inflammation-related airway mucus hypersecretion and dysfunction of expectoration, and the subsequent mucus blockage of the bronchioles at critical stage is attributed to hypoxemia, complications, and even death. Traditional Chinese medicine (TCM) has rich experience in expectorant, including treatment of COVID-19 patients with airway mucus dysfunction, yet little is known about the mechanisms. This study is aiming to explore the potential biological basis of TCM herbal expectorant for treating COVID-19.ObjectiveTo get core herbs with high used frequency applications in the actions of expectoration by using association rule algorithm and to investigate the multitarget mechanisms of core herbs in expectorant formulae for COVID-19 therapies.MethodsForty prescriptions for expectorant were retrieved from TCM Formulae. The ingredient compounds and targets of core herbs were collected from the TCMSP database, Gene-Cards, and NCBI. The protein interaction network (PPI) was constructed by SRING, and the network analysis was done by Cytoscape software. Bioconductor was applied for functional enrichment analysis of targets.ResultsThe core herbs of expectorant could regulate core pathways (MAP kinase activity, cytokine receptor binding, G-protein-coupled receptor binding, etc.) via interactions of ingredients (glycyrol, citromitin, etc.) on mucin family to eliminate phlegm.ConclusionTCM herbal expectorant could regulate MAPK and cytokine-related pathways, thereby modulating Mucin-family to affect mucus generation and clearance and eventually retarding the deterioration of COVID-19 disease.