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Publication
Journal: Journal of Thoracic and Cardiovascular Surgery
December/5/2021
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Journal: Enferm Infecc Microbiol Clin (Engl Ed)
December/5/2021
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Journal: Journal of Thoracic and Cardiovascular Surgery
December/5/2021
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Journal: Best Practice and Research in Clinical Haematology
December/5/2021
Abstract
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a subset of high-risk B-ALL associated with high relapse risk and inferior clinical outcomes across the pediatric-to-adult age spectrum. Ph-like ALL is characterized by frequent IKZF1 alterations and a kinase-activated gene expression profile similar to that of Philadelphia chromosome-positive (Ph+) ALL, yet lacks the canonical BCR-ABL1 rearrangement. Advances in high-throughput sequencing technologies during the past decade have unraveled the genomic landscape of Ph-like ALL, revealing a diverse array of kinase-activating translocations and mutations that may be amenable to targeted therapies that have set a remarkable precision medicine paradigm for patients with Ph + ALL. Collaborative scientific efforts to identify and characterise Ph-like ALL during the past decade has directly informed current precision medicine trials investigating the therapeutic potential of tyrosine kinase inhibitor-based therapies for children, adolescents, and adults with Ph-like ALL, although the most optimal treatment paradigm for this high-risk group of patients has yet to be established. Herein, we describe the epidemiology, clinical features, and biology of Ph-like ALL, highlight challenges in implementing pragmatic and cost-effective diagnostic algorithms in the clinic, and describe the milieu of treatment strategies under active investigation that strive to decrease relapse risk and improve long-term survival for patients with Ph-like ALL as has been successfully achieved for those with Ph + ALL.
Keywords: ABL; Acute lymphoblastic leukemia; CRLF2; Clinical trials; JAK/STAT; Philadelphia chromosome-like; Precision medicine; Tyrosine kinase inhibitor.
Publication
Journal: Trends in Pharmacological Sciences
December/5/2021
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects ~11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients. Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics.
Keywords: afferents; cross-organ sensitization; cyclic guanosine monophosphate; irritable bowel syndrome; linaclotide; pain.
Publication
Journal: Vaccine
December/5/2021
Abstract
Biodistribution studies of adenovirus-based vaccines support their clinical development by evaluating their spread and persistence following in vivo administration. AZD1222 (ChAdox1 nCov-19) is a replication-deficient non-human adenovirus-vectored vaccine for coronavirus disease 2019. In this nonclinical study, the biodistribution of AZD1222 was assessed in mice for 29 days following intramuscular injection. Results show that AZD1222 was safe and well tolerated, with a spread that was largely confined to administration sites and the proximal sciatic nerve, with low levels observed in sites that are involved in rapid clearance of particulates by the reticuloendothelial system. Accordingly, levels of AZD1222 decreased from Day 2 to Day 29, indicating clearance. There were no quantifiable levels of AZD1222 in the blood, brain, spinal cord, and reproductive tissue, suggesting a lack of widespread or long-term distribution of AZD1222 vector DNA throughout the body following its administration.
Keywords: AZD1222; Biodistribution; COVID-19; ChAdOx1 nCov-19.
Publication
Journal: Food Chemistry
December/5/2021
Abstract
Simultaneous evaluations over the whole practical range of peroxidation, including the initiation and propagation phases, provide more informative and reliable data than single-parameter analyses being mostly employed only over the course of the initiation phase. Besides an overview on the dominant mechanisms governing the initiation and propagation phases, this article highlights a number of unifying parameters that represent inclusively the two phases. Then, the reliable method to calculate induction period and critical reverse micelle concentration of lipid hydroperoxides as the two interstitial parameters when transitioning from the initiation to the propagation phase is reviewed. Next, a reconsidered form of the conventional methodology on the kinetics of chain-breaking antioxidants is presented. After that, the Arrhenius kinetic and thermodynamic Eyring-Polanyi parameters calculated from the initiation, composite, and decomposition rate constants are compared in order to assess oxidative stabilities. Finally, shelf-life predictions based on a number of proposed end-points of peroxidation are addressed.
Keywords: Antioxidant; Arrhenius; Eyring-Polanyi; Lipid hydroperoxides; Oxidizability; Shelf-life.
Publication
Journal: Best Practice and Research in Clinical Haematology
December/5/2021
Abstract
Four categories of important factors improving outcome of young adults and older adolescents with acute lymphoblastic leukemia (ALL) are biologic type, clinical trials, pediatric vs. adult treatment regimen, and psychosocial challenges. Overall, the outcome of ALL in the age group has improved and beginning to catch up with that in children, as exemplified by CALGB 10403, a pediatric treatment regimen. Each is dependent for optimum development, however, on progress in the others. Without adequate psychosocial support and improvement, progress in clinical trials, translational research, and pediatric regimen application is impaired. Without clinical trials, advances in translational research, optimal pediatric regimen application and adequate psychosocial research are restricted. Overall, we have improved the outcome and outlook of ALL in AYAs, as exemplified by CALGB 10403, but we and our current and future patients still have a long way to go.
Keywords: Acute lymphoblastic leukemia; Clinical trials; Incidence peak; Pediatric treatment regimen; Psychosocial care; Young adults.
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Publication
Journal: Best Practice and Research in Clinical Haematology
December/5/2021
Abstract
Older patients with acute myeloid leukemia (AML) face a dismal prognosis. Although venetoclax-based therapy has led to improved outcomes among unfit older patients with AML, it is not curative and its efficacy and long-term outcomes among fit older patients is unclear. This review provides insights into factors that influence treatment choices among older patients with AML and what we would need to know for venetoclax-based therapy to replace standard intensive 7 + 3 induction therapy.
Keywords: 7+3; AML; Acute myeloid leukemia; Azacytidine; CR; Complete remission; Intensive chemotherapy; OS; Overall survival; Venetoclax.
Publication
Journal: Annales de Pathologie
December/5/2021
Abstract
Vulvar melanoma is a rare tumour, of poorly known pathogenesis, which presents particularities compared to cutaneous melanoma: more frequently achromic and very often multifocal, it is of the lentiginous histological type (MLM), with in half of the cases lentiginous melanocytic hyperplasia at a distance.
Keywords: Mélanome vulvaire; Vulvar melanoma.
Publication
Journal: Journal of Thoracic and Cardiovascular Surgery
December/5/2021
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Publication
Journal: Internal Medicine
December/5/2021
Abstract
Keywords: Serous cystic neoplasm; pancreatic cyst; von Hippel-Lindau disease.
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Publication
Journal: Journal of Diabetes and its Complications
December/5/2021
Abstract
Introduction: Offspring of diabetic mothers have five times higher risk of cardiovascular abnormalities than in normal pregnancies. These cardiac anomalies involve fetal cardiac morphological and functional changes. Here, we investigate subclinical cardiovascular abnormalities, including structural and functional changes among infants of diabetic mothers.
Material and methods: A prospective cohort study was carried out from March 2017 to September 2020 at a South Indian tertiary care center. One hundred ninety-eight newborns delivered from non-diabetic mothers, well-controlled diabetic mothers (WCDM), and poorly controlled diabetic mothers (PCDM) were studied. Neonates and infantile echocardiographic imaging were performed at the first week of life, at 6-weeks, and 6-months of life. Cardiac structure and function were assessed using 2D, M-mode, Conventional Doppler, and Tissue Doppler imaging.
Results: Out of the total (198) infants, 66 (33.3%) were from the non-diabetic (control) mothers, 60 (30.3%) from the WCDM, and 72 (36.4%) were from the PCDM groups. In both WCDM and PCDM groups, the mean gestational ages at birth were shorter than the control group (37.19 ± 0.82, 36.02 ± 2.15, and 37.91 ± 1.33 weeks respectively). There was a high incidence of neonatal hypoglycemia (p-value <0.001), NICU stay >7 days (p-value <0.018), and persistent fetal transitional cardiac shunt (p-value <0.03) among poorly controlled DM group in comparison to others. Tissue deformation imaging showed a significant reduction in left ventricular global strain and strain rate in the neonatal heart from poorly controlled diabetic mothers. Myocardial wall thickness among neonates of diabetic mothers was higher compared to controls. LV TEI was higher in PCDM groups in comparison with WCDM and control groups; (0.59 ± 0.11, 0.46 ± 0.35, and 0.37 ± 0.12 respectively, p-value =0.01). Similarly, RV TEI was high in the PCDM (0.56 ± 0.09) group compared to the WCDM group (0.33 ± 0.12) and control group (0.28 ± 0.10).
Conclusions: Infants of diabetic mothers are at higher risk of developing cardiac abnormalities, including structural and functional defects. The highest increase in interventricular septal thickening found in poorly controlled diabetic mothers' neonates will disrupt both ventricles' functions, followed by WCDM and the control group.
Keywords: Cardiac anomalies; Echocardiography; Gestational diabetes; Infant health; Tissue Doppler imaging; Tissue deformation.
Publication
Journal: Cell Death and Disease
December/5/2021
Abstract
High dietary sugar (HDS) is a modern dietary concern that involves excessive consumption of carbohydrates and added sugars, and increases the risk of metabolic disorders and associated cancers. However, epigenetic mechanisms by which HDS induces tumor progression remain unclear. Here, we investigate the role of heterochromatin, an important yet poorly understood part of the epigenome, in HDS-induced tumor progression of Drosophila Ras/Src and Ras/scrib tumor systems. We found that increased heterochromatin formation with overexpression of heterochromatin protein 1a (HP1a), specifically in tumor cells, not only decreases HDS-induced tumor growth/burden but also drastically improves survival of Drosophila with HDS and Ras/Src or Ras/scrib tumors. Moreover, HDS reduces heterochromatin levels in tumor cells. Mechanistically, we demonstrated that increased heterochromatin formation decreases wingless (wg) and Hippo (Hpo) signaling, thereby promoting apoptosis, via inhibition of Yorkie (Yki) nuclear accumulation and upregulation of apoptotic genes, and reduces DNA damage in tumor cells under HDS. Taken together, our work identified a novel epigenetic mechanism by which HP1a-mediated heterochromatin formation suppresses HDS-induced tumor progression likely by decreasing wingless and Hippo signaling, increasing apoptosis, and maintaining genome stability. Our model explains that the molecular, cellular, and organismal aspects of HDS-aggravated tumor progression are dependent on heterochromatin formation, and highlights heterochromatin as a therapeutic target for cancers associated with HDS-induced metabolic disorders.
Publication
Journal: L'Encephale
December/5/2021
Abstract
Objective: The purpose of this review was to provide an overview of the methods used to measure social network site use among adolescents. Such a review is important given the number and diversity of sites and the prevalence of their use among adolescents.
Methods: A systematic review of the literature was conducted in line with PRISMA guidelines to arrive at an analysis of 58 peer-reviewed studies indexed in PubMed, PsychInfo, or Scopus. To be included in the review, articles had to be peer-reviewed, available in full text, and published in French or English. For inclusion, studies were required to pertain to adolescents aged between 11 and 18 years; to focus on social network site use and indicate how their use was estimated. Studies that simultaneously examined social network sites and general internet use or video games and only provided a combined analysis were excluded. The keywords for the search were: social media use, social media usage, social media misuse, measure, teen, and adolescents.
Results: In the literature, different methods were used to operationalize the use of social network sites: quantitative methods with the measurement of frequency and duration of use of social network sites, and qualitative methods to measure the different activities adolescents engage in on such sites. In this review, 28 articles investigated the use of social media through a measurement of frequency and 22 articles through a measurement of the duration of use. Most of the studies focused on social network sites in general, without specifying which sites in particular were considered by the respondents when answering the question. However, some articles provided cross measures of quantitative and qualitative measurements resulting in the examination of both the frequency of use and the time spent on specific activities on social network sites.
Conclusions: The present review highlights the great diversity in the methods used to measure the use of social network sites among adolescents. The reliance on frequency-based measurements without taking into account the specificities of the activities or sites involved limits the investigation of their impact on adolescent functioning and behaviors. Given the observed discrepancies in the literature concerning the measurement of social network site use among adolescents and their associated biases, the development of specific instruments is needed to advance in this important field of research.
Keywords: Adolescents; Measure; Mesure; Revue systématique; Réseaux sociaux; Social network sites; Systematic review; Usage; Utilisation.
Publication
Journal: BJPsych Open
December/5/2021
Abstract
Background: COVID-19 has rapidly spread across the world. Women may be especially vulnerable to depression and anxiety as a result of the pandemic.
Aims: This study attempted to assess how gender affects risk perceptions, anxiety levels and behavioural responses to the COVID-19 pandemic in Pakistan, to recommend gender-responsive health policies.
Methods: A cross-sectional online survey was conducted. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale, and questions on their risk perceptions, preventive behaviour and information exposure. Multiple logistic regression analysis was used to assess the effects of factors such as age, gender and household income on anxiety levels.
Results: Of the 1391 respondents, 478 were women and 913 were men. Women considered their chances of survival to be relatively lower than men (59% v. 73%). They were also more anxious (62% v. 50%) and more likely to adopt precautionary behaviour, such as avoiding going to the hospital (78% v. 71%), not going to work (72% v. 57%) and using disinfectants (93% v. 86%). Men were more likely to trust friends, family and social media as reliable sources of COVID-19 information, whereas women were more likely to trust doctors.
Conclusions: Women experience a disproportionate burden of the psychological and social impact of the pandemic compared with men. Involving doctors in healthcare communication targeting women might prove effective. Social media and radio programmes may be effective in disseminating COVID-19-related information to men.
Keywords: COVID-19; Risk perception; anxiety disorders; depressive disorders; low- and middle-income countries.
Publication
Journal: Food Research International
December/5/2021
Abstract
Rye (Secale cereale) is a rich source of macromolecules, especially starch, fiber, and proteins which encourages the researchers and industries to use it for various purposes including bakery products, beverages and edible films formulation. However, despite many nutritional and health benefiting properties, rye has not been explored up to its full potential. Interest of consumers in formulating foods with high fiber and phenolic compounds has generated our interest in compiling the detailed information on rye. The present review on rye grains summarizes the existing scientific data on rye macronutrients (starch, arabinoxylan, β-glucan, fructan and proteins) and their corresponding industrial importance. Detailed description in this review unfolds the potential of rye grains for human nutrition. This review provides comprehensive knowledge and fills the remaining gap between the previous and latest scientific findings. Comprehensive information on rye nutrients along with health benefits will help to open a new era for scientific world and industrial sectors.
Keywords: Food products; Health benefits; Nutritional composition; Rye; Starch.
Publication
Journal: Food Research International
December/5/2021
Abstract
The protein-polysaccharide conjugates formed by Maillard reaction can be used as novel emulsifiers in the food industry. Proteins and polysaccharides have extensive sources, and their emulsifying properties are highly dependent on their structural features. The Maillard conjugates can be prepared from conventional and novel methods, and these methods have different advantages and limitations in industrial applications. After an appropriate glycation, the conjugates show some modified or enhanced functional properties, including solubility, emulsifying property, thermal stability, foaming capacity, and gelation property. However, the research on the structure-function relationship of both proteins and polysaccharides is limited. It is necessary to well understand the characteristics of these biopolymers, and select appropriate conditions to control the process of Maillard reaction. Overall, the Maillard conjugates show great potential as the emulsifiers and stabilizers in the emulsion system. This review introduces the sources and structural characteristics of commonly used proteins and polysaccharides for Maillard reaction, outlines the methods (dry-heating, wet-heating, electrospinning, ultrasound, pulsed electric field, and microwave) for preparing Maillard conjugates and focuses on the improved functional properties (solubility, emulsifying, foaming and thermal properties) and the potential mechanisms.
Keywords: Functional properties; Maillard conjugates; Polysaccharide; Preparation; Protein; Source.
Publication
Journal: Best Practice and Research in Clinical Haematology
December/5/2021
Abstract
Myelodysplastic syndrome is a heterogeneous disease with survival probabilities ranging from a few months to several years. Allogeneic hematopoietic cell transplantation (HCT) remains the only curative treatment. Although access (up to 75 years) and outcome of HCT have improved steadily in recent years, high relapse rates and, to a lower extent, treatment related mortalities are a persisting problem. Reduction of tumor burden before HCT has been shown to decrease relapse incidence and often overall survival (OS) in hematological malignancies but the role of pretransplant therapy in MDS remains controversial. We reviewed the role of pretransplant therapy on outcome in MDS patients. No prospective randomized trial addressed this issue so far. Retrospective studies have shown that pretransplant therapy reduces the risk of relapse, but does not improve survival. In addition, registry studies from diagnosis with standard protocols are proposed in order to exclude patient selection. With the availability of new, more effective and low-toxicity therapies, it may be possible to achieve a significant improvement of OS in the future.
Keywords: Allogeneic stem cell transplantation; Chemotherapy; Hypomethylating agents; MDS.
Publication
Journal: Dalton Transactions
December/5/2021
Abstract
The stoichiometric reactivity of a β-diketiminato (BDI) magnesium silanide towards a variety of organic isocyanates has been assessed. While the primary outcome of reactions of t-BuNCO, DippNCO and CyNCO was the production of β-diketiminato magnesium siloxide adducts of the isonitrile resulting from isocyanate deoxygenation, analogous treatment with i-PrNCO led to multiple products, four of which have been positively identified. Although the specificity of this latter reaction was hampered by competitive isocycanate addition at the γ-methine carbon of the BDI supporting ligand, the identification of [{i-PrNCO}CH{(Me)CNDipp}Mg{Me2PhSi}C(O)Ni-Pr]6 provided corroborative evidence for the likely generation of sila-amidate intermediates in all four reactions under study. The formation of [{Me2PhSi}C(O)NR]- anions as the most likely initial species formed en route to isonitrile and siloxide formation was, therefore, validated by a computational density functional theory (DFT) study.
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Journal: Enferm Infecc Microbiol Clin (Engl Ed)
December/5/2021
Publication
Journal: Health Research Policy and Systems
December/5/2021
Abstract
Background: The use of research evidence as an input for health decision-making is a need for most health systems. There are a number of approaches for promoting evidence use at different levels of the health system, but knowledge of their effectiveness is still scarce. The objective of this overview was to evaluate the effectiveness of knowledge communication and dissemination interventions, strategies or approaches targeting policy-makers and health managers.
Methods: This overview of systematic reviews used systematic review methods and was conducted according to a predefined and published protocol. A comprehensive electronic search of 13 databases and a manual search in four websites were conducted. Both published and unpublished reviews in English, Spanish or Portuguese were included. A narrative synthesis was undertaken, and effectiveness statements were developed, informed by the evidence identified.
Results: We included 27 systematic reviews. Three studies included only a communication strategy, while eight only included dissemination strategies, and the remaining 16 included both. None of the selected reviews provided "sufficient evidence" for any of the strategies, while four provided some evidence for three communication and four dissemination strategies. Regarding communication strategies, the use of tailored and targeted messages seemed to successfully lead to changes in the decision-making practices of the target audience. Regarding dissemination strategies, interventions that aimed at improving only the reach of evidence did not have an impact on its use in decisions, while interventions aimed at enhancing users' ability to use and apply evidence had a positive effect on decision-making processes. Multifaceted dissemination strategies also demonstrated the potential for changing knowledge about evidence but not its implementation in decision-making.
Conclusions: There is limited evidence regarding the effectiveness of interventions targeting health managers and policy-makers, as well as the mechanisms required for achieving impact. More studies are needed that are informed by theoretical frameworks or specific tools and using robust methods, standardized outcome measures and clear descriptions of the interventions. We found that passive communication increased access to evidence but had no effect on uptake. Some evidence indicated that the use of targeted messages, knowledge-brokering and user training was effective in promoting evidence use by managers and policy-makers.
Keywords: Decision-making/makers; Evidence-informed policy-making/makers; Knowledge translation; Manager.
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Publication
Journal: Journal of Pediatric Surgery
December/5/2021
Abstract
Background: Emanuel Syndrome (ES), a rare chromosomal disorder caused by a supernumerary chromosome 22 derivative (der(22)t(11;22)), was identified in a fetus with congenital diaphragmatic hernia (CDH) at our fetal center. We aimed to identify a precedent for clinical care and patient outcomes to guide family decision-making.
Methods: This non-funded and non-registered study queried the entire CDH Registry (CDHR) including >10,000 patients since 1995 and conducted a systematic literature review for patients with concomitant ES and CDH.
Results: Literature review captured 12 citations and identified 9 patients with CDH+ES from over 400 known ES cases. Given the rarity of the disease and to reduce bias, there were no exclusion criteria aside from non-English language. Of these 9, two underwent surgical CDH repair with neither surviving. The CDHR identified 6 patients with ES, all reported after 2013 and prenatally diagnosed. Median estimated gestational age was 39 weeks (range 37-40) and median birth weight was 2.72 kg (range 2.4-3.4 kg). 3 patients died within the first few postnatal days; surgical repair was not offered due to "anomalies" and "pulmonary hypertension" in two and one family chose comfort measures. The other 3 patients underwent surgical repair, and 2 were supported with ECMO. Two patients survived to discharge, incurring surgical comorbidities associated with severe CDH including gastrostomy dependence, tracheostomy, and CDH recurrence.
Conclusions: ES patients with CDH have potential to tolerate repair and survive to discharge, however with significant additional morbidity combined with severe challenges inherent to ES. This represents the largest series of patients with CDH and ES to date.
Level of evidence: IV (Case series with no comparison group).
Keywords: Congenital diaphragmatic hernia; Emanuel syndrome; Extracorporeal life support.
Publication
Journal: Best Practice and Research in Clinical Haematology
December/5/2021
Abstract
Higher risk myelodysplastic syndromes are defined as a subset of disease with higher risk of AML transformation and poor overall survival. For decades, therapeutic options for high-risk MDS have been limited to allogeneic stem cell transplant (the only option for cure but limited to only a handful of patients) or hypomethylating agents, with the goal to alter the natural history of disease, delay progression and improve survival, while addressing cytopenias, transfusion requirements and improving quality of life. Recent developments in DNA sequencing and other technologies have shed significant light into the pathogenesis of MDS and led to rational and targeted drug development across a variety of therapeutic vulnerabilities, including disruption of protein ubiquitination through NAE inhibition, selective modulation of macrophage activity and immune checkpoint inhibition through blockade of TIM-3. This review highlights some of the most promising agents in recent drug development and their therapeutic efficacy in the management of high-risk MDS, and further explores the rationale behind potential combinatorial approaches using an HMA backbone to synergistically improve treatment outcomes.
Keywords: Anti-CD47; Myelodysplastic syndromes; NEDD8-activating enzyme; Novel therapies; TIM-3; TP53.
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