bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat
Authors: Xu Lin , Krishna Ashok , Stewart Sharron , Shea Katherine , Racz Rebecca , Weaver James L. , Volpe Donna A. , Pilli Nageswara R. , Narayanasamy Suresh , Florian Jeffry , Patel Vikram , Matta Murali K. , Stone Marc B. , Zhu Hao , Davis Michael C. , Strauss David G. , Rouse Rodney 
Published: June 2021

AbstractFollowing a decision to require label warnings for concurrent use of opioids and benzodiazepines and increased risk of respiratory depression and death, the US Food and Drug Administratioin (FDA) recognized that other sedative psychotropic drugs may be substituted for benzodiazepines and be used concurrently with opioids. In some cases, data on the ability of these alternatives to depress respiration alone or in conjunction with an opioid are lacking. A nonclinical in vivo model was developed that could detect worsening respiratory depression when a benzodiazepine (diazepam) was used in combination with an opioid (oxycodone) compared to the opioid alone based on an increased arterial partial pressure of carbon dioxide (pCO2). The current study used that model to assess the impact on respiration of non‐benzodiazepine sedative psychotropic drugs representative of different drug classes (clozapine, quetiapine, risperidone, zolpidem, trazodone, carisoprodol, cyclobenzaprine, mirtazapine, topiramate, paroxetine, duloxetine, ramelteon, and suvorexant) administered alone and with oxycodone. At clinically relevant exposures, paroxetine, trazodone, and quetiapine given with oxycodone significantly increased pCO2 above the oxycodone effect. Analyses indicated that most pCO2 interaction effects were due to pharmacokinetic interactions resulting in increased oxycodone exposure. Increased pCO2 recorded with oxycodone‐paroxetine co‐administration exceeded expected effects from only drug exposure suggesting another mechanism for the increased pharmacodynamic response. This study identified drug‐drug interaction effects depressing respiration in an animal model when quetiapine or paroxetine were co‐administered with oxycodone. Clinical pharmacodynamic drug interaction studies are being conducted with these drugs to assess translatability of these findings.
Predicting current and future global distribution of invasive Ligustrum lucidum W.T. Aiton: Assessing emerging risks to biodiversity hotspots
Authors: Montti Lía , Velazco Santiago José Elías , Travis Justin M. J. , Grau H. Ricardo 
Published: June 2021

AbstractAimBiological invasions represent one of the main anthropogenic drivers of global change with a substantial impact on biodiversity. This impact can be particularly acute in biodiversity hotspots. Ligustrum lucidum W.T. Aiton is a tree species native of China that, from as early as the eighteenth century, has been introduced broadly around the globe, becoming a serious invasive species. We aim to predict L. lucidum's current and future potential distributions at a global scale and assess the degree to which biodiversity hotspots are at risk of invasion.LocationAll continents.MethodsUsing global presence data, climatic and edaphic variables, we developed an ensemble model to predict current and future periods (2050 and 2080) global distribution of L. lucidum. Susceptible countries and hotspots of biodiversity were identified.ResultsImportant regions within China and neighbouring countries are likely to be environmentally suitable, but they are not currently occupied. Biodiversity hotspots in South America are highlighted as being at current risk of invasion. Notably, climate change may increase risks across large extents of biodiversity hotspots, mainly in South America and Africa, especially by 2080 period.Main conclusionsCurrent and future potential distribution of L. lucidum overlaps with biodiversity hotspots worldwide. Control of L. lucidum is a challenge once established. Thus, species distribution modelling helps to identify risk areas, guiding their early detection in current or future suitable areas. Our findings can be useful as a guide to develop region‐specific invasion management strategies to prevent and/or control this species' spread.
A descriptive cost‐analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high‐dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma
Authors: Monteith Bethany E. , Venner Christopher P. , Cheung Matthew C. , Pater Joe , Shepherd Lois , Richardson Harriet , Reece Donna , Gul Engin , Lalancette Marc , Castonguay Vincent , Kukreti Vishal , Tiedemann Rodger , Phua Chai , Bhella Sita , Dudebout Jill , Sherry Max , Yen Hope , Chen Bingshu E. , Hay Annette E. 
Published: June 2021

AbstractBackgroundThe prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high‐dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data.MethodsThe primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020).ResultsThe cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27‐$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs – $162 471.65/pt or $11 251.50/pt per cycle. Fifty‐six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange.ConclusionsHigh‐dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice‐weekly carfilzomib‐based regimens.
Bimodal expression of potential drug target CLL‐1 (CLEC12A) on CD34+ blasts of AML patients
Authors: Ngai Lok Lam , Ma Connie Y. , Maguire Orla , Do An D. , Robert Alberto , Logan Aaron C. , Griffiths Elizabeth A. , Nemeth Michael J. , Green Cherie , Pourmohamad Tony , van Kuijk Bo J. , Snel Alexander N. , Kwidama Zinia W. , Venniker‐Punt Bianca , Cooper James , Manz Markus G. , Gjertsen Bjørn T. , Smit Linda , Ossenkoppele Gert J. , Janssen Jeroen J. W. M. , Cloos Jacqueline , Sumiyoshi Teiko 
Published: June 2021

AbstractObjectivesThis study aims to retrospectively assess C‐lectin‐like molecule 1 (CLL‐1) bimodal expression on CD34+ blasts in acute myeloid leukemia (AML) patients (total N = 306) and explore potential CLL‐1 bimodal associations with leukemia and patient‐specific characteristics.MethodsFlow cytometry assays were performed to assess the deeper immunophenotyping of CLL‐1 bimodality. Cytogenetic analysis was performed to characterize the gene mutation on CLL‐1‐negative subpopulation of CLL‐1 bimodal AML samples.ResultsThe frequency of a bimodal pattern of CLL‐1 expression of CD34+ blasts ranged from 8% to 65% in the different cohorts. Bimodal CLL‐1 expression was most prevalent in patients with MDS‐related AML (P = .011), ELN adverse risk (P = .002), NPM1 wild type (WT, P = .049), FLT3 WT (P = .035), and relatively low percentages of leukemia‐associated immunophenotypes (P = .006). Additional immunophenotyping analysis revealed the CLL‐1− subpopulation may consist of pre‐B cells, immature myeloblasts, and hematopoietic stem cells. Furthermore, (pre)‐leukemic mutations were detected in both CLL‐1+ and CLL‐1− subfractions of bimodal samples (N = 3).ConclusionsC‐lectin‐like molecule 1 bimodality occurs in about 25% of AML patients and the CLL‐1− cell population still contains malignant cells, hence it may potentially limit the effectiveness of CLL‐1‐targeted therapies and warrant further investigation.
Citizen‐centered financial reporting translation: The preparers’ perspective
Authors: Bracci Enrico , Biondi Lucia , Kastberg Gustaf 
Published: June 2021

AbstractIn recent years, the urge to make public sector organizations accountable has resulted in a wide range of citizen‐centered financial reporting tools that aim to overcome the limits of traditional financial reporting. To date, the debate on these public accountability innovations has mainly focused on the reasons underpinning their adoption from the users’ perspective, while how preparers affect accountability in the process of constructing such documents is empirically less investigated. By drawing on Callon's concept of translation, this paper aims to analyze how the preparers of citizens‐centered financial reports perceive and translate public accountability into practice. In fact, localized translation of public accounting innovation may reveal divergences and ambiguity inherent in the public accountability principles shaped by concurring actors, events, and technologies. The research is qualitative and interpretative, through a longitudinal case study in a municipality, observing the process of construction of a citizen‐centered financial reporting tool (i.e., Popular Financial Reporting—PFR). The originality of the paper lies in its contribution to the debate about how public accountability tools are translated into practice by providing evidence of the dynamics that lead an organization along the implementation path. Our findings confirm that the output of the process is the result of the interaction of different networks of interest. Consequently, the final document may vary consistently from the initial project and the general principles of the framework followed.
The effect of nursing intervention based on the staged behaviour change on recovery, quality of life, and self‐efficacy of diabetic patients with scalds
Authors: Li Cuikun , Chen Zhihua , Gao Bingquan , Yang Mingming , Ren Liqing , Li Juan , Zhang Yulan , Yang Meng 
Published: June 2021

AbstractThis study aimed to explore the impact of nursing intervention based on staged behaviour change (SBC) on the quality of life (QoL) and self‐efficacy of diabetic patients with scalds. From January 2020 to January 2021, a total of 82 consecutive cases with diabetes and scalds were prospectively enrolled in this study. They were divided into the SBC group (41 cases were given SBC‐based nursing intervention) and the control group (41 cases were given routine intervention) using the random number table method. The granulation tissue growth time and wound healing time were compared between the two groups. Pain intensity, QoL, self‐efficacy, and score of wound exudation at 3, 7, and 15 days after intervention were observed. The granulation tissue growth time and wound healing time of the SBC group were lower than those of the control group with statistical difference (P < 0.05). The 3‐, 5‐, and 7‐day pain intensity of the SBC group were all lower than those of the control group, with statistical difference (P < 0.05, respectively). Before intervention, there were no significant differences in mental health, role emotional, social function, vitality status, physical pain, role physical, physical function, and general health between the two groups (P > 0.05, respectively). After intervention, the above indicators of the SBC group were significantly higher than those of the control group (P < 0.05, respectively). Before intervention, there were no significant differences between the two groups in communication with doctors, emotional communication, role function, symptom management, medication as prescribed, and control of water and salt intake and nutrition (P > 0.05, respectively). After intervention, the above indicators in the SBC group were all significantly higher than those in the control group (P < 0.05, respectively). The score of wound exudation of the SBC group was lower than that of the control group after intervention (P < 0.05). SBC‐based nursing intervention can effectively improve the QoL and self‐efficacy of diabetic patients with scalds and can effectively promote wound healing, and can be recommended for clinical use.
A call for caution regarding infection‐acquired COVID‐19 immunity: The potentially unintended effects of “immunity passports” and how to mitigate them
Authors: Green Ricky , Biddlestone Mikey , Douglas Karen M. 
Published: June 2021

AbstractResearch suggests that emerging information about infection‐acquired COVID‐19 immunity should be interpreted with caution. The introduction of “immunity passports” that would enable people who have recovered from COVID‐19 to travel freely and return to work may therefore have detrimental consequences if not managed carefully. In two studies, we examined how perceived (suspected or imagined) recovery from COVID‐19, and the concept of immunity passports, influence people’s intentions to engage in behaviors aimed to reduce the spread of COVID‐19. We also consider ways to lessen potential negative effects. In Study 1 (N = 1604), participants asked to imagine that they had recovered from COVID‐19 reported lower social distancing intentions compared to a control condition. Participants who suspected (versus imagined) that they had recovered from past infection did not report lower preventative intentions compared to the control condition, even at high levels of certainty of past infection. In Study 2 (N = 1732), introducing the idea of immunity passports also reduced social distancing intentions compared to a control condition. The latter effect was, however, attenuated when cautious information about the equivocal science on COVID‐19 was also presented to participants. Participants who suspected that they had COVID‐19 in the past (compared to the control condition) revealed a similar pattern of results, but only at higher levels of certainty of past infection. Caution regarding infection‐acquired COVID‐19 immunity and immunity passports will be crucial in the COVID‐19 response. Implications for premature pandemic announcements, as well as their potential remedies, are discussed.
LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells
Authors: He Guozhang , Kan Shuang , Xu Shaohua , Sun Xuchen , Li Rong , Shu Wei , Chen Ming 
Published: June 2021

AbstractEndothelial cells (ECs) respond to blood shear stress by changing their morphology is important for maintaining vascular homeostasis. Studies have documented a relationship between endothelial cell shape and the stress flow, and however, the mechanism underlying this cytoskeletal rearrangement due to shear stress remains uncertain. In this paper, we demonstrate that laminar shear stress (LSS) significantly reduces latexin (LXN) expression in ECs. By using siRNA and cell imaging, we demonstrated that LXN knockdown results in the morphologic change and F‐actin remodelling just like what LSS does in ECs. We further demonstrate that LXN interacts with Filamin A (FLNA) and regulates FLNA proteolytic cleavage and nuclei translocation. By constructing LXN‐/‐ mice and ApoE‐/‐LXN‐/‐ double knockout mice, we evaluated the effect of LXN knockout on aortic endothelium damage in mice. We found that LXN deficiency significantly improves vascular permeability, vasodilation and atherosclerosis in mice. Our findings provide confident evidence, for the first time, that LXN is a novel regulator for morphological maintenance of ECs, and LXN deficiency has a protective effect on vascular homeostasis. This provides new strategies and drug targets for the treatment of vascular diseases.
Prefrailty, impairment in physical function, and risk of incident heart failure among older adults
Authors: Segar Matthew W. , Singh Sumitabh , Goyal Parag , Hummel Scott L. , Maurer Mathew S. , Forman Daniel E. , Butler Javed , Pandey Ambarish 
Published: June 2021

AbstractObjectiveEvaluate the association between prefrailty and the risk of heart failure (HF) among older adults.Design, setting, and participantsThis prospective, community‐based cohort study included participants from the Atherosclerotic Risk in Communities study who underwent detailed frailty assessment using Fried Criteria and physical function assessment using the Short Performance Physical Battery (SPPB) score. Individuals with prevalent HF and frailty were excluded.Main outcomes and measuresAdjusted association between prefrailty (vs robust), physical function measures (SPPB score, grip strength, and gait speed), and incident HF (overall and HF subtypes, HF with reduced [HFrEF, EF < 50%] and preserved ejection fraction [HFpEF]) were assessed using Cox proportional hazards models.ResultsAmong 5210 participants (mean age 75 years, 58% women), 2565 (49.2%) were identified as prefrail. In cross‐sectional analysis, prefrail individuals had a higher burden of chronic myocardial injury (troponin, Std β = 0.08 [0.05–0.10]) and neurohormonal stress (NT‐ProBNP, Std β = 0.03 [0.02–0.05]) after adjustment for potential confounders. Over a median follow‐up of 4.6 years, there were 232 (4.5%) HF events (HFrEF: 102; HFpEF: 97). Prefrailty was associated with an increased risk of HF after adjusting for potential clinical confounders and cardiac biomarkers (aHR [95% CI] = 1.65 [1.24–2.20]). Among HF subtypes, prefrailty was associated with an increased risk of HFpEF but not HFrEF (aHR [95% CI] = 1.73 [1.11–2.70] and 1.38 [0.90–2.10], respectively). A lower SPPB score was also associated with an increased risk of overall HF and HFpEF, but not HFrEF. Among individual components, increased gait speed were associated with a lower risk of HFpEF, but not HFrEF.Conclusions and relevanceSubtle abnormalities in physiological reserve (prefrailty) and impairment in physical function (SPPB) were both significantly associated with a higher risk of incident HF, particularly HFpEF. These findings highlight the potential role of routine assessment of geriatric syndromes for early identification of HF risk.
Do nonobese patients with Behçet’s disease have insulin resistance?
Authors: Cebeci Kahraman Filiz , Kayataş Kadir , Savaş Erdoğan Sevil , Onsun Nahide 
Published: June 2021

AbstractBackgroundSome studies have investigated the relationship between Behçet's disease (BD) and insulin resistance; however, since they did not exclude obese patients from their sample, it remains unclear whether BD itself causes insulin resistance independently of obesity.MethodsThe study included 60 patients with BD and 45 age‐, gender‐, and body mass index (BMI)–matched healthy controls. Obese patients with a BMI of ≥30 kg/m² were excluded. Insulin resistance according to the homeostasis model assessment for insulin resistance (HOMA‐IR) and quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose, and one‐hour and two‐hour plasma glucose in the oral glucose tolerance test (OGTT 1‐h and OGTT 2‐h PG, respectively) were evaluated in all patients.ResultsThe mean fasting plasma glucose levels and the rate of those with impaired glucose tolerance according to OGTT 2‐h PG were significantly higher in the BD patients compared to the controls. The rates of those with insulin resistance according to HOMA‐IR and QUICKI were significantly higher in the BD patients than in the controls. When compared to the control group, the rates of those with impaired fasting glucose and impaired glucose tolerance were significantly higher, and the mean QUICKI value was significantly lower in the active group, in contrast to the inactive group.ConclusionsInsulin resistance occurs in BD patients independently of obesity. In the follow‐up of BD patients, especially in the active phase, not only fasting blood glucose but also other diagnostic tests for insulin resistance should be added to the examination panels.
Critical COVID‐19 is associated with distinct leukocyte phenotypes and transcriptome patterns
Authors: Christensen E. E. , Jørgensen M. J. , Nore K. G. , Dahl T. B. , Yang K. , Ranheim T. , Huse C. , Lind A. , Nur S. , Stiksrud B. , Jenum S. , Tonby K. , Holter J. C. , Holten A. R. , Halvorsen B. , Dyrhol‐Riise A. M. 
Published: June 2021

AbstractBackgroundPrognostic markers for disease severity and identification of therapeutic targets in COVID‐19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID‐19 patients with different disease severity at admission and longitudinally during hospitalization.MethodsPeripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS‐CoV‐2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS‐CoV‐2‐negative bacterial sepsis (n = 5) and healthy controls (n = 10).ResultsCOVID‐19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naïve CD4 and CD8 T cells. Activation (CD25 and HLA‐DR) and exhaustion (PD‐1) markers on T cells were increased compared with controls, but comparable between COVID‐19 severity groups. Non‐classical monocytes and monocytic HLA‐DR expression decreased whereas monocytic PD‐L1 and CD142 expression increased with COVID‐19 severity. RNA sequencing exhibited increased plasma B‐cell activity in critical COVID‐19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease.ConclusionCritical COVID‐19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T‐cell immune response. Plasma B‐cell activity and calprotectin were higher in critical COVID‐19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID‐19 should be further explored.
Hardness Development in Resin Composite Core Materials
Authors: Lien Wen , Roberts Howard , Vandewalle Kraig 
Published: June 2021

AbstractPurposeTo investigate the hardness characteristics of 13 contemporary resin core materials.Materials and methodsSpecimens (n = 12) were fabricated using stainless steel molds with top surfaces of dual‐cure products photopolymerized while additional groups were allowed to self‐cure. Twelve Knoop hardness indentations 500 microns apart were obtained of photopolymerized top and bottom sample surfaces as well as the self‐cured sample surface with the mean recorded as the representative sample hardness. Testing was completed at 10 minutes, 1 hour, and 24 hours. In addition, hardness values were compared to that obtained from polished coronal dentin samples. Mean data between groups were analyzed with Kruskal‐Wallis/Dunn's, within groups with repeated measures ANOVA/Tukey's.ResultsHardness results were material dependent. All but two products demonstrated a 0.8 bottom/top Knoop hardness ratio at 10 minutes. Product's self‐cure cure reaction did not attain hardness similarity with any photopolymerized top surfaces and while some materials were found to have similar dentin hardness to resin top surface ratio similarity, only one product had hardness equal to or greater than that of dentin during any time period.ConclusionsUnder this study's conditions, hardness development was material dependent and all but two products demonstrated adequate hardness‐derived degree of cure assessment at 10 minutes after preparation. Self‐cured samples demonstrated hardness increase; however, no self‐cured material achieved hardness similarity to photopolymerized top surfaces. None of the materials achieved hardness similarity to dentin and only one product demonstrated hardness greater than that of dentin.