bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial contrast extravasation in severe seat belt‐related female breast trauma on CT: Conservative management at a level 1 trauma centre
Authors: Teh Derek T , Weber Dieter G , Wylie Elizabeth J 
Published: March 2020

SummarySeat belt‐related female breast trauma (SFBT) is an uncommon cause of haemorrhage following motor vehicle collision. Classification systems have been used to grade the severity of SFBT, ranging from mild class I to severe class IV injuries with evidence of active haemorrhage. In the case of class IV injuries, contrast extravasation represents active haemorrhage, prompting angiographic embolisation or surgery to arrest the bleed. Contrary to the majority of reports published in the literature, our institution has been successful with conservative management of class IV SFBT. None of the patients required specific intervention to control haemorrhage from SFBT.
Case Series: Rapid Induction Onto Long Acting Buprenorphine Injection for High Potency Synthetic Opioid Users
Authors: Mariani John J. , Mahony Amy , Iqbal Muhammad N. , Luo Sean X. , Naqvi Nasir H. , Levin Frances R. 
Published: March 2020

Background and ObjectivesHighly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.MethodsIn an open‐label, uncontrolled trial to test the feasibility of extended‐release buprenorphine (BXR) injection treatment of heroin‐using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms.ResultsTwo participants received the BXR injection on the second day of the induction and three participants on the third day.Discussion and ConclusionAll five participants were retained at least 1‐month postinduction.Scientific SignificanceIt may be feasible to provide BXR treatment to HPSO‐positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00–00)
Semen endocannabinoids are correlated to sperm quality in a cohort of 200 young Swiss men
Authors: Zufferey Fanny , Donzé Nicolas , Rahban Rita , Senn Alfred , Stettler Eric , Rudaz Serge , Nef Serge , Rossier Michel F. 
Published: March 2020

AbstractBackgroundA role for endocannabinoids in the male and female reproductive systems has been highlighted during the recent decades. Some of these compounds bind the cannabinoid CB1 receptor, which is abundantly expressed in the central nervous system but also present in the reproductive system, while others act as ‘entourage compounds’ modulators.ObjectivesThe present study aimed at evaluating the relationship between sperm quality and endocannabinoid profiles in a cohort of 200 young Swiss men and whether the presence of specific xenobiotics could influence these profiles.Materials and methodsSemen analysis was performed according to WHO guidelines. Endocannabinoid profiles in blood and semen, as well as bisphenol A and S in urine, were determined by LC‐MSMS methods. The presence of selected drugs was tested in urine by immunological screening, and urinary tetrahydrocannabinol (THC) metabolites were quantified by GC‐MS.ResultsAnandamide concentrations in seminal fluid and oleoylethanolamide (OEA) concentrations in blood serum appeared inversely correlated with sperm motility, while semen palmytoylethanolamide (PEA) was positively linked to sperm concentration. Moreover, OEA and PEA in seminal fluid were associated with better sperm morphology. Interestingly, the concentrations of the same endocannabinoids measured in both blood and semen were not correlated, and the presence of THC metabolites in some individuals was linked to lower concentrations of endocannabinoids.ConclusionsIn the context of the general decline of the sperm count observed within the male population, endocannabinoids in semen constitute a class of promising biochemical markers that open new perspectives as a complement for the usual evaluation of semen quality or for the toxicological screening of individuals' exposure to putative endocrine disruptors.
Forging ahead or moving back: dilemmas and disappointments of novel agents for myeloproliferative neoplasms
Authors: McLornan Donal P. , Harrison Claire N. 
Published: March 2020

SummaryThe common ‘Philadelphia chromosome’‐negative myeloproliferative neoplasms (MPN) comprise essential thrombocythaemia, polycythaemia vera and myelofibrosis. These are clinically diverse disorders and present many challenges during their course, ranging from the management of very indolent, chronic‐phase disease through to very aggressive stages frequently associated with poor quality of life, heavy symptom burdens and potentially life expectancies of <18 months. Their management also requires expertise in thrombosis and haemostasis in addition to marrow failure, debilitating symptom control and balancing the ‘pros and cons’ of intensive therapy such as allogeneic stem cell transplant versus novel and established therapies. In the past 15 years this field has seen rapid advances following an understanding of the pivotal importance of constitutive Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling, the interplay of the wider genomic landscape and the development of updated diagnostic criteria, prognostic scores and targeted therapies. In this article, we review the successes and failures of novel agents and approaches to MPN management.
Differential hepatoprotective role of the cannabinoid CB1 and CB2 receptors in paracetamol‐induced liver injury
Authors: Rivera Patricia , Vargas Antonio , Pastor Antoni , Boronat Anna , López‐Gambero Antonio Jesús , Sánchez‐Marín Laura , Medina‐Vera Dina , Serrano Antonia , Pavón Francisco Javier , de la Torre Rafael , Agirregoitia Ekaitz , Lucena María Isabel , Rodríguez de Fonseca Fernando , Decara Juan , Suárez Juan 
Published: March 2020

Background and PurposeProtective mechanisms of the endogenous cannabinoid system against drug‐induced liver injury (DILI) are actively being investigated regarding the differential regulatory role of the cannabinoid CB1 and CB2 receptors in liver fibrogenesis and inflammation.Experimental ApproachThe 2‐arachidonoylglycerol (2‐AG)‐related signalling receptors and enzymatic machinery, and inflammatory/fibrogenic factors were investigated in the liver of a mouse model of hepatotoxicity induced by acute and repeated overdoses (750 mg·kg−1·day−1) of paracetamol (acetaminophen), previously treated with selective CB1 (ACEA) and CB2 (JWH015) agonists (10 mg·kg−1), or lacking CB1 and CB2 receptors.Key ResultsAcute paracetamol increased the expression of CB2, ABHD6 and COX‐2, while repeated paracetamol increased that of CB1 and COX‐2 and decreased that of DAGLβ. Both acute paracetamol and repeated paracetamol decreased the liver content of acylglycerols (2‐AG, 2‐LG and 2‐OG). Human liver samples from a patient suffering APAP hepatotoxicity confirmed CB1 and CB2 increments. Acute paracetamol‐exposed CB2 KO mice had higher expression of the fibrogenic αSMA and the cytokine IL‐6 and lower apoptotic cleaved caspase 3. CB1 deficiency enhanced the repeated APAP‐induced increases in αSMA and cleaved caspase 3 and blocked those of CYP2E1, TNF‐α, the chemokine CCL2 and the circulating γ‐glutamyltransferase (γGT). Although JWH015 reduced the expression of αSMA and TNF‐α in acute paracetamol, ACEA increased the expression of cleaved caspase 3 and CCL2 in repeated paracetamol.Conclusion and ImplicationsThe differential role of CB1 versus CB2 receptors on inflammatory/fibrogenic factors related to paracetamol‐induced hepatotoxicity should be considered for designing alternative therapies against DILI.
Low‐concentration DMSO accelerates skin wound healing by Akt/mTOR‐mediated cell proliferation and migration in diabetic mice
Authors: Guo Wei , Qiu Wei , Ao Xiang , Li Weiqiang , He Xiao , Ao Luoquan , Hu Xueting , Li Zhan , Zhu Ming , Luo Donglin , Xing Wei , Xu Xiang 
Published: March 2020

Background and PurposeDMSO has been found to promote tissue repair. However, the role of DMSO in diabetic skin wound healing and the underlying molecular mechanisms are still unclear.Experimental ApproachThe effects of DMSO on wound healing were evaluated by HE staining, immunohistochemistry and collagen staining using a wound model of full‐thickness skin resection on the backs of non‐diabetic or diabetic mice. Real‐time cell analysis and 5‐ethynyl‐2′‐deoxyuridine incorporation assays were used to study the effect of DMSO on primary fibroblast proliferation. A transwell assay was used to investigate keratinocyte migration. The associated signalling pathway was identified by western blotting and inhibitor blocking. The effect of DMSO on the translation rate of downstream target genes was studied by RT‐qPCR of polyribosome mRNA.Key ResultsWe found that low‐concentration DMSO significantly accelerated skin wound closure by promoting fibroblast proliferation in both nondiabetic and diabetic mice. In addition, increased migration of keratinocytes may also contribute to accelerated wound healing, which was stimulated by increased TGF‐β1 secretion from fibroblasts. Furthermore, we demonstrated that this effect of DMSO depends on Akt/mTOR‐mediated translational control and the promotion of the translation of a set of cell proliferation‐related genes. As expected, DMSO‐induced wound healing and cell proliferation were impaired by rapamycin, an inhibitor of Akt/mTOR signalling.Conclusion and ImplicationsDMSO can promote skin wound healing in diabetic mice by activating the Akt/mTOR pathway. Low‐concentration DMSO presents an alternative medication for chronic cutaneous wounds, especially for diabetic patients.
In silico and in vitro studies of a number PILs as new antibacterials against MDR clinical isolate Acinetobacter baumannii
Authors: Trush Maria M. , Kovalishyn Vasyl , Hodyna Diana , Golovchenko Olexandr V. , Chumachenko Svitlana , Tetko Igor V. , Brovarets Volodymyr S. , Metelytsia Larysa 
Published: March 2020

AbstractQSAR analysis of a set of previously synthesized phosphonium ionic liquids (PILs) tested against Gram‐negative multidrug‐resistant clinical isolate Acinetobacter baumannii was done using the Online Chemical Modeling Environment (OCHEM). To overcome the problem of overfitting due to descriptor selection, fivefold cross‐validation with variable selection in each step of the model development was applied. The predictive ability of the classification models was tested by cross‐validation, giving balanced accuracies (BA) of 76%–82%. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with a reasonable accuracy within the applicability domain (BA = 83%–89%). The models were applied to screen a virtual chemical library with expected activity of compounds against MDR Acinetobacter baumannii. The eighteen most promising compounds were identified, synthesized, and tested. Biological testing of compounds was performed using the disk diffusion method in Mueller‐Hinton agar. All tested molecules demonstrated high anti‐A. baumannii activity and different toxicity levels. The developed classification SAR models are freely available online at http://ochem.eu/article/113921 and could be used by scientists for design of new more effective antibiotics.
Coexistence of autosomal dominant polycystic kidney disease type 1 and hereditary renal hypouricemia type 2: A model of early‐onset and fast cyst progression
Authors: Peces Ramón , Mena Rocio , Peces Carlos , Cuesta Emilio , Selgas Rafael , Barruz Pilar , Lapunzina Pablo , Nevado Julián 
Published: March 2020

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid‐filled cyst development leading to end‐stage renal disease. The rate of disease progression in ADPKD exhibits high inter‐ and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well‐delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24‐year‐old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next‐generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.
Mortality trends around the one‐year survival mark after heart, liver, and lung transplantation in the United States
Authors: Nathan Ashwin S. , Blebea Catherine , Chatterjee Paula , Thomasson Arwin , Diamond Joshua M. , Groeneveld Peter W. , Giri Jay , Goldberg Hilary J. , Courtwright Andrew M. 
Published: March 2020

AbstractIntroductionOne‐year post‐transplant survival is a significant quality measure for solid organ transplant programs in the United States. It is not known whether the use of this metric is associated with changes in life‐sustaining clinical practices that would delay mortality for solid organ recipients until just beyond the one‐year time point.MethodsWe compared trends in mortality in the time period immediately preceding the one‐year post‐transplant mark compared to the period immediately after using second‐order Cox proportional hazard regression models.ResultsAmong recipients of heart, liver, and lung transplantation, mortality did not decrease significantly in the period immediately before day 365 or increase in the 14 days thereafter. There was an increased adjusted hazard of mortality in the 30 days following day 365 among lung transplant recipients (HR 1.33, 95% CI 1.03‐1.72, P = .03) with a 0.76% absolute mortality rate (94 deaths) in month 12 following lung transplantation and a 1.14% absolute mortality rate in month 13 (113 deaths).ConclusionAlthough we did not find evidence that life‐sustaining treatment is routinely continued until just beyond the one‐year mark in heart and liver transplantation recipients, there was an unexpected increased risk of mortality in the 30 days following day 365 among lung transplant recipients.
Temporal trends and outcomes of patients waiting on left ventricular assist devices and inotropes for heart transplantation
Authors: Briasoulis Alexandros , Adegbala Oluwole , Akintoye Emmanuel , Alvarez Paulino 
Published: March 2020

AbstractWe sought to evaluate the trends and outcomes of patients with left ventricular assist devices (LVADs) and inotropes at the time of listing for heart transplantation. Adults with an LVAD implanted and listed with 1A status were identified in the United Network for Organ Sharing (UNOS) registry between 2010 and 2017. Patients were grouped according to the presence or absence of inotropes at the time of listing and transplantation. A total of 2714 patients were included in the study including 664 patients on inotropes at the time of listing, 235 at the time of transplantation, and 118 on inotropes both at listing and at the time of transplantation. Patients on LVAD and inotropes at the time of listing were more frequently supported with a right ventricular assist device (RVAD) (P < .001), had higher risk of death in the waiting list (sub‐hazard ratio [SHR] = 1.48, 95% CI 1.14‐1.90, P = .002), and were less likely to be transplanted (SHR = 0.70, 95% CI 0.63‐0.78, P < .001) compared with those not on inotropes, after adjusting for described confounders. Approximately 1 in 10 LVAD recipients listed as status 1A are on inotropic therapy at the time of heart transplantation. Patients on LVAD and inotropes have worse outcomes in terms of survival and lower rates of transplantation.
Primary Care Prescription Drug Use and Related Actionable Drug‐Gene Interactions in the Danish Population
Authors: Lunenburg Carin Adriana Theodora Catharina , Hauser Alexander Sebastian , Ishtiak‐Ahmed Kazi , Gasse Christiane 
Published: March 2020

Pharmacogenetics (PGx) aims to improve drug therapy using the individual patients’ genetic make‐up. Little is known about the potential impact of PGx on the population level, possibly hindering implementation of PGx in clinical care. Therefore, we investigated how many patients use actionable PGx drugs, have actionable genotypes or phenotypes and which patients could benefit the most of PGx testing. We included PGx recommendations from two international PGx consortia (Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG)). Using data from publically accessible sales information drawn from the Danish Register of Medicinal Product Statistics (MEDSTAT), we identified the number of users of actionable prescription PGx drugs among the total Danish population in 2017. We estimated actionable genotypes or phenotypes based on reported frequencies from literature. We identified 49 drug‐gene interactions related to 41 unique prescription drugs. The estimated median frequency of actionable genotypes or phenotypes among prescription drug users was 25% (interquartile range 7–26%). Six of 41 drugs were used more than twice as much in women. Actionable PGx drugs were most frequently used by 45–79 year old patients (62%), followed by 25–44 year old patients (18%). Almost half of the actionable PGx drugs (19/41) were psychotropics (i.e., antidepressants, antipsychotics, or psychostimulants). PGx testing can have a substantial impact on the population, as one in four prescription drug users has an actionable genotype or phenotype and could thus benefit from PGx testing. We advocate for prospective panel‐based PGx testing at the time of the first PGx drug prescription (“as needed”), with PGx results ready prior to start of the first, and all future, therapies.
Combined continuous glucose monitoring and subcutaneous insulin infusion versus self‐monitoring of blood glucose with optimized multiple injections in people with type 1 diabetes: A randomized crossover trial
Authors: Dicembrini Ilaria , Pala Laura , Caliri Mariasmeralda , Minardi Silvia , Cosentino Claudia , Monami Matteo , Mannucci Edoardo 
Published: March 2020

AbstractAimTo investigate the efficacy of a combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) versus an optimized degludec‐based multiple daily injections (MDI) regimen + self‐monitoring of blood glucose (SMBG) in people with type 1 diabetes with regard to optimizing glucose control.Material and methodsThe trial included 28 individuals who underwent a 4‐week run‐in phase, and were then randomized 1:1 to: (a) CSII + CGM followed by MDI + SMBG or (b) an MDI basal‐bolus regimen followed by CSII + CGM.ResultsIn patients randomized to the CSII + CGM → MDI + SMBG arm, a significant reduction in glycated haemoglobin (HbA1c) versus baseline was found at the end of the first phase (CSII + CGM) without significant variation in the following MDI + SMBG phase. In the arm randomized to the MDI + SMBG → CSII + CGM sequence, a significant improvement in HbA1c was observed in the first phase (MDI + SMBG), together with a further decrease in the following CSII + CGM phase. In the comparison of the two treatments using a mixed linear model, CSII + CGM was superior to MDI + SMBG with respect to change in HbA1c (P = 0.001).ConclusionsThis study suggests that CSII + CGM improves glycaemic control without relevant safety issues in type 1 diabetes, in comparison with MDI + SMBG.
Response of the cerebral vasculature to systemic carbon monoxide administration—Regional differences and sexual dimorphism
Authors: Oliveira Sara R. , Castelhano João , Sereno José , Vieira Helena L. A. , Duarte Carlos B. , Castelo‐Branco Miguel 
Published: March 2020

AbstractPrevious studies about the modulation of the vasculature by CO were performed exclusively in male or sexually immature animals. Understanding the sex differences regarding systemic drug processing and pharmacodynamics is an important feature for safety assessment of drug dosing and efficacy. In this work, we used CORM‐A1 as source of CO to examine the effects of this gasotransmitter on brain perfusion and the sex‐dependent differences. Dynamic contrast‐enhanced imaging (DCE)‐based analysis was used to characterize the properties of CO in the modulation of cerebral vasculature in vivo, in adult C57BL/6 healthy mice. Perfusion of the temporal muscle, maxillary vein and in hippocampus, cortex and striatum was analysed for 108 min following CORM‐A1 administration of 3 or 5 mg/kg. Under control conditions, brain perfusion was lower in females when compared with males. Under CO treatment, females showed a surprisingly overall reduced perfusion compared with controls (F = 3.452, p = .0004), while no major alterations (or even the expected increase) were observed in males. Cortical structures were only modulated in females. A striking female‐dominated vasoconstriction effect was observed in the hippocampus and striatum following administration of CO, in this mixed‐sex cohort. As these two regions are implicated in episodic and procedural memory formation, CO may have a relevant impact in learning and memory.
Clinical and genetic features of patients with amyotrophic lateral sclerosis in southern China
Authors: Chen W. , Xie Y. , Zheng M. , Lin J. , Huang P. , Pei Z. , Yao X. 
Published: March 2020

Background and purposeAmyotrophic lateral sclerosis (ALS)‐related genes and mutations have been increasingly discovered recently and an improved understanding of genotype–phenotype relationships may help to predict the disease course and refine genetic diagnosis.MethodsWe collected clinical data and blood samples from 268 patients and used next‐generation sequencing to comprehensively assay genetic variations in a panel of known ALS genes from 2015 to 2019.ResultsAmong these patients, the mean age of onset was 52.30 ± 10.42 years with a mean diagnosis delay of 15.90 ± 11.88 months. Patients with SOD1, TARDBP and FUS variants were more likely to suffer from familial ALS. Additionally, carriers of FUS variants displayed the earliest onset, followed by those with SOD1 variants. Patients with NEFH variants showed a closer link to pesticide exposure. Patients with SETX variants were prone to bulbar onset with moderate anxiety problems. No genotype–phenotype relations were found in SPG11 and ERBB4 mutants.ConclusionOur findings uncovered some genotype–phenotype relationships and may help to predict the disease course of patients with ALS in southern China.