bluuebunny/crossref_metadata_2025_split huggingface dataset:
MR imaging features of multiple biliary hamartomas (Von Meyenburg Complex): A pictorial review and differential diagnosis
Authors: Boraschi Piero , Scalise Paola , Tarantini Gaia , Colombatto Piero , Donati Francescamaria 
Published: March 2021

SummaryBiliary hamartomas (BHs) are rare malformative cystic/cystic‐like lesions of the liver affecting the biliary tree, named after Hanns von Meyenburg who described them for the first time and still known with this eponym to this day. They usually lack clinical symptoms, and abnormalities in liver function tests are unusual; thus, it is typically an incidental finding of liver imaging. Despite being benign lesions, BHs can pose clinical challenges; the first one is differential diagnosis with other more relevant pathological conditions. Therefore, knowledge of MR imaging findings of BHs is helpful for a prompt and correct diagnosis, avoiding unnecessary invasive procedures and/or an excessive number of radiological investigations. This pictorial review is aimed to depict the most typical MR imaging features of multiple biliary hamartomas (von Meyenburg Complex), in order to familiarize the diagnosis and facilitate the differentiation from other hepato‐biliary cystic diseases.
An atypically located pleomorphic adenoma: Radiological and pathological correlation
Authors: Teh Joelin , Dessauvagie Ben , Kessell Meredith , Dissanayake Deepthi , Wylie Elizabeth J 
Published: March 2021

SummaryPleomorphic adenoma is a common benign salivary gland neoplasm which very rarely occurs in the breast. Its radiologic and pathologic appearance may be mistaken for other benign or malignant lesions such as a fibroadenoma or invasive ductal carcinoma. Due to the risk of local recurrence and, rarely, malignant transformation, wide local excision with clear margins is recommended. As such, a correct diagnosis of this lesion is important to ensure appropriate surgical treatment. We report a case of an atypically located pleomorphic adenoma with radiologic‐pathologic correlation in an asymptomatic 63‐year‐old woman.
Cell‐type specific expression and behavioral impact of galanin and GalR1 in the locus coeruleus during opioid withdrawal
Authors: Foster Stephanie L. , Galaj Ewa , Karne Saumya L. , Ferré Sergi , Weinshenker David 
Published: March 2021

AbstractThe neuropeptide galanin is reported to attenuate opioid withdrawal symptoms, potentially by reducing neuronal hyperactivity in the noradrenergic locus coeruleus (LC) via galanin receptor 1 (GalR1). We evaluated this mechanism by using RNAscope in situ hybridization to characterize GalR1 mRNA distribution in the dorsal pons and to compare galanin and GalR1 mRNA expression in tyrosine hydroxylase‐positive (TH+) LC cells at baseline and following chronic morphine or precipitated withdrawal. We then used genetically altered mouse lines and pharmacology to test whether noradrenergic galanin (NE‐Gal) modulates withdrawal symptoms. RNAscope revealed that, while GalR1 signal was evident in the dorsal pons, 80.7% of the signal was attributable to TH− neurons outside the LC. Galanin and TH mRNA were abundant in LC cells at baseline and were further increased by withdrawal, whereas low basal GalR1 mRNA expression was unaltered by chronic morphine or withdrawal. Naloxone‐precipitated withdrawal symptoms in mice lacking NE‐Gal (GalcKO‐Dbh) were largely similar to WT littermates, indicating that loss of NE‐Gal does not exacerbate withdrawal. Complementary experiments using NE‐Gal overexpressor mice (NE‐Gal OX) and systemic administration of the galanin receptor agonist galnon revealed that increasing galanin signaling also failed to alter behavioral withdrawal, while suppressing noradrenergic transmission with the alpha‐2 adrenergic receptor agonist clonidine attenuated multiple symptoms. These results indicate that galanin does not acutely attenuate precipitated opioid withdrawal via an LC‐specific mechanism, which has important implications for the general role of galanin in regulation of somatic and affective opioid responses and LC activity.
Supporting parents as essential care partners in neonatal units during the SARS‐CoV‐2 pandemic
Authors: van Veenendaal Nicole R. , Deierl Aniko , Bacchini Fabiana , O’Brien Karel , Franck Linda S. ,   the International Steering Committee for Family Integrated Care
Published: March 2021

ABSTRACTAimTo review the evidence on safety of maintaining family integrated care practices and the effects of restricting parental participation in neonatal care during the SARS‐CoV‐2 pandemic.MethodsMEDLINE, EMBASE, PsycINFO and CINAHL databases were searched from inception to the 14th of October 2020. Records were included if they reported scientific, empirical research (qualitative, quantitative or mixed methods) on the effects of restricting or promoting family integrated care practices for parents of hospitalised neonates during the SARS‐CoV‐2 pandemic. Two authors independently screened abstracts, appraised study quality and extracted study and outcome data.ResultsWe retrieved 803 publications and assessed 75 full‐text articles. Seven studies were included, reporting data on 854 healthcare professionals, 442 parents, 364 neonates and 26 other family members, within 286 neonatal units globally. The pandemic response resulted in significant changes in neonatal unit policies and restricting parents' access and participation in neonatal care. Breastfeeding, parental bonding, participation in caregiving, parental mental health and staff stress were negatively impacted.ConclusionThis review highlights that SARS‐CoV‐2 pandemic‐related hospital restrictions had adverse effects on care delivery and outcomes for neonates, families and staff. Recommendations for restoring essential family integrated care practices are discussed.
Drug–drug interactions with warfarin: A systematic review and meta‐analysis
Authors: Wang Mei , Zeraatkar Dena , Obeda Michael , Lee Munil , Garcia Cristian , Nguyen Laura , Agarwal Arnav , Al‐Shalabi Farah , Benipal Harsukh , Ahmad Afreen , Abbas Momina , Vidug Kristina , Holbrook Anne 
Published: March 2021

AimsThe objective of this paper is to systematically review the literature on drug–drug interactions with warfarin, with a focus on patient‐important clinical outcomes.MethodsMEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug–drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsOf 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56–1.94), many antimicrobials (OR = 1.63; 95% CI 1.45–1.83), NSAIDs including COX‐2 NSAIDs (OR = 1.83; 95% CI 1.29–2.59), SSRIs (OR = 1.62; 95% CI 1.42–1.85), mirtazapine (OR = 1.75; 95% CI 1.30–2.36), loop diuretics (OR = 1.92; 95% CI 1.29–2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin‐related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64–0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens.ConclusionsThis review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug–drug interactions leading to thromboembolic outcomes or death.
Statistical inference in abstracts of 3 influential clinical pharmacology journals analysed using a text‐mining algorithm
Authors: Amiri Marjan , Deckert Markus , Michel Martin C. , Poole Charles , Stang Andreas 
Published: March 2021

AimsTo describe the trend in the prevalence of statistical inference in 3 influential clinical pharmacology journals.MethodsWe applied a computer‐based algorithm to abstracts of 3 clinical pharmacology journals published in 1976–2016 to identify statistical inference and its subtypes. Furthermore, we manually reviewed a random sample of 300 articles to access algorithm's performance in finding statistical inference in abstracts and as a screening tool for presence and absence of statistical inference in full text.ResultsThe algorithm identified 59% (13 375/22 516 [mid‐P 95% confidence interval {CI}, 59–60%]) article abstracts with statistical inference. The percentage of abstracts with statistical inference was similar in 1976 and 2016, 48% (179/377 [mid‐P 95%CI, 42–52%]) vs. 49% (386/791 [mid‐P 95%CI, 45–52%]). Statistical reporting pattern varied among journals. Among abstracts containing any statistical inference in the publications from 1976 to 2016, null‐hypothesis significance testing was the most prevalent reported statistical inference. The algorithm had high sensitivity, specificity, positive predictive value and negative predictive value for finding statistical inferences in abstract. While positive predictive value for predicting the statistical inference in full text (including abstract, text, tables and figures) was high, negative predictive value was low.ConclusionDespite journals’ editorials and statistical associations' guidelines, most authors focused on testing rather than estimation. In the future, better statistical reporting might be ensured by improving the statistical knowledge of authors and an addition of statistical guides to journals' instruction to authors to the extent that editors would like their statistical inference preferences to be incorporated into submitted manuscripts.
Inverse probability weighted estimators of vaccine effects accommodating partial interference and censoring
Authors: Chakladar Sujatro , Rosin Samuel , Hudgens Michael G. , Halloran M. Elizabeth , Clemens John D. , Ali Mohammad , Emch Michael E. 
Published: March 2021

AbstractEstimating population‐level effects of a vaccine is challenging because there may be interference, that is, the outcome of one individual may depend on the vaccination status of another individual. Partial interference occurs when individuals can be partitioned into groups such that interference occurs only within groups. In the absence of interference, inverse probability weighted (IPW) estimators are commonly used to draw inference about causal effects of an exposure or treatment. Tchetgen Tchetgen and VanderWeele proposed a modified IPW estimator for causal effects in the presence of partial interference. Motivated by a cholera vaccine study in Bangladesh, this paper considers an extension of the Tchetgen Tchetgen and VanderWeele IPW estimator to the setting where the outcome is subject to right censoring using inverse probability of censoring weights (IPCW). Censoring weights are estimated using proportional hazards frailty models. The large sample properties of the IPCW estimators are derived, and simulation studies are presented demonstrating the estimators' performance in finite samples. The methods are then used to analyze data from the cholera vaccine study.
Discovery of a novel, potent and selective small‐molecule inhibitor of PD‐1/PD‐L1 interaction with robust in vivo anti‐tumour efficacy
Authors: Liu Chenglong , Zhou Feilong , Yan Ziqin , Shen Lian , Zhang Xichen , He Fenglian , Wang Heng , Lu Xiaojie , Yu Ker , Zhao Yujun , Zhu Di 
Published: March 2021

Background and purposePD‐1/PD‐L1 antibodies have achieved great success in clinical treatment. However, monoclonal antibody drugs also have challenges, such as high manufacturing costs, poor diffusion, low oral bioavailability and limited penetration into tumour tissue. The development of small‐molecule inhibitors of PD‐1/PD‐L1 interaction represents a promising perspective to overcome the above challenges in cancer immunotherapy.Experimental approachWe explored structural activity relationships and used biochemical assays to generate a lead compound (ZE132). CD8+ T‐cells killing assay and Ifng expression assay were used to verify the in vitro cellular activity of ZE132. Off‐target study was performed to verify the selectivity. Syngeneic mouse models were used to verify the in vivo activity of ZE132 in tumour immune microenvironment (TIME). We also performed pharmacokinetics profiling in mice and The Cancer Genome Atlas database analysis.Key resultsZE132 can effectively inhibit the PD‐1/PD‐L1 interactions in vitro, and it has a potent affinity to PD‐L1. ZE132 shows robust anti‐tumour effects in vivo, better than anti‐PD‐1 antibody. In the analysis of TIME, we found that ZE132 treatment promotes cytotoxic T‐cell tumour infiltration and induces IL‐2 expression. In addition, ZE132 elicits strong inhibitory effects on the mRNA expression of TGF‐β, which may serve as a potential biomarker to predict responsiveness to PD‐1/PD‐L1 immunotherapies.Conclusion and implicationsWe identified a new lead compound ZE132 targeting PD‐1/PD‐L1 interactions, not only showing favourable drug‐like properties in vitro and in vivo but also showing the advantage of overcoming the barrier of TIME compared to anti‐PD‐1 antibody.
Emerging therapies and their delivery for treating age‐related macular degeneration
Authors: Thomas Chloe N. , Sim Dawn A. , Lee Wen Hwa , Alfahad Nada , Dick Andrew D. , Denniston Alastair K. , Hill Lisa J. 
Published: March 2021

Age‐related macular degeneration (AMD) is the most common cause of blindness in the Western world and is characterised in its latter stages by retinal cell death and neovascularisation and earlier stages with the loss of parainflammatory homeostasis. Patients with neovascular AMD (nAMD) are treated with frequent intraocular injections of anti‐vascular endothelial growth factor (VEGF) therapies, which are not only unpopular with patients but carry risks of sight‐threatening complications. A minority of patients are unresponsive with no alternative treatment available, and some patients who respond initially eventually develop a tolerance to treatment. New therapeutics with improved delivery methods and sustainability of clinical effects are required, in particular for non‐neovascular AMD (90% of cases and no current approved treatments). There are age‐related and disease‐related changes that occur which can affect ocular drug delivery. Here, we review the latest emerging therapies for AMD, their delivery routes and implications for translating to clinical practice.LINKED ARTICLESThis article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc
Dual inhibition of CB1 receptors and iNOS, as a potential novel approach to the pharmacological management of acute and long COVID‐19
Authors: Cinar Resat , Iyer Malliga R. , Kunos George 
Published: March 2021

COVID‐19 (SARS‐CoV‐2) causes multiple inflammatory complications, resulting not only in severe lung inflammation but also harm to other organs. Although the current focus is on the management of acute COVID‐19, there is growing concern about long‐term effects of COVID‐19 (Long Covid), such as fibroproliferative changes in the lung, heart and kidney. Therefore, the identification of therapeutic targets not only for the management of acute COVID‐19 but also for preventing Long Covid are needed, and would mitigate against long‐lasting health burden and economic costs, in addition to saving lives. COVID‐19 induces pathological changes via multiple pathways, which could be targeted simultaneously for optimal effect. We discuss the potential pathologic function of increased activity of the endocannabinoid/CB1 receptor system and inducible NO synthase (iNOS). We advocate a polypharmacology approach, wherein a single chemical entity simultaneously interacts with CB1 receptors and iNOS causing inhibition, as a potential therapeutic strategy for COVID‐19‐related health complications.LINKED ARTICLESThis article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc
Donor‐recipient body size mismatch has no impact on outcomes after deceased donor whole liver transplantation: Role of donor liver size measurement
Authors: Kubal Chandrashekhar A. , Mihaylov Plamen , Fridell Jonathan , Cabrales Arianna , Nikumbh Tejas , Timsina Lava , Soma Daiki , Ekser Burcin , Mangus Richard 
Published: March 2021

AbstractThe role of donor‐recipient body size mismatch (DRSM) on outcomes after whole liver transplantation (LT) is not clearly defined. At our center, in presence of considerable DRSM, objective assessment of the donor liver by a radiology or intraoperative evaluation by procuring surgeon was incorporated. To evaluate the impact of DRSM on graft outcomes with this approach, adult deceased donor whole liver transplants between July 2001 and December 2017 at our center were studied. DRSM was considered when the donor‐recipient body surface area (BSA) ratio (DR‐BSAr) was either <0.69 or >1.25. There were 54 (3.2%) transplants with DR‐BSAr <0.69 and 61 (3.6%) with DR‐BSAr >1.25. One‐year graft survival was 85% vs. 89% vs. 89%; (p = .64) for transplants with DR‐BSArs of <0.69, 0.69–1.25, and >1.25, respectively. Early allograft dysfunction (EAD) (28% vs. 27% vs. 37%; p = .07), post‐transplant coagulopathy, bilirubinemia, and renal function were also comparable. In conclusion, with the actual measurement of the donor liver and recipient abdominal cavity, significant DRSM did not have a negative impact on early and long‐term outcomes. Routine measurement of donor liver size by radiology may be incorporated in liver allocation to improve utilization.
Efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus and established cardiovascular disease using insulin: AVERTIS CVsubstudy
Authors: Lingvay Ildiko , Greenberg Michelle , Gallo Silvina , Shi Harry , Liu Jie , Gantz Ira 
Published: March 2021

AbstractAimTo assess the efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) inadequately controlled by insulin.Materials and methodsVERTIS CV was the cardiovascular outcome study for ertugliflozin. Patients were randomly assigned to placebo, or ertugliflozin 5 mg or 15 mg once daily. We report the results of a substudy in patients on a stable dose of insulin ≥20 units/d. The primary endpoint was glycated haemoglobin (HbA1c) change from baseline to 18 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG), body weight (BW), the proportion of patients with HbA1c <53 mmol/mol (<7%), systolic blood pressure (SBP), diastolic blood pressure and insulin dose.ResultsOf 8246 patients randomized in VERTIS CV, 1065 were included in the substudy (68.2% men, mean [SD] age 64.8 [7.8] years, T2DM duration 16.7 [9.0] years, HbA1c 8.4 [1.0]%). At week 18, the least squares (LS) mean change from baseline in HbA1c was significantly greater with ertugliflozin 5 mg and 15 mg versus placebo (placebo‐adjusted LS mean change −0.58%, 95% confidence interval [CI] −0.71, −0.44 and −0.65%, 95% CI −0.78, −0.51, respectively;P< 0.001 for both). Ertugliflozin significantly reduced FPG, BW and SBP. In women, the incidence of genital mycotic infections was higher with ertugliflozin (3.5%) versus placebo (0.0%). The incidence of symptomatic hypoglycaemia was similar across treatment groups.ConclusionsErtugliflozin added to insulin improved glycaemic control, BW and SBP versus placebo at 18 weeks in patients with T2DM and ASCVD.
The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics: Analysis of the CREDENCE trial
Authors: Arnott Clare , Li Jing‐Wei , Cannon Christopher P. , de Zeeuw Dick , Neuen Brendon L. , Heerspink Hiddo J. L. , Charytan David M. , Agarwal Anubha , Huffman Mark D. , Figtree Gemma A. , Bakris George , Chang Tara I‐Hsin , Feng Kent , Rosenthal Norman , Zinman Bernard , Jardine Meg J. , Perkovic Vlado , Neal Bruce , Mahaffey Kenneth W. 
Published: March 2021

AbstractHeart failure is prevalent in those with type 2 diabetes and chronic kidney disease, and is associated with significant mortality and morbidity. In the CREDENCE trial, canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In the current analysis we sought to determine whether the effect of canagliflozin on HHF/CV death differed in subgroups defined by key baseline participant characteristics. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Canagliflozin was associated with a reduction in the relative risk of HHF/CV death regardless of age, sex, history of heart failure or CV disease, and the use of loop diuretics or glucagon‐like peptide‐1 receptor agonists (all pinteraction > .114). The absolute benefit of canagliflozin was greater in those at highest baseline risk, such as those with CV disease (50 fewer events/1000 patients treated over 2.5 years vs. 20 fewer events in those without CV disease) or advanced kidney disease (estimated glomerular filtration rate [eGFR] 30–45 mL/min/1.73m2: 61 events prevented/1000 patients treated over 2.5 years vs. 23 events in eGFR 60–90 mL/min/1.73m2). Canagliflozin consistently reduces the proportional risk of HHF/CV death across a broad range of subgroups with greater absolute benefits in those at highest baseline risk.