bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thiopurines vs methotrexate: Comparing tolerability and discontinuation rates in the treatment of inflammatory bowel disease
Authors: Vasudevan Abhinav , Parthasarathy Nina , Con Danny , Nicolaides Steven , Apostolov Ross , Chauhan Ayushi , Bishara Maria , Luber Raphael P. , Joshi Neetima , Wan Anna , Rickard James A. , Long Tony , Connoley Declan , Sparrow Miles P. , Gibson Peter R. , van Langenberg Daniel R. 
Published: August 2020

SummaryBackgroundThere are safety concerns regarding immunomodulators (thiopurines and methotrexate) for treatment of inflammatory bowel disease (IBD).AimTo compare the long‐term tolerability, and persistence of thiopurine and methotrexate therapy in IBD.MethodsA retrospective cohort study was performed at two hospitals between 1 January 2004 and 31 December 2016 for patients commenced on thiopurines or methotrexate for IBD. Treatment discontinuation rates, intolerances and disease activity were obtained from medical records.ResultsThere were 782 patients commenced on immunomodulator therapy; 244 (31%) on methotrexate with folate (67% subcutaneous therapy) and 538 (69%) on thiopurine (73% azathioprine). Median follow‐up was 42 vs 47 months (P = 0.09). In patients on thiopurines, median 6‐TGN was 298 pmol/8 x 108 RBCs, while the median dose of methotrexate was 25 mg weekly. Methotrexate recipients had a higher rate of prior immunomodulator intolerance, were typically older and had a longer disease duration (54% vs 3%, median 43 vs 36 years, 6 vs 5 years, respectively, each P < 0.05). Overall, 208 (27%) discontinued therapy due to adverse events, (40% on methotrexate vs 19% on thiopurines, P < 0.001), including nausea (18% vs 4%), fatigue (7% vs 2%) and hepatotoxicity (8% vs 2%, each P < 0.001). Hospitalisations from adverse events (0.8% vs 0.9%) and serious infections (9% vs 12%), and deaths (1% vs 0%) were comparable between groups (all P > 0.05). Discontinuation due to adverse events occurred later in patients on methotrexate than on thiopurines (median 7 vs 5 months, P = 0.08).ConclusionDiscontinuation of methotrexate occurred at rates twice that of dose‐optimised thiopurine therapy.
Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome?
Authors: Andersen Freja Drost , Simonsen Ulf , Andersen Charlotte Uggerhøj 
Published: August 2020

AbstractOpioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha‐adrenoceptors, muscarinic and histamine receptors, human ether‐a‐go‐go‐channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.
Steady‐state pharmacokinetic and pharmacodynamic profiling of colistin in critically ill patients with multi‐drug–resistant gram‐negative bacterial infections, along with differences in clinical, microbiological and safety outcome
Authors: Ram Kishna , Sheikh Salim , Bhati Rahul Kumar , Tripathi Chakra Dhar , Suri Jagdish Chander , Meshram Girish Gulab 
Published: August 2020

AbstractLimited data are present regarding the steady‐state pharmacokinetics and pharmacodynamics of colistin in critically ill patients suffering from multi‐drug–resistant gram‐negative bacterial (MDR‐GNB) infections. We aimed to profile the steady‐state pharmacokinetics and pharmacodynamics of colistin in critically ill patients with MDR‐GNB infections, along with determining the predictors that could influence the clinical, microbiological and safety outcome. We recruited 30 critically ill patients suffering from MDR‐GNB infections in our prospective open‐label study. Intravenous colistimethate sodium (CMS) 2 million IU was administered concurrently with inhalational CMS 1 million IU every 8 hours. Steady‐state plasma colistin levels were measured. Logistic regression analysis was used to identify various predictors of clinical, microbiological and safety outcome. A large variability was observed in the steady‐state colistin pharmacokinetic/pharmacodynamic parameters, along with the factors that influenced the clinical, microbiological and safety outcome. In conclusion, steady‐state colistin pharmacokinetic and pharmacodynamic parameters observed in our study were largely consistent with those reported in previous studies. High acute physiology and chronic health evaluation II scores were associated with poor clinical outcome. Log‐transformed colistin maximum concentration, area under the plasma concentration curve for 8 hours, apparent total body clearance and apparent volume of distribution were significantly associated with the safety outcome.
Nonparametric trend estimation in functional time series with application to annual mortality rates
Authors: Martínez‐Hernández Israel , Genton Marc G. 
Published: August 2020

AbstractWe address the problem of trend estimation for functional time series. Existing contributions either deal with detecting a functional trend or assuming a simple model. They consider neither the estimation of a general functional trend nor the analysis of functional time series with a functional trend component. Similarly to univariate time series, we propose an alternative methodology to analyze functional time series, taking into account a functional trend component. We propose to estimate the functional trend by using a tensor product surface that is easy to implement, to interpret, and allows to control the smoothness properties of the estimator. Through a Monte Carlo study, we simulate different scenarios of functional processes to show that our estimator accurately identifies the functional trend component. We also show that the dependency structure of the estimated stationary time series component is not significantly affected by the error approximation of the functional trend component. We apply our methodology to annual mortality rates in France.
Medullary tyrosine hydroxylase catecholaminergic neuronal populations in sudden unexpected death in epilepsy
Authors: Patodia Smriti , Tan Ian , Ellis Matthew , Somani Alyma , Scheffer Ingrid E. , Sisodiya Sanjay M. , Thom Maria 
Published: August 2020

AbstractSudden unexpected death in epilepsy (SUDEP) is mechanistically complex and one probable cause is seizure‐related respiratory dysfunction. Medullary respiratory regulatory nuclei include the pre‐Bötzinger complex (pre‐BötC) in the ventrolateral medulla (VLM), the medullary raphé nuclei (MR) and nucleus of solitary tract in the dorsomedial medulla (DMM). The region of the VLM also contains intermingled tyrosine hydroxylase (TH) catecholaminergic neurones which directly project to the pre‐BötC and regulate breathing under hypoxic conditions and our aim was to evaluate these neurones in SUDEP cases. In post‐mortem cases from three groups [SUDEP (18), epilepsy controls (8) and non‐epilepsy controls (16)] serial sections of medulla (obex + 2 to + 13 mm) were immunolabeled for TH. Three regions of interest (ROI) were outlined (VLM, DMM and MR) and TH‐immunoreactive (TH‐IR) neurones were evaluated using automated detection for overall labeling index (neurones and processes) and neuronal densities and compared between groups and relative to obex level. C‐fos immunoreactivity was also semi‐quantitatively evaluated in these regions. We found no significant difference in the density of TH‐IR neurones or labeling index between the groups in all regions. Significantly more TH‐IR neurones were present in the DMM region than VLM in non‐epilepsy cases only (P < 0.01). Regional variations in TH‐IR neurones with obex level were seen in all groups except SUDEP. We also identified occasional TH neurones in the MR region in all groups. There was significantly less c‐fos labeling in the VLM and MR in SUDEP than non‐epilepsy controls but no difference with epilepsy controls. In conclusion, in this series we found no evidence for alteration of total medullary TH‐IR neuronal numbers in SUDEP but noted some differences in their relative distribution in the medulla and c‐fos neurones compared to control groups which may be relevant to the mechanism of death.
The importance of trace element analyses in detrital Cr‐spinel provenance studies: An example from the Upper Triassic of the Barents Shelf
Authors: Harstad Trond Svånå , Mørk E. Mai Britt , Slagstad Trond 
Published: August 2020

AbstractInvestigations of sandstone provenance often involve U–Pb dating and chemical/mineralogical investigations of detrital minerals that are stable in sediments. As most stable detrital minerals are from felsic–intermediate rocks, investigations of the only mafic–ultramafic mineral considered stable in sediments, chromian spinel (Cr‐spinel), can reveal contributions from mafic–ultramafic sources. Cr‐spinel chemical compositions are tied to petrogenesis, making it possible to identify the nature of, and differentiate between, potential sources. Earlier detrital Cr‐spinel studies have focused on major and minor element compositions, however, the advent of laser‐ablation analytical techniques now allow routine mineral trace element analyses. Here, we integrate major, minor and trace element compositions of detrital Cr‐spinel from sandstones with a well‐characterised provenance from the Triassic (Anisian to Early Norian) Snadd and De Geerdalen formations of the Barents Shelf. The analysed Cr‐spinel compositions are depleted in the major element cations Fe3+, Al and Mg and enriched in Cr and Fe2+. Relative to MORB chromite, the minor and trace element data show high concentrations of Zn, Co and Mn, low concentrations of Ni and Ga and variable concentrations of Ti, V and Sc. The major element compositions of the detrital Cr‐spinel are similar to ophiolite‐associated Cr‐spinel, while the trace element compositions indicate a more complex petrogenesis influenced by metamorphic alteration. The compositional variations between sample locations are small, suggesting similar source rocks for the detrital Cr‐spinel throughout the study area. The most likely sources of the Cr‐spinel grains are metamorphosed ophiolite complexes in the Uralian Orogen, in accordance with earlier provenance studies. The novel addition of trace element compositions to detrital Cr‐spinel studies adds significant source‐sensitive information.
Lipid accumulation in macrophages confers protumorigenic polarization and immunity in gastric cancer
Authors: Luo Qin , Zheng Naisheng , Jiang Li , Wang Tingting , Zhang Peng , Liu Yi , Zheng Peiming , Wang Weiwei , Xie Guohua , Chen Lei , Li Dongdong , Dong Ping , Yuan Xiangliang , Shen Lisong 
Published: August 2020

AbstractHeterotypic interactions between tumor cells and macrophages can enable tumor progression and hold potential for the development of therapeutic interventions. However, the communication between tumors and macrophages and its mechanism are poorly understood. Here, we find that tumor‐associated macrophages (TAM) from tumor‐bearing mice have high amounts of lipid as compared to macrophages from tumor‐free mice. TAM also present high lipid content in clinical human gastric cancer patients. Functionally, TAM with high lipid levels are characterized by polarized M2‐like profiling, and exhibit decreased phagocytic potency and upregulated programmed death ligand 1 (PD‐L1) expression, blocking anti–tumor T cell responses to support their immunosuppressive function. Mechanistically, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identifies the specific PI3K pathway enriched within lipid‐laid TAM. Lipid accumulation in TAM is mainly caused by increased uptake of extracellular lipids from tumor cells, which leads to the upregulated expression of gamma isoform of phosphoinositide 3‐kinase (PI3K‐γ) polarizing TAM to M2‐like profiling. Correspondingly, a preclinical gastric cancer model is used to show pharmacological targeting of PI3K‐γ in high‐lipid TAM with a selective inhibitor, IPI549. IPI549 restores the functional activity of macrophages and substantially enhances the phagocytosis activity and promotes cytotoxic‐T‐cell‐mediated tumor regression. Collectively, this symbiotic tumor‐macrophage interplay provides a potential therapeutic target for gastric cancer patients through targeting PI3K‐γ in lipid‐laden TAM.
lncARSR sponges miR‐34a‐5p to promote colorectal cancer invasion and metastasis via hexokinase‐1‐mediated glycolysis
Authors: Li Shuai , Zhu Kongxi , Liu Lan , Gu Jiaoyang , Niu Huanmin , Guo Jianqiang 
Published: August 2020

AbstractAerobic glycolysis metabolic reprogramming is one of the most important hallmarks of malignant tumors. Increasing evidence indicates that long non‐coding RNAs (lncRNAs) are able to regulate glycolysis metabolic reprogramming and promote cancer progression by functioning as competing endogenous RNAs. lncARSR is a newly identified onco‐lncRNA in renal cancer, but its potential role in metastatic colorectal cancer (CRC) remains unclear. Here, we analyzed specimens from 89 patients with CRC and demonstrated that lncARSR was highly expressed in CRC tissues and negatively associated with survival. Positron emission tomography‐computed tomography imaging with fluoro‐2‐d‐deoxyglucose F18 to evaluate glucose uptake showed that lncARSR expression was positively correlated with maximum standardized uptake values. Functionally, ectopic expression of lncARSR promoted the invasion, metastasis, and glycolysis metabolic reprogramming of CRC cells in vitro and in vivo, while these activities were inhibited by silencing lncARSR expression. Molecularly, lncARSR sponged miR‐34a‐5p and further mediated hexokinase 1 (HK1)‐related aerobic glycolysis in vitro and in vivo. Clinically, high lncARSR and HK1 expression predicted poor survival of patients with CRC, especially when combined with low miR‐34a‐5p expression. Collectively, we identified lncARSR as an onco‐lncRNA in CRC and demonstrated that the combination of lncARSR/miR‐34a‐5p/HK1 may be a potential prognostic biomarker of CRC.
Maternal Support of Children’s Math Learning in Associations Between Family Income and Math School Readiness
Authors: Lombardi Caitlin M. , Dearing Eric 
Published: August 2020

This study examined maternal support of children’s math learning at 36 months (n = 140) as a mediator of the association between early childhood family income and children’s counting and calculation skills at 4½ and 6–7 years. Family income was associated with this measure of children’s math school readiness, but the association was almost entirely indirect and mediated by observed maternal support of children’s numerical skills at 36 months. Maternal support of children’s spatial concept and general learning (cognitive stimulation and sensitivity) were not significant mediators of this association. Results suggest that income‐based gaps in counting and calculation skills at school entry may be due in part to the constraints that low family income places on early numerical learning support.
In vivo confocal microscopy and trachomatous conjunctival scarring: Predictors for clinical progression
Authors: Hoffman Jeremy J. , Massae Patrick , Weiss Helen A. , Makupa William , Burton Matthew J. , Hu Victor H. 
Published: August 2020

AbstractImportanceIn vivo confocal microscopy (IVCM) provides high‐resolution images of the ocular surface and has been validated in trachomatous conjunctival scarring.BackgroundThis study used IVCM to identify parameters associated with clinical scarring progression.DesignProspective cohort study.ParticipantsA total of 800 participants in Northern Tanzania with trachomatous scarring.MethodsParticipants underwent clinical examination, photography and IVCM at baseline and 24‐months. Clinical progression of scarring was defined by comparing baseline and 24‐month photographs. Masked grading of IVCM images was used to identify scarring at both time points. Multivariable logistic regression was used to assess factors associated with clinical progression.Main Outcome MeasuresRisk factors associated with clinical scarring progression.ResultsClinical and IVCM assessment of 800 participants were performed at baseline, with 617 (77.1%) seen at 24‐months. Of these, 438 of 617 (71.0%) had gradable IVCM images at both time points and 342 of 438 (78.1%) of these could be graded as showing definite clinical progression or no progression on image comparison. Clinical progression was found to occur in 79 of 342 (23.1%). After adjusting for age and sex, clinical scarring progression was strongly associated with a high IVCM connective tissue organization score at both baseline (odds ratio [OR] = 1.84 for each increase in scarring category; P = .002) and 24‐months (OR = 1.60; P = .02). Dendritiform cells present at 24‐months were strongly associated with clinical scarring progression after adjustment (OR = 2.62; P = .03).Conclusions and RelevanceQuantitative IVCM parameters, including connective tissue organization score and the presence of dendritiform cells, are associated with disease progression and may be useful markers in trachoma and other conjunctival fibrotic diseases.
Cutaneous Epstein‐Barr virus‐associated smooth muscle tumor in immunosuppression
Authors: Matin Rubeta N. , Ieremia Eleni 
Published: August 2020

AbstractA 36‐year‐old renal transplant recipient presented 15 months post‐transplantation with a cutaneous spindle cell neoplasm with features of smooth muscle differentiation treated with local excision. 1.4 years later, a magnetic resonance imaging liver scan with gadolinium demonstrated multiple bilobar enhancing hepatic lesions, in keeping with metastases. A core biopsy revealed morphological appearances similar to the previous cutaneous spindle cell neoplasm. Epstein‐Barr virus early RNA (EBER) in situ hybridization demonstrated strong diffuse staining of both cutaneous and liver tumor cells for EBER indicative of Epstein‐Barr virus (EBV) infection. This is a rare presentation of multifocal EBV‐associated smooth muscle tumors first presenting in the skin in an adult renal transplant recipient, which, despite being multifocal and involving the liver, may confer a better prognosis than predicted.
Considerations for stakeholder engagement and COVID‐19 related clinical trials’ conduct in sub‐Saharan Africa
Authors: Folayan Morenike Oluwatoyin , Brown Brandon , Haire Bridget , Babalola Chinedum Peace , Ndembi Nicaise 
Published: August 2020

ABSTRACTThe aim of this study is to determine how stakeholder engagement can be adapted for the conduct of COVID‐19‐related clinical trials in sub‐Saharan Africa. Nine essential stakeholder engagement practices were reviewed: formative research; stakeholder engagement plan; communications and issues management plan; protocol development; informed consent process; standard of prevention for vaccine research and standard of care for treatment research; policies on trial‐related physical, psychological, financial, and/or social harms; trial accrual, follow‐up, exit trial closure and results dissemination; and post‐trial access to trial products or procedures. The norms, values, and practices of collectivist societies in Sub‐Saharan Africa and the low research literacy pose challenges to the conduct of clinical trials. Civil‐society organizations, members of community advisory boards and ethics committees, young persons, COVID‐19 survivors, researchers, government, and the private sector are assets for the implementation and translation of COVID‐19 related clinical trials. Adapting ethics guidelines to the socio‐cultural context of the region can facilitate achieving the aim of stakeholder engagement.
A rare cause of newborn central cyanosis
Authors: Wałdoch Anna , Sabiniewicz Robert , Kwiatkowska Joanna 
Published: August 2020

AbstractPulmonary arteriovenous malformations are rare congenital vascular anomalies. They are usually associated with congenital hemorrhagic hemangioma. The hemodynamic effect of fistulas depends on their size, as well as the location. The most common manifestations include central cyanosis, ischemic stroke, murmur over the lung fields, cardiomegaly and, less often, heart failure. We present the case of a child who was admitted to the Department of Pediatric Cardiology and Congenital Heart Defects due to central cyanosis and heart murmur.
Maxillofacial injuries in pregnancy following domestic abuse: A challenge in management
Authors: Agarwal Padmanidhi , Chug Ashi , Bhatt Sumit , Kumar Shailesh , Jain Kanav 
Published: August 2020

AbstractDomestic violence against women remains one of the most difficult obstacles in the growth of civilization. The maxillofacial region is commonly involved, and injuries are complex to characterize and manage due to diverse presentations, underlying physiological changes and sometimes an association with pregnancy complications, creating a challenge for the operating surgeon. This case report discusses the clinical presentation of maxillofacial injuries sustained by a pregnant woman who also had obstetric complications. The management of such trauma by a multidisciplinary squad led by the maxillofacial surgery team is outlined. Increasing awareness among oral healthcare providers for the early identification of interpersonal abuse along with timely intervention and adequate referral is important. Close monitoring and follow‐up are also mandatory.
Dental students' experience and perceived confidence level in different restorative procedures
Authors: Hattar Susan , AlHadidi Abeer , Altarawneh Sandra , Hamdan Ahmad A. S. , Shaini Firas J. , Wahab Fouad Kadim 
Published: August 2020

AbstractPurposeGraduating confident students who are able to flourish and develop in their future careers is an importance outcome of the dental education. This study aims to evaluate self‐perceived level of confidence of fifth‐year dental students in different restorative‐related tasks and the relationship between their clinical training and its corresponding confidence.MethodsFifth‐year graduate dental students (n = 202) were asked to fill a questionnaire that rated their level of confidence in different clinical restorative dentistry tasks. Additionally, they were asked about the number of times they performed tasks prior to attempting the equivalent competency and in which sub‐specialty they felt the most confident.ResultsCompleted responses were received from 120 students giving a response rate of 59%. Students felt the most prepared and confident in direct restorations and simple endodontic treatment, and they seemed less confident in indirect restorations and complex endodontic treatment. Regarding the steps of indirect restorations, students expressed least confidence in crown preparation compared to impression making and try‐in procedures (P < .05). Students rated their confidence highest in operative dentistry, followed by endodontics and lastly fixed prosthodontics.ConclusionThe results highlight the areas in which students exhibit the least confidence. Enhancement of student clinical skills and directed exposure is necessary to raise the level of perceived confidence which will reflect positively on their current and future professional performance.