bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outpatient management of deep vein thrombosis using direct oral anticoagulants is safe and efficient
Authors: Lim Hui Yin , Lambros Pani , Krishnamoorthi Brintha , Chellaram Vinod , Ho Prahlad W. 
Published: July 2020

AbstractDirect oral anticoagulants (DOACs) are increasingly becoming the treatment of choice for venous thromboembolism (VTE). To ensure safe prescription and prevent delay of supply for dischargeable patients with deep venous thrombosis (DVT) presenting to the Emergency Department (ED) outside pharmacy hours, we implemented a “Rivaroxaban after‐hours pack” system, that requires prescribers to assess suitability via criteria detailed in a decision support system GuidanceMS, prior to pack provision. Pharmacist and clinic follow up is also provided. To assess the safety and effectiveness of the program, a retrospective case series review was undertaken of DVT patients discharged from the ED with an after‐hours pack from April 2015 to December 2017. Patients were assessed for compliance with recommendations for treatment from their baseline demographics, biochemistry, medication history, bleeding and thrombotic risk. Any bleeding episodes or clot extension were recorded. The number of admissions for hospital DVT treatment for the study period was compared to the preceding 30 months. Of the 120 patients reviewed, all patients had adequate renal function, 96.3% had liver function tests <3× the upper limit normal. Three patients (2.5%) had active malignancy and no patients had a mechanical valve or antiphospholipid syndrome. All patients received a pharmacist telephone follow‐up education conversation and referral to Thrombosis Outpatients. Twelve patients reported clinically relevant non‐major bleeding, while two patients had clot extension despite compliance. There was marked reduction in hospital and/or hospital‐in‐the‐home admissions compared to the previous 30 months (P < 0.001). In conclusion, all DVT patients were safely prescribed Rivaroxaban using this system, with a reduction in hospital and/or hospital‐in‐the‐home admissions. This system is efficient in ensuring safe provision of Rivaroxaban outside of pharmacy hours, with potential for extension to the primary care setting.
Effects of suppressing bioavailability of insulin‐like growth factor on age‐associated intervertebral disc degeneration
Authors: Kritschil Rebecca , Zhang Zhongying , Lei Changbin , Zhong Jiongbiao , Dong Qing , Lee Joon , Conover Cheryl A. , Sowa Gwendolyn , Vallejo Abbe N. , Vo Nam 
Published: July 2020

AbstractSuppression of the insulin‐like growth factor‐1 (IGF‐1) signaling pathway reduces age‐related disorders and increases lifespan across species, making the IGF‐1 pathway a key regulator of aging. Previous in vitro intervertebral disc cell studies have reported the pro‐anabolic effect of exogenously adding IGF‐1 on matrix production. However, the overall effects of suppressing IGF‐1 signaling on age‐related intervertebral disc degeneration (IDD) is not known. Here, the effects of suppressing IGF‐1 signaling on age‐related IDD in vivo were examined using PAPPA−/− mice. These are animals with targeted deletion of pregnancy‐associated plasma protein A (PAPPA), the major protease that cleaves inhibitory IGF binding proteins that control bioavailability of IGF‐1 for cell signaling. Compared to age‐matched wild‐type (Wt) littermates, reduced levels of matrix proteoglycan (PG) and aggrecan were seen in discs of 23‐month old PAPPA−/− mice. Decreased aggrecanolysis and expression of two key catabolic markers, matrix metalloproteinase‐3 and a disintegrin and metalloproteinase with thrombospondin motifs‐4, were also observed in discs of old PAPPA−/− mice compared to Wt littermates. Suppressing IGF‐1 signaling has been implicated to shift cellular metabolism toward maintenance rather than growth and decreasing cellular senescence. Along this line, discs of old PAPPA−/− mice also exhibited lower cellular senescence, assessed by p53 and lamin B1 markers. Collectively, the data reveal complex regulation of disc matrix homeostasis by PAPPA/IGF‐1 signaling during chronologic aging, that is, reduced IGF‐1 bioavailability confers the benefit of decreasing disc cellular senescence and matrix catabolism but also the disadvantage of decreasing disc PG matrix anabolism. This pathway requires further mechanistic elucidation before IGF‐1 could be considered as a therapeutic growth factor for treating IDD.
Local food consumption during travel: Interaction of ıncentive‐disincentive factors, togetherness, and hedonic value
Authors: Dedeoğlu Bekir Bora , Çalışkan Caner , Sabbağ Çiğdem 
Published: July 2020

AbstractThis study addresses the local food consumption experience as it takes place while traveling. The mediating effects of incentive (novelty) and disincentive (risk avoidance, familiarity) factors, sense of togetherness, and hedonic value, and their effect on the travel experience, were investigated. The study also considered the moderating effect of gender. The data showed a significant relationship between togetherness and hedonic value. Perceptions of novelty were shown to affect togetherness positively. Furthermore, the effect of risk avoidance on togetherness was found to be more determinative for male respondents, whereas the effect of familiarity on togetherness was more determinative for female respondents.
The Effects of Laryngoscope Shape and Needle Position on Distal Airway Pressure in Jet Ventilation
Authors: Pertile Joshua , Mellenthin Michelle , Wagner Jennifer , DeBoer Emily M. , Fink Daniel , Smith Bradford 
Published: July 2020

ObjectivesLaryngoscopes and subglottiscopes of multiple shapes and lengths are used in airway surgery to maintain an open airway; protect the trachea; and provide a place to mount the light, evacuator, and ventilation needle. Despite differences in scopes and ventilation needle mounting positions, the same jet pressures are typically used. We hypothesized that different scopes and scope configurations would affect distal airway pressure magnitude and homogeneity.Study DesignA laboratory investigation of distal airway pressures in a lung modelduring low frequency jet ventilation.MethodsA three‐dimensional airway model based on the computed tomography scan of a 15‐year old healthy male was fabricated with pressure transducers at the fifth airway generation. A laryngoscope and a subglottiscope were each mounted in the model coaxial with the trachea. Parameters including scope depth and needle mounting position were adjusted, and the effects on distal airway pressure were recorded.ResultsChanging the scope depth from 1 to 3 cm past the laryngeal inlet had a limited effect on distal airway pressure. Needle mounting angle in the laryngoscope strongly influenced distal airway pressure, with a 7° angle change yielding a 67.5% increase. Compared to a loose needle centered in the trachea 1 cm past the laryngeal inlet, the subglottiscope and laryngoscope showed up to 16% and 150% increases in distal airway pressure, respectively.ConclusionDifferent scopes or changes in the configuration, such as the needle angle, strongly influence distal airway pressure. Our findings indicate that different jet pressures are required for different scopes and that a stable needle mount is a critical design consideration to prevent changes in minute ventilation due to needle movement.Level of EvidenceNA (Basic Research) Laryngoscope, 131:E354–E357, 2021
Toward Chiral Sensing and Spectroscopy Enabled by All‐Dielectric Integrated Photonic Waveguides
Authors: Vázquez‐Lozano J. Enrique , Martínez Alejandro 
Published: July 2020

AbstractChiral spectroscopy is a powerful technique enabling to identify optically the chirality of matter. So far, most experiments to check the chirality of matter or nanostructures have been performed through arrangements wherein both the optical excitation and detection are realized via circularly polarized light propagating in free space. However, for the sake of miniaturization, it would be desirable to perform chiral spectroscopy in photonic integrated platforms, with the additional benefit of massive parallel detection, low‐cost production, repeatability, and portability. Here it is shown that all‐dielectric photonic waveguides can support chiral modes under proper combination of fundamental eigenmodes. Two mainstream configurations are investigated: a dielectric wire with square cross section and a slotted waveguide. Three different scenarios in which such waveguides could be used for chiral detection are numerically analyzed: waveguides as near‐field probes, evanescent‐induced chiral fields, and chiroptical interaction in void slots. In all the cases, a metallic nanohelix is considered as a chiral probe, though all the approaches can be extended to other kinds of chiral nanostructures as well as matter. These results establish that chiral applications such as sensing and spectroscopy could be realized in standard integrated optics, in particular, with silicon‐based technology.
Sequence‐Defined Heteromultivalent Precision Glycomacromolecules Bearing Sulfonated/Sulfated Nonglycosidic Moieties Preferentially Bind Galectin‐3 and Delay Wound Healing of a Galectin‐3 Positive Tumor Cell Line in an In Vitro Wound Scratch Assay
Authors: Freichel Tanja , Heine Viktoria , Laaf Dominic , Mackintosh Eleanor E. , Sarafova Sophia , Elling Lothar , Snyder Nicole L. , Hartmann Laura 
Published: July 2020

AbstractWithin this work, a new class of sequence‐defined heteromultivalent glycomacromolecules bearing lactose residues and nonglycosidic motifs for probing glycoconjugate recognition in carbohydrate recognition domain (CRD) of galectin‐3 is presented. Galectins, a family of β‐galactoside‐binding proteins, are known to play crucial roles in different signaling pathways involved in tumor biology. Thus, research has focused on the design and synthesis of galectin‐targeting ligands for use as diagnostic markers or potential therapeutics. Heteromultivalent precision glycomacromolecules have the potential to serve as ligands for galectins. In this work, multivalency and the introduction of nonglycosidic motifs bearing either neutral, amine, or sulfonated/sulfated groups are used to better understand binding in the galectin‐3 CRD. Enzyme‐linked immunosorbent assays and surface plasmon resonance studies are performed, revealing a positive impact of the sulfonated/sulfated nonglycosidic motifs on galectin‐3 binding but not on galectin‐1 binding. Selected compounds are then tested with galectin‐3 positive MCF 7 breast cancer cells using an in vitro would scratch assay. Preliminary results demonstrate a differential biological effect on MCF 7 cells with high galectin‐3 expression in comparison to an HEK 293 control with low galectin‐3 expression, indicating the potential for sulfonated/sulfated heteromultivalent glycomacromolecules to serve as preferential ligands for galectin‐3 targeting.
Lacrimo‐auriculo‐dento‐digital syndrome: A novel mutation in a Korean family and review of literature
Authors: Ryu Young Hye , Kyun Chae Jong , Kim Jung‐Wook , Lee Soyoung 
Published: July 2020

AbstractBackgroundLacrimo‐auriculo‐dento‐digital (LADD) syndrome is a rare autosomal dominant disorder caused by mutations in one of the three genes: fibroblast growth factor receptor 2 (FGFR2), FGFR3, or FGF10. Affected patients have hypoplasia/aplasia of lacrimal ducts/glands, hypoplasia/aplasia of salivary glands, dental anomalies, ear anomalies, hearing loss, and digital anomalies.Case PresentationProband was an 11‐year‐old male with xerostomia, xerophthalmia, and a referring diagnosis of Sjogren syndrome. He presented with microdontia, hypodontia, low‐set/cupped ear auricles, and hearing loss in the left ear.MethodsWhole exome sequencing (WES) was performed on proband. Variations and segregation within the family were verified using Sanger sequencing.ResultsMolecular studies revealed a novel heterozygous missense mutation in exon 11 of FGFR2: c.1547C>T (p.Ala516Val), compatible with LADD syndrome.ConclusionTo the best of our knowledge, this is the first report of a family with LADD syndrome in Korea. The combination of xerostomia and xerophthalmia, seen in patients with LADD syndrome, may be misdiagnosed as Sjogren syndrome. WES may be a useful clinical tool in ascertaining the affected gene in patients with suspected genetic disorders. Here, a literature review and summary of 23 case reports/series of LADD syndrome are presented, which may help to identify patients with this condition.
Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability
Authors: Mehvari Sepideh , Larti Farzaneh , Hu Hao , Fattahi Zohreh , Beheshtian Maryam , Abedini Seyedeh Sedigheh , Arzhangi Sanaz , Ropers Hans‐Hilger , Kalscheuer Vera M. , Auld Daniel , Kahrizi Kimia , Riazalhosseini Yasser , Najmabadi Hossein 
Published: July 2020

AbstractBackgroundThe X chromosome has historically been one of the most thoroughly investigated chromosomes regarding intellectual disability (ID), whose etiology is attributed to many factors including copy number variations (CNVs). Duplications of the long arm of the X chromosome have been reported in patients with ID, short stature, facial anomalies, and in many cases hypoplastic genitalia and/or behavioral abnormalities.MethodsHere, we report on a large Iranian family with X‐linked ID caused by a duplication on the X chromosome identified by whole genome sequencing in combination with linkage analysis.ResultsSeven affected males in different branches of the family presented with ID, short stature, seizures, facial anomalies, behavioral abnormalities (aggressiveness, self‐injury, anxiety, impaired social interactions, and shyness), speech impairment, and micropenis. The duplication of the region Xq13.2q13.3, which is ~1.8 Mb in size, includes seven protein‐coding OMIM genes. Three of these genes, namely SLC16A2, RLIM, and NEXMIF, if impaired, can lead to syndromes presenting with ID. Of note, this duplicated region was located within a linkage interval with a LOD score >3.ConclusionOur report indicates that CNVs should be considered in multi‐affected families where no candidate gene defect has been identified in sequencing data analysis.
Loss of Uncoupling Protein 3 Attenuates Western Diet–Induced Obesity, Systemic Inflammation, and Insulin Resistance in Rats
Authors: Lomax Tyler M. , Ashraf Sadia , Yilmaz Gizem , Harmancey Romain 
Published: July 2020

ObjectiveUncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet‐induced obesity in rats.MethodsMale UCP3 knockout rats (ucp3−/−) and wild‐type littermates (ucp3+/+) were fed a high‐fat, high‐carbohydrate Western diet for 21 weeks. Body composition was analyzed by EchoMRI. Whole‐body insulin sensitivity and rates of tissue glucose uptake were determined by using hyperinsulinemic‐euglycemic clamp. Changes in tissue physiology were interrogated by microscopy and RNA sequencing.ResultsLoss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3−/− rats also exhibited preserved insulin sensitivity and increased glucose uptake in interscapular brown adipose tissue (iBAT). Brown adipocytes from ucp3−/− rats were protected from cellular degeneration caused by lipid accumulation and from reactive oxygen species–induced protein sulfonation. Increased glutathione levels in iBAT from ucp3−/− rats were linked to upregulation of genes encoding enzymes from the transsulfuration pathway in that tissue.ConclusionsLoss of UCP3 partially protects rats from diet‐induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.
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Identification of the distinct genomic features in gastroesophageal junction adenocarcinoma and its Siewert subtypes
Authors: Geng Qirong , Lao Jiawen , Zuo Xiaoyu , Chen Shangxiang , Bei Jin‐Xin , Xu Dazhi 
Published: July 2020

AbstractRates of gastroesophageal junction adenocarcinomas (GEJAs) have shown an alarming increase; however, the genetic background of GEJA and its Siewert classification have yet to be uncovered. Here, 60 paired tumor and normal DNA samples from GEJA patients were analyzed by whole‐exome sequencing. Among them, 13 were Siewert type I, 14 were type II, and 33 were type III. A predominance of C/G>T/A substitutions was discovered in GEJA, followed by C/G>A/T substitutions. Notably, Siewert type I and type II/III display distinct sets of driver genes, mutational spectrum, and recurrently disrupted pathways. Siewert type I showed similarity to esophageal adenocarcinomas (EACs) and the chromosomal instability subtype of stomach adenocarcinomas, while Siewert type II/III showed similarity to the genomic stable subtype of stomach adenocarcinoma. We also found that mutation of FBXW7, a driver gene of GEJA, was enriched in Siewert type I. Our data identify differences between GEJA and stomach/EACs at the genomic level and provide evidence for differential treatment based on Siewert classification of GEJA. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Expansion of the renal capsular stroma, ureteric bud branching defects and cryptorchidism in mice with Wilms tumor 1 gene deletion in the stromal compartment of the developing kidney
Authors: Weiss Anna‐Carina , Rivera‐Reyes Reginaldo , Englert Christoph , Kispert Andreas 
Published: July 2020

AbstractDevelopment of the mammalian kidney is orchestrated by reciprocal interactions of stromal and nephrogenic mesenchymal cells with the ureteric bud epithelium. Previous work showed that the transcription factor Wilms tumor 1 (WT1) acts in the nephrogenic lineage to maintain precursor cells, to drive the epithelial transition of aggregating precursors into a renal vesicle and to specify and maintain the podocyte fate. However, WT1 is expressed not only in the nephrogenic lineage but also transiently in stromal progenitors in the renal cortex. Here we report that specific deletion of Wt1 in the stromal lineage using the Foxd1cre driver line results at birth in cryptorchidism and hypoplastic kidneys that harbour fewer and enlarged ureteric bud tips and display an expansion of capsular stroma into the cortical region. In vivo and ex vivo analysis at earlier stages revealed that stromal loss of Wt1 reduces stromal proliferation, and delays and alters branching morphogenesis, resulting in a variant architecture of the collecting duct tree with an increase of single at the expense of bifurcated ureteric bud tips. Molecular analysis identified a transient reduction of Aldh1a2 expression and of retinoic acid signalling activity in stromal progenitors, and of Ret in ureteric bud tips. Administration of retinoic acid partly rescued the branching defects of mutant kidneys in culture. We propose that WT1 maintains retinoic acid signalling in the cortical stroma, which, in turn, assures proper levels and dynamics of Ret expression in the ureteric bud tips, and thus normal ramification of the ureteric tree. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Height after photon craniospinal irradiation in pediatric patients treated for central nervous system embryonal tumors
Authors: Mizumoto Masashi , Oshiro Yoshiko , Pan Haitao , Wang Fang , Kaste Sue C. , Gajjar Amar , Chemaitilly Wassim , Merchant Thomas E. 
Published: July 2020

AbstractBackgroundWe modeled height after craniospinal irradiation (CSI) in pediatric patients with central nervous system (CNS) embryonal tumors to identify factors that impair stature.ProcedureDuring 1996‐2012, 212 pediatric patients (131 male) with CNS embryonal tumors received postoperative CSI: 23.4 Gy (n = 147) or ≥36 Gy (n = 65), similar postirradiation chemotherapy, and were followed for at least 5 years without tumor progression or other event. The group was further characterized by age at CSI and hormone‐replacement therapy received. Models were developed to identify factors associated with growth impairment and estimate final height.ResultsWith median follow up of 10.2 years (range 5.0‐20.4 years), the mean final height z‐scores at 18 years of age, compared to United States standards, were −1.3 for female and −1.5 for male survivors. Younger age at the time of CSI, higher CSI dose, and female sex were associated with height impairment. Factors associated with higher growth rates before 15 years of age were older age at CSI, male sex, CSI dose < 36 Gy, replacement therapy for growth hormone (GH) and central adrenal insufficiency, and white race. Growth after age 15 in male survivors was associated with treatment of gonadotropin deficiency. Linear mixed‐effects models were developed using clinical factors to estimate final height, demonstrate the unique growth curve of this cohort, and interactions between clinical variable and radiation dose.ConclusionsCSI significantly impaired height at current doses used to treat standard‐ or high‐risk CNS embryonal tumors. Measures to reduce the impact of CSI on height should be sought, with our models serving as benchmarks.
A pharmacist‐managed dosing algorithm for darbepoetin alfa and iron sucrose in hemodialysis patients: A randomized, controlled trial
Authors: van den Oever Francisca Johanna , Heetman‐Meijer Carolien F. M. , Birnie Erwin , Vasbinder Erwin C. , Swart Eleonora L. , Schrama Yvonne C. 
Published: July 2020

AbstractThe attainment of target hemoglobin levels in hemodialysis patients is low. Several factors play a role, such as hyporesponsiveness to erythropoiesis‐stimulating agents (ESA), but also suboptimal prescribing of ESA and iron. The goal of this study was to investigate if a pharmacist‐managed dosing algorithm for darbepoetin alfa (DA) and iron sucrose improves the attainment of target hemoglobin levels. In this randomized controlled trial, 200 hemodialysis patients from a Dutch teaching hospital were included. In the intervention group (n = 100), a pharmacist monthly provided dose recommendations for DA and iron sucrose based on dosing algorithms. The control group (n = 100) received usual care. In the intervention group, the percentage per patient within the target range (PTR) for hemoglobin (target range 6.8‐7.4 mmol/L) and iron status was higher than in the control group (for hemoglobin median 38.5% vs 23.1%, P = .001 and for iron status median 21.1% vs 8.3%, P = .003). The percentage of high hemoglobin levels (>8.1 mmol/L) was lower in the intervention group (median 0.0% vs 7.7%, P = .034). The weekly dose of DA was lower in the intervention group (median 34.0 vs 46.9 mcg, P = .020), whereas iron dose was higher (median 75 vs 0 mg). No difference was found for the percentage of hemoglobin levels below the target range. In conclusion, a pharmacist‐managed dosing algorithm for DA and iron sucrose increased the attainment of target levels for hemoglobin and iron status, reduced the percentage of high hemoglobin levels, and was associated with a lower DA and a higher iron sucrose dose.