bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anterior Chamber Angle Evaluation Using Gonioscopy: Consistency and Agreement between Optometrists and Ophthalmologists
Authors: Phu Jack , Wang Henrietta , Khuu Sieu K. , Zangerl Barbara , Hennessy Michael P. , Masselos Katherine , Kalloniatis Michael 
Published: October 2019

SIGNIFICANCEIn our intermediate-tier glaucoma care clinic, we demonstrate fair to moderate agreement in gonioscopy examination between optometrists and ophthalmologists, but excellent agreement when considering open versus closed angles. We highlight the need for increased consistency in the evaluation and recording of angle status using gonioscopy.PURPOSEThe consistency of gonioscopy results obtained by different clinicians is not known but is important in moving toward practice modalities such as telemedicine and collaborative care clinics. The purpose of this study was to evaluate the description and concordance of gonioscopy results among different practitioners.METHODSThe medical records of 101 patients seen within a collaborative care glaucoma clinic who had undergone gonioscopic assessment by two clinicians (one optometrist and either one general ophthalmologist [n = 50] or one glaucoma specialist [n = 51]) were reviewed. The gonioscopy records were evaluated for their descriptions of deepest structure seen, trabecular pigmentation, iris configuration, and other features. These were compared between clinicians (optometrist vs. ophthalmologist) and against the final diagnosis.RESULTSOverall, 51.9 and 59.8% of angles were graded identically in terms of deepest visible structure when comparing between optometrist versus general ophthalmologist and optometrist versus glaucoma specialist, respectively. The concordance increased when considering ±1 of the grade (67.4 and 78.5%, respectively), and agreement with the final diagnosis was high (>90%). Variations in angle grading other than naming structures were observed (2.0, 30, and 3.9% for optometrist, general ophthalmologist, and glaucoma specialist, respectively). Most of the time, trabecular pigmentation or iris configuration was not described.CONCLUSIONSFair to moderate concordance in gonioscopy was achieved between optometrists and ophthalmologists in a collaborative care clinic in which there is consistent feedback and clinical review. To move toward unified medical records and a telemedicine model, improved consistency of record keeping and angle description is required.
Correlation of p16 Expression on Cancer and Stromal Cells With Clinicopathologic and Immunohistochemical Features of Lobular Breast Carcinoma
Authors: Harbhajanka Aparna , Lamzabi Ihab , Bitterman Pincas , Reddy Vijaya B. , Ghai Ritu , Gattuso Paolo 
Published: October 2019

Background:
Cancer-associated fibroblasts, play a central role in the tumor-stroma interaction and promote tumorigenesis. However, it is still unclear how these processes are regulated. The aim of this study is to investigate p16 expression in cancer and stromal cells of invasive lobular carcinoma (ILC).

Design:
Clinicopathologic parameters and immunohistochemical stains for estrogen receptor (ER), progesterone receptor, E-cadherin, and human epidermal growth factor receptor 2 of 70 ILC cases were retrieved. In addition, immunohistochemical were performed for p53, p16, and cyclin D1. The p16 expression in cancer and stromal cells were correlated with different clinicopathologic parameters.

Results:
Of the 70 cases, 8 cases were p16− cancer and stromal cells, 14 cases p16− cancer and p16+ stromal cells, 14 cases p16+ cancer and p16− stromal cells, and 34 cases p16+ cancer and stromal cells. Thirty-one of the 59 cases showed axillary lymph node metastases. Nodal involvement, recurrence, and metastasis of ILC with p16+ cancer cells and p16− stromal cells were more frequent compared with other groups. ILC with p16+ cancer and p16− stromal cells were frequently negative for ER, progesterone receptor, and cyclin D1, p53 positive and triple negative compared with other groups. There was no recurrence and metastasis in ILC with p16− cancer and p16+ stromal cells. ILC with p16+ cancer and stromal cells were significantly node negative and were positive for ER and cyclin D1 compared with other groups.

Conclusions:
ILC with p16+ cancer and p16− stromal cells were characterized by frequent nodal involvement, recurrence, and metastatic propensity. These results suggest that p16, has novel anticancer properties capable of suppressing cancer cell migration and invasion and pharmacologic restoration of p16 level in stromal fibroblasts may be exploited as therapeutic strategy to prevent nodal or distant metastasis.
Pediatric Rehabilitation Therapies Differ in Intensity
Authors: Ambuehl Maria , van Hedel Hubertus J. A. , Labruyère Rob 
Published: October 2019

ObjectiveWhen investigating dose-response relationships in rehabilitation studies, dose is often equated with duration of therapy. However, according to the American College of Sports Medicine, dose consists of the factors frequency, intensity, time, and type. Thereby, especially quantification of intensity needs improvement to have a more precise estimate of the dose. Thus, the aim was to investigate the intensity during mobility-focused, real-life pediatric rehabilitation therapies.DesignEleven participants (5 girls, 12.5 ± 2.1 yrs old) with neurological disorders and independent mobility wore accelerometers at wrists and ankles and a portable heart rate monitor during several of the following therapies: sports therapy, mobility-focused physiotherapy, medical training therapy, and robot-assisted gait training. Intensity of physical activity was quantified by activity counts (measured via accelerometers) and heart rate.ResultsTherapy duration did not correlate with intensity. At the same time, we found significant differences between intensities of different therapies.ConclusionDifferent therapies elicit different levels of intensity in children with neuromotor disorders. Heart rate and activity counts are suited to estimate the intensity of a therapy and provide complementary information. We recommend against using the duration of a therapy as a proxy for the dose to make statements about dose-response relationships.To Claim CME CreditsComplete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCMECME ObjectivesUpon completion of this article, the reader should be able to: (1) Appraise the importance of measuring the intensity of various types of inpatient rehabilitation therapy for determining the dose; (2) Describe the differences in intensities between different training forms and name factors that influence this intensity; and (3) Discuss the influence of the functional level of a patient on his/her potential to engage in physically intensive therapy sessions.LevelAdvanced.AccreditationThe Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this journal-based CME activity for a maximum of1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Endoscopy-Assisted Intraoral Removal of Elongated Styloid Process: Mini-Invasive Surgical Treatment of Eagle Syndrome
Authors: Terenzi Valentina , Giovannetti Filippo , Barbera Giorgio , Raponi Ingrid , Valentini Valentino 
Published: October 2019

Abstract
The aim of this work is to illustrate a transoral mini-invasive approach to safely remove elongated styloid process in Eagle syndrome. A 34-year-old Asian male came to our center referring pharyngeal and cervical pain on the right side on swallowing and opening the mouth. Computed tomography showed elongation of the right styloid process. Surgical removal was performed through endoscopy-assisted intraoral approach using a pituitary curette to perform dissection and piezosurgery for the osteotomy. Surgical intervention was completed in 25 minutes. Postoperative period was uneventful except for transient (12 hours) right facial palsy that resolved spontaneously. Two months after surgery, patient referred resolution of symptoms. This technique is easy to perform and permits to obtain good result with reduction of surgical time and with low risk of complication.
Problematic Internet Use in Children and Adolescents: Associations with psychiatric disorders and impairment
Authors: Restrepo Anita , Scheininger Tohar , Clucas Jon , Alexander Lindsay , Salum Giovanni A. , Georgiades Kathy , Paksarian Diana , Merikangas Kathleen R. , Milham Michael P. 
Published: October 2019

ABSTRACTObjectiveHere, we leveraged the ongoing, large-scale Child Mind Institute Healthy Brain Network, a transdiagnostic self-referred, community sample of children and adolescents (ages 5-21), to examine the associations between Problematic Internet Use (PIU) and psychopathology, general impairment, physical health and sleep disturbances.MethodsA total sample of 564 (190 female) participants between the ages of 7-15 (mean = 10.80, SD = 2.16), along with their parents/guardians, completed diagnostic interviews with clinicians, answered a myriad of self-report questionnaires, and underwent physical testing as part of the Healthy Brain Network protocol.ResultsPIU was positively associated with depressive disorders (aOR = 2.34; CI: 1.18-4.56; p = .01), the combined subtype of ADHD (aOR = 1.79; CI: 1.08-2.98; p = .02), greater levels of impairment (Standardized Beta = 4.79; CI: 3.21-6.37; p < .01) and increased sleep disturbances (Standardized Beta = 3.01; CI: 0.58-5.45; p = .02), even when accounting for demographic covariates and psychiatric comorbidity.ConclusionThe association between PIU and psychopathology, as well as its impact on impairment and sleep disturbances, highlight the urgent need to gain an understanding of mechanisms in order to inform public health recommendations on internet use in U.S. youth.
Is e-cigarette use in non-smoking young adults associated with later smoking? A systematic review and meta-analysis
Authors: Khouja Jasmine N , Suddell Steph F , Peters Sarah , Taylor Amy E , Munafò Marcus R 
Published: October 2019

AbstractObjectiveThe aim of this review was to investigate whether e-cigarette use compared to non-use in young non-smokers is associated with subsequent cigarette smoking.Data sourcesPubMed, Embase, Web of Science, Wiley Cochrane Library databases, and the 2018 Society for Research on Nicotine and Tobacco and Society for Behavioural Medicine conference abstracts.Study selectionAll studies of young people (up to age 30 years) with a measure of e-cigarette use prior to smoking and an outcome measure of smoking where an odds ratio could be calculated were included (excluding reviews and animal studies).Data ExtractionIndependent extraction was completed by multiple authors using a pre-prepared extraction form.Data synthesisOf 9,199 results, 17 studies were included in the meta-analysis. There was strong evidence for an association between e-cigarette use among non-smokers and later smoking (OR 4.59, 95% CI 3.60 to 5.85) when the results were meta-analysed in a random effects model. However, there was high heterogeneity (I2 = 88%).ConclusionsWhilst the association between e-cigarette use among non-smokers and subsequent smoking appears strong, the available evidence is limited by the reliance on self-report measures of smoking history without biochemical verification. None of the studies included negative controls which would provide stronger evidence for whether the association may be causal. Much of the evidence also failed to consider the nicotine content of e-liquids used by non-smokers meaning it is difficult to make conclusions about whether nicotine is the mechanism driving this association.
Surgical Intervention for Paediatric Infusion-Related Extravasation Injury: A Systematic Review
Authors: Little MR , Dupré S , Wormald JCR , Gardiner MD , Gale C , Jain A 
Published: October 2019

AbstractObjectivesThis systematic review aims to assess the quality of literature supporting surgical interventions for paediatric extravasation injury and to determine and summarize their outcomes.MethodsWe performed a systematic review by searching Ovid MEDLINE and EMBASE as well as AMED, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews andclinicaltrials.govfrom inception to February 2019. All studies other than case reports were eligible for inclusion if the population was younger than 18 years old, there was a surgical intervention aimed at treating extravasation injury and they reported on outcomes. Risk of bias was graded according to the National Institutes of Health (NIH) study quality assessment tools.Results26 studies involving 728 children were included – one before-and-after study and 25 case series. Extravasation injuries were mainly confined to skin and subcutaneous tissues but severe complications were also encountered, including amputation (one toe and one below elbow). Of the surgical treatments described, the technique of multiple puncture wounds and instillation of saline and/or hyaluronidase was the most commonly used. However, there were no studies in which its effectiveness was tested against another treatment or a control and details of functional and aesthetic outcomes were generally lacking.ConclusionThere is a lack of high quality evidence to support treatment of extravasation injury in children. A definitive trial of extravasation injuries, or a centralized extravasation register using a universal grading scheme and core outcome set with adequate follow-up, are required to provide evidence to guide clinician decision-making.Strengths and LimitationsA systematic review was performed according to PRISMA guidelines and registered on PROSPEROTwo authors used a bespoke inclusion/exclusion form to independently assess study eligibilityStudies were eligible for inclusion if the population was younger than 18 years old, if there was a surgical intervention aimed at treating extravasation injury in any setting and if they reported on short- or long-term outcomesTwo researchers also independently assessed the included studies’ risk of methodological bias using the National Institutes of Health (NIH) study quality assessment tools18 years old may represent a relatively arbitrary cut-off age to differentiate between ‘paediatric’ and ‘adult’ in terms of extravasation injury
Platinum chemotherapy induces lymphangiogenesis in cancerous and healthy tissues that can be prevented with adjuvant anti-VEGFR3 therapy
Authors: Harris Alexandra R. , Esparza Savieay , Azimi Mohammad S. , Cornelison Robert , Azar Francesca N. , Llaneza Danielle C. , Belanger Maura , Mathew Alexander , Tkachenko Svyatoslav , Perez Matthew J. , Rosean Claire Buchta , Bostic Raegan R. , Cornelison R. Chase , Tate Kinsley M. , Peirce-Cottler Shayn M. , Paquette Cherie , Mills Anne , Landen Charles N. , Saucerman Jeff , Dillon Patrick M. , Pompano Rebecca R. , Rutkowski Melanie A. , Munson Jennifer M. 
Published: October 2019

AbstractChemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drugs drain via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used class of chemotherapeutics, to directly induce systemic lymphangiogenesis and activation. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We saw similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increases cancer metastasis as compared to no pre-treatment. These platinum-induced phenomena could be blocked by VEGFR3 inhibition. These findings have implications for cancer patients receiving platinums and may support the inclusion of anti-VEGFR3 therapy into treatment regimens or differential design of treatment regimens to alter these potential effects.SummaryPlatinum chemotherapy induces VEGFR3-dependent lymphangiogenesis, priming tissues for metastasis of breast cancer. Inhibition of VEGFR3 via antibody blockade can reverse these effects.
Coexistence of lipid phases stabilizes interstitial water in the outer layer of mammalian skin
Authors: MacDermaid Christopher M. , Hall Kyle Wm. , DeVane Russell H. , Klein Michael L. , Fiorin Giacomo 
Published: October 2019

ABSTRACTThe lipid matrix in the outer layer of mammalian skin, the stratum corneum, has been previously investigated by multiple biophysical techniques, aimed at identifying hydrophilic and lipophilic pathways of permeation. While consensus is developing over the microscopic structure of the lipid matrix, no molecular-resolution model describes the permeability of all chemical species simultaneously. Using molecular dynamics simulations of a model mixture of skin lipids, the self-assembly of the lipid matrix lamellae has been studied. At higher humidity, the resulting lamellar phase is maintained by partitioning excess water into isolated droplets of controlled size and spatial distribution. The droplets may fuse together to form intra-lamellar water channels, thereby providing a pathway for the permeation of hydrophilic species. These results reconcile competing data on the outer skin’s structure and broaden the scope of molecular-based methods to improve the safety of topical products and to advance transdermal drug delivery.
Sensitization of knee-innervating sensory neurons by tumor necrosis factor-α activated fibroblast-like synoviocytes: an in vitro, co-culture model of inflammatory pain
Authors: Chakrabarti Sampurna , Hore Zoe , Pattison Luke A. , Lalnunhlimi Sylvine , Bhebhe Charity N. , Callejo Gerard , Bulmer David C. , Taams Leonie S. , Denk Franziska , Smith Ewan St. John 
Published: October 2019

AbstractPain is a principal contributor to the global burden of arthritis with peripheral sensitization being a major cause of arthritis-related pain. Within the knee joint, distal endings of dorsal root ganglion neurons (knee neurons) interact with fibroblast-like synoviocytes (FLS) and the inflammatory mediators they secrete, which are thought to promote peripheral sensitization. Correspondingly, RNA-sequencing has demonstrated detectable levels of pro-inflammatory genes in FLS derived from arthritic patients. This study confirms that stimulation with tumor necrosis factor (TNF-α), results in expression of pro-inflammatory genes in mouse and human FLS (derived from OA and RA patients), as well as increased secretion of cytokines from mouse TNF-α stimulated FLS (TNF-FLS). Electrophysiological recordings from retrograde labelled knee neurons co-cultured with TNF-FLS, or supernatant derived from TNF-FLS, revealed a depolarized resting membrane potential, increased spontaneous action potential firing and enhanced TRPV1 function, all consistent with a role for FLS in mediating the sensitization of pain-sensing nerves in arthritis. Therefore, data from this study demonstrate the ability of FLS activated by TNF-α to promote neuronal sensitization, results that highlight the importance of both non-neuronal and neuronal cells to the development of pain in arthritis.
Transcriptome Analysis of Desquamative Interstitial Pneumonia (DIP)
Authors: Saito Shigeki , Kolls Jay K. , Liu Yaozhong , Higashi Yusuke , Ohkochi Shinya , Kondoh Yasuhiro , Lasky Joseph A. , Suzuki Takuji 
Published: October 2019

ABSTRACTDesquamative interstitial pneumonia (DIP) is a rare diffuse parenchymal lung disease of unclear etiology. A recent study showed that mice overexpressing granulocyte macrophage colony-stimulating factor (GM-CSF) in lungs develop DIP-like disease, suggesting that pulmonary GM-CSF may be involved in the pathogenesis of DIP. To determine if GM-CSF is involved in human DIP lungs, we performed transcriptome analysis on human DIP lung tissue. We also extended transcriptome analysis to respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), which has been thought to be in the same spectrum of disease. The analysis revealed that DIP has a distinct transcriptome profile compared to both RB-ILD and non-diseased lung controls. It also suggested that GM-CSF was a key upstream regulator in the DIP transcriptome and that the GM-CSF signaling pathway was highly activated in DIP tissue. Further bioinformatics analysis using xCell, a novel computational method that assesses enrichments of individual cell types based on gene expression, suggested that DIP is enriched for gene signatures of macrophages and other immune cells such as dendritic cells and B cells. In conclusion, our analysis shows that DIP is characterized by a GM-CSF signature, and thus GM-CSF is likely to be involved in the pathogenesis of DIP. Our analysis also suggests that immune cells other than alveolar macrophages, such as B cells, may also be involved in the pathogenesis of DIP.
The usage of human IGHJ genes follows a particular nonrandom selection: The recombination signal sequence affects the usage of human IGHJ genes
Authors: Shi Bin , Dong Xiaoheng , Ma Qingqing , Sun Suhong , Ma Long , Yu Jiang , Wang Xiaomei , Pan Juan , He Xiaoyan , Su Danhua , Yao Xinsheng 
Published: October 2019

ABSTRACTThe formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the “12/23” rule and the “beyond 12/23” rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with physiological and various pathological conditions by high-throughput sequencing. Our results showed that IGHJ gene frequency follows a similar pattern where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10%∼20%), and IGH2/IGHJ1 is used at low frequency (<4%) under whether physiological or various pathological conditions. Furthermore, analysis of the recombination signal sequences suggested that the conserved nonamer and heptamer and certain 23 bp spacer length may affect the initial IGHD-IGHJ recombination, which results in different frequencies of IGHJ genes among the initial BCR-H repertoire. Based on this “background repertoire”, we recommend that re-evaluation and further investigation are needed when analyzing the significance and mechanism of IGHJ gene frequency in self-tolerance selection and the clonal proliferative response.