bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human cytomegalovirus pp65 peptide-induced autoantibodies cross-reacts with TAF9 protein and induces lupus-like autoimmunity in BALB/c mice
Authors: Hsieh Ao-Ho , Kuo Chang-Fu , Chou I-Jun , Tseng Wen-Yi , Chen Yen-Fu , Yu Kuang-Hui , Luo Shue-Fen 
Published: June 2020

AbstractHuman cytomegalovirus (HCMV) has been linked to the triggering of systemic lupus erythematosus (SLE). We proposed that B cell epitope region of HCMV phosphoprotein 65 (HCMVpp65)422–439 mimics an endogenous antigen and initiates lupus-like autoimmunity. Amino acid homology between HCMVpp65422-439 and TAF9134-144 (TATA-box binding protein associated factor 9, TAF9) was investigated using a similarity search in NCBI protein BLAST program (BLASTP). A murine model was used to confirm their antigenicity and ability to induce lupus-like symptoms. HCMVpp65422-439 induced immune responses with the presence of specific antibodies against HCMVpp65422-439 and TAF9134-144, as well as anti-nuclear and anti-double-stranded (ds)DNA antibodies that are characteristic of SLE. In addition, the majority of HCMVpp65422-439 and TAF9134-144 immunized mice developed proteinuria, and their renal pathology revealed glomerulonephritis with typical abnormalities, such as mesangial hypercellularity and immune complex deposition. Immunoglobulin eluted from the glomeruli of HCMVpp65422-439 immunized mice showed cross-reactivity with TAF9134-144 and dsDNA. Increased anti-TAF9 antibody activity was also observed in the sera from SLE patients compared with healthy people and disease controls. Molecular mimicry between HCMVpp65 peptide and host protein has the potential to drive lupus-like autoimmunity. This proof-of-concept study highlights the mechanisms underlying the link between HCMV infection and the induction of SLE.
Machine learning approaches to drug response prediction: challenges and recent progress
Authors: Adam George , Rampášek Ladislav , Safikhani Zhaleh , Smirnov Petr , Haibe-Kains Benjamin , Goldenberg Anna 
Published: June 2020

AbstractCancer is a leading cause of death worldwide. Identifying the best treatment using computational models to personalize drug response prediction holds great promise to improve patient’s chances of successful recovery. Unfortunately, the computational task of predicting drug response is very challenging, partially due to the limitations of the available data and partially due to algorithmic shortcomings. The recent advances in deep learning may open a new chapter in the search for computational drug response prediction models and ultimately result in more accurate tools for therapy response. This review provides an overview of the computational challenges and advances in drug response prediction, and focuses on comparing the machine learning techniques to be of utmost practical use for clinicians and machine learning non-experts. The incorporation of new data modalities such as single-cell profiling, along with techniques that rapidly find effective drug combinations will likely be instrumental in improving cancer care.
A pragmatic randomized waitlist-controlled effectiveness and cost-effectiveness trial of digital interventions for depression and anxiety
Authors: Richards Derek , Enrique Angel , Eilert Nora , Franklin Matthew , Palacios Jorge , Duffy Daniel , Earley Caroline , Chapman Judith , Jell Grace , Sollesse Sarah , Timulak Ladislav 
Published: June 2020

AbstractUtilization of internet-delivered cognitive behavioural therapy (iCBT) for treating depression and anxiety disorders in stepped-care models, such as the UK’s Improving Access to Psychological Therapies (IAPT), is a potential solution for addressing the treatment gap in mental health. We investigated the effectiveness and cost-effectiveness of iCBT when fully integrated within IAPT stepped-care settings. We conducted an 8-week pragmatic randomized controlled trial with a 2:1 (iCBT intervention: waiting-list) allocation, for participants referred to an IAPT Step 2 service with depression and anxiety symptoms (Trial registration: ISRCTN91967124). The primary outcomes measures were PHQ-9 (depressive symptoms) and GAD-7 (anxiety symptoms) and WSAS (functional impairment) as a secondary outcome. The cost-effectiveness analysis was based on EQ-5D-5L (preference-based health status) to elicit the quality-adjust life year (QALY) and a modified-Client Service Receipt Inventory (care resource-use). Diagnostic interviews were administered at baseline and 3 months. Three-hundred and sixty-one participants were randomized (iCBT, 241; waiting-list, 120). Intention-to-treat analyses showed significant interaction effects for the PHQ-9 (b = −2.75, 95% CI −4.00, −1.50) and GAD-7 (b = −2.79, 95% CI −4.00, −1.58) in favour of iCBT at 8-week and further improvements observed up to 12-months. Over 8-weeks the probability of cost-effectiveness was 46.6% if decision makers are willing to pay £30,000 per QALY, increasing to 91.2% when the control-arm’s outcomes and costs were extrapolated over 12-months. Results indicate that iCBT for depression and anxiety is effective and potentially cost-effective in the long-term within IAPT. Upscaling the use of iCBT as part of stepped care could help to enhance IAPT outcomes. The pragmatic trial design supports the ecological validity of the findings.
Sphingosine-1-phosphate receptor modulator FTY720 attenuates experimental myeloperoxidase-ANCA vasculitis in a T cell-dependent manner
Authors: Wang Luo-Yi , Sun Xiao-Jing , Wang Chen , Chen Su-Fang , Li Zhi-Ying , Chen Min , Little Mark A. , Zhao Ming-Hui 
Published: June 2020

Abstract
Sphingosine-1-phosphate (S1P) is a pleiotropic lysosphingolipid derived from the metabolism of plasma membrane lipids. The interaction between S1P and its ubiquitously expressed G-protein-coupled receptors (S1PR1-5) is crucial in many pathophysiological processes. Emerging evidence suggested a potential role for S1P receptors in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In the present study, we investigated the effects of three different S1P receptors modulators (FTY720, SEW2871 and TY52156) in a recognized rat model of experimental autoimmune vasculitis (EAV). The effects of treatments were evaluated with clinico-pathological parameters including hematuria, proteinuria, crescent formation, pulmonary hemorrhage, etc. In vitro functional studies were performed in a Jurkat T-cell line following stimulations of serum from myeloperoxidase-AAV patients. We found that only the FTY720 treatment significantly alleviated hematuria and proteinuria, and diminished glomerular crescent formation, renal tubulointerstitial lesions and pulmonary hemorrhage in EAV. The attenuation was accompanied by less renal T-cell infiltration, up-regulated mRNA of S1PR1 and down-regulated IL-1β in kidneys, but not altered circulating ANCA levels, suggesting that the therapeutic effects of FTY720 were B-cell independent. Further in vitro studies demonstrated that FTY720 incubation could significantly inhibit the proliferation, adhesion, and migration, and increase apoptosis of T cells. In conclusion, the S1P modulator FTY720 could attenuate EAV through the reduction and inhibition of T cells, which might become a novel treatment of ANCA-associated vasculitis.
Biobanking in der Psychiatrie
Authors: Luckhaus Christian , Roosterman Dirk , Juckel Georg 
Published: June 2020

ZusammenfassungBiobanking in der Medizin betrifft den Aufbau und Betrieb von umfangreichen biologischen Probendepots in Verbindung mit umfassenden Datenarchiven, die klinische und biografische Probandeninformationen enthalten. Hierdurch sollen Proben von kontrollierter hoher und konstanter Qualität für zukünftige Forschungsprojekte bereitgestellt werden. Eine wesentliche Zielsetzung ist es, diverse Blutkomponenten für unterschiedliche biochemische Analysen und experimentelle Ansätze zu asservieren einschließlich verschiedener isolierter Blutzellfraktionen. Bei geeigneter Kryokonservierung können Blutzellen nach dem Auftauen revitalisiert werden, um als in-vitro-Zellmodelle mit biologischen Merkmalen des Spenderorganismus verwendet zu werden. Durch Optimierung der präanalytischen Methoden kann die präanalytische Varianz reduziert und dadurch eine höhere Präzision der analytischen Daten erreicht werden. Dies ist für multivariate Analysen biologischer Systeme („omics“) und die Biomarkerforschung von besonderer Bedeutung. Biobanking in der Psychiatrie hat die spezielle Herausforderung, eine höhere Kompatibilität diagnostischer Zuordnungen mit biologischen Entitäten zu erreichen, als dies durch die gegenwärtigen Diagnosekategorien gem. ICD-10 oder DSM-V ermöglicht wird. Dazu können diagnostische oder transdiagnostische Subgruppen stratifiziert werden, anhand biologisch verankerter klinischer Zusatzkriterien oder psychobiologischer Funktionsparameter. Ein wichtiger ethischer Aspekt im Zusammenhang mit Biobanking ist die Erfordernis für eine erweiterte Einwilligung („broad consent“) der Spender in künftige, noch zu spezifizierende Forschungsprojekte. Der organisatorische, logistische und ökonomische Aufwand für den Aubau und Betrieb einer Biobank ist erheblich, scheint aber berechtigt mit Blick auf hierdurch erreichbare Qualitätsverbesserungen der biomedizinischen Forschung, insbesondere im Bereich der Translation und klinischen Anwendungsentwicklung.
Non-Binarität – Behandlung aus psychotherapeutischer Perspektive: Ein Kommentar zur neuen S3-Leitlinie
Authors: Löwenberg Hagen 
Published: June 2020

ZusammenfassungNon-binäre Behandlungssuchende sind in der neuen S3-Leitlinie genau wie in den neuen Diagnosemanualen (DSM-5, ICD-11) ausdrücklich inkludiert. Damit stehen ihnen alle in der S3-Leitlinie angeführten Behandlungsmöglichkeiten bei Geschlechtsinkongruenz bzw. Geschlechtsdysphorie zur Verfügung. Gleichwohl sind einige Besonderheiten zu beachten. Non-Binarität begegnet uns in der psychotherapeutischen Praxis in Erscheinungsformen, die von nicht geschlechterrollenkonformem Erleben in unterschiedlichen Lebensbereichen bis zu expliziter Identifizierung als non-binär reichen. Typische Probleme bei Non-Binarität sind Unsichtbarkeit, Vulnerabilität und Diskriminierung. In der Gesundheitsversorgung begegnen non-binäre Behandlungssuchende besonderen Schwierigkeiten. Die Anerkennung der geschlechtlichen Identifizierung und die Würdigung des persönlichen Leids sind bei der psychotherapeutischen Unterstützung und Vorbereitung auf körpermodifizierende Maßnahmen von großer Bedeutung. Es wird für selbstbestimmte, individuelle Lösungen nach gemeinsamer Exploration der zur Verfügung stehenden Möglichkeiten plädiert. Dabei können im Einzelfall neben den in der Leitlinie aufgeführten evidenzbasierten Maßnahmen auch experimentelle Körpermodifikationen eine Berechtigung haben.
Rechtliche Bedeutung der S3-Leitlinie für Trans*Personen: Erfahrungen aus der Praxis einer Beratungsstelle
Authors: Neander Klaus-Dieter 
Published: June 2020

ZusammenfassungDer Beitrag greift die Erwartungen der Trans*Personen an die neue S3-Leitlinie auf. Die Trans*Personen scheitern bei Kostenübernahmeanträgen bei den Krankenkassen häufig daran, dass die Krankenkassen eigene Begutachtungsregeln aufgestellt haben, die in vielen Entscheidungspunkten von denen abweichen, die von der Trans*Community akzeptiert werden. Mit der Veröffentlichung der S3-Leitlinie verbinden die Betroffenen die Hoffnung, dass die Leitlinie verbindlich regelt, wann die Kostenträger bestimmte Leistungen übernehmen müssen. Die Prüfung der juristischen und standesrechtlichen Regelungen für Ärzt_innen ergibt allerdings, dass Leitlinien reinen Empfehlungscharakter haben. Eine Verpflichtung zur Kostenübernahme lässt die Leitlinie nicht zu.
Reconstruction of Large Bone Defects and Complex Non-Unions Using a Free Fibular Bone Graft and a Supplementary Allograft
Authors: Gaida Selina , Schweigkofler Uwe , Moll Wibke , Sauerbier Michael , Hoffmann Reinhard 
Published: June 2020

AbstractLarge bone defects or complex pseudarthrosis represent an interdisciplinary challenge. Established surgical procedures include autogenous cancellous bone graft, the Masquelet technique or bone transfer via segment transport as well as free microvascular bone transplantation. However, the successful use of all these techniques requires a specialized center with great interdisciplinary expertise. In the following case series we describe the technique of free fibula transplantation and additional allograft. In both cases a good functional result with full mechanical strength of the affected extremity and satisfactory patient comfort has been achieved. In the second case, implant failure with the necessity of revision endoprosthetics occurred during the procedure.
Epidemiological Features and Clinical Repercussions of Supernumerary Teeth in a Multicenter Study: A Review of 518 Patients with Hyperdontia in Spanish Population
Authors: Brinkmann Jorge Cortés-Bretón , Martínez-Rodríguez Natalia , Martín-Ares María , Sanz-Alonso Javier , Marino Juan Santos , Suárez García Maria Jesús , Dorado Cristina Barona , Martínez-González Jose María 
Published: June 2020

AbstractObjectives The aim of this study was to establish the prevalence of supernumerary teeth (ST) in a sector of the population of Madrid, as well as possible complications associated with the presence of these teeth.Materials and Methods The study investigated patients (n = 28,114) who sought dental care at the Oral Surgery Service of three different centers between May 2005 and April 2018. Cases that did not present this numeric dental developmental variation were discarded, registering only those presenting ST.Statistical Analysis Statistical analysis consisted of univariate analysis (mean, standard deviation, median, etc.), bivariate analysis applying the chi-squared test, whereby statistical significance was established with a confidence interval (CI) of 95% (p < 0.05), and multivariate analysis by means of classification and decision trees.Results The study found ST in 518 patients, representing a prevalence of 1.84%. The 518 patients presented a total of 726 ST. Distomolars were the most common, representing 37.7% of the sample, followed by premolars (20.1%). About 70.5% of the sample were located in the maxilla and 78% of ST were impacted. Radiographs revealed that 39.7% of STs were associated with disorders. Supplementary morphology appeared in 52.1% of the sample.Conclusions Although mesiodens is considered the most common ST, the present study found distomolars and supernumerary premolars to be the most frequently occurring. Pathology was associated with 39.7% of the ST sample. Early diagnosis allows optimal patient management and treatment planning, with intervention at an appropriate time to prevent complications in development and so reduce later treatment need.
A Multicenter Study of Tongue Lesions from Thailand
Authors: Dhanuthai Kittipong , Kintarak Sompid , Subarnbhesaj Ajiravudh , Chamusri Nutchapon 
Published: June 2020

Abstract
Objective Tongue lesions constitute a considerable proportion of the oral lesions. Previous studies on tongue lesions were based on clinical studies. There has been a scarcity of the studies which are based on histopathological examination. This study aimed to determine the prevalence, demographic, and pathologic features of tongue lesions from Thailand.
Materials and Methods Biopsy records of the participating institutions were reviewed for lesions on the tongue diagnosed during 1998 to 2017. Demographic data were collected from the biopsy records. Locations were arbitrarily classified as dorsal, lateral, and ventral surfaces, tip of the tongue, and the combination of sites. Lesions of the tongue were classified as reactive/inflammatory, developmental, immune-mediated, cystic, benign, premalignant, malignant, infectious, and miscellaneous categories.
Statistical Analysis Data were analyzed by descriptive statistics using SPSS version 20.0.
Results Of the 44,188 accessioned cases, 2,153 cases (4.87%) were diagnosed from the tongue. The age of the patients ranged from 3 to 93 years with the mean ± standard deviation = 45.26 ± 20.48 years. The female-to-male ratio was 1.49:1. The majority of the tongue lesions were encountered at the lateral border of the tongue (47.66%). Most of the tongue lesions in the present study (53.74%) fell into the reactive/inflammatory category. Irritation fibroma was the most prevalent lesion (18.99%) followed by squamous cell carcinoma (16.91%), and mucus extravasation phenomenon (14.26%), respectively.
Conclusions This study offers new perspective into the study of tongue lesions apart from the clinically based studies. It also demonstrates the difference between the pediatric and the elderly patients. This study provides invaluable database for clinicians when formulating the clinical diagnosis of tongue lesions.
Metastatic Biphasic Primitive Tumor in the Mandible of a Child
Authors: Pinheiro Tiago Novaes , Leite Milena Gomes Melo , Bindá Fábio Arruda , Dutra André Luiz Tannus , Sarmento Naelka , Cabral Lioney Nobre , Consolaro Alberto , Bacchi Carlos Eduardo 
Published: June 2020

AbstractPediatric mandibular tumors present an aggressive biological behavior and difficult diagnosis. A wide range of odontogenic and nonodontogenic tumors comprise the spectrum of these lesions. We report a case of a 1-year-old male child patient showing facial asymmetry symptomatic of an expansive lesion extending throughout the body and ramus of the left hemimandible with a diameter of 8 cm. The histopathological report suggested a high-grade mucoepidermoid carcinoma (MEC), recommending further immunohistochemical investigation of the ectomesenchymal or neuroectodermal origin of the tumor cells. The patient evolved with extensive bilateral pleural effusion followed by metastasis in the middle third of the right humerus, and died 2 months after the first biopsy procedure by acute renal failure with tubular necrosis, before a final inconclusive immunohistochemical report was reached. The lack of resources for less-favored regions of Brazil impairs rapid biomolecular examinations such as immunohistochemical resulting in delay of appropriate therapeutic procedures.
Higher Prevalence of Periodontitis and Decayed, Missing and Filled Teeth in Patients with Psoriasis
Authors: Barros Fabiana Cervo de , Sampaio Janaina Nunes , Figueredo Carlos Marcelo da Silva , Carneiro Sueli , Fischer Ricardo Guimarães 
Published: June 2020

Abstract
Objective The aim of this study is to describe the prevalence and severity of periodontitis and decayed, missing and filled teeth (DMFT) index in patients with psoriasis. As a secondary aim, verify if periodontitis was a risk indicator for psoriasis.
Materials and Methods A total of 69 patients diagnosed with psoriasis (48.7 ± 14.6 years) and 74 healthy controls (40.3 ± 12.9 years) participated in the study. Probing pocket depth, clinical attachment loss (CAL), bleeding on probing, plaque index, and DMFT index were measured in all subjects. Periodontitis was defined as the presence of at least three interproximal sites with CAL ≥3 mm in different teeth and severe periodontitis should involve at least two interproximal sites in different teeth with CAL ≥5 mm.
Statistical Analysis The Mann–Whitney test was used to analyze the demographics and the clinical data. The significance level was 5%. A multivariate logistic regression was conducted, and the odds ratio were calculated to express the risk to develop psoriasis.
Results Patients with psoriasis had significantly more sites with CAL ≥3 mm (p < 0.03) and CAL ≥5 mm (p < 0.0001), less sites with plaque (p < 0.0001), fewer teeth (p < 0.0001), and a high DMFT index (p < 0.02) as compared with controls. Severe periodontitis was significantly more frequent (87.1% × 58.1%) and was a risk indicator for psoriasis after adjusting for sex, age, race, and smoking habits (odds ratio: 3.7, 95% confidence interval: 1.5–9.0, p < 0.003).
Conclusion Patients with psoriasis have higher prevalence of severe periodontitis and higher DMFT than control patients. Severe periodontitis may be a risk indicator for psoriasis.
Fragmentation of acetate-CoA ligase gives a clue to understand domain rearrangement history of NDP-forming acyl-CoA synthetase superfamily proteins
Authors: Chiba Yoko , Shitara Mariko , Takai Ken 
Published: June 2020

Abstract
NDP-forming type acyl-CoA synthetase superfamily proteins are known to have six essential subdomains (1, 2, 3, a, b, c) of which partition and order are varied, suggesting yet-to-be-defined subdomain rearrangement happened in its evolution. Comparison in physicochemical and biochemical characteristics between the recombinant proteins which we made from fragmented subdomains and wild-type protein, acetate-CoA ligase in a hyperthermophilic archaeon, consisting of two distinct subunits (α1-2-3 and βa-b-c) provided a clue to the mystery of its molecular evolutionary passage. Although solubility and thermostability of each fragmented subdomain turned out to be lower than that of wild-type, mixture of the three synthetic subunits of α1-2, α3, and βa-b-c had quaternary structure, thermostability, and enzymatic activity comparable to those of the wild-type. This suggests that substantial independence and mobility of subdomain 3 have enabled rearrangement of the subdomains; and thermostability of the subdomains has constrained the composition of the subunits.
Magnetic field generation in a laser-irradiated thin collisionless plasma target by return current electrons carrying orbital angular momentum
Authors: Shi Y , Weichman K , Kingham R J , Arefiev A V 
Published: June 2020

Abstract
Magnetized high energy density physics offers new opportunities for observing magnetic field-related physics for the first time in the laser–plasma context. We focus on one such phenomenon, which is the ability of a laser-irradiated magnetized plasma to amplify a seed magnetic field. We performed a series of fully kinetic 3D simulations of magnetic field amplification by a picosecond-scale relativistic laser pulse of intensity 4.2 × 1018 W cm−2 incident on a thin overdense target. We observe axial magnetic field amplification from an initial 0.1 kT seed to 1.5 kT over a volume of several cubic microns, persisting hundreds of femtoseconds longer than the laser pulse duration. The magnetic field amplification is driven by electrons in the return current gaining favorable orbital angular momentum from the seed magnetic field. This mechanism is robust to laser polarization and delivers order-of-magnitude amplification over a range of simulation parameters.