bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoregulation by IL-7R-targeting antibody-drug conjugates: overcoming steroid-resistance in cancer and autoimmune disease
Authors: Yasunaga Masahiro , Manabe Shino , Matsumura Yasuhiro 
Published: August 2017

AbstractSteroid-resistance is a common complication in the treatment of malignancies and autoimmune diseases. IL-7/IL-7R signaling, which regulates lymphocyte growth and survival, has been implicated in the development of malignancies and autoimmune diseases. However, the biological significance of IL-7/IL-7R signaling in steroid treatment is poorly understood. Here, we identified a novel relationship between IL-7R signaling and steroid-resistance, and showed that an anti-IL-7R antibody conjugated with SN-38 (A7R-ADC-SN-38) has strong anti-tumor effects against both parental and steroid-resistant malignant cells. Furthermore, inflammation in the mouse autoimmune arthritis model was suppressed to greater extent by A7R-ADC conjugated to MMAE than by A7R-ADC-SN-38. Given that an increased proportion of IL-7R-positive cells is a common mechanism underlying the pathogenesis of autoimmunity, we found that specific depletion of this cell population abrogated the progression of disease. This suggests that the cytotoxicity and immunosuppressive capacity of A7R-ADC could be modulated to treat specific malignancies or autoimmune diseases through the introduction of different payloads, and represents a novel alternative to steroid therapy.
The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant
Authors: Tomás-Cortázar Julen , Martín-Ruiz Itziar , Barriales Diego , Pascual-Itoiz Miguel Ángel , de Juan Virginia Gutiérrez , Caro-Maldonado Alfredo , Merino Nekane , Marina Alberto , Blanco Francisco J. , Flores Juana María , Sutherland James D. , Barrio Rosa , Rojas Adriana , Martínez-Chantar María Luz , Carracedo Arkaitz , Simó Carolina , García-Cañas Virginia , Abecia Leticia , Lavín José Luis , Aransay Ana M. , Rodríguez Héctor , Anguita Juan 
Published: August 2017

AbstractSalp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein. Transcriptionally, the salivary protein provokes an acute effect that includes known activation markers, such as Il2 or Cd44, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with Salp15 does not result in B cell anergy or the generation of myeloid suppressor cells. However, Salp15 induces the increased expression of the ectoenzyme, CD73, in regulatory T cells and increased production of adenosine. Our study provides a profound characterization of the immunomodulatory activity of Salp15 and suggests that its long-term effects are due to the specific regulation of CD73.
Molecular mechanisms governing microRNA-125a expression in human hepatocellular carcinoma cells
Authors: Potenza Nicoletta , Panella Marta , Castiello Filomena , Mosca Nicola , Amendola Elena , Russo Aniello 
Published: August 2017

AbstractMicroRNA-125a-5p (miR-125a) is a vertebrate homolog of lin-4, the first discovered microRNA, and plays a fundamental role in embryo development by downregulating Lin-28 protein. MiR-125a is also expressed in differentiated cells where it generally acts as an antiproliferative factor by targeting membrane receptors or intracellular transductors of mitogenic signals. MiR-125a expression is downregulated in several tumors, including hepatocellular carcinoma (HCC) where it targets sirtuin-7, matrix metalloproteinase-11, VEGF-A, Zbtb7a, and c-Raf. In this study, we have isolated the transcription promoter of human miR-125a and characterized its activity in HCC cells. It is a TATA-less Pol II promoter provided with an initiator element and a downstream promoter element, located 3939 bp upstream the genomic sequence of the miRNA. The activity of the promoter is increased by the transcription factor NF-kB, a master regulator of inflammatory response, and miR-125a itself was found to strengthen this activation through inhibition of TNFAIP3, a negative regulator of NF-kB. This finding contributes to explain the increased levels of miR-125a observed in the liver of patients with chronic hepatitis B.
Cholesterol-modified Hydroxychloroquine-loaded Nanocarriers in Bleomycin-induced Pulmonary Fibrosis
Authors: Liu Li , Ren Jun , He Zhiyao , Men Ke , Mao Ye , Ye Tinghong , Chen Hua , Li Ling , Xu Bocheng , Wei Yuquan , Wei Xiawei 
Published: August 2017

AbstractAn increasing number of reports have suggested the use of hydroxychloroquine (HCQ) as an adjunct anti-cancer treatment to enhance the chemotherapeutic response, as well as for the treatment of several fibrotic skin diseases and cystic fibrosis. In this study, we synthesized a cholesterol-modified HCQ (Chol-HCQ) and hypothesized that a systemic delivery system with Chol-HCQ nanocarriers could be effective for the treatment of bleomycin-induced pulmonary fibrosis. Chol-HCQ significantly inhibits the proliferation of rat lung fibroblasts, regulates inflammation and ameliorates bleomycin-induced pulmonary fibrosis in rats. It regulates the expression of pro-inflammatory cytokines, such as TNF-α; reduces the infiltration of inflammatory neutrophils; and inhibits the phosphorylation of NF-κB. Chol-HCQ also reduces the expression of connective tissue growth factor (CTGF) and phosphorylation of extracellular regulated protein kinase (p-ERK) in rats with bleomycin-induced pulmonary fibrosis. Chol-HCQ nanocarriers reduce early pulmonary inflammation and inhibit the CTGF/ERK signalling pathway in bleomycin-induced pulmonary fibrosis. These results demonstrate that Chol-HCQ liposomes suppress pulmonary inflammation and reduce pulmonary fibrosis induced by bleomycin. The systemic administration safety of Chol-HCQ liposomes was confirmed after intravenous administration for 28 days in rats. The present study provides evidence that Chol-HCQ liposomes may be a potential therapeutic agent for inflammation associated with pulmonary fibrosis.
Precision cardio-oncology: understanding the cardiotoxicity of cancer therapy
Authors: Han Xinqiang , Zhou Yun , Liu Wendi 
Published: August 2017

AbstractCurrent oncologic treatments have brought a strong reduction in mortality in cancer patients. However, the cancer therapy-related cardiovascular complications, in particular chemo-therapy and radiation therapy-induced cardiotoxicities are a major cause of morbidity and mortality in people living with or surviving cancer. The simple fact is that all antineoplastic agents and radiation therapy target tumor cells but also result in collateral damage to other tissues including the cardiovascular system. The commonly used anthracycline chemotherapy agents can induce cardiomyopathy and congestive heart failure. Targeted therapies with human epidermal growth factor antibodies, tyrosine kinase inhibitors or vascular endothelial growth factor antibodies, and the antimetabolites also have shown to induce cardiomyopathy and myocardial ischemia. Cardiac arrhythmias and hypertension have been well described with the use of tyrosine kinase inhibitors and antimicrotubule agents. Pericarditis can happen with the use of cyclophosphamide or cytarabine. Mediastinal radiation can cause constrictive pericarditis, myocardial fibrosis, valvular lesions, and coronary artery disease. Despite significant progresses in the understanding of the molecular and pathophysiologic mechanisms behind the cardiovascular toxicity of cancer therapy, there is still lack of evidence-based approach for the monitoring and management of patients. This review will focus mainly on the recent advances in the molecular mechanisms of cardiotoxicity related to common cancer therapies while introducing the concept of cardio-oncology service. Applying the general principles of multi-disciplinary approaches toward the diagnosis, prevention, monitoring, and treatment of cancer therapy-induced cardiomyopathy and heart failure will also be discussed.
Applying Item Response Theory to the Development of a Screening Adaptation of the Goldman-Fristoe Test of Articulation–Second Edition
Authors: Brackenbury Tim , Zickar Michael J. , Munson Benjamin , Storkel Holly L. 
Published: August 2017

Purpose
Item response theory (IRT) is a psychometric approach to measurement that uses latent trait abilities (e.g., speech sound production skills) to model performance on individual items that vary by difficulty and discrimination. An IRT analysis was applied to preschoolers' productions of the words on the Goldman-Fristoe Test of Articulation–Second Edition (GFTA-2) to identify candidates for a screening measure of speech sound production skills.

Method
The phoneme accuracies from 154 preschoolers, with speech skills on the GFTA-2 ranging from the 1st to above the 90th percentile, were analyzed with a 2-parameter logistic model.

Results
A total of 108 of the 232 phonemes from stimuli in the sounds-in-words subtest fit the IRT model. These phonemes, and subgroups of the most difficult of these phonemes, correlated significantly with the children's overall percentile scores on the GFTA-2. Regression equations calculated for the 5 and 10 most difficult phonemes predicted overall percentile score at levels commensurate with other screening measures.

Conclusions
These results suggest that speech production accuracy can be screened effectively with a small number of sounds. They motivate further research toward the development of a screening measure of children's speech sound production skills whose stimuli consist of a limited number of difficult phonemes.
Single channel 224 Gbit/s (56‐GBaud) PAM‐16 transmission using linear digital pre‐distortion
Authors: Yang Chao , Li Wei , Yu Shaohua 
Published: August 2017

With linear digital pre‐distortion (DPD) and 8‐bit digital to analogue converter (DAC), a single channel 224 Gbit/s (56‐GBaud) 16‐level pulse amplitude modulation (PAM‐16) signal is experimentally transmitted over a 100 m standard single‐mode fibre (SSMF) for the first time using intensity modulation and direct detection (IM/DD). The 3 dB bandwidth of the whole system is around 22 GHz, which is far below the bandwidth of the 56‐GBuad PAM‐16 signal. The strong inter‐symbol interference caused by the limited system bandwidth is pre‐compensated by the proposed linear DPD technique. The experimental results indicate that the linear DPD process can effectively avoid the noise enhancement by the aggressive feed‐forward equalisation at the receiver, and also improves the system performance at the cost of additional finite impulse response filter at the transmitter.
Trichophyton rubrum-Syndrom und Tinea incognita unter immunsuppressiver Behandlung mit Leflunomid und Fumarsäureestern bei Patienten mit rheumatoider Arthritis und Psoriasis vulgaris
Authors: Nenoff P. , Fischer S. , Schulze I. , Krüger C. 
Published: August 2017

ZusammenfassungEin 70-jähriger Patient mit rheumatoider Arthritis (Anti-CCP-Antikörper positiv), Nikotinabusus und Arteriosklerose wurde immunsuppressiv mit Leflunomid 20 mg und Prednisolon 50 mg täglich behandelt. Am Körperstamm traten großflächige, ekzematisierte, randbetonte, zentrifugal wachsende erythrosquamöse Läsionen auf. Die Haut der rechten Hand und beider Füße war trocken, schuppend und atrophisch. Außerdem bestanden gelbbraune Onychodystrophien aller Fingernägel der rechten Hand sowie aller Zehennägel. Das Blankophor®-Präparat aus Hautschuppen war positiv, kulturell und mit PCR ließ sich Trichophyton (T.) rubrum nachweisen. Die ausgeprägte Tinea corporis wurde mit einer Antimykotika- und Glukokortikoid-haltigen Creme behandelt, wegen der Tinea unguium kam Terbinafin zur Anwendung. Ein 68-jähriger Psoriatiker erhielt bereits seit 1979 Fumarsäureester zur systemischen antipsoriatischen Therapie. Seit einigen Monaten entwickelten sich an Flanken, Rücken, gluteal, an den Waden, prätibial und an den Oberschenkeln blass-rote erythrosquamöse Plaques im Sinne einer Tinea corporis incognita. Das Nativpräparat war positiv, kulturell und mit PCR gelang aus insgesamt 6 Lokalisationen der Nachweis von T. rubrum. Da eine systemische antimykotische Behandlung abgelehnt wurde, kam Terbinafin-Creme im Wechsel mit Clotrimazol- + Betamethason-Creme zur Anwendung.Die großflächige und generalisierte Tinea corporis mit Onychomykose erfüllte bei beiden Patienten die Kriterien eines sog. T. rubrum-Syndroms. Dieses, aber auch die Tinea incognita, entwickeln sich in der Regel infolge einer Autoinokulation von einer vorbestehenden Tinea pedis et unguium. Disponierender Faktor für das T. rubrum-Syndrom, aber auch für die Tinea incognita, ist nicht selten eine immunsupprimierende Therapie, hier durch Glukokortikoide, Leflunomid sowie Fumarsäureester.
Skabies-Massenausbruch in einem Altenheim für Demenzkranke
Authors: Montag A. 
Published: August 2017

ZusammenfassungDargestellt wird ein Massenanfall mit 75 Skabies-Infizierten unterschiedlichen Schweregrades in den geschlossenen Wohnbereichen für Demenzkranke eines großen Pflegeheims am Stadtrand einer deutschen Großstadt.Der Ablauf der tatsächlichen Ereignisse, einschließlich der damit verbundenen diagnostischen und therapeutischen Herausforderungen, wird ebenso eingehend beschrieben wie die Maßnahmen, die zur Eindämmung der Infektion eingeleitet wurden. Zusammen mit den Rahmenbedingungen, die zum dargestellten Massenausbruch geführt haben, werden die genannten Aspekte abschließend einer umfassenden kritischen Würdigung unterzogen.
Reizdarm, Zöliakie, Weizenallergie, Weizensensitivität – die Schwierigkeit, die Spreu vom Weizen zu trennen
Authors: Leiß Ottmar 
Published: August 2017

ZusammenfassungErnährungsfaktoren spielen eine wichtige Rolle bei Auslösung und Verschlimmerung von Bauchschmerzen, Blähungen und Durchfall bei Patienten mit Reizdarmsyndrom (RDS). Seit Abgrenzung eines neuen Krankheitsbildes zwischen RDS und Zöliakie, der non-celiac gluten sensitivity/Weizensensitivität, und seit Erscheinen eines in Laienkreisen viel beachteten Bestsellers zu negativen gesundheitlichen Effekten von Weizen, hat eine glutenfreie Ernährung seit einigen Jahren erheblich an Popularität zugenommen.In einer Übersicht werden die Unterschiede zwischen RDS, Zöliakie, Weizenallergie und Weizensensitivität dargestellt und Studien, die den Weizenbestandteilen Gluten oder Fruktanen/FODMAPs (fermentierbaren Oligo-, Di-, Monosacchariden und Polyolen) eine auslösende Rolle zusprechen, erörtert. Vor- und Nachteile einer glutenfreien Diät und FODMAP-armen Ernährung werden diskutiert. Abschließend wird erläutert, bei welchem Patienten zu einer glutenfreien Ernährung und bei welchem Patienten zu einer FODMAP-armen Ernährung geraten werden sollte.
Leishmaniasis auf Mallorca: Vorstellung eines ungewöhnlichen Verlaufs unter Immunsuppression
Authors: Gebhardt M. , Ostermann M. , Fischer M. 
Published: August 2017

ZusammenfassungDas spanische Festland und die Balearen sind Endemiegebiete für die kutane und viszerale Leishmaniasis durch Leishmania infantum. Die kutane Leishmaniasis ist die häufigste Verlaufsform. Der Hauptvektor, die Sandmücke Phlebotomus perniciosus, ist im gesamten Inselgebiet von Mallorca zu finden. Die Leishmaniasis zeichnet sich durch eine Vielzahl von klinischen Erscheinungsbildern aus. Der Immunstatus des Patienten spielt hierbei eine relevante Rolle für den Verlauf der Erkrankung und das Ansprechen der Therapie.
Hashimoto’s Thyroiditis is an Important Risk Factor of Papillary Thyroid Microcarcinoma in Younger Adults
Authors: Liu Yujuan , Li Chengqian , Zhao Wenjuan , Wang Yangang 
Published: August 2017

AbstractThe association between autoimmune thyroid disease and thyroid cancer remains unclear. We performed a matched case-control study to assess the association between Hashimoto’s thyroiditis and papillary thyroid microcarcinoma (PTMC). A total of 927 PTMC cases and 927 age- and gender- matched controls selected from the same population were recruited. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association between Hashimoto’s thyroiditis and PTMC. Conditional logistic regression analysis was carried out, and stratified analyses by age, gender and types of thyroid antibodies were also performed. Hashimoto’s thyroiditis was significantly associated with increased risk of PTMC (OR=1.87, 95% CI 1.49–2.34, p<0.001). Stratified analysis by thyroid antibodies also found obvious associations of PTMC risk with TPOAb positivity (OR=1.58, p=0.001) and TGAb positivity (OR=2.35, p<0.001). Stratified analyses by age showed that the association between Hashimoto’s thyroiditis and PTMC risk was more significant in younger adults aged between 18 and 30 years (OR=11.48, p<0.001). Further stratified analyses by thyroid antibodies also found that the associations of PTMC risk with TPOAb positivity or TGAb positivity were more significant in younger adults aged between 18 and 30, and the ORs were 8.27 (p<0.001) and 12.71 (p<0.001), respectively. This study suggests an obvious relationship between Hashimoto’s thyroiditis and PTMC risk, and Hashimoto’s thyroiditis is an important risk of PTMC in younger adults.
CDK8/19 Mediator kinases potentiate induction of transcription by NFκB
Authors: Chen Mengqian , Liang Jiaxin , Ji Hao , Yang Zhengguan , Altilia Serena , Hu Bing , Schronce Adam , McDermott Martina S. J. , Schools Gary P. , Lim Chang-uk , Oliver David , Shtutman Michael S. , Lu Tao , Stark George R. , Porter Donald C. , Broude Eugenia V. , Roninson Igor B. 
Published: August 2017

Significance
Nuclear factor-κB (NFκB) transcription factors have been implicated in several major diseases, including inflammatory disorders, viral infections, and cancer. NFκB-inhibiting drugs typically have side effects, possibly due to sustained NFκB suppression. The ability to affect induced, but not basal, NFκB activity could provide therapeutic benefit without associated toxicity. We report that the transcription-regulating kinases CDK8/19 potentiate NFκB activity, including the expression of tumor-promoting proinflammatory cytokines, by enabling the completion of NFκB-initiated transcription. CDK8/19 inhibitors suppress the induction of gene expression by NFκB or other transcription factors, but generally do not affect basal expression of the same genes. The role of CDK8/19 in newly induced transcription identifies these kinases as mediators of transcriptional reprogramming, a key aspect of development, differentiation, and pathological processes.
Snaptron: querying splicing patterns across tens of thousands of RNA-seq samples
Authors: Wilks Christopher , Gaddipati Phani , Nellore Abhinav , Langmead Ben 
Published: August 2017

Abstract

Motivation
As more and larger genomics studies appear, there is a growing need for comprehensive and queryable cross-study summaries. These enable researchers to leverage vast datasets that would otherwise be difficult to obtain.

Results
Snaptron is a search engine for summarized RNA sequencing data with a query planner that leverages R-tree, B-tree and inverted indexing strategies to rapidly execute queries over 146 million exon-exon splice junctions from over 70 000 human RNA-seq samples. Queries can be tailored by constraining which junctions and samples to consider. Snaptron can score junctions according to tissue specificity or other criteria, and can score samples according to the relative frequency of different splicing patterns. We describe the software and outline biological questions that can be explored with Snaptron queries.

Availability and implementation
Documentation is at http://snaptron.cs.jhu.edu. Source code is at https://github.com/ChristopherWilks/snaptron and https://github.com/ChristopherWilks/snaptron-experiments with a CC BY-NC 4.0 license.

Supplementary information
Supplementary data are available at Bioinformatics online.
From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century
Authors: Choudhuri Supratim , Patton Geoffrey W , Chanderbhan Ronald F , Mattia Antonia , Klaassen Curtis D 
Published: August 2017

Abstract
Toxicology has made steady advances over the last 60+ years in understanding the mechanisms of toxicity at an increasingly finer level of cellular organization. Traditionally, toxicological studies have used animal models. However, the general adoption of the principles of 3R (Replace, Reduce, Refine) provided the impetus for the development of in vitro models in toxicity testing. The present commentary is an attempt to briefly discuss the transformation in toxicology that began around 1980. Many genes important in cellular protection and metabolism of toxicants were cloned and characterized in the 80s, and gene expression studies became feasible, too. The development of transgenic and knockout mice provided valuable animal models to investigate the role of specific genes in producing toxic effects of chemicals or protecting the organism from the toxic effects of chemicals. Further developments in toxicology came from the incorporation of the tools of “omics” (genomics, proteomics, metabolomics, interactomics), epigenetics, systems biology, computational biology, and in vitro biology. Collectively, the advances in toxicology made during the last 30–40 years are expected to provide more innovative and efficient approaches to risk assessment. A goal of experimental toxicology going forward is to reduce animal use and yet be able to conduct appropriate risk assessments and make sound regulatory decisions using alternative methods of toxicity testing. In that respect, Tox21 has provided a big picture framework for the future. Currently, regulatory decisions involving drugs, biologics, food additives, and similar compounds still utilize data from animal testing and human clinical trials. In contrast, the prioritization of environmental chemicals for further study can be made using in vitro screening and computational tools.