bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of expanded diagnostic criteria for avoidant/restrictive food intake disorder on clinical comparisons with anorexia nervosa
Authors: Becker Kendra R. , Keshishian Ani C. , Liebman Rachel E. , Coniglio Kathryn A. , Wang Shirley B. , Franko Debra L. , Eddy Kamryn T. , Thomas Jennifer J. 
Published: December 2018

AbstractObjectiveAvoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) are restrictive eating disorders. There is a proposal before the American Psychiatric Association to broaden the current DSM‐5 criteria for ARFID, which currently require dietary intake that is inadequate to support energy or nutritional needs. We compared the clinical presentations of ARFID and AN in an outpatient sample to determine how a more inclusive definition of ARFID, heterogeneous for age and weight status, is distinct from AN.MethodsAs part of standard care, 138 individuals with AN or ARFID completed an online assessment battery and agreed to include their responses in research.ResultsIndividuals with ARFID were younger, reported earlier age of onset, and had higher percent median BMI (%mBMI) than those with AN (all ps < .001). Individuals with ARFID scored lower on measures of eating pathology, depression, anxiety, and clinical impairment (all ps < .05), but did not differ from those with AN on restrictive eating (p = .52), and scored higher on food neophobia (p < .001).DiscussionAllowing psychosocial impairment to be sufficient for an ARFID diagnosis resulted in a clinical picture of ARFID such that %mBMI was higher (and in the normal range) compared with AN. Differences in gender distribution, age, and age of onset remained consistent with previous research. Both groups reported similar levels of dietary restriction, although ARFID can be distinguished by relatively higher levels of food neophobia. Currently available measures of eating pathology may capture certain ARFID symptoms, but highlight the need for measures of impairment relative to ARFID.
Transcriptional regulation of the endocannabinoid system in a rat model of binge‐eating behavior reveals a selective modulation of the hypothalamic fatty acid amide hydrolase gene
Authors: Pucci Mariangela , Micioni Di Bonaventura Maria Vittoria , Zaplatic Elizabeta , Bellia Fabio , Maccarrone Mauro , Cifani Carlo , D'Addario Claudio 
Published: December 2018

AbstractObjectiveBinge‐eating episodes are recurrent and are defining features of several eating disorders. Thus binge‐eating episodes might influence eating disorder development of which exact underlying mechanisms are still largely unknown.MethodsHere we focused on the transcriptional regulation of the endocannabinoid system, a potent regulator of feeding behavior, in relevant rat brain regions, using a rat model in which a history of intermittent food restriction and a frustration stress induce binge‐like palatable food consumption.ResultsWe observed a selective down‐regulation of fatty acid amide hydrolase (faah) gene expression in the hypothalamus of rats showing the binge‐eating behavior with a consistent reduction in histone 3 acetylation at lysine 4 of the gene promoter. No relevant changes were detected for any other endocannabinoid system components in any brain regions under study, as well as for the other epigenetic mechanisms investigated (DNA methylation and histone 3 lysine 27 methylation) at the faah gene promoter.DiscussionOur findings suggest that faah transcriptional regulation is a potential biomarker of binge‐eating episodes, with a relevant role in the homeostatic regulation of food intake.
Activation of integrated stress response pathway regulates IL‐1β production through posttranscriptional and translational reprogramming in macrophages
Authors: Naz Saima , Battu Srikanth , Khan Rafiq Ahmad , Afroz Sumbul , Giddaluru Jeevan , Vishwakarma Sandeep Kumar , Satti Vishnupriya , Habeeb Md Aejaz , Khan Aleem Ahmed , Khan Nooruddin 
Published: December 2018

AbstractImmune cells sense and programme its cellular machinery appropriately to the environmental changes through the activation of cytoprotective adaptive pathway so‐called the “integrated stress response (ISR)”. However, the mechanisms implicated in ISR‐induced protective responses are poorly understood. Here, we show that ISR activation by arsenite (Ar) results in suppression of IL‐1β production in macrophages and inhibition of DSS‐induced colitis in a murine model through a novel posttranscriptional and translation regulatory (PTR) mechanism. Ar triggers PTR events through eIF2α‐phosphorylation, which results in the attenuation of active polysome formation leading to the accumulation of translationally stalled IL‐1β mRNAs. Translationally stalled IL‐1β mRNAs recruit RNA‐binding proteins (TIA‐1/TIAR), resulting in the formation of RBP‐RNA complexes known as stress granules (SGs). The SGs bound IL‐1β mRNAs might undergo degradation through induction of autophagy. Also, we show that Ar posttranslationally impairs processing and secretion of IL‐1β by diminishing inflammasome activation. Altogether, this study unveils a novel mechanism of IL‐1β regulation and further suggests that pharmacological activation of cytoprotective ISR pathway might provide an effective therapeutic intervention against inflammatory diseases.
ID2 and ID3 are indispensable for Th1 cell differentiation during influenza virus infection in mice
Authors: Han Xiaojuan , Liu Hongtao , Huang Huarong , Liu Xinyuan , Jia Baoqian , Gao George Fu , Zhang Fuping 
Published: December 2018

AbstractAntigen‐specific Th1 cells could be a passage to the infection sites during infection to execute effector functions, such as help CD8+ T cells to localize in these sites by secretion of anti‐viral cytokines‐IFN‐γ or direct cytotoxicity of antigen‐bearing cells. However, the molecular components that modulate Th1 cell differentiation and function in response to viral infection remain incompletely understood. Here, we reported that both inhibitor of DNA binding 3(Id3) protein and inhibitor of DNA binding 2(Id2) protein promoted Th1 cell differentiation. Depletion of Id3 or Id2 led to severe defect of Th1 cell differentiation during influenza virus infection. Whereas depletion of both Id3 and Id2 in CD4+ T cells restrained Th1 cell differentiation to a greater extent, indicating that Id3 and Id2 nonredundantly regulate Th1 cell differentiation. Moreover, deletion of E‐proteins, the antagonists of Id proteins, greatly enhanced Th1 cell differentiation. Mechanistic study indicated that E‐proteins suppressed Th1 cell differentiation by directly binding to the regulatory elements of Th1 cell master regulator T‐bet and regulate T‐bet expression. Thus, our findings identified Id‐protein's importance for Th1 cells and clarified the nonredundant role of Id3 and Id2 in regulating Th1 cell differentiation, providing novel insight that Id3‐Id2‐E protein axis are essential for Th1 cell polarization.
High‐dimensional single‐cell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis
Authors: Fuchs Sebastian , Sawas Nadia , Staedler Nicolas , Schubert David A. , D'Andrea Annalisa , Zeiser Robert , Piali Luca , Hruz Petr , Frei Andreas P. 
Published: December 2018

AbstractImmune checkpoints are regulators of immune cells and play key roles in the modulation of immune responses. The role of checkpoints in autoimmune disease is poorly understood but likely to be central since checkpoint inhibition during cancer treatment can cause autoimmunity. We generated a high‐dimensional single‐cell proteomics data set from PBMCs of healthy individuals and patients with ulcerative colitis (UC) by mass cytometry, enabling systems‐wide analyses of immune cell frequencies and cell type‐specific expression patterns of 12 immune checkpoints. Subtle but significant changes in immune cell frequencies and checkpoint expression were observed between UC patients on different treatment regimens and between patients and healthy controls. Most strikingly, UC patients showed a reduced number of peripheral NK‐cells and those cells showed an altered phenotype including increased TIGIT expression. Based on these results, we modulated NK‐cell function ex vivo through targeting of TIGIT pathway members. In summary, we describe a pattern of changes in immune cell abundance and checkpoint expression as a basis for UC patient stratification and we show modulation of a corresponding immune cell subset through checkpoint targeting. Our approach can be used for the identification of pathogenic immune cell subsets and guide target selection in autoimmunity and chronic inflammation.
Social cure and social curse: Social identity resources and adjustment to acquired brain injury
Authors: Muldoon Orla T. , Walsh R. Stephen , Curtain Mariah , Crawley Lorraine , Kinsella Elaine L. 
Published: December 2018

AbstractThere is increasing evidence that identification with social groups can protect and enhance health, establishing a kind of ‘social cure’. However, for those affected by chronic or disabling conditions such as acquired brain injury (ABI), their identity may also represent a burden, a form of ‘social curse’. The present study explored the identity benefits and burdens available to 15 participants living with ABI using semi‐structured interviews. The qualitative data was then analysed systematically using thematic analysis. The findings highlight social identity changes as central to the experience of brain injury. Participants reported changes in their social networks and social group memberships after injury. Identity loss and reduced social support were described as disabling. Engagement in meaningful group activity with others affected by ABI and access to affected peers enabled new group‐based resources such as social support. In this way, group activity can be seen as a form of identity enactment that can drive social cure effects. Similarly, adaptation to life after injury was demonstrably linked to social identity processes pointing to the importance of a social cure approach to rehabilitation.
An automated food protein isolation approach on preparative scale by two‐dimensional liquid chromatography with active modulation interface
Authors: Melfi Maria Teresa , Nardiello Donatella , Natale Anna , Quinto Maurizio , Centonze Diego 
Published: December 2018

AbstractIn this work, an automated 2D‐LC approach for protein isolation from egg samples on preparative scale is proposed. The method is based on the use of a C18 guard column installed in a switching valve to focus the proteins coming from the first dimension column, before their elution in the second column. For the first dimension separation, a size‐exclusion column, packed with 3 μm ultrapure silica particles was used. An RP column based on core‐shell technology was used for the second dimension separation. A standard mixture of BSA, β‐lactoglobulin, and glucose oxidase, chosen as a protein model system, was used to optimize the chromatographic separation conditions. The fully automated workflow allowed to isolate, in a single‐chromatographic analysis, a protein amount of 50 μg for each peak fraction, with a total time of 15 min for the first separation and additional 30 min of the second separation for each trapped protein. The final aim was the development of proper analytical tools for protein isolation from foodstuffs to be used for the molecular identification by MS, as well as for biotherapeutic uses, allergy testing, and large‐scale investigations in biological systems.
Basal cell carcinomas developing independently from BAP1‐tumor predisposition syndrome in a patient with bilateral uveal melanoma
Authors: Melzer Charlotte , Sharma Amit , Peters Sophia , Aretz Stefan , Biswas Arijit , Holz Frank G. , Loeffler Karin U. , Herwig‐Carl Martina C. 
Published: December 2018

AbstractBasal cell carcinomas (BCC) have been recently included into the spectrum of BAP1‐tumor predisposition syndrome (TPDS). Uveal melanoma (UM) is also a tumor often observed in patients with this hereditary tumor syndrome, in particular bilateral UM is highly suspicious for BAP1‐TPDS although no patient has been reported yet. Based on our index patient with BAP1‐TPDS with bilateral UM (choroid OD, oculus dexter; iris OS, oculus sinister), several BCCs and thyroid cancer as well as a family history for cancer, this paper analyzes hints and pitfalls to diagnose this syndrome clinically and histologically. A previously undescribed germline variant, namely a heterozygous deletion of a single nucleotide on position 2001 (c.2001delG;p.[Thr668Profs*24] in exon 16 of the BAP1 gene), was identified. Structural changes in the C‐terminal of the BAP1 protein were observed by in silico analysis. While the excised iris melanoma showed loss of BAP1 nuclear staining by immunohistochemical staining, the BCCs of our patient (and in the control group, n = 13) were BAP1 positive. Genetic analysis of the BCC of the ocular adnexae confirmed a remaining intact BAP1 copy. The constellation of (bilateral) UM in combination with BCC should raise suspicion for a BAP1‐TPDS. As our BCCs probably developed independently from the BAP1‐TPDS and UMs frequently show loss of nuclear BAP1 staining, genetic analysis is mandatory to diagnose this syndrome.
Role of miRNAs in immune responses and immunotherapy in cancer
Authors: Cortez Maria Angelica , Anfossi Simone , Ramapriyan Rishab , Menon Hari , Atalar Semra Cemre , Aliru Maureen , Welsh James , Calin George A. 
Published: December 2018

AbstractIn the past decade, the study of mechanisms of cancer immunity has seen a prominent boom, which paralleled the increased amount of research on the clinical efficacy of immune checkpoint blockade in several lethal types of cancers. This conspicuous effort has led to the development of successful immunotherapy treatment strategies, whose medical impact has been recognized by the awarding of 2018 Nobel Prize in Physiology or Medicine to the two pioneers of check point inhibitor research, Tasuku Honjo and James Allison. Despite these promising achievements, the differences in the clinical response rate in different cancer patients and the high risk of toxicity of immune‐based therapies represent crucial challenges. More remarkably, the causes responsible for different outcome (success vs failure) in patients with tumor having same histotype and clinical characteristics remain mostly unknown. MicroRNAs (miRNAs), small regulatory noncoding RNA molecules representing the most studied component of the dark matter of the human genome, are involved in the regulation of many pathways of cancer and immune cells. Therefore, understanding the role of miRNAs in controlling cancer immunity is necessary, as it can contribute to reveal mechanisms that can be modulated to improve the success of immunetherapy in cancer patients. Here, we discuss the latest findings on immune pathways regulated by miRNAs in cancer, miRNA‐mediated regulation of immune cells in the tumor microenvironment, and miRNAs as potential target for immunotherapies.
Non‐leukemic pediatric mixed phenotype acute leukemia/lymphoma: Genomic characterization and clinical outcome in a prospective trial for pediatric lymphoblastic lymphoma
Authors: Martin‐Guerrero Idoia , Salaverria Itziar , Burkhardt Birgit , Chassagne‐Clement Catherine , Szczepanowski Monika , Bens Susanne , Klapper Wolfram , Zimmermann Martin , Kabickova Edita , Bertrand Yves , Reiter Alfred , Siebert Reiner , Oschlies Ilske 
Published: December 2018

AbstractRare cases of hematological precursor neoplasms fulfill the diagnostic criteria of mixed phenotype acute leukemia (MPAL), characterized by expression patterns of at least two hematopoietic lineages, for which a highly aggressive behavior was reported. We present a series of 11 pediatric non‐leukemic MPAL identified among 146 precursor lymphoblastic lymphomas included in the prospective trial Euro‐LBL 02. Paraffin‐embedded biopsies of 10 cases were suitable for molecular analyses using OncoScan assay (n = 7), fluorescence in situ hybridization (FISH; n = 7) or both (n = 5). Except for one case with biallelic KMT2A (MLL) breaks, all cases analyzed by FISH lacked the most common translocations defining molecular subsets of lymphoblastic leukemia/lymphomas. Two non‐leukemic B‐myeloid MPALs showed the typical genomic profile of hyperdiploid precursor B‐cell lymphoblastic leukemia with gains of chromosomes 4, 6, 10, 14, 18, and 21. One B‐T MPAL showed typical aberrations of T‐cell lymphoblastic lymphoma, such as copy number neutral loss of heterozygosity (CNN‐LOH) at 9p targeting a 9p21.3 deletion of CDKN2A and 11q12.2‐qter affecting the ATM gene. ATM was also mutated in a T‐myeloid MPAL case with additional loss at 7q21.2‐q36.3 and mutation of NRAS, two alterations common in myeloid disorders. No recurrent regions of CNN‐LOH were observed. The outcome under treatment was good with all patients being alive in first complete remission after treatment according to a protocol for precursor lymphoblastic lymphoma (follow‐up 3‐10 years, median: 4.9 years). In summary, the present series of non‐leukemic MPALs widely lacked recurrently reported translocations in lymphoid/myeloid neoplasias and showed heterogeneous spectrum of chromosomal imbalances.
Spinal IL‐36γ/IL‐36R participates in the maintenance of chronic inflammatory pain through astroglial JNK pathway
Authors: Li Qian , Liu Shenbin , Li Lingling , Ji Xiaoli , Wang Min , Zhou Junmei 
Published: December 2018

AbstractEmerging evidence indicates that spinal neuroinflammation contributes to the maintenance of chronic inflammatory pain. IL‐36, as a novel member of the interleukin (IL)‐1 super‐family cytokines, plays an important role in inflammatory responses. The present study aimed to investigate the role of spinal IL‐36 and IL‐36 receptor (IL‐36R) signaling in the pathology of chronic inflammatory pain. IL‐36γ and IL‐36R, but not IL‐36α and IL‐36β, were persistently upregulated in the spinal cord of mice with intraplantar injections of complete Freund's adjuvant (CFA). Intrathecal administration of both IL‐36R antagonist (IL‐36Ra) and IL‐36γ siRNA significantly attenuated CFA‐induced chronic inflammatory pain behaviors. Furthermore, CFA‐induced IL‐36γ expression was mainly observed in spinal neurons whereas IL‐36R was primarily expressed in spinal astrocytes. Additionally, the intrathecal injection of IL‐36γ was sufficient to induce pain hypersensitivity and astrocyte activation in naive mice, and these effects could be inhibited by blocking c‐Jun N‐terminal kinase (JNK) phosphorylation. In vitro experiments also demonstrated that the IL‐36γ could induce astrocytic JNK activation and inflammatory cytokines release, which was mediated by IL‐36R. Finally, intrathecal injection of IL‐36γ‐activated astrocytes in a pJNK‐dependent manner induced mechanical allodynia and thermal hyperalgesia in naive mice. Collectively, these findings reveal that the neuronal/astrocytic interaction in the spinal cord by which neuronally produced IL‐36γ activates astrocytes via IL‐36R‐mediated JNK pathway is crucial for the maintenance of chronic inflammatory pain. Thus, IL‐36γ/IL‐36R‐mediated astrocyte signaling may be a suitable therapeutic target for chronic inflammatory pain.
Interleukin‐1beta released by microglia initiates the enhanced glutamatergic activity in the spinal dorsal horn during paclitaxel‐associated acute pain syndrome
Authors: Yan Xisheng , Li Fen , Maixner Dylan W. , Yadav Ruchi , Gao Mei , Ali Mourad Wagdy , Hooks Shelley B. , Weng Han‐Rong 
Published: December 2018

AbstractPatients receiving paclitaxel for cancer treatment often develop an acute pain syndrome (paclitaxel‐associated acute pain syndrome, P‐APS), which occurs immediately after paclitaxel treatment. Mechanisms underlying P‐APS remain largely unknown. We recently reported that rodents receiving paclitaxel develop acute pain and activation of spinal microglial toll like receptor 4 (TLR4) by paclitaxel penetrating into the spinal cord is a critical event in the genesis of P‐APS. Our current study dissected cellular and molecular mechanisms underlying the P‐APS. We demonstrated that bath‐perfusion of paclitaxel, at a concentration similar to that found in the cerebral spinal fluid in animals receiving i.v. paclitaxel (2 mg/kg), resulted in increased calcium activity in microglia instantly, and in astrocytes with 6 min delay. TLR4 activation in microglia by paclitaxel caused microglia to rapidly release interleukin‐1β (IL‐1β) but not tumor necrosis factor α, IL‐6, or interferon‐γ. IL‐1β release from microglia depended on capthepsin B. IL‐1β acted on astrocytes, leading to elevated calcium activity and suppressed glutamate uptake. IL‐1β also acted on neurons to increase presynaptic glutamate release and postsynaptic AMPA receptor activity in the spinal dorsal horn. Knockout of IL‐1 receptors prevented the development of acute pain induced by paclitaxel in mice. Our study indicates that IL‐1β is a crucial molecule used by microglia to alter functions in astrocytes and neurons upon activation of TLR4 in the genesis of P‐APS, and targeting the signaling pathways regulating the production and function of IL‐1β from microglia is a potential avenue for the development of analgesics for the treatment of P‐APS.
Preclinical stress originates in the rat optic nerve head during development of autoimmune optic neuritis
Authors: Stojic Aleksandar , Bojcevski Jovana , Williams Sarah K. , Bas‐Orth Carlos , Nessler Stefan , Linington Christopher , Diem Ricarda , Fairless Richard 
Published: December 2018

AbstractOptic neuritis is a common manifestation of multiple sclerosis, an inflammatory demyelinating disease of the CNS. Although it is the presenting symptom in many cases, the initial events are currently unknown. However, in the earliest stages of autoimmune optic neuritis in rats, pathological changes are already apparent such as microglial activation and disturbances in myelin ultrastructure of the optic nerves. αB‐crystallin is a heat‐shock protein induced in cells undergoing cellular stress and has been reported to be up‐regulated in both multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Therefore, we wished to investigate the timing and localization of its expression in autoimmune optic neuritis. Although loss of oligodendrocytes was not observed until the later disease stages accompanying immune cell infiltration and demyelination, an increase in oligodendrocyte αB‐crystallin was observed during the preclinical stages. This was most pronounced within the optic nerve head and was associated with areas of IgG deposition. Since treatment of isolated oligodendrocytes with sera from myelin oligodendrocyte glycoprotein (MOG)‐immunized animals induced an increase in αB‐crystallin expression, as did passive transfer of sera from MOG‐immunized animals to unimmunized recipients, we propose that the partially permeable blood–brain barrier of the optic nerve head may present an opportunity for blood‐borne components such as anti‐MOG antibodies to come into contact with oligodendrocytes as one of the earliest events in disease development.