bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt3a Neutralization Enhances T-cell Responses through Indirect Mechanisms and Restrains Tumor Growth
Authors: Pacella Ilenia , Cammarata Ilenia , Focaccetti Chiara , Miacci Stefano , Gulino Alessandro , Tripodo Claudio , Ravà Micol , Barnaba Vincenzo , Piconese Silvia 
Published: July 2018

AbstractThe Wnt/β-catenin pathway regulates T-cell functions, including the repression of effector functions to the advantage of memory development via Tcf1. In a companion study, we demonstrate that, in human cancers, Wnt3a/β-catenin signaling maintains tumor-infiltrating T cells in a partially exhausted status. Here, we have investigated the effects of Wnt3a neutralization in vivo in a mouse tumor model. Abundant Wnt3a was released, mostly by stromal cells, in the tumor microenvironment. We tested whether Wnt3a neutralization in vivo could rescue the effector capacity of tumor-infiltrating T cells, by administering an antibody to Wnt3a to tumor-bearing mice. This therapy restrained tumor growth and favored the expansion of tumor antigen–specific CD8+ effector memory T cells with increased expression of Tbet and IFNγ and reduced expression of Tcf1. However, the effect was not attributable to the interruption of T-cell–intrinsic β-catenin signaling, because Wnt3a/β-catenin activation correlated with enhanced, not reduced, T-cell effector functions both ex vivo and in vitro. Adoptively transferred CD8+ T cells, not directly exposed to the anti-Wnt3a antibody but infiltrating previously Wnt3a-neutralized tumors, also showed improved functions. The rescue of T-cell response was thus secondary to T-cell–extrinsic changes that likely involved dendritic cells. Indeed, tumor-derived Wnt3a strongly suppressed dendritic cell maturation in vitro, and anti-Wnt3a treatment rescued dendritic cell activities in vivo. Our results clarify the function of the Wnt3a/β-catenin pathway in antitumor effector T cells and suggest that Wnt3a neutralization might be a promising immunotherapy for rescuing dendritic cell activities. Cancer Immunol Res; 6(8); 953–64. ©2018 AACR.
Mechanisms by Which Dendritic Cells Present Tumor Microparticle Antigens to CD8+ T Cells
Authors: Ma Jingwei , Wei Keke , Zhang Huafeng , Tang Ke , Li Fei , Zhang Tianzhen , Liu Junwei , Xu Pingwei , Yu Yuandong , Sun Weiwei , Zhu LiYan , Chen Jie , Zhou Li , Liang Xiaoyu , Lv Jiadi , Fiskesund Roland , Liu Yuying , Huang Bo 
Published: July 2018

Abstract
Tumor cell–derived microparticles (T-MP) contain tumor antigen profiles as well as innate signals, endowing them with vaccine potential; however, the precise mechanism by which DCs present T-MP antigens to T cells remains unclear. Here, we show that T-MPs activate a lysosomal pathway that is required for DCs presenting tumor antigens of T-MPs. DCs endocytose T-MPs to lysosomes, where T-MPs increase lysosomal pH from 5.0 to a peak of 8.5 via NOX2-catalyzed reactive oxygen species (ROS) production. This increased pH, coupled with T-MP–driven lysosomal centripetal migration, promotes the formation of MHC class I–tumor antigen peptide complexes. Concurrently, endocytosis of T-MPs results in the upregulation of CD80 and CD86. T-MP–increased ROS activate lysosomal Ca2+ channel Mcoln2, leading to Ca2+ release. Released Ca2+ activates transcription factor EB (TFEB), a lysosomal master regulator that directly binds to CD80 and CD86 promoters, promoting gene expression. These findings elucidate a pathway through which DCs efficiently present tumor antigen from T-MPs to CD8+ T cells, potentiating T-MPs as a novel tumor cell–free vaccine with clinical applications. Cancer Immunol Res; 6(9); 1057–68. ©2018 AACR.
Response to Immune Checkpoint Inhibition in Two Patients with Alveolar Soft-Part Sarcoma
Authors: Lewin Jeremy , Davidson Scott , Anderson Nathaniel D. , Lau Beatrice Y. , Kelly Jacalyn , Tabori Uri , Salah Samer , Butler Marcus O. , Aung Kyaw L. , Shlien Adam , Dickson Brendan C. , Abdul Razak Albiruni R. 
Published: July 2018

Abstract
Alveolar soft-part sarcoma (ASPS) is a morphologically distinctive mesenchymal tumor characterized by a canonical ASPL–TFE3 fusion product. In the metastatic setting, standard cytotoxic chemotherapies are typically ineffective. Studies have suggested modest clinical response to multitargeted receptor tyrosine kinase inhibitors. Here, we report sustained partial responses in two patients with immune checkpoint inhibition treated with either durvalumab (anti–PD-L1) alone or in combination with tremelimumab (anti–CTLA-4), which appeared unrelated to tumor immune infiltrates or mutational burden. Genomic analysis of these patients, and other cases of ASPS, demonstrated molecular mismatch-repair deficiency signatures. These findings suggest that immune checkpoint blockade may be a useful therapeutic strategy for ASPS. Cancer Immunol Res; 6(9); 1001–7. ©2018 AACR.
Expanded CD56superbrightCD16+ NK Cells from Ovarian Cancer Patients Are Cytotoxic against Autologous Tumor in a Patient-Derived Xenograft Murine Model
Authors: Poznanski Sophie M. , Nham Tina , Chew Marianne V. , Lee Amanda J. , Hammill Joanne A. , Fan Isabella Y. , Butcher Martin , Bramson Jonathan L. , Lee Dean A. , Hirte Hal W. , Ashkar Ali A. 
Published: July 2018

Abstract
Natural killer (NK) cells are useful for cancer immunotherapy and have proven clinically effective against hematologic malignancies. However, immunotherapies for poor prognosis solid malignancies, including ovarian cancer, have not been as successful due to immunosuppression by solid tumors. Although rearming patients' own NK cells to treat cancer is an attractive option, success of that strategy is limited by the impaired function of NK cells from cancer patients and by inhibition by self-MHC. In this study, we show that expansion converts healthy donor and immunosuppressed ovarian cancer patient NK cells to a cytotoxic CD56superbrightCD16+ subset with activation state and antitumor functions that increase with CD56 brightness. We investigated whether these expanded NK cells may overcome the limitations of autologous NK cell therapy against solid tumors. Peripheral blood- and ascites-derived NK cells from ovarian cancer patients were expanded and then adoptively transferred into cell-line and autologous patient-derived xenograft models of human ovarian cancer. Expanded ovarian cancer patient NK cells reduced the burden of established tumors and prolonged survival. These results suggest that CD56bright NK cells harbor superior antitumor function compared with CD56dim cells. Thus, NK cell expansion may overcome limitations on autologous NK cell therapy by converting the patient's NK cells to a cytotoxic subset that exerts a therapeutic effect against autologous tumor. These findings suggest that the value of expanded autologous NK cell therapy for ovarian cancer and other solid malignancies should be clinically assessed. Cancer Immunol Res; 6(10); 1174–85. ©2018 AACR.
ПРИХИЛЬНІСТЬ ДО ДОВГОТРИВАЛОЇ ВТОРИННОЇ ПРОФІЛАКТИКИ ПІСЛЯ ІНФАРКТУ МІОКАРДА
Authors: Hrebenyk M. V. , Levchyk I. V. 
Published: July 2018

Мета: оцінити прихильність до довготривалого лікування хворих після інфаркту міокарда (ІМ) залежно від реваскуляризації.Матеріали і методи. Обстежено 152 хворих із інфарктом міокарда, яких поділено на групи: 1а – прихильні (за анкетуванням Morisky-Green), із перкутанним коронарним втручанням (ПКВ) (n=47), 1б – прихильні, без ПКВ (n=30); 2а – не прихильні, із ПКВ (n=25), 2б – не прихильні, без ПКВ (n=50). Оцінювали зміни клініко-лабораторних та ехокардіографічних значень.Результати. У всіх хворих не зменшувався індекс маси тіла, а 2/3 курять і досі. Серед осіб 1а групи, на відміну від решти груп, знижувались частота серцевих скорочень (ЧСС), систолічний та діастолічний артеріальний тиск (САТ та ДАТ), глюкоза та холестерол, і через 24 місяці зміни утримувались. Також у них достовірно змінювалась геометрія серця.Висновки. Після ІМ зберігається частковий комплаєнс. У цих пацієнтів встановлено дуже низьку прихильність до немедикаментозних методів вторинної профілактики та заходів із корекції факторів ризику і модифікації стилю життя, що зумовлює необхідність оптимізації організаційно-профілактичних заходів на амбулаторному етапі.
ІНФОРМАЦІЙНЕ ЗАБЕЗПЕЧЕННЯ СФЕРИ ОХОРОНИ ЗДОРОВ’Я УКРАЇНИ ПРОДУКЦІЄЮ, ОТРИМАНОЮ ПРИ ВИКОНАННІ НАУКОВИХ РОЗРОБОК УСТАНОВАМИ ГАЛУЗІ У 2014–2016 рр.
Authors: Zakrutko L. I. , Gorban Ye. M. , Bilan L. G. , Movchun N. O. 
Published: July 2018

Мета: дослідити інформаційне забезпечення сфери охорони здоров’я України продукцією, отриманою при виконанні наукових розробок установами галузі у 2014–2016 рр.Матеріали і методи. Проведено ретроспективний аналіз реєстрів галузевих нововведень, переліку наукової (науково-технічної) продукції, призначеної для впровадження досягнень медичної науки у сферу охорони здоров’я, звітів установ щодо моніторингу впровадження наукової (науково-технічної) продукції протягом 2014–2016 років з моменту її створення.Результати. За період 2014–2016 рр. переважну більшість нововведень для впровадження у сферу охорони здоров’я було запропоновано ВМНЗ галузі. Кваліметрична характеристика нововведень за назвою лікарської (провізорської) спеціальності у 2016 р. показала, що високе кількісне співвідношення припадає на 10 спеціальностей (22,2 % від загальної кількості проаналізованих спеціальностей). Найбільше запропоновано у 2016 р. нові способи лікування (34,8 %) та нові способи діагностики (28,1 %) серед загальної кількості нововведень.Висновки. Результати аналізу щорічної динаміки запропонованих для впровадження в практику охорони здоров’я України інновацій протягом 2014–2016 рр. свідчить, що за рядом напрямів розробки відповідають нагальним пріоритетам сфери охорони здоров’я.
Iron Overload Exacerbates the Risk of Hemorrhagic Transformation After tPA (Tissue-Type Plasminogen Activator) Administration in Thromboembolic Stroke Mice
Authors: García-Yébenes Isaac , García-Culebras Alicia , Peña-Martínez Carolina , Fernández-López David , Díaz-Guzmán Jaime , Negredo Pilar , Avendaño Carlos , Castellanos Mar , Gasull Teresa , Dávalos Antoni , Moro María A. , Lizasoain Ignacio 
Published: July 2018

Background and Purpose—
Recanalization with tPA (tissue-type plasminogen activator) is the only pharmacological therapy available for patients with ischemic stroke. However, the percentage of patients who may receive this therapy is limited by the risk of hemorrhagic transformation (HT)—the main complication of ischemic stroke. Our aim is to establish whether iron overload affects HT risk, to identify mechanisms that could help to select patients and to prevent this devastating complication.

Methods—
Mice fed with control or high-iron diet were subjected to thromboembolic stroke, with or without tPA therapy at different times after occlusion. Blood samples were collected for determination of malondialdehyde, matrix metalloproteinases, and fibronectin. Brain samples were collected 24 hours after occlusion to determine brain infarct and edema size, hemorrhage extension, IgG extravasation, and inflammatory and oxidative markers (neutrophil infiltration, 4-hydroxynonenal, and matrix metalloproteinase-9 staining).

Results—
Despite an increased rate of recanalization, iron-overload mice showed less neuroprotection after tPA administration. Importantly, iron overload exacerbated the risk of HT after early tPA administration, accelerated ischemia-induced serum matrix metalloproteinase-9 increase, and enhanced basal serum lipid peroxidation. High iron increased brain lipid peroxidation at most times and neutrophil infiltration at the latest time studied.

Conclusions—
Our data showing that iron overload increases the death of the compromised tissues, accelerates the time of tPA-induced reperfusion, and exacerbates the risk of HT may have relevant clinical implications for a safer thrombolysis. Patients with stroke with iron overload might be at high risk of HT after fibrinolysis, and, therefore, clinical studies must be performed to confirm our results.
When Neglect Isn’t Working Anymore: The Unlikely Success of the Tuxedo Party
Authors: Cronin Keri , Fowler Tim , Hagar Douglas 
Published: July 2018

Abstract
In 2012, Tuxedo Stan, a domestic long-hair cat, “ran for mayor” of Halifax, Nova Scotia, and a year later Stan’s brother, Earl Grey, “ran for premier” of Nova Scotia. What separated Stan and Earl Grey (who ran under the banner of the Tuxedo Party) from other politically minded felines was that the Tuxedo Party campaigns were not stunt or joke campaigns. While the cats could obviously not take office, the two campaigns were nonetheless political advocacy campaigns, with a clearly articulated message to make life better for feral and stray cats. This paper argues that the Tuxedo Party successfully elevated the issue onto the political agenda through their savvy mix of social media, and the use of positive imagery of cats in their campaigns.
Afro-Pessimism and the (Un)Logic of Anti-Blackness
Authors: Olaloku-Teriba Annie 
Published: July 2018

AbstractIn the coming months and years, the left faces a historic juncture. On the one hand, racist violence is on the rise across the West, and the political class seems intent on mobilising both overt and subtle racism. On the other hand, strategies of anti-racist organising, which have developed on both sides of the Atlantic, have reached a theoretical impasse. I argue that now, more than ever, a serious project of historical and intellectual retrieval is necessary. This article interrogates the theoretical limitations of ‘anti-blackness’ as an analysis of racialised oppression. Through the thought of Frantz Fanon and Steve Biko, among others, I argue that theories of ‘anti-blackness’, specifically those rooted in Afro-pessimism, are predicated on a theoretical shift away from relational social theory to identitarian essentialism which obscures, rather than illuminates, the processes of racialisation which undergird racial oppression.
Perceived Barriers to Physical Activity Among Low-Income Latina Women at Risk for Type 2 Diabetes
Authors: Chang Claire , Khurana Sonia , Strodel Rachel , Camp Anne , Magenheimer Elizabeth , Hawley Nicola 
Published: July 2018

Purpose The purpose of this study was to examine perceived barriers to physical activity among low-income Latina women who were at risk for type 2 diabetes, as well as the demographic factors that influence these perceived barriers. Methods Recruited in the waiting room of a community health center in a low-income neighborhood (n = 160), Latina women between the ages of 18 and 49 years completed a survey to assess demographic characteristics and perceived barriers to physical inactivity. Descriptive statistics, chi-square tests, and multivariate regression analyses were conducted to identify barriers to physical activity and the associations between demographic factors and perceived barriers. Results The most commonly perceived barriers to physical activity in the study sample were lack of willpower and lack of energy. After adjusting for other characteristics, overweight/obese participants were more likely than women of normal weight to report social influence and fear of injury as important barriers to exercise. In addition, women whose preferred language was Spanish were more likely than women whose preferred language was English to perceive lack of time, and social influence as important barriers. Conclusions The effective encouragement of physical activity among Latina women at risk for type 2 diabetes must address the perceived barriers of lack of willpower and lack of energy. Although all women at risk for type 2 diabetes could benefit from counseling and other strategies to encourage physical activity, these efforts should be targeted toward Spanish-speaking overweight/obese women, who are more likely to perceive barriers to exercise.
Predictors of Adverse Outcomes in Free Flap Reconstruction: A Single‐Institution Experience
Authors: Farquhar Douglas R. , Masood Maheer M. , Pappa Andrew K. , Patel Samip N. , Hackman and Trevor G. 
Published: July 2018

ObjectiveUnderstanding the independent predictors of poor outcomes in free flap surgery is essential for patient selection. We aim to determine the independent predictors of major complications, flap survival, and extended hospital stays.Study DesignRetrospective cohort study.SettingTertiary medical center.Subjects and MethodsWe reviewed medical records from all vascularized tissue transfers in the head and neck between 2007 and 2014 at our institution. We recorded demographics, medical comorbidities, disease characteristics, flap characteristics, and intraoperative events. We defined outcomes as major complications in the 30‐day postoperative period, flap death or partial flap survival, and a length of stay ≥14 days. We used bivariate and multivariate methods to test for associations.ResultsOf 170 free flap operations, 44% had major complications; 11% fully or partially failed; and 27% required an extended hospital stay. Independent predictors of major complications were age ≥60 years (odds ratio [OR], 3.7; P =. 001), revision surgery (OR, 3.5; P =. 004), and a prior neck dissection (OR, 3.5; P =. 004). Independent predictors of flap failure were revision surgery (OR, 4.1, P =. 01) and the use of a plate (OR, 3.7; P =. 03). Revision surgery was independently associated with a longer stay (OR, 3.0; P =. 01), and the use of a radial forearm flap was associated with a shorter stay (OR, 0.3, P =. 047).ConclusionThese results underscore that caution is warranted in revision flap surgery, patients with prior neck operations, and patients aged ≥60 years.
Traditional and augmented reality mirror therapy for patients with chronic phantom limb pain (PACT study): results of a three-group, multicentre single-blind randomized controlled trial
Authors: Rothgangel Andreas , Braun Susy , Winkens Bjorn , Beurskens Anna , Smeets Rob 
Published: July 2018

Objective: To compare the effects of traditional mirror therapy (MT), a patient-centred teletreatment (PACT) and sensomotor exercises without a mirror on phantom limb pain (PLP). Design: Three-arm multicentre randomized controlled trial. Setting: Rehabilitation centres, hospital and private practices. Subjects: Adult patients with unilateral lower limb amputation and average PLP intensity of at least 3 on the 0–10 Numeric Rating Scale (NRS). Interventions: Subjects randomly received either four weeks of traditional MT followed by a teletreatment using augmented reality MT, traditional MT followed by self-delivered MT or sensomotor exercises of the intact limb without a mirror followed by self-delivered exercises. Main measures: Intensity, frequency and duration of PLP and patient-reported outcomes assessing limitations in daily life at baseline, 4 weeks, 10 weeks and 6 months. Results: In total, 75 patients received traditional MT ( n = 25), teletreatment ( n = 26) or sensomotor exercises ( n = 24). Mean (SD) age was 61.1 (14.2) years and mean (SD) pain intensity was 5.7 (2.1) on the NRS. Effects of MT at four weeks on PLP were not significant. MT significantly reduced the duration of PLP at six months compared to the teletreatment ( P = 0.050) and control group ( P = 0.019). Subgroup analyses suggested significant effects on PLP in women, patients with telescoping and patients with a motor component in PLP. The teletreatment had no additional effects compared to self-delivered MT at 10 weeks and 6 months. Conclusion: Traditional MT over four weeks was not more effective than sensomotor exercises without a mirror in reducing PLP, although significant effects were suggested in some subgroups.
Long-term effects of vestibular rehabilitation and head-mounted gaming task procedure in unilateral vestibular hypofunction: a 12-month follow-up of a randomized controlled trial
Authors: Viziano Andrea , Micarelli Alessandro , Augimeri Ivan , Micarelli Domenico , Alessandrini Marco 
Published: July 2018

Objective: To investigate the long-term effects of adding virtual reality–based home exercises to vestibular rehabilitation in people with unilateral vestibular hypofunction. Design: Follow-up otoneurological examination in two randomized groups following a previous one-month trial. Setting: Tertiary rehabilitation center. Subjects: A total of 47 patients with unilateral vestibular hypofunction, one group ( n = 24) undergoing conventional vestibular rehabilitation and the other one ( n = 23) implementing, in addition, head-mounted gaming home exercises, 20 minutes per day for one month. Interventions: One year after completing rehabilitation, patients underwent testing with static posturography, video head impulse test, self-report questionnaires, and a performance measure. Main measures: Vestibulo-ocular reflex gain, posturographic parameters such as length, surface, and fast Fourier transform power spectra, self-report, and gait performance measure scores. Results: Vestibulo-ocular reflex gain was significantly better with respect to pretreatment in both groups. The mixed-method group showed significantly higher gain scores: mean (standard deviation (SD)) at 12 months was 0.71 (0.04), versus 0.64 (0.03) for the vestibular rehabilitation–only group ( P < 0.001). Accordingly, some classical posturography scores such as surface with eyes open and length with eyes closed and low-frequency power spectra were significantly different between groups, with the virtual reality group showing improvement ( P < 0.001). Self-report measures were significantly better in both groups compared to pretreatment, with significant improvement in the mixed-method group as compared to conventional rehabilitation alone: Dizziness Handicap Inventory mean total score was 24.34 (2.8) versus 35.73 (5.88) with a P-value <0.001. Conclusion: Results suggest that head-mounted gaming home exercises are a viable, effective, additional measure to improve long-term vestibular rehabilitation outcomes.
The levels of NF-κB p50 and NF-κB p65 play a role in thyroid carcinoma malignancy in vivo
Authors: Le Fei , Zhang Jing-Yu , Liu Wei , Huang Xian-Ming , Luo Wen-Zheng 
Published: July 2018

Background To investigate the relationship between the levels of nuclear factor (NF)-κB p50 and NF-κB p65 and tumour characteristics in patients with thyroid carcinoma. Methods This prospective study enrolled consecutive patients with thyroid carcinoma. Tumour samples were collected and the levels of NF-κB p50 and NF-κB p65 protein and mRNA were measured using immunohistochemistry and quantitative real-time reverse transcription–polymerase chain reaction (qRT–PCR). Results A total of 73 patients with thyroid carcinoma were included in the study (20 males; 53 females; mean ± SD age, 44.8 ± 12.7 years, range, 18–76 years). There were no significant differences in sex, age and pathological type between the NF-κB p50 positive group and the NF-κB p50 negative group, but tumour diameter and lymph node metastasis were significantly higher in the NF-κB p50 positive group compared with the NF-κB p50 negative group. Similar findings were observed for NF-κB p65. The levels of NF-κB p50 were positively correlated with NF-κB p65 in samples of thyroid carcinoma ( rs = 0.653). Conclusion The levels of NF-κB p50 and NF-κB p65 in samples of thyroid carcinoma were positively associated with tumour diameter and the presence of lymph node metastasis.