bluuebunny/crossref_metadata_2025_split huggingface dataset:
Producing a new website for a paediatric liaison mental health team with our service users
Authors: Adams Alexander , Davies Virginia , Stubbs Bethany 
Published: November 2020

IntroductionOnline resources are an important source of information about mental health issues and services for children and young people. Our service’s website had an out-of-date appearance and was aimed at professionals. More importantly, comments in our routinely collected patient experience data indicated that service users did not know what to expect when coming to our service.MethodsWe followed the model for improvement by testing out changes in plan, do, study and act cycles that included a review of recently updated child and adolescent mental health services’ and youth charities’ websites, designing a new web page for our service and then testing out the website in focus groups. We used routinely collected patient experience data to assess impact on wider patient satisfaction.ResultsFocus groups involving patients, parents and professionals judged the new website to be clearer, more attractive and easier to understand. Routine patient experience data did not reveal any website-specific feedback.ConclusionThis study demonstrates that it is easy and possible to create an attractive and accessible website for a mental health service using quality improvement methodology. In order to capture and integrate ongoing feedback about a service’s website from service users, routinely collected patient experience measures would need to ask specific questions related to this area. In this study, preproject and postproject patient experience data did not generate any specific comments.
Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity
Authors: Efimova Iuliia , Catanzaro Elena , Van der Meeren Louis , Turubanova Victoria D , Hammad Hamida , Mishchenko Tatiana A , Vedunova Maria V , Fimognari Carmela , Bachert Claus , Coppieters Frauke , Lefever Steve , Skirtach Andre G , Krysko Olga , Krysko Dmitri V 
Published: November 2020

BackgroundImmunotherapy represents the future of clinical cancer treatment. The type of cancer cell death determines the antitumor immune response and thereby contributes to the efficacy of anticancer therapy and long-term survival of patients. Induction of immunogenic apoptosis or necroptosis in cancer cells does activate antitumor immunity, but resistance to these cell death modalities is common. Therefore, it is of great importance to find other ways to kill tumor cells. Recently, ferroptosis has been identified as a novel, iron-dependent form of regulated cell death but whether ferroptotic cancer cells are immunogenic is unknown.MethodsFerroptotic cell death in murine fibrosarcoma MCA205 or glioma GL261 cells was induced by RAS-selective lethal 3 and ferroptosis was analyzed by flow cytometry, atomic force and confocal microscopy. ATP and high-mobility group box 1 (HMGB1) release were detected by luminescence and ELISA assays, respectively. Immunogenicity in vitro was analyzed by coculturing of ferroptotic cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and activation/maturation of BMDCs (CD11c+CD86+, CD11c+CD40+, CD11c+MHCII+, IL-6, RNAseq analysis). The tumor prophylactic vaccination model in immune-competent and immune compromised (Rag-2−/−) mice was used to analyze ferroptosis immunogenicity.ResultsFerroptosis can be induced in cancer cells by inhibition of glutathione peroxidase 4, as evidenced by confocal and atomic force microscopy and inhibitors’ analysis. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2−/− mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells.ConclusionsThese results pave the way for the development of new therapeutic strategies for cancers based on induction of ferroptosis, and thus broadens the current concept of immunogenic cell death and opens the door for the development of new strategies in cancer immunotherapy.
Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells
Authors: Sun Roger , Sundahl Nora , Hecht Markus , Putz Florian , Lancia Andrea , Rouyar Angela , Milic Marina , Carré Alexandre , Battistella Enzo , Alvarez Andres Emilie , Niyoteka Stéphane , Romano Edouard , Louvel Guillaume , Durand-Labrunie Jérôme , Bockel Sophie , Bahleda Rastilav , Robert Charlotte , Boutros Celine , Vakalopoulou Maria , Paragios Nikos , Frey Benjamin , Soria Jean-Charles , Massard Christophe , Ferté Charles , Fietkau Rainer , Ost Piet , Gaipl Udo , Deutsch Eric 
Published: November 2020

BackgroundCombining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions.MethodsClinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient’s response.ResultsA total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables.ConclusionsThese results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.
PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy
Authors: Simon Sylvain , Voillet Valentin , Vignard Virginie , Wu Zhong , Dabrowski Camille , Jouand Nicolas , Beauvais Tiffany , Khammari Amir , Braudeau Cécile , Josien Régis , Adotevi Olivier , Laheurte Caroline , Aubin François , Nardin Charles , Rulli Samuel , Gottardo Raphael , Ramchurren Nirasha , Cheever Martin , Fling Steven P , Church Candice D , Nghiem Paul , Dreno Brigitte , Riddell Stanley R , Labarriere Nathalie 
Published: November 2020

BackgroundClinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.MethodsWe isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8+ T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.ResultsWe documented that the frequency of circulating PD-1+TIGIT+ (DPOS) CD8+ T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.ConclusionsOur results provide a convincing rationale for monitoring this PD-1+TIGIT+ circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.
Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia
Authors: Ward David D , Wallace Lindsay M K , Rockwood Kenneth 
Published: November 2020

ObjectiveTo determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype.MethodsA frailty index was calculated using the deficit-accumulation approach in participants aged 50 years and older from the National Alzheimer’s Coordinating Center. Cognitive status was determined by clinical evaluation. Using multistate transition models, we assessed the extent to which an increasing degree of frailty affected the probabilities of transitioning between not cognitively impaired (NCI), MCI, and dementia.ResultsParticipants (n=14 490) had a mean age of 72.2 years (SD=8.9 years; range=50–103 years). Among those NCI at baseline (n=9773), each 0.1 increment increase in the frailty index was associated with a higher risk of developing MCI and a higher risk of progressing to dementia. Among those with MCI at baseline (n=4717), higher frailty was associated with a higher risk of progressing to dementia, a lower probability of being reclassified as NCI, and a higher likelihood of returning to MCI in those that were reclassified as NCI. These risk effects were present and similar in both carriers and non-carriers of the APOE ε4 allele.ConclusionAmong older Americans, health-deficit accumulation affects the likelihood of progressive cognitive impairment and the likelihood of cognitive improvement independently of a strong genetic risk factor for dementia. Frailty represents an important risk factor for cognitive dysfunction and a marker of potential prognostic value.
Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a systematic literature research
Authors: Kerschbaumer Andreas , Smolen Josef S , Nash Peter , Doerner Thomas , Dougados Maxime , Fleischmann Roy , Geissler Klaus , McInnes Iain B , Takeuchi Tsutomu , Trauner Michael , Winthrop Kevin , de Wit Maarten , Boehncke Wolf-Henning , Falzon Louise , van der Heijde Desirée 
Published: November 2020

ObjectivesReview of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs).MethodsA systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation.Results3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn’s disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed.ConclusionJAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.
Treatment of mild-to-moderate pelvic inflammatory disease with a short-course azithromycin-based regimen versus ofloxacin plus metronidazole: results of a multicentre, randomised controlled trial
Authors: Dean Gillian , Soni Suneeta , Pitt Rachel , Ross Jonathan , Sabin Caroline , Whetham Jennifer 
Published: November 2020

Objective
A multicentre, randomised non-inferiority trial compared the efficacy and safety of 14 days of ofloxacin and metronidazole (standard-of-care (SoC)) versus a single dose of intramuscular ceftriaxone followed by 5 days of azithromycin and metronidazole (intervention arm (IA)) in women with mild-to-moderate pelvic inflammatory disease (PID).

Methods
Women with a clinical diagnosis of PID presenting at sexual health services were randomised to the SoC or IA arms. Treating clinicians and participants were not blinded to treatment allocation but the clinician performing the assessment of primary outcome was blinded. The primary outcome was clinical cure defined as ≥70% reduction in the modified McCormack pain score at day 14–21 after starting treatment. Secondary outcomes included adherence, tolerability and microbiological cure.

Results

Of the randomised population 72/153 (47.1%) reached the primary end point in the SoC arm, compared with 68/160 (42.5%) in the IA (difference in cure 4.6% (95% CI −15.6% to 6.5%). Following exclusion of 86 women who were lost to follow-up, attended outside the day 14–21 follow-up period, or withdrew consent, 72/107 (67.3%) had clinical cure in the SoC arm compared with 68/120 (56.7%) in the IA, giving a difference in cure rate of 10.6% (95% CI −23.2% to 1.9%). We were unable to demonstrate non-inferiority of the IA compared with SoC arm. Women in the IA took more treatment doses compared with the SoC group (113/124 (91%) vs 75/117 (64%), p=0.0001), but were more likely to experience diarrhoea (61% vs 24%, p<0.0001). Of 288 samples available for analysis,
Mycoplasma genitalium
was identified in 10% (28/288), 58% (11/19) of which had baseline antimicrobial resistance-associated mutations.

Conclusion

A short-course azithromycin-based regimen is likely to be less effective than the standard treatment with ofloxacin plus metronidazole. The high rate of baseline antimicrobial resistance supports resistance testing in those with
M. genitalium
infection to guide appropriate therapy.

Trial registration number
2010-023254-36.
Catastrophizing Has a Better Prediction for TMD Than Other Psychometric and Experimental Pain Variables
Authors: Willassen Lisa , Johansson Anders Arne , Kvinnsland Siv , Staniszewski Kordian , Berge Trond , Rosén Annika 
Published: November 2020

Temporomandibular disorders (TMDs) are characterized by moderate to severe pain in the masticatory muscles and/or the temporomandibular joint (TMJ). The present study is a part of a multidisciplinary project, initiated by the Norwegian Ministry of Health. The main purpose of this study is to compare a cohort of TMD patients to healthy individuals regarding experimental pain, the degree of disability caused by living with pain and psychometric variables, and to investigate which of these variables is the best predictor for TMD patients. We hypothesised that TMD patients have more disability when living with pain and lower pain thresholds than healthy controls, and those psychometric variables are stronger predictors than pain thresholds provoked by experimental pain. Sixty TMD patients were matched by sex and age to sixty healthy individuals without TMD symptoms or other musculoskeletal symptoms in the head and neck region. All subjects completed a questionnaire that included psychometric characteristics, that is, a one- and two-item version of the Pain Catastrophizing Scale, the Hospital Anxiety and Depression Scale (HADS), and the Roland Morris Scale (RMS), which measures disability when living with pain. They also underwent a clinical examination including the measurement of pain thresholds with electrical and pressure stimuli. The TMD patients had lower pain thresholds for experimental electrical and pressure stimuli compared with the controls (

P

< 0.05 and <0.001, respectively). They also scored higher than healthy individuals with disability living with pain (

P
<
0.001

), anxiety (

P
<
0.001

), depression (

P
<
0.001

), and catastrophizing (

P
<
0.001

). The results for anxiety, depression, and catastrophizing have been published earlier, and the reused data in this study are compared with RMS and pain thresholds. The conditional logistic regression model identified catastrophizing (OR = 2.42, CI 1.22–4.79) as a significant predictor of TMD patients. The results support this hypothesis and indicate that TMD patients have lower pain thresholds and more disability when living with pain compared to healthy individuals, where the strongest prediction for TMD was catastrophizing. Awareness of psychometric disabilities in TMD patients is of importance when considering the choice of treatment.
The Impact of Preconception TSH on the Reproductive Outcomes of Infertile Women Undergoing the First Fresh D3 Embryo Transfer Cycle
Authors: Zhang Yuchao , Wu Wenbin , Liu Yanli , Guan Yichun , Wang Xingling , Jia Liting 
Published: November 2020

Purpose. To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Methods. This was a retrospective study. Euthyroid patients undergoing the first fresh D3 embryo transfer from January 2018 to May 2019 were initially included. The patients were divided into a low-TSH (0.27–2.5 mIU/L) group and a high-normal TSH (2.5–4.2 Miu) group. The reproductive outcomes were compared between the groups. Results. A total of 1786 women were ultimately included, in which 1008 of whom had serum TSH levels between 0.27 and 2.5 mIU/L and 778 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.92, 1.30, and 0.88 and

P

= 0.416, 0.163, and 0.219). No significant differences were observed in terms of gestational age, single live birth rates, and birth weight, or birth length. Conclusion. High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Further studies are needed to test whether the results might be applicable to a wider population.
Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardiomyopathy
Authors: Xu Yuanwei , Li Weihao , Wan Ke , Liang Yaodan , Jiang Xincheng , Wang Jie , Mui David , Li Yangjie , Tang Siqi , Guo Jiajun , Guo Xinli , Liu Xiumin , Sun Jiayu , Zhang Qing , Han Yuchi , Chen Yucheng 
Published: November 2020

Background:
The prognosis of patients with idiopathic dilated cardiomyopathy (DCM) has improved remarkably in recent decades with guideline-directed medical therapy. Left ventricular (LV) reverse remodeling (LVRR) is one of the major therapeutic goals. Whether myocardial fibrosis or inflammation would reverse associated with LVRR remains unknown.

Methods:

A total of 157 prospectively enrolled patients with DCM underwent baseline and follow-up cardiovascular magnetic resonance examinations with a median interval of 13.7 months (interquartile range, 12.2–18.5 months). LVRR was defined as an absolute increase in LV ejection fraction of >10% to the final value of ≥35% and a relative decrease in LV end-diastolic volume of >10%. Statistical analyses were performed using paired
t
test and student
t
test, logistic regression analysis, and linear regression analysis.

Results:

Forty-eight (31%) patients reached LVRR. At baseline, younger age, worse New York Heart Association class, new-onset heart failure, lower LV ejection fraction, absence of late gadolinium enhancement, lower myocardial T2, and extracellular volume were significant predictors of LVRR. During the follow-up, patients with and without LVRR both showed a significant decrease of myocardial native T1 (LVRR: [baseline] 1303.0±43.6 ms; [follow-up] 1244.7±51.8 ms; without LVRR: [baseline] 1308.5±80.5 ms; [follow-up] 1287.6±74.9 ms, both
P
<0.001), matrix and cellular volumes while no significant difference was observed in T2 or extracellular volume values after treatment.

Conclusions:
In patients with idiopathic DCM, the absence of late gadolinium enhancement, lower T2, and extracellular volume values at baseline are significant predictors of LVRR. The myocardial T1, matrix, and cell volume decrease significantly in patients with LVRR after guideline-directed medical therapy.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: ChiCTR1800017058.
Consistent Transcription and Translation of Speech
Authors: Sperber Matthias , Setiawan Hendra , Gollan Christian , Nallasamy Udhyakumar , Paulik Matthias 
Published: November 2020

The conventional paradigm in speech translation starts with a speech recognition step to generate transcripts, followed by a translation step with the automatic transcripts as input. To address various shortcomings of this paradigm, recent work explores end-to-end trainable direct models that translate without transcribing. However, transcripts can be an indispensable output in practical applications, which often display transcripts alongside the translations to users. We make this common requirement explicit and explore the task of jointly transcribing and translating speech. Although high accuracy of transcript and translation are crucial, even highly accurate systems can suffer from inconsistencies between both outputs that degrade the user experience. We introduce a methodology to evaluate consistency and compare several modeling approaches, including the traditional cascaded approach and end-to-end models. We find that direct models are poorly suited to the joint transcription/translation task, but that end-to-end models that feature a coupled inference procedure are able to achieve strong consistency. We further introduce simple techniques for directly optimizing for consistency, and analyze the resulting trade-offs between consistency, transcription accuracy, and translation accuracy. 1