bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in access and prescription of vedolizumab and ustekinumab in paediatric patients with inflammatory bowel disease: a UK-wide study
Authors: Auth Marcus Karl-Heinz , Ashton James John , Jones Kelsey D J , Rodrigues Astor , Thangarajah Dhamyanthi , Devadason David , Lee Gemma , Ayaz Mashhood , Lee Huey Miin , Kammermeier Jochen 
Published: August 2023

BackgroundTherapeutic options for paediatric inflammatory bowel disease (IBD) are limited, especially for younger children. Unlike in adults, vedolizumab and ustekinumab are not licensed for paediatric use in the UK. We aimed to understand the real-world access to, and use of, these therapies in the paediatric population.MethodsWe surveyed UK IBD centres to assess the incident use of vedolizumab and ustekinumab from 1 January 2021 to 31 December 2021. We collected information on funding, dose escalations and therapeutic drug monitoring.Results18 of 21 centres responded, covering an estimated 5260 patients. One hundred and thirteen were started on vedolizumab, prescription incidence 2.2%, median prescriptions per centre was 4 (range 1–20). Considering ustekinumab, 73 patients were commenced, prescription incidence 1.4%. Median prescription per centre was 3.5 (range 1–13). Prescription rates at each centre were not predicted by patient number cared for at that centre (p=0.2). Dose escalation was common in vedolizumab (66.7% centres) and ustekinumab (55.5%).Funding strategies varied substantially, and multiple funding sources were used; 12 of 18 centres (66.7%) reported funding through routine National Health Service (NHS) England/Scottish arrangements. There was local NHS trust funding in 8 of 18 centres (44.4%). Individual funding requests (IFRs) were used in 5 of 18 (27.8%), although IFRs are reserved for patients with unique additional characteristics. Four centres were unable to achieve funding in pre-pubescent children.ConclusionsThere is widespread use of vedolizumab and ustekinumab across the UK, although practice is highly variable. Access to therapy appeared to differ substantially. There is a growing disparity between international guidelines and real-world practice. Establishing early and effective therapy in all patients remains a priority.
Pseudomyopia as an independent risk factor for myopia onset: a prospective cohort study among school-aged children
Authors: Sun Wei , Yu Mingkun , Wu Jianfeng , Han Xiaotong , Jan Catherine , Song Jike , Jiang Wenjun , Xu Zihang , Wu Ziyun , Xu Jing , Hu Yuanyuan , Bi Hongsheng 
Published: August 2023

AimTo investigate whether pseudomyopia is an independent risk factor for myopia onset based on a population-based cohort study.MethodsNon-myopic children were recruited from schools in rural and urban settings of Shangdong province, China. Baseline examinations started in September 2020 and all participants were invited for a 6-month follow-up. Pseudomyopia was defined as spherical equivalent (SE) ≤−0.50 diopters (D) before cycloplegia and >−0.50D after cycloplegia. Myopia was defined as cycloplegic SE ≤−0.50D.ResultsA total of 2328 children (baseline age: 4–17 years) were included in the final analysis. During the 6-month follow-up, 21.1% (355/1680) pseudomyopic eyes developed myopia, and 3.8% (110/2879) non-myopic and non-pseudomyopic eyes developed myopia. After adjusting for multiple myopia risk factors, including baseline cycloplegic SE, near work and outdoor time, pseudomyopia was found to be an independent risk factor for myopia onset (relative risk=2.52, 95% CI 1.86 to 3.42). Additionally, pseudomyopic children with more myopic cycloplegic SE (p<0.001), smaller difference between cycloplegic and non-cycloplegic SE (DIFF, p<0.001), and higher binocular amplitude of accommodation (p<0.001) had higher risk of myopia development.ConclusionThis is an important longitudinal study to prove that pseudomyopia is an independent risk factor for myopia development among school-aged children.
CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma
Authors: Liu Xiaomeng , Tang Rong , Xu Jin , Tan Zhen , Liang Chen , Meng Qingcai , Lei Yubin , Hua Jie , Zhang Yiyin , Liu Jiang , Zhang Bo , Wang Wei , Yu Xianjun , Shi Si 
Published: August 2023

ObjectivePancreatic ductal adenocarcinoma (PDAC) is among the most immunosuppressive tumour types. The tumour immune microenvironment (TIME) is largely driven by interactions between immune cells and heterogeneous tumour cells. Here, we aimed to investigate the mechanism of tumour cells in TIME formation and provide potential combination treatment strategies for PDAC patients based on genotypic heterogeneity.DesignHighly multiplexed imaging mass cytometry, RNA sequencing, mass cytometry by time of flight and multiplex immunofluorescence staining were performed to identify the pro-oncogenic proteins associated with low immune activation in PDAC. An in vitro coculture system, an orthotopic PDAC allograft tumour model, flow cytometry and immunohistochemistry were used to explore the biological functions of cysteine-rich intestinal protein 1 (CRIP1) in tumour progression and TIME formation. RNA sequencing, mass spectrometry and chromatin immunoprecipitation were subsequently conducted to investigate the underlying mechanisms of CRIP1.ResultsOur results showed that CRIP1 was frequently upregulated in PDAC tissues with low immune activation. Elevated CRIP1 expression induced high levels of myeloid-derived suppressor cell (MDSC) infiltration and fostered an immunosuppressive tumour microenvironment. Mechanistically, we primarily showed that CRIP1 bound to nuclear factor kappa-B (NF-κB)/p65 and facilitated its nuclear translocation in an importin-dependent manner, leading to the transcriptional activation of CXCL1/5. PDAC-derived CXCL1/5 facilitated the chemotactic migration of MDSCs to drive immunosuppression. SX-682, an inhibitor of CXCR1/2, blocked tumour MDSC recruitment and enhanced T-cell activation. The combination of anti-PD-L1 therapy with SX-682 elicited increased CD8+T cell infiltration and potent antitumor activity in tumour-bearing mice with high CRIP1 expression.ConclusionsThe CRIP1/NF-κB/CXCL axis is critical for triggering immune evasion and TIME formation in PDAC. Blockade of this signalling pathway prevents MDSC trafficking and thereby sensitises PDAC to immunotherapy.
Best practices in phase III clinical trials on DMTs for multiple sclerosis: a systematic analysis and appraisal of published trials
Authors: Mascarenas-Garcia Marta , Rivero-de-Aguilar Alejandro , Pérez-Ríos Mónica , Ruano-Raviña Alberto , Llaneza-Gonzalez Miguel Angel , Candal-Pedreira Cristina , Rey-Brandariz Julia , Varela-Lema Leonor 
Published: August 2023

BackgroundGreat advances have been made in the field of multiple sclerosis (MS) therapy due to the publication of numerous randomised clinical trials (RCTs). In this study, we carried out a critical appraisal of phase III RCTs of disease-modifying therapies (DMTs) for MS published after 2010, intending to identify critical areas of improvement.MethodsWe performed a systematic search of published RCTs on MS from January 2010 until December 2021. RCTs were assessed using an ad-hoc tool. This tool was developed based on existing generic methodological instruments and MS-specific guidelines and methodological papers. It included 14 items grouped in 5 domains: methodological quality, adequacy and measurement of outcomes, adverse event reporting, applicability and relevance of results, and transparency and conflict of interest.ResultsWe identified 31 phase III RCTs. Most of them were fully compliant in terms of sample size (87%), randomisation (68%), blinding (61%), participant selection (68%), adverse event reporting (84%) and clinical relevance (52%). Only a few were compliant in terms of participant description (6%), comparison (42%), attrition bias (26%), adequacy of outcome measures (26%), applicability (23%), transparency (36%) and conflict of interest (6%). None were compliant in terms of analysis and reporting of outcomes. The most common limitations related to the absence of comorbidity data, unjustified use of placebo, inadequacy of outcomes design and absence of protocol and/or prospective registration.ConclusionsRCTs for DMTs in MS have relevant and frequent limitations. These should be addressed to enhance their quality, transparency and external validity.
Characterising symptom clusters in patients with atrial fibrillation undergoing catheter ablation
Authors: Hobensack Mollie , Zhao Yihong , Scharp Danielle , Volodarskiy Alexander , Slotwiner David , Reading Turchioe Meghan 
Published: August 2023

ObjectiveThis study aims to leverage natural language processing (NLP) and machine learning clustering analyses to (1) identify co-occurring symptoms of patients undergoing catheter ablation for atrial fibrillation (AF) and (2) describe clinical and sociodemographic correlates of symptom clusters.MethodsWe conducted a cross-sectional retrospective analysis using electronic health records data. Adults who underwent AF ablation between 2010 and 2020 were included. Demographic, comorbidity and medication information was extracted using structured queries. Ten AF symptoms were extracted from unstructured clinical notes (n=13 416) using a validated NLP pipeline (F-score=0.81). We used the unsupervised machine learning approach known as Ward’s hierarchical agglomerative clustering to characterise and identify subgroups of patients representing different clusters. Fisher’s exact tests were used to investigate subgroup differences based on age, gender, race and heart failure (HF) status.ResultsA total of 1293 patients were included in our analysis (mean age 65.5 years, 35.2% female, 58% white). The most frequently documented symptoms were dyspnoea (64%), oedema (62%) and palpitations (57%). We identified six symptom clusters: generally symptomatic, dyspnoea and oedema, chest pain, anxiety, fatigue and palpitations, and asymptomatic (reference). The asymptomatic cluster had a significantly higher prevalence of male, white and comorbid HF patients.ConclusionsWe applied NLP and machine learning to a large dataset to identify symptom clusters, which may signify latent biological underpinnings of symptom experiences and generate implications for clinical care. AF patients’ symptom experiences vary widely. Given prior work showing that AF symptoms predict adverse outcomes, future work should investigate associations between symptom clusters and postablation outcomes.
The MIDORA trial: a phase II, randomised, double-blind, placebo-controlled, mechanistic insight and dosage optimisation study of the efficacy and safety of dazodalibep in patients with rheumatoid arthritis
Authors: Kivitz Alan , Wang Liangwei , Alevizos Ilias , Gunsior Michele , Falloon Judith , Illei Gabor , St Clair E William 
Published: August 2023

ObjectivesTo evaluate the safety, efficacy and response duration of four different dosing regimens of dazodalibep (DAZ), a non-antibody biological antagonist of CD40L, in patients with rheumatoid arthritis (RA).MethodsThis double-blind study included adult patients with moderate-to-severe active RA with a positive test for serum rheumatoid factor and/or anticitrullinated protein antibodies, an inadequate response to methotrexate, other conventional disease-modifying antirheumatic drugs or tumour necrosis factor-α inhibitors, and no prior treatment with B-cell depleting agents. Eligible participants were randomised equally to five groups receiving intravenous infusions of DAZ or placebo. The primary endpoint was the change from baseline in the Disease Activity Score-28 with C reactive protein (DAS28-CRP) at day 113. Participants were followed through day 309.ResultsThe study randomised 78 eligible participants. The change from baseline in DAS28-CRP (least squares means±SE) at day 113 was significantly greater for all DAZ groups (−1.83±0.28 to −1.90±0.27; p<0.05) relative to PBO (−1.06±0.26); significant reductions in DAS28-CRP were also observed for all DAZ groups at day 309. The distribution of adverse events was generally balanced among DAZ and PBO groups (74% and 63%, respectively). There were four serious adverse events deemed by investigators to be unrelated to study medication.ConclusionsDAZ treatment for all dosage regimens significantly reduced DAS28-CRP at day 113 relative to PBO. The safety data suggest an acceptable safety and tolerability profile. Treatment effects at day 113 and the prolonged duration of responses after DAZ cessation support the use of longer dosing intervals.Trial registration numberNCT04163991
Pain and sleep after open-heart surgery-inhalation peppermint essence: double-blind randomized clinical trial
Authors: Maghami Mahla , Pour‑Abbasi Mohammad-Sadegh , Yadollahi Safoura , Maghami Mahboobeh , Azizi-fini Ismail , Afazel Mohammad-Reza 
Published: August 2023

ObjectiveThe aim of this study was to determine the effect of inhaling peppermint essence on pain relief and sleep quality after open-heart surgery.MethodsIn a double-blind randomised clinical trial carried out in Iran in 2020, 64 cardiac patients were selected by convenience sampling and randomly allocated to aromatherapy (n=32) and placebo (n=32) groups. The aromatherapy and control groups received inhaled aromatherapy using peppermint essence and distilled water, respectively. Data gathering tools were the Numeric Pain Rating Scale and St Mary’s Hospital Sleep Questionnaire. Data were analysed using an independent t-test, χ2test, Mann–Whitney U test and generalised estimating equation analysis.ResultsThe mean severity of pain in the aromatherapy and placebo groups was 3.22±0.88 and 4.56±0.90, respectively, which was a statistically significant difference (p=0.0001). The mean sleep scores after the intervention on day 1 were 20.10±4.90 and 25.76±6.36 in the aromatherapy and placebo groups, respectively, and 18.63±5.56 and 22.62±5.69, respectively, on day 2. The difference between the two groups was statistically significantly different after the intervention in terms of sleep quality (p<0.05).ConclusionAromatherapy attenuated pain and improved sleep quality after open-heart surgery. Peppermint essence aromatherapy is therefore recommended after surgery.
Magnetic-field-driven rise and fall of a bipartite entanglement in a spin-liquid phase of a spin-1/2 Heisenberg branched chain
Authors: Ghannadan Azadeh , Karl’ová Katarína , Strečka Jozef 
Published: August 2023

AbstractThe spin-1/2 Heisenberg branched chain with the unit cell composed of three spins in the main backbone and one spin at a side branching of one-dimensional chain is investigated with the help of density-matrix renormalization group (DMRG) and quantum Monte Carlo (QMC) methods. The DMRG simulations were employed to calculate zero-temperature magnetization curves and to construct the ground-state phase diagram, which is composed from four different ground states classified as gapped zero-plateau and one-half plateau phase, a gapless spin-liquid phase and a fully saturated phase. It is shown that the one-half magnetization plateau vanishes at the Kosterlitz–Thouless quantum critical point, which is wedged into a parameter space of the gapless quantum spin-liquid phase. The bipartite quantum entanglement between four distinct nearest-neighbor pairs of the spin-1/2 Heisenberg branched chain is quantified through the concurrence. It is found that the concurrence varies continuously within the quantum spin-liquid phase, where it may display a continuous rise, a continuous fall or eventually an intriguing rise-and-fall behavior. On the contrary, the concurrence is kept constant within two gapful zero- and one-half plateau phases. Temperature and magnetic-field dependencies of the magnetization and magnetic susceptibility computed within the QMC method uncover clear signatures of the quantum critical point at finite temperatures.
Identifying Neighborhoods with Cervical Cancer Disparities for Targeted Community Outreach and Engagement by an NCI-Designated Cancer Center: A Geospatial Approach
Authors: Lee Ming S. , Elliott Nancy S. , Bethel Valerie D. , Balise Raymond R. , Kobetz Erin N. 
Published: August 2023

Abstract

Background:
Cervical cancer disparities exist in the United States with the highest incidence in Hispanic women and the highest mortality in Black women. Effective control of cervical cancer in the population requires targeted interventions tailored to community composition in terms of race, ethnicity, and social determinants of health (SDOH).

Methods:
Using cancer registry and SDOH data, geospatial hot spot analyses were carried out to identify statistically significant neighborhood clusters with high numbers of cervical cancer cases within the catchment area of an NCI-Designated Cancer Center. The locations, racial and ethnic composition, and SDOH resources of these hot spots were used by the center's community outreach and engagement office to deploy mobile screening units (MSU) for intervention in communities with women facing heightened risk for cervical cancer.

Results:
Neighborhood hot spots with high numbers of cervical cancer cases in south Florida largely overlap with locations of poverty. Cervical cancer hot spots are associated with a high percentage of Hispanic cases and low SDOH status, including low income, housing tenure, and education attainment.

Conclusions:
A geospatially referenced cancer surveillance platform integrating cancer registry, SDOH, and cervical screening data can effectively identify targets for cervical cancer intervention in neighborhoods experiencing disparities.

Impact:
Guided with a data-driven surveillance system, MSUs proactively bringing prevention education and cervical screening to communities with more unscreened, at-risk women are an effective means for addressing disparities associated with cervical cancer control.
Keeping IPMNs in Check: A Novel Role for the Transcription Factor NKX6-2 in Preserving an Indolent Cell Identity in Pancreatic Cystic Lesions
Authors: Ben-Shmuel Aviad , Scherz-Shouval Ruth 
Published: August 2023

Summary:In this issue of Cancer Discovery, Sans and colleagues identify the transcription factor NKX6-2 as a principal element in maintaining the low-grade gastric cell phenotype of intraductal papillary mucinous neoplasms (IPMN) in the pancreas. Their discoveries in patient cohorts and dissection in animal models provide a novel molecular understanding underpinning IPMN differentiation, with implications for risk stratification and therapeutic intervention in pancreatic cancer.See related article by Sans et al., p. 1844 (7).
Computational Quantification of Cancer Immunoediting
Authors: Liu Kun , He Shengyuan , Sun Shangqin , Zhang Xinxin , He Yanzhen , Quan Fei , Pang Bo , Xiao Yun 
Published: August 2023

Abstract
The remarkable success of cancer immunotherapy has revolutionized cancer treatment, emphasizing the importance of tumor–immune interactions in cancer evolution and treatment. Cancer immunoediting describes the dual effect of tumor–immune interactions: inhibiting tumor growth by destroying tumor cells and facilitating tumor escape by shaping tumor immunogenicity. To better understand tumor–immune interactions, it is critical to develop computational methods to measure the extent of cancer immunoediting. In this review, we provide a comprehensive overview of the computational methods for quantifying cancer immunoediting. We focus on describing the basic ideas, computational processes, advantages, limitations, and influential factors. We also summarize recent advances in quantifying cancer immunoediting studies and highlight future research directions. As the methods for quantifying cancer immunoediting are continuously improved, future research will further help define the role of immunity in tumorigenesis and hopefully provide a basis for the design of new personalized cancer immunotherapy strategies.
Ncoa2 Promotes CD8+ T cell–Mediated Antitumor Immunity by Stimulating T-cell Activation via Upregulation of PGC-1α Critical for Mitochondrial Function
Authors: Zhong Xiancai , Wu Hongmin , Ouyang Ching , Zhang Wencan , Shi Yun , Wang Yi-Chang , Ann David K. , Gwack Yousang , Shang Weirong , Sun Zuoming 
Published: August 2023

Abstract
Nuclear receptor coactivator 2 (Ncoa2) is a member of the Ncoa family of coactivators, and we previously showed that Ncoa2 regulates the differentiation of induced regulatory T cells. However, it remains unknown if Ncoa2 plays a role in CD8+ T-cell function. Here, we show that Ncoa2 promotes CD8+ T cell–mediated immune responses against tumors by stimulating T-cell activation via upregulating PGC-1α expression to enhance mitochondrial function. Mice deficient in Ncoa2 in T cells (Ncoa2fl/fl/CD4Cre) displayed defective immune responses against implanted MC38 tumors, which associated with significantly reduced tumor-infiltrating CD8+ T cells and decreased IFNγ production. Consistently, CD8+ T cells from Ncoa2fl/fl/CD4Cre mice failed to reject tumors after adoptive transfer into Rag1−/− mice. Further, in response to TCR stimulation, Ncoa2fl/fl/CD4Cre CD8+ T cells failed to increase mitochondrial mass, showed impaired oxidative phosphorylation, and had lower expression of PGC-1α, a master regulator of mitochondrial biogenesis and function. Mechanically, T-cell activation–induced phosphorylation of CREB triggered the recruitment of Ncoa2 to bind to enhancers, thus, stimulating PGC-1α expression. Forced expression of PGC-1α in Ncoa2fl/fl/CD4Cre CD8+ T cells restored mitochondrial function, T-cell activation, IFNγ production, and antitumor immunity. This work informs the development of Ncoa2-based therapies that modulate CD8+ T cell–mediated antitumor immune responses.
Envisioning Rhythm: Exploring the Visual Dimension of Natural Ecosystems through Digital Media
Authors: Chang Pai-Ling , Li Peng-Peng 
Published: August 2023

Abstract
For the study described here the authors combined digital technology with 3D printing to explore the feasibility of visualizing the rhythm of natural ecosystems. The achievements of this study were nine pieces of 3D-printed works. The authors discussed the Chinese Taoist view on ecological philosophy, aesthetics, and ecofeminism; probed the spiritual meaning of nature; and adopted technologies to visualize the rhythm of nature. By doing so, the authors aimed to reveal a new form of dialogue between humans and nature, disclose the visual signs of the vital rhythm of nature, and propose a new form of artistic creation based on biotechnology.