bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of tumor intrinsic BANF1 activates antitumor immune responses via cGAS-STING and enhances the efficacy of PD-1 blockade
Authors: Wang Minglei , Huang Yiheng , Chen Minxin , Wang Weiyan , Wu Fei , Zhong Tao , Chen Xiaozheng , Wang Fei , Li Yang , Yu Jinming , Wu Meng , Chen Dawei 
Published: August 2023

BackgroundBANF1 is well known as a natural opponent of cyclic GMP-AMP synthase (cGAS) activity on genomic self-DNA. However, the roles of BANF1 in tumor immunity remain unclear. Here, we investigate the possible impact of BANF1 on antitumor immunity and response to immunotherapy.MethodsThe Cancer Genome Atlas public data were analyzed to evaluate the relevance of the expression of BANF1, patients’ survival and immune cell infiltration. We monitored tumor growth and explored the antitumor efficacy of targeting tumor-intrinsic BANF1 in combination with anti-programmed cell death protein-1 (PD-1) in MC38 or B16F10 tumor models in both immunocompetent and immunodeficient mice. Flow cytometry, immunofluorescence and T cells depletion experiments were used to validate the role of BANF1 in tumor immune microenvironment reprogramming. RNA sequencing was then used to interrogate the mechanisms how BANF1 regulated antitumor immunity.ResultsWe show that upregulated expression of BANF1 in tumor tissues is significantly associated with poor survival and is negatively correlated with immune cell infiltration. Deficiency of BANF1 in tumor cells markedly antagonizes tumor growth in immunocompetent but not immunocompromised mice, and enhances the response to immunotherapy in murine models of melanoma and colon cancer. In the immunotherapy clinical cohort, patients with high BANF1 expression had a worse prognosis. Mechanistically, BANF1 knockout activates antitumor immune responses mediated by cGAS-synthase-stimulator of interferon genes (cGAS-STING) pathway, resulting in an immune-activating tumor microenvironment including increased CD8+T cell infiltration and decreased myeloid-derived suppressor cell enrichment.ConclusionsBANF1 is a key regulator of antitumor immunity mediated by cGAS-STING pathway. Therefore, our study provides a rational that targeting BANF1 is a potent strategy for enhancing immunotherapy for cancer with BANF1 upregulation.
Can the courts be viewed as an appropriate vehicle to settle clinical unease?
Authors: Wren Bernadette , Ruck Keene Alexander 
Published: August 2023

This paper is an exploration of the state of ‘clinical unease’ experienced by clinicians in contexts where professional judgement—grounded in clinical knowledge, critical reflection and a sound grasp of the law—indicates that there is more than one ethically defensible way to proceed. The question posed is whether the courts can be viewed as an appropriate vehicle to settle clinical unease by providing a ruling that clarifies the legal and ethical issues arising in the case, even in situations where there is no dispute between the patient (or her proxies) and the healthcare team.The concept of ‘clinical unease’ is framed with reference to the broader experience of clinical decision-making, and distinguished from other widely discussed phenomena in the healthcare literature like moral distress and conscientious objection. A number of reported cases are briefly examined where the courts were invited to rule in circumstances of apparent ‘unease’. The respective responsibilities of clinicians and courts are discussed: in particular, their capability and readiness to respond to matters of ethical concern.Four imagined clinical scenarios are outlined where a clinical team might welcome a court adjudication, under current rules. Consideration is given to the likelihood of such cases being heard, and to whether there may be better remedies than the courts. There are final reflections on what clinicians may actually wish for in seeking court involvement, and on whether a willingness to engage with the experience of clinical unease may lead to greater sensitivity towards the value perspectives of others.
Exploration of the representation of the allied health professions in senior leadership positions in the UK National Health Service
Authors: Eddison Nicola , Healy Aoife , Darke Nina , Jones Mary , Leask Millar , Roberts Gwen L , Chockalingam Nachiappan 
Published: August 2023

BackgroundAllied health professionals (AHPs) are an important group within the National Health Service (NHS) in the UK and make up a large portion of the workforce. Investment in AHP leadership is believed to lead to improvements in patient care, resource use, collaboration and innovation. This study aims to assess the current state of AHP strategic leadership within the NHS.MethodsA freedom of information (FOI) request was sent to all NHS Trusts and health boards (HBs) within the UK NHS. The questions focused on the AHP workforce, with a particular interest in the chief AHPs (or equivalent roles) working in an NHS setting. Analysis of the FOI used a range of descriptive statistics.ResultsOf the 217 Trusts/HBs contacted, responses were received from 160 (74%). The majority (81%) reported that they employed a Chief AHP or equivalent role, with only 14% of these having a position on the Trust/HB executive board. There were 50 different job titles reported as the titles for the chief AHP or equivalent roles: with director of AHPs (18.6%), lead AHP (13.9%) and chief AHP (11.6%) being the most reported titles. The results identified an inequity of representation of AHP professions within senior AHP leadership; with most of these roles (70%) held by physiotherapists and occupational therapists.ConclusionChanges in AHP strategic leadership are needed to address the inequities identified in this study. Addressing these issues is required to enable inclusive leadership, which is crucial to improve the contribution of AHPs to healthcare.
Imaging in diagnosis, monitoring and outcome prediction of large vessel vasculitis: a systematic literature review and meta-analysis informing the 2023 update of the EULAR recommendations
Authors: Bosch Philipp , Bond Milena , Dejaco Christian , Ponte Cristina , Mackie Sarah Louise , Falzon Louise , Schmidt Wolfgang A , Ramiro Sofia 
Published: August 2023

ObjectivesTo update the evidence on imaging for diagnosis, monitoring and outcome prediction in large vessel vasculitis (LVV) to inform the 2023 update of the European Alliance of Associations for Rheumatology recommendations on imaging in LVV.MethodsSystematic literature review (SLR) (2017–2022) including prospective cohort and cross-sectional studies (>20 participants) on diagnostic, monitoring, outcome prediction and technical aspects of LVV imaging. Diagnostic accuracy data were meta-analysed in combination with data from an earlier (2017) SLR.ResultsThe update retrieved 38 studies, giving a total of 81 studies when combined with the 2017 SLR. For giant cell arteritis (GCA), and taking clinical diagnosis as a reference standard, low risk of bias (RoB) studies yielded pooled sensitivities and specificities (95% CI) of 88% (82% to 92%) and 96% (95% CI 86% to 99%) for ultrasound (n=8 studies), 81% (95% CI 71% to 89%) and 98% (95% CI 89% to 100%) for MRI (n=3) and 76% (95% CI 67% to 83%) and 95% (95% CI 71% to 99%) for fluorodeoxyglucose positron emission tomography (FDG-PET, n=4), respectively. Compared with studies assessing cranial arteries only, low RoB studies with ultrasound assessing both cranial and extracranial arteries revealed a higher sensitivity (93% (95% CI 88% to 96%) vs 80% (95% CI 71% to 87%)) with comparable specificity (94% (95% CI 83% to 98%) vs 97% (95% CI 71% to 100%)). No new studies on diagnostic imaging for Takayasu arteritis (TAK) were found. Some monitoring studies in GCA or TAK reported associations of imaging with clinical signs of inflammation. No evidence was found to determine whether imaging severity might predict worse clinical outcomes.ConclusionUltrasound, MRI and FDG-PET revealed a good performance for the diagnosis of GCA. Cranial and extracranial vascular ultrasound had a higher pooled sensitivity with similar specificity compared with limited cranial ultrasound.
Neonatal serious illness: operational definition
Authors: Guttmann Katherine , Silverman Rachel , Weintraub Andrea S 
Published: August 2023

Objectives(1) To operationalise our previously published definition of neonatal serious illness by applying it to a patient cohort and (2) to evaluate timing of palliative care consultation, goals of care discussions and meeting serious illness criteria.MethodsThis was a retrospective chart review. Inborn neonates delivered between January 2006 and December 2020 who died prior to neonatal intensive care unit discharge were identified through EPIC query. Kruskal-Wallis and Mann-Whitney-U tests were used to compare time intervals relating to transition to serious illness across causes of death and other factors. χ2tests were used to examine frequency of goals of care conversations by factors.ResultsEighty-eight per cent of patients met criteria for neonatal serious illness within 48 hours of life. There were no significant differences in transition to serious illness between preterm and term infants. Time to identification of serious illness varied significantly by cause of death. Palliative care was consulted for 5.7% of patients.ConclusionAll patients met criteria for serious illness early in life based on our definition. This definition may be useful for identifying neonates with serious illness in time to provide support. Additional work is needed to apply this definition prospectively to explore its utility for clinical care and research.
Guideline concordance for timely chest imaging after new presentations of dyspnoea or haemoptysis in primary care: a retrospective cohort study
Authors: Koo Minjoung Monica , Mounce Luke T A , Rafiq Meena , Callister Matthew E J , Singh Hardeep , Abel Gary A , Lyratzopoulos Georgios 
Published: August 2023

BackgroundGuidelines recommend urgent chest X-ray for newly presenting dyspnoea or haemoptysis but there is little evidence about their implementation.MethodsWe analysed linked primary care and hospital imaging data for patients aged 30+ years newly presenting with dyspnoea or haemoptysis in primary care during April 2012 to March 2017. We examined guideline-concordant management, defined as General Practitioner-ordered chest X-ray/CT carried out within 2 weeks of symptomatic presentation, and variation by sociodemographic characteristic and relevant medical history using logistic regression. Additionally, among patients diagnosed with cancer we described time to diagnosis, diagnostic route and stage at diagnosis by guideline-concordant status.ResultsIn total, 22 560/162 161 (13.9%) patients with dyspnoea and 4022/8120 (49.5%) patients with haemoptysis received guideline-concordant imaging within the recommended 2-week period. Patients with recent chest imaging pre-presentation were much less likely to receive imaging (adjusted OR 0.16, 95% CI 0.14–0.18 for dyspnoea, and adjusted OR 0.09, 95% CI 0.06–0.11 for haemoptysis). History of chronic obstructive pulmonary disease/asthma was also associated with lower odds of guideline concordance (dyspnoea: OR 0.234, 95% CI 0.225–0.242 and haemoptysis: 0.88, 0.79–0.97). Guideline-concordant imaging was lower among dyspnoea presenters with prior heart failure; current or ex-smokers; and those in more socioeconomically disadvantaged groups.The likelihood of lung cancer diagnosis within 12 months was greater among the guideline-concordant imaging group (dyspnoea: 1.1% vs 0.6%; haemoptysis: 3.5% vs 2.7%).ConclusionThe likelihood of receiving urgent imaging concords with the risk of subsequent cancer diagnosis. Nevertheless, large proportions of dyspnoea and haemoptysis presenters do not receive prompt chest imaging despite being eligible, indicating opportunities for earlier lung cancer diagnosis.
Fragmentation of care between intensive and primary care settings and opportunities for improvement
Authors: Leggett Nina , Emery Kate , Rollinson Thomas C , Deane Adam , French Craig , Manski Nankervis Jo-Anne , Eastwood Glenn , Miles Briannah , Merolli Mark , Ali Abdelhamid Yasmine , Haines Kimberley Joy 
Published: August 2023

PurposeTo explore the gaps in care provided across the transitions from the intensive care unit (ICU) to primary care, in order to improve post-ICU care.MethodsSemistructured interviews with three participant groups: intensivists, general practitioners (GPs) and patients and carers with framework analysis of textual data were used to investigate experiences of transitions of care post-ICU. Participants were purposively sampled for diversity. Eligible patients were adults, mechanically ventilated for >24 hours, with access to a video-enabled device. Exclusion criteria were non-English speaking and any cognitive/neurological limitation precluding interview participation.ResultsA total of 46 interviews (15 patients, 8 caregivers, 15 intensivists and 8 GPs) were completed. Eight themes were identified, and categorised into three healthcare tiers.Tier 1, health system factors: (1) fragmentation of care; (2) communication gaps; (3) limited awareness and recognition of issues beyond the ICU; (4) lack of a specialised ICU follow-up pathway;Tier 2, clinician factors: (5) relationships among ICU, hospitals, GPs and patients and carers; (6) need for clinician role definition and clarity in ICU follow-up;Tier 3, patient and carer factors: (7) patient autonomy and self-actualisation and (8) the evolving caregiver role. A conceptual model was developed, highlighting bidirectional feedback loops between hospital and primary care.ConclusionThis study identified gaps in care between ICU discharge and reintegration with primary care from the lived experience of patients, caregivers, intensivists and GPs. These data provide foci for future interventional research to improve the integration of care for this vulnerable and underserved cohort.
Micropolar Elasticity in Physically-Based Animation
Authors: Löschner Fabian , Fernández-Fernández José Antonio , Jeske Stefan Rhys , Longva Andreas , Bender Jan 
Published: August 2023

We explore micropolar materials for the simulation of volumetric deformable solids. In graphics, micropolar models have only been used in the form of one-dimensional Cosserat rods, where a rotating frame is attached to each material point on the one-dimensional centerline. By carrying this idea over to volumetric solids, every material point is associated with a microrotation, an independent degree of freedom that can be coupled to the displacement through a material's strain energy density. The additional degrees of freedom give us more control over bending and torsion modes of a material. We propose a new orthotropic micropolar curvature energy that allows us to make materials stiff to bending in specific directions.
For the simulation of dynamic micropolar deformables we propose a novel incremental potential formulation with a consistent FEM discretization that is well suited for the use in physically-based animation. This allows us to easily couple micropolar deformables with dynamic collisions through a contact model inspired from the Incremental Potential Contact (IPC) approach. For the spatial discretization with FEM we discuss the challenges related to the rotational degrees of freedom and propose a scheme based on the interpolation of angular velocities followed by quaternion time integration at the quadrature points.
In our evaluation we validate the consistency and accuracy of our discretization approach and demonstrate several compelling use cases for micropolar materials. This includes explicit control over bending and torsion stiffness, deformation through prescription of a volumetric curvature field and robust interaction of micropolar deformables with dynamic collisions.
A comparison of linear consistent correction methods for first-order SPH derivatives
Authors: Westhofen Lukas , Jeske Stefan , Bender Jan 
Published: August 2023

A well-known issue with the widely used Smoothed Particle Hydrodynamics (SPH) method is the neighborhood deficiency. Near the surface, the SPH interpolant fails to accurately capture the underlying fields due to a lack of neighboring particles. These errors may introduce ghost forces or other visual artifacts into the simulation.
In this work we investigate three different popular methods to correct the first-order spatial derivative SPH operators up to linear accuracy, namely the Kernel Gradient Correction (KGC), Moving Least Squares (MLS) and Reproducing Kernel Particle Method (RKPM). We provide a thorough, theoretical comparison in which we remark strong resemblance between the aforementioned methods. We support this by an analysis using synthetic test scenarios. Additionally, we apply the correction methods in simulations with boundary handling, viscosity, surface tension, vorticity and elastic solids to showcase the reduction or elimination of common numerical artifacts like ghost forces. Lastly, we show that incorporating the correction algorithms in a state-of-the-art SPH solver only incurs a negligible reduction in computational performance.
“It's Probably Just Hemorrhoids”: A Qualitative Exploration of the Lived Experiences and Perceptions of Long-term Survivors of Early-Onset Colorectal Cancer
Authors: Rogers Charles R. , Korous Kevin M. , De Vera Mary A. , Shaukat Aasma , Brooks Ellen , Rifelj Kelly Krupa , Henley Candace , Johnson Wenora , Rogers Tiana N. 
Published: August 2023

Abstract

Background:
Colorectal cancer among adults aged &lt;50 years [early-onset colorectal cancer (EOCRC)] is projected to be the leading cause of cancer-related death by 2030. Although evidence-based guidelines for colorectal cancer screening now recommend beginning screening at age 45, the needs of many at-risk young adults are potentially being overlooked. Unanswered questions also remain regarding the effects of EOCRC on quality-of-life and psychosocial outcomes. This qualitative study explored the lived experiences and perceptions of a sample of adult EOCRC survivors in the United States through one-on-one interviews.

Methods:
An EOCRC advocate survivor team member led 27 structured virtual interviews using a 10-question interview guide. Data were analyzed using a 9-step inductive approach.

Results:
Participants were geographically diverse. Most were women (66.6%) who self-identified as non-Hispanic White (85.2%). The mean age at interview was 40.19 ± 5.99; at diagnosis, 33.93 ± 5.90. Six overarching themes emerged: signs and symptoms, risk factors, system-level factors, quality of life, social support, and reflection.

Conclusions:
The specific needs of individuals in this younger population of patients with colorectal cancer should be considered during treatment and future interventions and throughout survivorship.

Impact:
While the reasons for the increasing incidence of EOCRC are currently unknown, the lived experiences and perceptions of EOCRC survivors noted in this study highlight specific needs of this population that can inform educational materials, comprehensive care, future research, and policy change.
Prediagnostic Hormone Levels and Risk of Testicular Germ Cell Tumors: A Nested Case–Control Study in the Janus Serum Bank
Authors: Wu Zeni , Trabert Britton , Guillemette Chantal , Caron Patrick , Bradwin Gary , Graubard Barry I. , Weiderpass Elisabete , Ursin Giske , Langseth Hilde , McGlynn Katherine A. 
Published: August 2023

Abstract

Background:
It has been hypothesized that poorly functioning Leydig and/or Sertoli cells of the testes, indicated by higher levels of serum gonadotropins and lower levels of androgens, are related to the development of testicular germ cell tumors (TGCT). To investigate this hypothesis, we conducted a nested case–control study within the Janus Serum Bank cohort.

Methods:
Men who developed TGCT (n = 182) were matched to men who did not (n = 364). Sex steroid hormones were measured using LC/MS. Sex hormone binding globulin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were quantified by direct immunoassay. Multivariable logistic regression was used to calculate ORs and 95% confidence intervals (CI) for associations between hormone levels and TGCT risk.

Results:
Higher FSH levels [tertile (T) 3 vs. T2: OR = 2.89, 95% CI = 1.83–4.57] were associated with TGCT risk, but higher LH levels were not (OR = 1.26, 95% CI = 0.81–1.96). The only sex steroid hormone associated with risk was androstane-3α, 17β-diol-3G (3α-diol-3G; OR = 2.37, 95% CI = 1.46–3.83). Analysis by histology found that increased FSH levels were related to seminoma (OR = 3.55, 95% CI = 2.12–5.95) but not nonseminoma (OR = 1.19, 95% CI = 0.38–3.13). Increased levels of 3α-diol-3G were related to seminoma (OR = 2.29, 95% CI = 1.35–3.89) and nonsignificantly related to nonseminoma (OR = 2.71, 95% CI = 0.82–8.92).

Conclusions:
Higher FSH levels are consistent with the hypothesis that poorly functioning Sertoli cells are related to the development of TGCT. In contrast, higher levels of 3α-diol-3G do not support the hypothesis that insufficient androgenicity is related to risk of TGCT.

Impact:
Clarifying the role of sex hormones in the development of TGCT may stimulate new research hypotheses.
Accelerating Cancer Histopathology Workflows with Chemical Imaging and Machine Learning
Authors: Falahkheirkhah Kianoush , Mukherjee Sudipta S. , Gupta Sounak , Herrera-Hernandez Loren , McCarthy Michael R. , Jimenez Rafael E. , Cheville John C. , Bhargava Rohit 
Published: August 2023

Histopathology has remained a cornerstone for biomedical tissue assessment for over a century, with a resource-intensive workflow involving biopsy or excision, gross examination, sampling, tissue processing to snap frozen or formalin-fixed paraffin-embedded blocks, sectioning, staining, optical imaging, and microscopic assessment. Emerging chemical imaging approaches, including stimulated Raman scattering (SRS) microscopy, can directly measure inherent molecular composition in tissue (thereby dispensing with the need for tissue processing, sectioning, and using dyes) and can use artificial intelligence (AI) algorithms to provide high-quality images. Here we show the integration of SRS microscopy in a pathology workflow to rapidly record chemical information from minimally processed fresh-frozen prostate tissue. Instead of using thin sections, we record data from intact thick tissues and use optical sectioning to generate images from multiple planes. We use a deep learning–based processing pipeline to generate virtual hematoxylin and eosin images. Next, we extend the computational method to generate archival-quality images in minutes, which are equivalent to those obtained from hours/days-long formalin-fixed, paraffin-embedded processing. We assessed the quality of images from the perspective of enabling pathologists to make decisions, demonstrating that the virtual stained image quality was diagnostically useful and the interpathologist agreement on prostate cancer grade was not impacted. Finally, because this method does not wash away lipids and small molecules, we assessed the utility of lipid chemical composition in determining grade. Together, the combination of chemical imaging and AI provides novel capabilities for rapid assessments in pathology by reducing the complexity and burden of current workflows.

Significance:
Archival-quality (formalin-fixed paraffin-embedded), thin-section diagnostic images are obtained from thick-cut, fresh-frozen prostate tissues without dyes or stains to expedite cancer histopathology by combining SRS microscopy and machine learning.