bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race and ethnicity in the COVID-19 Critical Care Consortium: demographics, treatments, and outcomes, an international observational registry study
Authors: Griffee Matthew J. , Thomson David A. , Fanning Jonathon , Rosenberger Dorothea , Barnett Adrian , White Nicole M. , Suen Jacky , Fraser John F. , Li Bassi Gianluigi , Cho Sung-Min ,   On behalf of the COVID-19 Critical Care Consortium, Dalton Heidi J. , Laffey John , Brodie Daniel , Fan Eddy , Torres Antoni , Chiumello Davide , Elhazmi Alyaa , Hodgson Carol , Ichiba Shingo , Luna Carlos , Murthy Srinivas , Nichol Alistair , Ng Pauline Yeung , Ogino Mark , Marwali Eva , Grasselli Giacomo , Bartlett Robert , Burrell Aidan , Elhadi Muhammed , Motos Anna , Barbé Ferran , Zanella Alberto 
Published: December 2023

Abstract
Background
Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries.

Methods
We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality.

Results
Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US.

Conclusions
Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background.
*Note: “Coloured” is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa.
Apoptosis-related factors are relevant to progression of pancreatic neuroendocrine tumors
Authors: Amano Shota , Hirashita Teijiro , Kawano Yoko , Nishida Haruto , Orimoto Hiroki , Kawamura Masahiro , Kawasaki Takahide , Masuda Takashi , Endo Yuichi , Ohta Masayuki , Daa Tsutomu , Inomata Masafumi 
Published: December 2023

Abstract
Background
Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection.

Methods
Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan–Meier method and compared with the log-rank test.

Results
GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044).

Conclusions
Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.
SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion
Authors: Liu Yafeng , Han Tao , Wu Jing , Zhou Jiawei , Guo Jianqiang , Miao Rui , Xu Zhi , Xing Yingru , Bai Ying , Hu Dong 
Published: December 2023

Abstract
Background
The occurrence of epithelial-mesenchymal transition (EMT) and immune evasion is considered to contribute to poor prognosis in lung adenocarcinoma (LUAD). Therefore, this study aims to explore the key oncogenes that promote EMT and immune evasion and reveal the expression patterns, prognostic value, and potential biological functions.

Methods
Firstly, we identified gene modules associated with EMT and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Next, we utilized differential analysis and machine learning to identify the key genes and validate them. Moreover, we analyzed the correlation between key genes and tumor microenvironment remodeling, drug sensitivity, as well as mutation frequency. Furthermore, we explored and validated their malignant biological characteristics through in vitro experiments and clinical samples. Finally, potential drugs for LUAD were screened based on CMap and validated through experiments.

Results
Firstly, WGCNA analysis revealed that red and green modules were highly correlated with EMT and TIDE. Among them, upregulated expression of SPOCK1 was observed in lung adenocarcinoma tissues and was associated with poor prognosis. Additionally, patients in the high SPOCK1 group showed more activation of malignant oncogenic pathways, higher infiltration of immunosuppressive components, and a higher frequency of mutations. The knockdown of SPOCK1 suppressed invasion and metastasis capabilities of lung adenocarcinoma cells, and the high expression of SPOCK1 was associated with low infiltration of CD8+ T cells. Therapeutic aspects, SPOCK1 can be a candidate indicator for drug sensitivity and CMap showed that VER-155008 was the drug candidate with the largest perturbation effect on the SPOCK1 expression profile. In vitro and in vivo experiments validated the cancer-inhibitory effect of VER-155008 in LUAD.

Conclusion
This study revealed through comprehensive bioinformatics analysis and experimental analysis that SPOCK1 can promote EMT and immune escape in LUAD, and it may serve as a promising candidate prognostic biomarker and therapeutic target for LUAD.
Rudolph, the kids’ ward reindeer: a scoping review of the effects of support animals on the well-being of healthcare staff
Authors: Erren Thomas C. , Wallraff Jonas , Wild Ursula , Shaw David M. , Lewis Philip 
Published: December 2023

Abstract
Background
Many systematic reviews identify support animals or animal assisted activity as a beneficial and standard practice in several medical disciplines for patients (children, adolescents, and adults) and residents in care homes. A variety of animals are used such as dogs, cats, ponies, horses, alpacas, reindeer, penguins, rabbits, and tarantulas. Our objective was to explore the evidence regarding effects of animal assisted activity on a further population of interest; namely, healthcare staff.

Methods
We asked the question “how do support animals in healthcare settings affect the well-being of healthcare staff?” As an addendum, we were also interested in what - possibly more unique - animals have visited healthcare settings at Christmas time in particular. We conducted a scoping literature review using PubMed and Web of Science (search as of 26 April 2023).

Results
Twenty studies (in the USA, Australia, Europe; dogs: n = 19; cats: n = 1) since 2002 included: studies with biological measures (n = 3), longitudinal survey studies with analyses (n = 5), cross-sectional survey studies with analyses (n = 2), and cross-sectional survey studies with descriptive statistics (n = 10). Overall, animal assisted activities appear to be well-received by staff and there do not seem to be negative impacts on staff well-being.

Conclusions
Relevant positive effects and avenues of research are identified. Our review suggests that, but not exactly how, animal assisted activity benefits staff. Study evidence is limited with most studies being cross-sectional, descriptive, having low participant numbers, and mostly only involving dogs. Nonetheless, the evidence is mostly positive. The potential of animal assisted activities impacting positively on staff well-being warrants systematic research. Gaps in hard-fact-evidence should not deter us – especially at the festive season – to encourage work with, and systematic research regarding, support animals that provide warmth, empathy, comfort, and more in healthcare settings.
Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned
Authors: López de Sá Alfonso , Díaz-Tejeiro Cristina , Poyatos-Racionero Elisa , Nieto-Jiménez Cristina , Paniagua-Herranz Lucía , Sanvicente Adrián , Calvo Emiliano , Pérez-Segura Pedro , Moreno Víctor , Moris Francisco , Ocana Alberto 
Published: December 2023

AbstractAntibody–drug conjugates (ADCs) have emerged as a novel therapeutic strategy that has successfully reached patient treatment in different clinical scenarios. ADCs are formed by an antibody against a specific tumor-associated antigen (TAA), a cytotoxic payload, and a chemical linker that binds both. To this regard, most efforts have been focused on target identification, antibody design and linker optimization, but other relevant aspects for clinical development have not received the necessary attention. In this article using data from approved ADCs, we evaluated all characteristics of these agents, including payload physicochemical properties, in vitro potency, drug antibody ratio (DAR), exposure–response relationships, and clinical development strategies. We suggest that compounds with best options for clinical development include those with optimal payload physicochemical properties and cleavable linkers that would lead to a bystander effect. These modalities can facilitate the development of ADCs in indications with low expression of the TAA. Early clinical development strategies including changes in the schedule of administration with more frequent doses are also discussed in the context of an efficient strategy. In conclusion, we highlight relevant aspects that are needed for the optimal development of ADCs in cancer, proposing options for improvement.
Ankle osteoarthritis: an online survey of current treatment practices of UK‐based podiatrists and physiotherapists
Authors: Callaghan Michael J. , Gala Jinal Pravin , Roddy Edward 
Published: December 2023

AbstractBackgroundPatients with painful ankle osteoarthritis (OA) have a mixed experience of non‐surgical management which they may attribute to a lack of guidance for clinicians on usual care treatment. Therefore, the purpose of this study was to survey the current clinical practices of UK‐based physiotherapists and podiatrists for the treatment of painful ankle osteoarthritis (OA).MethodsUK‐based physiotherapists and podiatrists who treat patients with ankle OA completed a self‐administered online questionnaire about their professional and clinical service characteristics, diagnostic criteria, treatment aims, preferred treatment options, and treatment outcome measures. Data were collected anonymously and stored on JISC online survey. ‘Usual care’ was defined as a combination of ‘Always’, and ‘Frequently’, and ‘Not usual care’ was defined as ‘Sometimes’ ‘Rarely,’ ‘Never’, and ‘not applicable’ combined. Statistically significant differences in responses between the physiotherapists and podiatrists were analysed using X2 tests for each treatment modality. Statistical significance was set at p < 0.05.ResultsBetween 1st June 2021 and 31st August 2021, 100 responses were received; 2 were invalid. Of the 98 valid responses, 63 were from physiotherapists and 35 from podiatrists. The most common treatment aims in both professions were to reduce pain (n = 87, 89%) and improve quality of life (n = 82, 84%). 50 respondents (51%) offered 3 or 4 treatment sessions and 53 respondents (54%) saw patients for 30–40 min at the first treatment session.The five most common modalities used by physiotherapists were patient education (n = 63, 100%), teaching self‐management (n = 58, 92%), lifestyle modification (n = 54, 86%), ankle strengthening (n = 55, 87%), and proprioception exercises (n = 54, 86%). For podiatrists, these were patient education (n = 35, 100%), ankle strengthening (n = 31, 89%), activity pacing (n = 28, 80%), lifestyle modification (n = 27, 77%), and gait training (n = 27, 77%).ConclusionsThis first‐ever survey revealed physiotherapists’ and podiatrists’ current practices to treat painful ankle OA. This study provides a better understanding of how ankle OA is treated in UK current clinical practice and can inform future clinical trials to compare current practice with new treatment modalities.
Evaluating the use of paralogous protein domains to increase data availability for missense variant classification
Authors: Gunning Adam Colin , Wright Caroline Fiona 
Published: December 2023

Abstract
Background
Classification of rare missense variants remains an ongoing challenge in genomic medicine. Evidence of pathogenicity is often sparse, and decisions about how to weigh different evidence classes may be subjective. We used a Bayesian variant classification framework to investigate the performance of variant co-localisation, missense constraint, and aggregating data across paralogous protein domains (“meta-domains”).

Methods
We constructed a database of all possible coding single nucleotide variants in the human genome and used PFam predictions to annotate structurally-equivalent positions across protein domains. We counted the number of pathogenic and benign missense variants at these equivalent positions in the ClinVar database, calculated a regional constraint score for each meta-domain, and assessed this approach versus existing missense constraint metrics for classifying variant pathogenicity and benignity.

Results
Alternative pathogenic missense variants at the same amino acid position in the same protein provide strong evidence of pathogenicity (positive likelihood ratio, LR+  = 85). Additionally, clinically annotated pathogenic or benign missense variants at equivalent positions in different proteins can provide moderate evidence of pathogenicity (LR+  = 7) or benignity (LR+  = 5), respectively. Applying these approaches sequentially (through PM5) increases sensitivity for classifying pathogenic missense variants from 27 to 41%. Missense constraint can also provide strong evidence of pathogenicity for some variants, but its absence provides no evidence of benignity.

Conclusions
We propose using structurally equivalent positions across related protein domains from different genes to augment evidence for variant co-localisation when classifying novel missense variants. Additionally, we advocate adopting a numerical evidence-based approach to integrating diverse data in variant interpretation.
Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer’s polygenic risk reveals autobiographical deficits and cingulate cortex correlates
Authors: Lancaster Thomas , Creese Byron , Escott-Price Valentina , Driver Ian , Menzies Georgina , Khan Zunera , Corbett Anne , Ballard Clive , Williams Julie , Murphy Kevin , Chandler Hannah 
Published: December 2023

Abstract
Background
Genome-wide association studies demonstrate that Alzheimer’s disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility.

Methods
Here, we recruited sixteen clinically asymptomatic individuals (mean age 67; range 58–76) with either extremely low / high AD-PRS (defined as at least 2 standard deviations from the wider sample mean (N = 4504; NEFFECTIVE = 90)) with comparable age sex and education level. We assessed group differences in autobiographical memory and T1-weighted structural neuroimaging features.

Results
We observed marked reductions in autobiographical recollection (Cohen’s d =  − 1.66; PFDR = 0.014) and midline structure (cingulate) thickness (Cohen’s d =  − 1.55, PFDR = 0.05), with no difference in hippocampal volume (P > 0.3). We further confirm the negative association between AD-PRS and cingulate thickness in a larger study with a comparable age (N = 31,966, β =  − 0.002, P = 0.011), supporting the validity of our approach.

Conclusions
These observations conform with multiple streams of prior evidence suggesting alterations in cingulate structures may occur in individuals with higher AD genetic risk. We were able to use a genetically informed research design strategy that significantly improved the efficiency and power of the study. Thus, we further demonstrate that the recall-by-genotype of AD-PRS from wider samples is a promising approach for the detection, assessment, and intervention in specific individuals with increased AD genetic risk.
Predicting positron emission tomography brain amyloid positivity using interpretable machine learning models with wearable sensor data and lifestyle factors
Authors: Kimura Noriyuki , Aota Tomoki , Aso Yasuhiro , Yabuuchi Kenichi , Sasaki Kotaro , Masuda Teruaki , Eguchi Atsuko , Maeda Yoshitaka , Aoshima Ken , Matsubara Etsuro 
Published: December 2023

Abstract
Background
Developing a screening method for identifying individuals at higher risk of elevated brain amyloid burden is important to reduce costs and burden to patients in clinical trials on Alzheimer’s disease or the clinical setting. We developed machine learning models using objectively measured lifestyle factors to predict elevated brain amyloid burden on positron emission tomography.

Methods
Our prospective cohort study of non-demented, community-dwelling older adults aged ≥ 65 years was conducted from August 2015 to September 2019 in Usuki, Oita Prefecture, Japan. One hundred and twenty-two individuals with mild cognitive impairment or subjective memory complaints (54 men and 68 women, median age: 75.50 years) wore wearable sensors and completed self-reported questionnaires, cognitive test, and positron emission tomography imaging at baseline. Moreover, 99 individuals in the second year and 61 individuals in the third year were followed up. In total, 282 eligible records with valid wearable sensors, cognitive test results, and amyloid imaging and data on demographic characteristics, living environments, and health behaviors were used in the machine learning models. Amyloid positivity was defined as a standardized uptake value ratio of ≥ 1.4. Models were constructed using kernel support vector machine, Elastic Net, and logistic regression for predicting amyloid positivity. The mean score among 10 times fivefold cross-validation repeats was utilized for evaluation.

Results
In Elastic Net, the mean area under the receiver operating characteristic curve of the model using objectively measured lifestyle factors alone was 0.70, whereas that of the models using wearable sensors in combination with demographic characteristics and health and life environment questionnaires was 0.79. Moreover, 22 variables were common to all machine learning models.

Conclusion
Our machine learning models are useful for predicting elevated brain amyloid burden using readily-available and noninvasive variables without the need to visit a hospital.

Trial registration
This prospective study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of Oita University Hospital (UMIN000017442). A written informed consent was obtained from all participants. This research was performed based on the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.
Towards a socially vibrant city: exploring urban typologies and morphologies of the emerging “CityWalks” in Dubai
Authors: Kordi Alaa Omar , Galal Ahmed Khaled 
Published: December 2023

AbstractVertical urbanization to maximize land use in many cities has led to a shortage of urban spaces that could adequately meet people's needs. In response, CityWalk has emerged as a new urban form to solve this problem by attracting people to go from inside closed buildings to outside walks. Thus, it is promoting health, economy, and tourism. Locally in the United Arab Emirates (UAE), especially in Dubai, a limited number of CityWalks have been developed. Despite the increasing popularity of CityWalks, there has been a gap in research examining their distinct emerging urban typologies and their urban configuration. This study seeks to address this gap by first conceptualizing CityWalk as an emerging urban public space based on the exploration of global and local experiences. Second, the study categorized the morphological configuration of three selected case studies of CityWalks in Dubai using Geographic Information System (GIS) tools. These case studies represent three different developments of CityWalks in three different contexts in the UAE. First, CityWalks within the inner city's urban context are represented by ‘City Walk’ in Al Wasel. Second, CityWalks surrounded by the sea represented by 'The Walk’ in Marsa Dubai. Third, CityWalks developed next to traditional buildings represented by ‘Al Seef’ in Al Hamriya. The findings of the research investigations reveal that the emerging ‘CityWalks’ developments in each of the three different urban contexts in Dubai do not represent a single familiar urban space typology but rather a ‘harmonious’ blend of global and local urban design typologies. In addition, the urban morphological analysis of these three urban developments underscores the distinctive characteristics of each of them in terms of street network, urban form, urban compactness, land use, and shading. This contributes to better understanding of these emerging urban forms and hence pave the way for more research about their socio-economic robustness to ultimately contribute to more successful future designs of ‘CityWalks’ in Dubai and other cities in the region.