bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and prognostic validation of a three-level NHG-like deep learning-based model for histological grading of breast cancer
Authors: Sharma Abhinav , Weitz Philippe , Wang Yinxi , Liu Bojing , Vallon-Christersson Johan , Hartman Johan , Rantalainen Mattias 
Published: January 2024

AbstractBackgroundHistological grade is a well-known prognostic factor that is routinely assessed in breast tumours. However, manual assessment of Nottingham Histological Grade (NHG) has high inter-assessor and inter-laboratory variability, causing uncertainty in grade assignments. To address this challenge, we developed and validated a three-level NHG-like deep learning-based histological grade model (predGrade). The primary performance evaluation focuses on prognostic performance.MethodsThis observational study is based on two patient cohorts (SöS-BC-4,N = 2421 (training and internal test); SCAN-B-Lund,N = 1262 (test)) that include routine histological whole-slide images (WSIs) together with patient outcomes. A deep convolutional neural network (CNN) model with an attention mechanism was optimised for the classification of the three-level histological grading (NHG) from haematoxylin and eosin-stained WSIs. The prognostic performance was evaluated by time-to-event analysis of recurrence-free survival and compared to clinical NHG grade assignments in the internal test set as well as in the fully independent external test cohort.ResultsWe observed effect sizes (hazard ratio) for grade 3 versus 1, for the conventional NHG method (HR = 2.60 (1.18–5.70 95%CI,p-value = 0.017)) and the deep learning model (HR = 2.27, 95%CI 1.07–4.82,p-value = 0.033) on the internal test set after adjusting for established clinicopathological risk factors. In the external test set, the unadjusted HR for clinical NHG 2 versus 1 was estimated to be 2.59 (p-value = 0.004) and clinical NHG 3 versus 1 was estimated to be 3.58 (p-value < 0.001). For predGrade, the unadjusted HR for predGrade 2 versus 1 HR = 2.52 (p-value = 0.030), and 4.07 (p-value = 0.001) for preGrade 3 versus 1 was observed in the independent external test set. In multivariable analysis, HR estimates for neither clinical NHG nor predGrade were found to be significant (p-value > 0.05). We tested for differences in HR estimates between NHG and predGrade in the independent test set and found no significant difference between the two classification models (p-value > 0.05), confirming similar prognostic performance between conventional NHG and predGrade.ConclusionRoutine histopathology assessment of NHG has a high degree of inter-assessor variability, motivating the development of model-based decision support to improve reproducibility in histological grading. We found that the proposed model (predGrade) provides a similar prognostic performance as clinical NHG. The results indicate that deep CNN-based models can be applied for breast cancer histological grading.
The use of healthcare systems data for RCTs
Authors: Toader Alice-Maria , Gamble Carrol L. , Dodd Susanna , Williamson Paula R. 
Published: January 2024

Abstract
Background
Healthcare systems data (HSD) has the potential to optimise the efficiency of randomised controlled trials (RCTs), by decreasing trial-specific data demands. Therefore, the use of HSD in trials is expected to increase. In 2019, it was estimated that 47% of NIHR-funded trials were planning to use HSD. We aim to understand the extent and nature of its current use and its evolution over time.

Methods
We identified a cohort of RCTs within the NIHR Journals Library that commenced after 2019 and were described as being in progress on 6 June 2022. Details on the source and use of HSD were extracted from eligible RCTs. The use of HSD was categorised according to whether it was used as the sole data source for outcomes and whether the outcomes were primary or secondary. HSD is often insufficient for patient-reported outcomes (PROs). We aimed to determine methods used by trialists for collecting PRO data alongside HSD.

Results
Of the 84 eligible studies, 52 (62%) planned to use HSD and 79 (94%) planned to collect PROs. The number of RCTs planning to use HSD for at least one outcome was 28 (54%) with 24 of these planning to use HSD as the sole data source for at least one outcome.
The number of studies planning to use HSD for primary and secondary outcomes was 10 (20%) and 21 (40%) respectively. The sources of HSD were National Health Service (NHS) Digital (n = 37, 79%), patient registries (n = 7, 29%), primary care (n = 5, 21%), The Office for National Statistics (ONS) (n = 3, 13%) and other (n = 2, 8%).
PROs were collected for 92% of the trials planning to use HSD. Methods for collection of PROs included in-person (n = 26, 54%), online (n = 22, 46%), postal (n = 18, 38%), phone (n = 14, 29%) and app (n = 2, 4%).

Conclusions
HSD is being used in around two thirds of the studies but cannot yet be used to support PRO data collection within the cohort we examined. Comparison with an earlier cohort demonstrates an increase in the number of RCTs planning to use HSD.
Using healthcare systems data for outcomes in clinical trials: issues to consider at the design stage
Authors: Toader Alice-Maria , Campbell Marion K. , Quint Jennifer K. , Robling Michael , Sydes Matthew R , Thorn Joanna , Wright-Hughes Alexandra , Yu Ly-Mee , Abbott Tom. E. F. , Bond Simon , Caskey Fergus J. , Clout Madeleine , Collinson Michelle , Copsey Bethan , Davies Gwyneth , Driscoll Timothy , Gamble Carrol , Griffin Xavier L. , Hamborg Thomas , Harris Jessica , Harrison David A. , Harji Deena , Henderson Emily J. , Logan Pip , Love Sharon B. , Magee Laura A. , O’Brien Alastair , Pufulete Maria , Ramnarayan Padmanabhan , Saratzis Athanasios , Smith Jo , Solis-Trapala Ivonne , Stubbs Clive , Farrin Amanda , Williamson Paula 
Published: January 2024

Abstract
Background
Healthcare system data (HSD) are increasingly used in clinical trials, augmenting or replacing traditional methods of collecting outcome data. This study, PRIMORANT, set out to identify, in the UK context, issues to be considered before the decision to use HSD for outcome data in a clinical trial is finalised, a methodological question prioritised by the clinical trials community.

Methods
The PRIMORANT study had three phases. First, an initial workshop was held to scope the issues faced by trialists when considering whether to use HSDs for trial outcomes. Second, a consultation exercise was undertaken with clinical trials unit (CTU) staff, trialists, methodologists, clinicians, funding panels and data providers. Third, a final discussion workshop was held, at which the results of the consultation were fed back, case studies presented, and issues considered in small breakout groups.

Results
Key topics included in the consultation process were the validity of outcome data, timeliness of data capture, internal pilots, data-sharing, practical issues, and decision-making. A majority of consultation respondents (n = 78, 95%) considered the development of guidance for trialists to be feasible. Guidance was developed following the discussion workshop, for the five broad areas of terminology, feasibility, internal pilots, onward data sharing, and data archiving.

Conclusions
We provide guidance to inform decisions about whether or not to use HSDs for outcomes, and if so, to assist trialists in working with registries and other HSD providers to improve the design and delivery of trials.
Development and validation of a nomogram for predicting in-hospital mortality of patients with cervical spine fractures without spinal cord injury
Authors: Xing Zhibin , Cai Lingli , Wu Yuxuan , Shen Pengfei , Fu Xiaochen , Xu Yiwen , Wang Jing 
Published: January 2024

Abstract
Background
The incidence of cervical spine fractures is increasing every day, causing a huge burden on society. This study aimed to develop and verify a nomogram to predict the in-hospital mortality of patients with cervical spine fractures without spinal cord injury. This could help clinicians understand the clinical outcome of such patients at an early stage and make appropriate decisions to improve their prognosis.

Methods
This study included 394 patients with cervical spine fractures from the Medical Information Mart for Intensive Care III database, and 40 clinical indicators of each patient on the first day of admission to the intensive care unit were collected. The independent risk factors were screened using the Least Absolute Shrinkage and Selection Operator regression analysis method, a multi-factor logistic regression model was established, nomograms were developed, and internal validation was performed. A receiver operating characteristic (ROC) curve was drawn, and the area under the ROC curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the discrimination of the model. Moreover, the consistency between the actual probability and predicted probability was reflected using the calibration curve and Hosmer–Lemeshow (HL) test. A decision curve analysis (DCA) was performed, and the nomogram was compared with the scoring system commonly used in clinical practice to evaluate the clinical net benefit.

Results
The nomogram indicators included the systolic blood pressure, oxygen saturation, respiratory rate, bicarbonate, and simplified acute physiology score (SAPS) II. The results showed that our model had satisfactory predictive ability, with an AUC of 0.907 (95% confidence interval [CI] = 0.853–0.961) and 0.856 (95% CI = 0.746–0.967) in the training set and validation set, respectively. Compared with the SAPS-II system, the NRI values of the training and validation sets of our model were 0.543 (95% CI = 0.147–0.940) and 0.784 (95% CI = 0.282–1.286), respectively. The IDI values of the training and validation sets were 0.064 (95% CI = 0.004–0.123; P = 0.037) and 0.103 (95% CI = 0.002–0.203; P = 0.046), respectively. The calibration plot and HL test results confirmed that our model prediction results showed good agreement with the actual results, where the HL test values of the training and validation sets were P = 0.8 and P = 0.95, respectively. The DCA curve revealed that our model had better clinical net benefit than the SAPS-II system.

Conclusion
We explored the in-hospital mortality of patients with cervical spine fractures without spinal cord injury and constructed a nomogram to predict their prognosis. This could help doctors assess the patient’s status and implement interventions to improve prognosis accordingly.
The Multidimensional Assessment of Interoceptive Awareness, version 2 (MAIA-2): psychometric properties in a Dutch non-clinical sample
Authors: Scheffers Mia , Coenen Jaisey , Moeijes Janet , de Haan Albertine , van Busschbach Jooske , Bellemans Tina 
Published: January 2024

Abstract
Background
Interoceptive awareness is a multidimensional construct that refers to the sensation, interpretation, and integration of signals within the body. There is increasing evidence that problems with interoceptive awareness form an important component of mental health problems. The Multidimensional Assessment of Interoceptive Awareness 2 (MAIA-2) is presently the most used self-report questionnaire to measure interoceptive awareness. The aim of the present study is to psychometrically evaluate the Dutch version of the MAIA-2.

Method
The psychometric properties of the MAIA-2-NL were examined in a non-clinical sample of 1054 participants aged between 18 and 83. Internal consistency and test-retest reliability were investigated. Factor structure was examined by exploratory factor analysis (EFA), followed by confirmatory factor analysis (CFA).

Results
Internal consistency was good, with McDonald’s omega (ω) ranging from 0.67 to 0.89. Test-retest reliability was moderate to good, with intraclass correlation coefficients (ICC) ranging from 0.67 to 0.79. Factor analyses suggested a six-factor structure, combining the original subscales Noticing with Emotional awareness and Self-regulation with Body listening. However, a CFA based on the original eight factors showed a somewhat better fit than the CFA based on six factors.

Conclusion
The MAIA-2-NL is a reliable and valid instrument to measure interoceptive awareness in healthy Dutch adults. We recommend to maintain the original 37 items.
Association between body weight perception and actual body mass index among adult women in Erbil city, Iraq
Authors: Shabu Sherzad A. , Saka Mariwan H. , Boya Manhal N. , Ahmed Hamdia M. , Zaki Sahar M. , Hettinga Florentina , Shabila Nazar P. 
Published: January 2024

Abstract
Background
The misperception of body weight can significantly affect individuals' health behaviors, such as physical activity, diet, and weight management. This study aimed to examine the association between body weight perception and actual body mass index (BMI) among adult women and explore the factors influencing this relationship.

Methods
Five hundred forty female individuals aged 18–65 participated in this cross-sectional study. The validated Global Physical Activity Questionnaire was used for data collection. The BMI of the participants was calculated from measured body weight and height. Body weight perception was assessed using a single questionnaire item. The association of BMI and body weight perception was assessed, and the result was categorized as underestimation, consistency, and overestimation. The Chi-square test was used to assess the association between the consistency of BMI and body weight perception by different sociodemographic factors. The kappa test was used to analyze the consistency of BMI and body weight perception.

Results
Of the 540 participants, 13.3% underestimated their body weight status, 79.1% accurately perceived their body weight status, and 7.6% overestimated their body weight status. Unmarried women (11.7%) were more likely than ever married (4.3%) to overestimate their body weight (p = 0.005). On multiple logistic regression, being unmarried (OR = 1.68 (95%CI 1.01–2.80)) was significantly associated with body weight misperception. Body weight perception and BMI categories showed a significantly good consistency (kappa = 0.612, p < 0.001). Correct perception of body weight was highest among the overweight, followed by normal weight and underweight individuals (82.1%, 75.8%, and 72.2%, respectively).

Conclusion
Body weight perception was well associated with actual body weight status. Unmarried women are more likely to misperceive body weight, particularly overestimating it. Underestimation of body weight was relatively high and much higher than the overestimation, which might keep obese individuals from weight loss activities. Preventing obesity should include awareness about body weight misperceptions.
Marijuana use may be associated with reduced prevalence of prostate cancer: A cross-sectional study using the national survey on drug use and health database.
Authors: Mohammed Turab J , Yu James , Qiao Yong , Kim Youngchul , Swede Helen , Wu Zhao , Mortensen Eric , Zhang Jingsong 
Published: January 2024

101 Background: Preclinical data from cell lines and animal xenograft models support the anti-tumor effects of cannabinoids in prostate cancer (PC). Methods: We performed a cross-sectional study to investigate this association using National Survey on Drug Use and Health (NSDUH) data consisting of 2503 participants accrued from 2002 to 2020. Key independent variable was defined as current, former, and never users of marijuana (MJ). Dependent variable was self-reported PC (yes, no). Other MJ-related variables evaluated: age at first use, number of days used in the past 30 days, use of medical MJ, legality of MJ use in state of residence. Demographic variables assessed as potential confounders or covariates were: age, sex, race/ethnicity, education, marital status, total family income, insurance status, sexual identity, residence status, served in armed forces, cigarette smoking, and alcohol consumption. Multivariate (MV) logistic regression was employed to calculate odds ratios (OR) and 95th percentile confidence intervals (CI) to quantify relationship with MJ use in relation to PC status. Results: Prevalence of PC was significantly lower among current MJ users (46/145, 31.7%), and former users (323/1021, 31.6%) in comparison to non-users (534/1337, 39.9%, p < 0.001). Older MJ users (≥ 65) had significantly lower prevalence of PC compared to nonusers (36.4% vs. 42.4%, p = 0.016). A similar significant reduction was documented among non-Hispanic white (NHW) MJ users when compared to nonusers (28.9% vs. 38.3%, p < 0.001). There were no significant differences in the prevalence of PC between MJ users and non-users among the young (50-64) or other race/ethnicity. In MV logistic regression analyses, former MJ use was associated with a lower prevalence of PC compared to never use (OR = 0.74, 95% CI 0.62 - 0.90, p=0.001). Current MJ use also was suggestive of reduced prevalence but did not reach statistical significance (OR=0.77, 95% CI 0.52 – 1.14, p=0.198) possibly due to low sample size. Conclusions: Our findings provide additional data to link MJ use with low prevalence of PC, particularly in NHW. Future prospective studies using regulatory approved medical MJ are warranted. [Table: see text]
The effect of radiotherapy on the course of disease in prostatic cancer with high metastatic burden.
Authors: Falick Tal , Blumenfeld Philip , Skripai Antoni , Wygoda Marc R. 
Published: January 2024

112 Background: Many retrospective studies suggest that local RT for the prostate in the metastatic setting improves overall survival, however the question of whether metastatic burden is an independent factor influencing the results of localized treatment was not directly addressed. Moreover, results are conflicting with the outcomes from prospective trials on the subject. Thus overall, there is a limited, conflicting and insufficient data on the effect of radiotherapy on prostate cancer patients with a significant metastatic burden. Here we show that RT treatment in prostate cancer patients with a significant metastatic burden (four or more bone metastases with one or more outside the vertebral bodies or pelvis or a visceral metastases) is beneficial and extends overall survival while reducing symptoms. Methods: We conducted a retrospective study examining 100 high metastatic burden prostate cancer patients treated in Hadassah Ein Karem Medical Center between the years of 2004-2022. Data was collected from the medical records of the hospital. Variables that were recorded include basic demographics, time and durations of hospitalization, cancer staging, treatment course, RT course, imaging after RT, vital status, clinical symptoms and PSA levels. Tumors could be of any grade (Gleason score 6–10) and T or N stage (T1-T4; N0-N1; M1). Prostate RT included external EBRT to the prostate with/ without pelvis. Radiotherapy dosage between 30-60 gy using conventional fractionation. Results: Overall Survival was higher in the RT group when compared to NRT group (P < 0.046). Progression free survival (PFS) was not significantly higher in the RT group as compared to the NRT group (P < 0.153). However, a trend towards better PFS was noted. Biochemical progression free survival was higher in the RT group when compared to NRT group (P < 0.033). Time without symptom worsening as defined by time since treatment beginning until worsening of a symptom or appearance of a new symptom reported by the patient included urinary incontinence, urinary urgency, and increased frequency, need for catheter or urinary obstruction. Time without symptom worsening was higher in the RT group as compared to NRT group (P < 0.017). The amount of hospitalization wasn’t significantly higher in the RT group when compared to NRT group (P < 0.460). The duration of hospitalization was significantly higher in the NRT group when compared to the RT group (P < 0.038). Conclusions: Here we show for the first time an increase of overall survival specifically in the high metastatic burden group when adding the RT to a standard treatment of choice (ADT with or without chemotherapy). We also demonstrate an improvement in QOL of our patients.
Baseline characteristics of patients with PSMA-PET–positive and –negative disease with high-risk of biochemical recurrence (BCR) after radical prostatectomy (RP) in the ongoing phase 3 PRIMORDIUM study.
Authors: Hadaschik Boris A. , Mottet Nicolas , Ost Piet , De Nunzio Cosimo , Tunariu Nina , Zaucha Renata , Brasso Klaus , Osman-Garcia Ignacio , Tural Deniz , Lukac Martin , Stitou Hind , Pissart Geneviève , Efficace Michela , Fanti Stefano 
Published: January 2024

119 Background: Positron emission tomography of radiolabeled prostate-specific membrane antigen (PSMA-PET) is more sensitive and specific than conventional imaging for the detection of lesions in patients with BCR prostate cancer. PRIMORDIUM (NCT04557059) includes standardized PSMA-PET imaging and enrolls PSMA-PET positive patients (≥1 locoregional lesion; interventional cohort) and PSMA-PET negative patients (no lesion; observational cohort); all patients are non-metastatic by conventional imaging at screening. Methods: We presented study methods at ESMO 2021 (Poster 649TiP). All patients enrolled in PRIMORDIUM have high-risk BCR (prostate specific antigen [PSA] doubling time ≤12 months or Gleason score ≥8) after RP. PSMA-PET-positive patients are randomized 1:1 to either the control arm (whole pelvic salvage radiotherapy [RT] + 6 months of luteinizing hormone-releasing hormone agonist [LHRHa]) or the interventional arm (RT + LHRHa + apalutamide 240 mg/day for 180 days); stereotactic body RT (SBRT) to ≤3 distant lesions is optional. PSMA-PET-negative patients are managed per routine clinical practice. Results: Key baseline characteristics of 198 enrolled patients at data cutoff (12-Jan-2023) are summarized in the table. Conclusions: The PRIMORDIUM study aims to evaluate the intensification of treatment with apalutamide for patients assessed with PSMA-PET. From 198 enrolled patients with high-risk BCR, positive PSMA-PET was documented in 44% of patients at a median of 39 months after RP and a median PSA of 0.51 ng/mL, while negative PSMA-PET was observed in 56% of patients at a median of 26 months after RP and a median PSA of 0.35 ng/mL. In this analysis, all PSMA-PET-positive patients had locoregional lesion(s) and 10% also had distant lesion(s) on PSMA-PET. Clinical trial information: NCT04557059 . [Table: see text]
Predictors of PSA response to Lu177-PSMA-617 in metastatic castration-resistant prostate cancer.
Authors: Hassoun Rebecca , Tann Mark , Sims Justin , Auxier Ashleigh , Althouse Sandra K. , Salous Tareq , King Jennifer , Adra Nabil 
Published: January 2024

135 Background: Lu177-PSMA-617 (Lu177) therapy is effective in a subgroup of patients with metastatic castration resistant prostate cancer (mCRPC). We evaluated PSA responses in subgroups of pts with mCRPC. Methods: Pts with mCRPC who progressed after androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy (or who have refused chemotherapy) were treated with Lu177. Baseline clinical/molecular characteristics and PSMA PET parameters were analyzed and association with PSA30 and PSA50 response was evaluated. Results: 97 pts were included. Median age was 73.4 (55.9, 90.2). At baseline PSMA PET: 78 pts had PSMA + disease in bone, 61 lymph nodes, 9 lungs, 5 liver, and 1 brain. 33 pts had 1 prior ARPI, 64 pts had ≥2 prior ARPI. 13 pts had no prior taxane regimen, 42 had 1 prior taxane, 31 had 2 prior taxanes and 11 had ≥3 taxane regimens. 17 pts had prior PARP inhibitor. With a median follow-up of 6.5 months (1.38-14.54) from starting Lu177 therapy, 56 (57.7%) pts achieved a PSA30 response, and 49 (50.5%) pts achieved a PSA50 response. 59 (60.8%) pts achieved any confirmed PSA response. Grade≥3 toxicity occurred in 9 pts. Differential PSA response by subgroups is listed in the Table. Conclusions: There is a trend with higher PSA30 and PSA50 response to Lu177 with higher SUVmean, higher SUVmax, and less prior taxane exposure. [Table: see text]