bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneity Without Rationality: A Kantian Approach to Self-Consciousness and Perceptual Content
Authors: Ginsborg Hannah 
Published: October 2024

Abstract
A number of philosophers, inspired by Kant’s view of self-consciousness as consciousness of spontaneity, have understood self-consciousness as requiring rational agency with respect to one’s beliefs and desires. This leads to a demanding conception of self-consciousness, which excludes the ascription of self-consciousness to children who are too young to appreciate reasons. I offer an interpretation of the role of spontaneity in perceptual experience which suggests that there can be spontaneity, in Kant’s sense, without rational agency. The consciousness of spontaneity, on my reading of Kant is the consciousness of normative constraint in one’s thinking, and, as I argue through consideration of sorting behaviour in small children, one can be conscious of normative constraint without recognizing reasons. This leads to a less demanding, but still recognizably Kantian, conception of self-consciousness, one which accommodates the idea that small children can be self-conscious.
Oligoribonucleotide interference-PCR-based methods for the sensitive and accurate detection of KRAS mutations
Authors: Fujita Hiroaki , Fujita Toshitsugu , Ishido Keinosuke , Hakamada Kenichi , Fujii Hodaka 
Published: October 2024

Abstract
Pancreatic cancer is an aggressive malignancy with a poor prognosis. Single-nucleotide mutations in the KRAS gene are detected in the majority of patients with pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. Identifying KRAS mutations by liquid biopsy could be effective for detecting de novo and recurrent PDAC; however, sensitive and accurate detection remains challenging. We examined the utility of oligoribonucleotide interference-PCR (ORNi-PCR) followed by real-time PCR or droplet digital PCR (ddPCR) for detecting KRAS single-nucleotide mutations by liquid biopsy. A model of cell-free DNA was used to demonstrate that the ORNi-PCR-based methods are more sensitive and accurate for detecting KRAS mutant DNA than conventional real-time PCR or ddPCR. ORNi-PCR-based methods could be useful for early detection of de novo and recurrent PDAC by liquid biopsy for cancer diagnosis.
Melanoma as a detection-dependent cancer: proxy measures of screening and surveillance associated with 3-year incidence of detection procedures for skin cancer in a national prospective study
Authors: Pandeya Nirmala , Olsen Catherine M , Neale Rachel E , Whiteman David C 
Published: October 2024

Abstract

Background
Increased levels of skin detection activities are suspected of driving recent rapid increases in melanoma incidence. While ecological studies report rising rates of skin biopsies in many industrialized populations, few studies have accessed individual-level clinical data to test the hypothesis that people exposed to skin screening and surveillance go on to experience higher levels of biopsies and excisions, and a higher incidence of melanoma.

Objectives
To measure the incidence rates of detection events and melanoma diagnoses in a national cohort during follow-up, stratified according to screening or surveillance activities in the index year.

Methods
We conducted a prospective cohort study of 10 674 200 adults using linked data from Australia’s universal health insurance scheme (2011–2016). Participants who underwent biopsies or who were diagnosed with skin cancer in 2011–12 were excluded. We then defined participants as surveilled, screened or unscreened for skin cancer based on medical claims occurring in 2013. We compared rates of biopsies, excisions for suspected melanoma and excisions for histologically confirmed melanoma during follow-up (2014–2016).

Results
After adjusting for sociodemographic factors, screened people were significantly more likely than unscreened people to undergo skin biopsies [rate ratio (RR) 2.59, 95% confidence interval (CI) 2.56–2.63], excisions for suspected melanoma (RR 2.57, 95% CI 2.53–2.60) and excisions for confirmed melanoma (hazard ratio 3.32, 95% CI 3.24–3.40) during follow-up. Similarly elevated rates of subsequent diagnostic events were observed for the surveilled group. Importantly, rates of detection and rates of melanoma remained elevated in each of the subsequent years of follow-up among those who were screened or surveilled in the index year.

Conclusions
People undergoing skin screening or surveillance subsequently experience higher rates of diagnostic scrutiny and higher rates of melanoma.
Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights
Authors: Honhar Praveen , Ebrahimian Sadabad Faranak , Tinaz Sule , Gallezot Jean-Dominique , Dias Mark , Naganawa Mika , Yang Yanghong , Henry Shannan , Hillmer Ansel T , Gao Hong , Najafzadeh Soheila , Comley Robert , Nabulsi Nabeel , Huang Yiyun , Finnema Sjoerd J , Carson Richard E , Matuskey David 
Published: October 2024

Abstract
[18F]FE-PE2I PET is a promising alternative to single positron emission computed tomography–based dopamine transporter (DAT) imaging in Parkinson’s disease. While the excellent discriminative power of [18F]FE-PE2I PET has been established, so far only one study has reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (∼3 mm isotropic) PET to provide an independent validation for the clinical correlates of [18F]FE-PE2I imaging in separate cross-sectional (28 participants with Parkinson’s disease, Hoehn–Yahr: 2 and 14 healthy individuals) and longitudinal (initial results from 6 participants with Parkinson’s disease with 2-year follow-up) cohorts. In the cross-sectional cohort, DAT availability in the putamen and substantia nigra of patients with Parkinson’s disease showed a significant negative association with total motor severity (r = −0.59, P = 0.002 for putamen; r = −0.46, P = 0.018 for substantia nigra), but not tremor severity. To our knowledge, this is the first observed association between motor severity in Parkinson’s disease and DAT availability in the substantia nigra. The associations with motor severity in most nigrostriatal regions improved if tremor scores were excluded from motor scores. Further, we found significant asymmetry in DAT availability in the putamen (∼28% lower DAT availability within the more-affected side of the putamen), and DAT-based asymmetry index for the putamen was correlated with asymmetry in motor severity (r = −0.60, P = 0.001). In the longitudinal study, [18F]FE-PE2I PET detected significant annual percentage reduction of DAT availability at the individual level in the putamen (9.7 ± 2.6%), caudate (10.5 ± 3.8%) and ventral striatum (5.5 ± 2.7%), but not the substantia nigra. Longitudinal per cent reduction in DAT availability within the putamen was strongly associated with increase in motor severity (r = 0.91, P = 0.011) at follow-up, demonstrating the high sensitivity of [18F]FE-PE2I PET in tracking longitudinal changes. These results provide further evidence for the utility of [18F]FE-PE2I as an important in vivo PET biomarker in future clinical trials of Parkinson’s disease.
Revisiting secondary mitral regurgitation threshold severity: insights and lessons from the RESHAPE-HF2 trial
Authors: Lancellotti Patrizio , Sugimoto Tadafumi , Bäck Magnus 
Published: October 2024

Abstract

Aims
This article revisits the severity threshold for secondary mitral regurgitation (MR), focusing on insights and lessons from the RESHAPE-HF2 trial. It aims to challenge the traditional effective regurgitant orifice area (EROA) threshold of ≥0.40 cm2 used for intervention, suggesting that earlier intervention may benefit patients with lower EROA. It also explores how transcatheter edge-to-edge repair (TEER) improves outcomes in patients with secondary MR and assesses the impact of left ventricular (LV) remodeling on treatment success.

Methods and Results
The RESHAPE-HF2 trial evaluated the use of TEER in patients with moderate-to-severe secondary MR, comparing outcomes in those with an EROA ≥0.2 cm2 and no extensive LV remodeling. TEER significantly reduced heart failure hospitalizations and improved quality of life in these patients. This supports the notion that patients with less severe MR, who still show symptoms despite optimal medical therapy, may benefit from earlier intervention. Comparisons with COAPT and MITRA-FR trials underscored the importance of selecting patients based on MR severity relative to LV dilatation.

Conclusions
The RESHAPE-HF2 trial highlights the need to reconsider the current EROA threshold for secondary MR intervention. TEER has shown to be beneficial even in patients with lower MR severity, suggesting that earlier intervention could improve outcomes. A more dynamic and integrated approach, considering both MR severity and LV remodeling, is essential for optimizing patient selection and treatment success.
Trends and risk factors analysis of aortic aneurysm mortality in China over thirty years: based on the global burden of disease 2019 data
Authors: Huang Hongliang , Tang Liming , Liu Chunjiang , Jin Gan 
Published: October 2024

Abstract

Objectives
This study aims to analyse the variation in mortality burden of aortic aneurysms (AAs) and explore the associated risk factors based on Global Burden of Disease (GBD) 2019 data, investigating the mortality burden of AA in China.

Methods and results
Using GBD 2019 data, the mortality burden of AA in China from 1990 to 2019 was analysed. The age-period-cohort model was utilized to analyse time trends, period, and cohort effects of four attributable risk factors of AA by age. In 2019, the total number of AA deaths in China increased by 136.1% compared to 1990, while the age-standardized mortality rate (ASMR) decreased by 6.8%. Male deaths and ASMR were higher than those of females, and ASMR increased with age. Whether viewed overall [average annual percent change (AAPC): −0.261, 95% confidence interval (CI): −0.383 to −0.138] or by sex (female AAPC: −0.812, 95% CI: −0.977 to −0.646; male AAPC: −0.011, 95% CI: −0.183–0.162), the ASMR for AA in China has shown a declining trend since 1990. Attributable risk factors such as high blood pressure, a diet high in sodium, smoking, and lead exposure increase AA mortality with age. Smoking mortality peaks between ages 80 and 85. The cyclical effect of high blood pressure on AA mortality significantly increases, while the cyclical effects of the other three risk factors decrease. For the population born after 1940, the cohort effect of high systolic blood pressure (SBP), a diet high in sodium, and smoking increased, while the cohort effect of lead exposure decreased. The local drift values of high SBP, a diet high in sodium, and smoking decreased, while the local drift value of lead exposure increased. High SBP was identified as the most significant attributable risk factor for AA mortality burden among both males and females, and smoking was another major attributable risk factor, particularly in males.

Conclusion
From 1990 to 2019, fatality due to AA in China increased notably, but the ASMR showed a decreasing trend. The mortality rate of AA was influenced by age, sex, and attributable risk factors, with elderly male smokers carrying a heavy burden of death. Moreover, tobacco control and treatment of hypertension should be strengthened to reduce the burden and its impact on AA.
Adult Socioeconomic Position Mediates the Association Between Childhood Socioeconomic Position and Later-Life Frailty Trajectory: A Nationally Representative Cohort Study
Authors: Guo Yanfei , Ng Nawi , Hassler Sven , Wu Fan , Jonasson Junmei Miao 
Published: October 2024

Abstract

Background and Objectives
Early-life risk factors influence the aging process in the short term and shape its trajectory in the long term. We aim to (1) explore the association between childhood socioeconomic position (cSEP) and frailty trajectories and (2) test whether adult socioeconomic position (aSEP) mediates the association between cSEP and frailty trajectories.

Research Design and Methods
We analyzed 4 waves of the China Health and Retirement Longitudinal Study data. The frailty index was estimated based on the number of individual deficits across 40 indicator variables. Principal component analysis was used to generate cSEP and aSEP. Group-based trajectory models were used to identify the patterns of frailty trajectories over time. Causal mediation analysis was conducted to determine whether the aSEP mediated the association between cSEP and frailty trajectories.

Results
We identified 3 distinct trajectories of frailty progression. Low cSEP was significantly associated with “High and increasing frailty trajectory” (odds ratio [OR] = 1.76, 95% confidence intervals [95% CI]: 1.38–2.23; adjusted OR = 1.55, 95% CI: 1.22–1.97). About 30% of the cSEP effect on rising frailty trajectory was mediated through the aSEP, and there is a significant gender disparity in the mediating effect of aSEP (18% among men and 51% among women, respectively).

Discussion and Implications
Our findings suggest that policies that initially benefit children will yield well-being benefits as they reach adulthood. Promoting ongoing cSEP advantages increases the likelihood of delaying frailty progression in later life. This study underscores the critical importance of addressing social determinants of health throughout one’s life course to foster healthy aging and diminish health disparities in later stages of life.
How we helped change the state lottery playslip
Authors: Rollinson Joseph , McIntosh Matthew , Ferguson Alex , Couch Josiah , Danley Bradley 
Published: October 2024

Abstract
A chat with friends about lottery numbers led one statistician and his dad to contact state lotteries across the USA and set up a unique undergraduate research group. Joseph Rollinson, Matthew McIntosh, Alex Ferguson, Josiah Couch and Bradley Danley recount the story so far
Beyond conventional wisdom: unexplored risk factors for penile fracture
Authors: Arikan Mehmet Gürkan , Akgul Burak , Turk Semih , Tantekin Ömer Onur , Çakiroğlu Basri , Arda Ersan 
Published: October 2024

Abstract

Background
Sexual intercourse is a predominant cause of penile fractures (PF).

Aim
To evaluate the relationship between body metrics and the severity of PF, identifying how anthropometric factors of patients and their partners influence the incidence and severity of PF.

Methods
This study analyzed 47 patients with PF over 9 years across multiple centers. Demographic and anthropometric data were collected for both patients and their partners. Injuries were categorized by the sexual position or activity causing them, including partner-related positions (man-on-top, woman-on-top, and doggy-style) and isolated actions (rolling-over, blunt trauma, masturbation, or manipulation). Statistical analysis was performed using the χ2-test.

Outcomes
The study aimed to uncover correlations between body metrics and the risk profile for PF, focusing on body mass index (BMI), weight, height, and age.

Results
The majority of PFs occurred during sexual activities (74.5%), particularly in “doggy” and “man-on-top” positions. Urethral involvement was observed in 10.6% of cases. Significant correlations were found between patient and partner ages (r = 0.915), patient BMI and weight (r = 0.874), patient height and weight (r = 0.502), and partner weight and BMI (r = 0.805). Higher BMI in patients was linked to delayed hospital visits (r = 0.377), and frequent sexual activity was strongly correlated with urethral complications (r = 0.727).

Clinical Implications
These findings emphasize the importance of considering body metrics in assessing PF risk and could guide future preventive strategies and clinical interventions.

Strengths & Limitations
The study’s strength lies in its comprehensive analysis of anthropometric factors and their correlation with PF severity. Limitations include a relatively small sample size and the potential for reporting bias in sexual activity data.

Conclusion
The study confirms sexual intercourse as the main cause of PF and highlights significant links between anthropometric factors and fracture severity. Higher BMI and weight in partners are associated with more centrally located fractures and urethral injuries, particularly in taller patients or those with larger partners.
Development and Validation of the Youth Back Activity Questionnaire
Authors: Selhorst Mitchell , Metzger Christina , Rice William , Ibinson Brittany , Mansfield Christine 
Published: October 2024

Design:
Psychometric study

Objective:
To develop a reliable and valid patient-reported outcome measure to assess functional ability in adolescents with low back pain (LBP) using the Rasch model.

Summary of Background Data:
LBP is quite common in adolescence. Currently, no method adequately measures the functional ability of adolescents with LBP. Widely used outcome measures for LBP are problematic in adolescents, with significant ceiling/floor effects.

Methods:
Two hundred adolescents (15.4 ± 1.9 years; 56% female) with LBP. This study was comprised of two parts: Part 1: Development of the Youth Back Activity Questionnaire (YouthBAQ) (n = 75), and Part 2: Psychometric evaluation of the newly designed YouthBAQ using the Rasch Model (n = 125). Participants also completed the Oswestry Disability Index (ODI) and Micheli Functional Scale (MFS), Data Analysis: Reliability and construct validity of the YouthBAQ were assessed using Rasch analyses. Correlations with the ODI and MFS were used to determine the convergent validity of the YouthBAQ.

Results:
Part 1: Based on the results of the Rasch analysis, 31 items were reduced to 14. Part 2. The 14-item YouthBAQ demonstrated good reliability and construct validity, with good item fit (>0.7 and <1.3), acceptable item hierarchy and spacing, response category functioning, unidimensionality (ratio >3:1), local independence (<0.30). The MFS demonstrated unacceptable reliability (person reliability = 0.62) and was not compared against the YouthBAQ. The ODI demonstrated acceptable reliability (person reliability =0.70), but poor construct validity among adolescents with LBP. The YouthBAQ demonstrated a moderate correlation with the ODI (r = 0.4).

Conclusion:
The YouthBAQ is a quick and easily understood measure of function with good validity and reliability in adolescents with LBP. The YouthBAQ is a more appropriate measure of functional ability than the ODI or MFS in this population.
The prognosis of patients with locally advanced cervical cancer undergoing surgical versus non-surgical treatment: a retrospective cohort study based on SEER database and a single-center data
Authors: Gao Xinyan , Kong Yan , Ning Ying , Tian Tian , Gai Xiaojing , Lei Ke , Cui Zhumei 
Published: October 2024

The aim of this study was to investigate the impact of surgical treatment on the survival prognosis of patients with locally advanced cervical cancer (LACC) and to identify factors that may influence the efficacy of surgery. Data from the SEER database (2000–2020) and a hospital (2013–2023) were collected for this investigation. Utilizing multivariable Cox regression analysis, Kaplan–Meier survival analysis, and log-rank tests, we assessed the effects of surgical intervention on overall survival (OS) and disease-specific survival (DSS) in LACC patients. Our results revealed that in the SEER database, the surgical group exhibited significantly better OS and DSS compared to the non-surgical group. Particularly noteworthy was the significantly higher survival rate in the surgical group for patients with tumor diameters less than 6 cm. Furthermore, both OS and DSS were improved in the surgical group regardless of whether the cancer was squamous cell carcinoma or adenocarcinoma. Additionally, patients who underwent surgery combined with radiotherapy had notably better OS and DSS compared to those who received chemoradiotherapy alone. Similarly, our hospital data showed that the surgical group demonstrated significantly better OS than the non-surgical group, especially for patients with tumors smaller than 6 cm in diameter. These findings suggest that surgery combined with radiotherapy may offer more favorable outcomes than chemoradiotherapy alone, particularly for LACC patients with smaller tumors.
Multisite DNA methylation alterations of peripheral blood mononuclear cells serve as novel biomarkers for the diagnosis of AIS/stage I lung adenocarcinoma: a multicenter cohort study
Authors: Li Peilong , Liu Shibiao , Wang Tiantian , Wang Fang , Li Juan , Qi Qiuchen , Zhang Shujun , Xie Yan , Li Jianping , Zhu Yongcai , Yang Suli , Yin Guotao , He Xiaoyi , Li Shijun , Xu Huiting , Xiong Mengqiu , Li Guanghua , Zhang Yi , Du Lutao , Wang Chuanxin 
Published: October 2024

Background:
Early diagnosis remains an obstacle for improving the outcome of lung adenocarcinoma (LUAD). DNA methylation changes in peripheral blood mononuclear cells (PBMCs) could reflect an immune response to tumorigenesis, providing the theoretical basis for early cancer diagnosis based on immune cell profiling.

Methods:
This multi-center study evaluated the DNA methylation patterns based on PBMCs samples from 1115 individuals at nine medical centers. Genome-wide DNA methylation profiling of PBMCs in a discovery cohort (35 LUAD patients and 50 healthy controls) was performed using Illumina 850K microarray. Candidate differentially methylated CpG positions (DMPs) were selected and validated in a two-step DMPs screening cohort (65 LUAD patients and 80 healthy controls) by pyrosequencing and multiple target region methylation enrichment sequencing (MTRMES). Then, an early LUAD Diagnostic Panel (LDP score) based on multisite methylation-specific chip-based digital PCR was constructed in a training set and then confirmed in a validation set from the LDP score development cohort (389 AIS/stage I LUAD patients and 293 healthy controls). Besides, we included 157 other cancer patients, including 52 gastric cancer (GC) patients, 50 breast cancer (BC) patients, and 55 colorectal cancer (CRC) patients to assess the specificity of the LDP score. In addition, we also evaluated the early warning ability of LDP score for LUAD in a prospective cohort (46 people who were at high-risk of developing LC).

Results:
A total of 1415 LUAD-specific DMPs were identified. Then, six DMPs were selected for validation and three DMPs were finally verified. The LDP score was constructed by combining the three DMPs, age, and sex, and showed an AUC of 0.916, sensitivity of 88.17%, and specificity of 80.20% in a combined set, outperforming traditional methods, such as CEA and CT (detection rate: 87.79% vs. 4.69%; 87.79% vs. 35.21%). This diagnostic performance was confirmed in sub-types of LUAD with clinical challenges, such as 6–20 mm LUAD (AUC: 0.914, 95% CI: 0.889–0.934) and ground-glass nodules (AUC: 0.916, 95% CI: 0.889–0.938). Importantly, our LDP score had significant improvement in terms of selecting high-risk individuals who should receive low-dose computed tomography (87.80% vs. 9.28%). Remarkably, the LDP score could predict LUAD around 2 years before clinical diagnosis in our prospective cohort.

Conclusions:
The novel developed LDP score represented a convenient and effective assay for the detection of AIS/stage I LUAD with high sensitivity and specificity, and had demonstrated unique advantages over traditional detection methods.