bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between sleep duration from midlife to late life and the risk of depressive symptoms: the Singapore Chinese Health Study
Authors: Li Huiqi , Tai Bee Choo , Pan An , Koh Woon-Puay 
Published: October 2024

Background
The prospective association between sleep duration and the development of late-life depressive symptomology is unclear.

Aims
To investigate sleep duration from midlife to late life in relation to risk of depressive symptoms in late life.

Method
A total of 14 361 participants from the Singapore Chinese Health Study were included in the present study. Daily sleep duration was self-reported at baseline (mean age of 52.4 years; 1993–98), follow-up 2 (mean age of 65.2 years; 2006–10) and follow-up 3 (mean age of 72.5 years; 2014–16) interviews. Depressive symptoms were evaluated using the Geriatric Depression Scale at follow-up 3 interviews. Modified Poisson regression models were performed to estimate relative risks and 95% confidence intervals of late-life depressive symptoms in relation to sleep duration at baseline and the two follow-up interviews.

Results
Compared with sleeping 7 h per day, a short sleep duration of ≤5 h per day at baseline (i.e. midlife) was related to a higher risk of depressive symptoms (relative risk 1.10, 95% CI 1.06–1.15), and this risk was not affected by subsequent prolongation of sleep. Conversely, a long sleep duration of ≥9 h per day at baseline was not related to risk of depressive symptoms. At follow-up 3 (i.e. late life), both short sleep (relative risk 1.20, 95% CI 1.16–1.25) and long sleep (relative risk 1.12, 95% CI 1.07–1.18) duration were cross-sectionally associated with depressive symptoms.

Conclusion
Short sleep duration in midlife, regardless of subsequent prolongation, is associated with an increased risk of depression in late life. Contrariwise, both short and long sleep duration in late life co-occur with depressive symptoms.
Disease trajectories before dementia: evidence from a large-scale community-based prospective study
Authors: Li Jialin , Xia Ding , Cui Mei , Wang Yingzhe , Li Jincheng , Jin Li , Chen Xingdong , Suo Chen , Jiang Yanfeng 
Published: October 2024

BackgroundSystemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.AimsBy characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.MethodUsing the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.ResultsOur study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.ConclusionsThis study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.
Quality of Treatment Selection for Medicare Beneficiaries With Cancer
Authors: Mitchell Aaron P. , Persaud Sonia , Mishra Meza Akriti , Fuchs Hannah E. , De Prabal , Tabatabai Sara , Chakraborty Nirjhar , Dey Pranam , Trivedi Niti U. , Mailankody Sham , Blinder Victoria , Green Angela , Epstein Andrew S. , Daly Bobby , Roeker Lindsey , Bach Peter B. , Gönen Mithat 
Published: October 2024

PURPOSE
The Medicare part D Low-Income Subsidy (LIS) improves access to oral cancer drugs, but provides no assistance for clinician-administered/part B drugs. This analysis assessed the association between LIS participation and receipt of optimal cancer treatment.

METHODS

We investigated initial systemic therapy using SEER-Medicare data (2015-2017) and National Comprehensive Cancer Network (NCCN) Evidence Blocks (EB) as the standard for treatment recommendations. We included cancer clinical scenarios wherein (1) ≥one treatment was optimal (higher efficacy and safety scores) versus other treatments; (2) identifiable in SEER-Medicare (eg, not defined by clinical data unavailable in registry data or claims); and (3) both EB and ASCO Value Framework agreed regarding optimal treatment. We fit logistic regression models to assess the association between receipt of systemic therapy (
v
no therapy) and patient and provider characteristics. Contingent on receipt of treatment, we modeled the likelihood of receiving a treatment ranked (by EB scores) within the highest or lowest quartile for that cancer type.

RESULTS
Nine thousand two hundred and ninety patients were included across 11 clinical scenarios. Fifty-seven percent (5,336) of patients received any systemic therapy and 43% (3,954) received no systemic therapy. Compared with non-LIS participants, LIS participants were less likely to receive any systemic therapy versus no systemic therapy (odds ratio, 0.64 [95% CI, 0.57 to 0.72]). Contingent on receiving systemic therapy, LIS participants received treatment ranked within the worst quartile 24.8% of the time, compared with 21.9% of non-LIS patients (adjusted prevalence difference, 4.3% [95% CI, 0.5 to 8.2]).

CONCLUSION
LIS participants were less likely to receive systemic therapy at all and were more likely to receive treatments that receive low NCCN EB scores.
5-Hydroxymethylated Biomarkers in Cell-Free DNA Predict Occult Colorectal Cancer up to 36 Months Before Diagnosis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: West-Szymanski Diana C. , Zhang Zhou , Cui Xiao-Long , Kowitwanich Krissana , Gao Lu , Deng Zifeng , Dougherty Urszula , Williams Craig , Merkle Shannon , He Chuan , Zhang Wei , Bissonnette Marc 
Published: October 2024

PURPOSE
Using the prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial samples, we identified cell-free DNA (cfDNA) candidate biomarkers bearing the epigenetic mark 5-hydroxymethylcytosine (5hmC) that detected occult colorectal cancer (CRC) up to 36 months before clinical diagnosis.

MATERIALS AND METHODS
We performed the 5hmC-seal assay and sequencing on ≤8 ng cfDNA extracted from PLCO study participant plasma samples, including n = 201 cases (diagnosed with CRC within 36 months of blood collection) and n = 401 controls (no cancer diagnosis on follow-up). We conducted association studies and machine learning modeling to analyze the genome-wide 5hmC profiles within training and validation groups that were randomly selected at a 2:1 ratio.

RESULTS
We successfully obtained 5hmC profiles from these decades-old samples. A weighted Cox model of 32 5hmC-modified gene bodies showed a predictive detection value for CRC as early as 36 months before overt tumor diagnosis (training set AUC, 77.1% [95% CI, 72.2 to 81.9] and validation set AUC, 72.8% [95% CI, 65.8 to 79.7]). Notably, the 5hmC-based predictive model showed comparable performance regardless of sex and race/ethnicity, and significantly outperformed risk factors such as age and obesity (assessed as BMI). Finally, when splitting cases at median weighted prediction scores, Kaplan-Meier analyses showed significant risk stratification for CRC occurrence in both the training set (hazard ratio, [HR], 3.3 [95% CI, 2.6 to 5.8]) and validation set (HR, 3.1 [95% CI, 1.8 to 5.8]).

CONCLUSION
Candidate 5hmC biomarkers and a scoring algorithm have the potential to predict CRC occurrence despite the absence of clinical symptoms and effective predictors. Developing a minimally invasive clinical assay that detects 5hmC-modified biomarkers holds promise for improving early CRC detection and ultimately patient outcomes.
Fully Automated Artificial Intelligence Solution for Human Epidermal Growth Factor Receptor 2 Immunohistochemistry Scoring in Breast Cancer: A Multireader Study
Authors: Krishnamurthy Savitri , Schnitt Stuart J. , Vincent-Salomon Anne , Canas-Marques Rita , Colon Eugenia , Kantekure Kanchan , Maklakovski Marina , Finck Wilfrid , Thomassin Jeanne , Globerson Yuval , Bien Lilach , Mallel Giuseppe , Grinwald Maya , Linhart Chaim , Sandbank Judith , Vecsler Manuela 
Published: October 2024

PURPOSE
The proven efficacy of human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate therapy for treating HER2-low breast cancers necessitates more accurate and reproducible HER2 immunohistochemistry (IHC) scoring. We aimed to validate performance and utility of a fully automated artificial intelligence (AI) solution for interpreting HER2 IHC in breast carcinoma.

MATERIALS AND METHODS
A two-arm multireader study of 120 HER2 IHC whole-slide images from four sites assessed HER2 scoring by four surgical pathologists without and with the aid of an AI HER2 solution. Both arms were compared with high-confidence ground truth (GT) established by agreement of at least four of five breast pathology subspecialists according to ASCO/College of American Pathologists (CAP) 2018/2023 guidelines.

RESULTS

The mean interobserver agreement among GT pathologists across all HER2 scores was 72.4% (N = 120). The AI solution demonstrated high accuracy for HER2 scoring, with 92.1% agreement on slides with high confidence GT (n = 92). The use of the AI tool led to improved performance by readers, interobserver agreement increased from 75.0% for digital manual read to 83.7% for AI-assisted review, and scoring accuracy improved from 85.3% to 88.0%. For the distinction of HER2 0 from 1+ cases (n = 58), pathologists supported by AI showed significantly higher interobserver agreement (69.8% without AI
v
87.4% with AI) and accuracy (81.9% without AI
v
88.8% with AI).

CONCLUSION
This study demonstrated utility of a fully automated AI solution to aid in scoring HER2 IHC accurately according to ASCO/CAP 2018/2023 guidelines. Pathologists supported by AI showed improvements in HER2 IHC scoring consistency and accuracy, especially for distinguishing HER2 0 from 1+ cases. This AI solution could be used by pathologists as a decision support tool for enhancing reproducibility and consistency of HER2 scoring and particularly for identifying HER2-low breast cancers.
Gestational Diabetes: An Update 60 Years After O’Sullivan and Mahan
Authors: McIntyre Harold David , Kampmann Ulla , Dalsgaard Clausen Tine , Laurie Josephine , Ma Ronald Ching Wan 
Published: October 2024

Abstract
Sixty years after the landmark publication by O'Sullivan and Mahan, the current paper seeks to review and place into context the importance of gestational diabetes (GDM) both as a marker of increased risk of adverse maternal and fetal pregnancy outcomes and as an indicator of future maternal and infant health risks. We review the evolution of GDM as a diagnosis, the ongoing debate regarding diagnostic approaches, the underlying pathophysiology, and the epidemiology and the importance of GDM in the context of the global epidemics of diabetes and obesity. Focusing on clinical management, we review lifestyle-based therapy and pharmacotherapy for GDM, consider obstetric management, and outline the short-term and lifelong health risks posed by a GDM diagnosis.
Psychiatric Comorbidities in Women With Complete Androgen Insensitivity Syndrome or Müllerian Duct Aplasia/Agenesis
Authors: Sorouri Khorashad Behzad , Kaabi Oumaima , Gardner Melissa D , Getahun Darios , Goodman Michael , Lash Timothy L , Lee Peter A , McCracken Courtney , May Joshua , Muzik Maria , Vupputuri Suma , Yacoub Rami , Sandberg David E 
Published: October 2024

Abstract

Context
Understanding mental health issues facing individuals with disorders/differences of sex development (DSD) is crucial for optimizing evidence-based practices in this population.

Objectives
This work aimed to compare the prevalence of psychiatric diagnoses among patients diagnosed with complete androgen insensitivity syndrome (CAIS) or müllerian duct aplasia/agenesis (MA) to male and female reference groups.

Methods
A retrospective cohort study was conducted among 3 large integrated health systems. Participants included all individuals with confirmed CAIS or MA enrolled in 1 of 3 Kaiser Permanente health-care systems between January 1, 1988, and January 31, 2017. For each DSD patient, age-, race/ethnicity- and health system–matched male and female referents with typical sex development were randomly selected. Outcome measurements were mental health diagnoses and use of psychiatric medications.

Results
The prevalence of anxiety and depressive disorders in the CAIS and MA cohorts was approximately twice as high as in male referents without DSD, but the corresponding differences relative to female referents were less evident. A subgroup of MA patients with uterine agenesis had a higher prevalence of bipolar disorder than either reference group, but these results were accompanied by wide CIs. Women with CAIS and MA more frequently filled psychiatric medications compared to male but not female referents.

Conclusion
On balance, these findings are reassuring, albeit requiring confirmation in other settings. Future studies using longitudinal designs and patient-reported outcomes are needed to evaluate changes in mental health status of CAIS and MA patients at different ages and different intervals following initial diagnosis.
Scoring System Assessing Risks of Growth in Sporadic Vestibular Schwannoma
Authors: Stastna Daniela , Macfarlane Robert , Axon Patrick , Mannion Richard , Donnelly Neil , Tysome James R. , Mathews Rajeev , Guilfoyle Mathew , Borsetto Daniele , Jayapalan Ronie , Lawes Indu , Buttimore Juliette , Bance Manohar 
Published: October 2024

BACKGROUND AND OBJECTIVES:
Surveillance studies offer sparse knowledge of predictors of future growth in sporadic vestibular schwannomas (VS).
Our aim was identification of these risk factors. We propose a scoring system to estimate the risk of growth in sporadic vestibular schwannoma.

METHODS:
This retrospective study is based on the demographic and radiological data of 615 adult patients under the surveillance for single VS in our center. Univariate analysis, multivariate regression, and Kaplan–Meier analysis were used when appropriate. The regression coefficient-based “VS score” was calculated based on Cox proportional-hazards regression.

RESULTS:
During surveillance, 285 tumors (46%) remained stable, 314 tumors (51%) grew, and 16 tumors (3%) shrank. The significant risks factors for future growth identified both in univariate and multivariate analyses were younger age at onset, cystic morphology, larger tumor volume, and cisternal location (as per Hannover grade). The proportion of growing tumors was 40%, 75%, and 96% among the homogeneous VS, primary cystic, and VS transformed to cystic, respectively. Moreover, tumor growth during the 1st year was significant predictor of continuous growth. Our “VS score” includes variables such as age, sex, morphology, and Hannover grade. The score extends between −3 and 6 points. Kaplan–Meier, confusion matrix, and receiver operating characteristic analysis proved high accuracy of our scoring model.

CONCLUSION:
Our retrospective study revealed that younger age, cystic morphology, cisternal extent, larger volume, and growth during 1st year were strong predictors of future growth. Moreover, we propose a scoring system that accurately estimates the risks of future tumor growth.
Eosinophil-Platelet Ratio as a Predictive Marker of the Postoperative Recurrence of a Chronic Subdural Hematoma
Authors: Yagi Kenji , Kanda Eiichiro , Hijikata Yasukazu , Tao Yoshifumi , Hishikawa Tomohito 
Published: October 2024

BACKGROUND AND OBJECTIVES:
Symptomatic chronic subdural hematoma (CSDH) is caused by repetitive hemorrhage and inflammation, which is commonly treated with burr-hole surgery and has a relatively high postoperative recurrence rate. A decrease in the platelet count is indicative of a hemorrhagic tendency, while an increase in the eosinophil count is associated with inflammation. Assessing the balance between platelet-associated hemostasis and eosinophil-associated inflammation using the indeterminate biomarker, the eosinophil-platelet ratio (EPR), may be essential. Therefore, in this study, the accuracy of the EPR in predicting postoperative CSDH recurrence was evaluated and their correlation was determined.

METHODS:
Data on symptomatic CSDHs of the cerebral hemisphere of patients who underwent burr-hole surgery at our institution between January 2013 and December 2022 were retrospectively reviewed. The EPR was calculated from preoperative peripheral blood examination data, and its correlation with postoperative CSDH recurrence was assessed. The hemispheres with CSDH were categorized into recurrence and nonrecurrence cohorts.

RESULTS:
Data from 459 cerebral hemispheres of 405 patients with symptomatic CSDH were analyzed. In the 459 cerebral hemispheres with CSDH, 39 (8.5%) had postoperative recurrence. CSDH patients with a high EPR (≥1 × 10−3) had a significantly higher recurrent rate than those with a low EPR (<1 × 10−3) (15 of 86 [17.4%] vs 24 of 373 [6.4%], P = .002). In the modified Poisson regression analysis, the crude and adjusted risk ratios of high EPR were 2.79 (95% CI: 1.53, 5.09) and 2.62 (95% CI: 1.40, 4.89), respectively.

CONCLUSION:
This study reveals that a high EPR is a useful predictive biomarker for postoperative CSDH recurrence. Cases of CSDH with a high EPR potentially require careful and close postoperative follow-up.
The Low-Income and Middle-Income Countries' Perspective on Global Neurosurgery Collaborations
Authors: Marchesini Nicolò , Kamalo Patrick , Foroglou Nikolaos , Garozzo Deborah , Gonzalez-Lopez Pablo , Ivanov Marcel , Lafuente Jesus , Olldashi Fatos , Paternò Vincenzo , Petr Ondra , Rotim Krešimir , Rzaev Jamil , Timothy Jake , Tisell Magnus , Visocchi Massimiliano , Negida Ahmed , Uche Enoch , Rasulic Lukas , Demetriades Andreas K. 
Published: October 2024

BACKGROUND AND OBJECTIVES:
Access to neurosurgical care is limited in low-income and middle-income countries (LMICs) and in marginalized communities in high-income countries (HICs). International partnerships represent one possible means of addressing this issue. Insights from surgeons in HICs have been explored, but data from LMICs' counterparts are scarce. We aimed to study the perspectives of neurosurgeons and trainees from LMICs regarding global neurosurgery (GN) collaborations and interests, motivators, and challenges in participating.

METHODS:
An online survey was conducted targeting neurosurgeons and trainees from LMICs. The survey explored demographics, previous experiences, ongoing activities, interests, and barriers related to GN activities. Data were collected between July 2022 and December 2022 and analyzed.

RESULTS:
Responses involved 436 individuals. The most represented region (25%) was sub-Saharan Africa, and most respondents were male (87.8%) aged 35-49 years. Interest in GN was high, with 91% after its developments. Most respondents (96.1%) expressed interest in training, professional, or research experience in HICs, but only 18.1% could cover the expenses. A majority (73.2%) strongly agreed to return to their home country for work after HIC training. Ongoing HIC-LMIC partnerships were reported by 27.8% of respondents. Clinical exposure emerged as the most relevant motivating factor (87%), while financial concerns, lack of opportunities, and lack of program support were identified as important barriers. Funding and dedicated time were highlighted as the most crucial facilitators.

CONCLUSION:
Understanding the perspectives of neurosurgeons and trainees from LMICs is essential to expanding HICs-LMICs collaborations and improving access to neurosurgical care worldwide. Financial support and targeted interventions are needed to address barriers and promote equitable partnerships in GN.
Making in vitro conditions more reflective of in vivo conditions for research on the teleost gastrointestinal tract
Authors: Bucking Carol , Bury Nic R. , Sundh Henrik , Wood Chris M. 
Published: October 2024

ABSTRACT
To date, the majority of in vitro or ex vivo fish gastrointestinal research has been conducted under unrealistic conditions. In a living fish, ionic conditions, as well as levels of ammonia, pH, HCO3− and PCO2 differ considerably between the different regions of the gastrointestinal tract. These factors also differ from those of the saline often used in gut research. Furthermore, the oxygen gradient from the serosa to the gut lumen is rarely considered: in contrast to the serosa, the lumen is a hypoxic/anoxic environment. In addition, the gut microbiome plays a significant role in gut physiology, increasing the complexity of the in vivo gut, but replicating the microbial community for in vitro studies is exceptionally difficult. However, there are ways in which we can begin to overcome these challenges. Firstly, the luminal chemistry and PO2 in each gut compartment must be carefully considered. Secondly, although microbiological culture techniques are improving, we must learn how to maintain the microbiome diversity seen in vivo. Finally, for ex vivo studies, developing mucosal (luminal) solutions that more closely mimic the in vivo conditions will better replicate physiological processes. Within the field of mammalian gut physiology, great advances in ‘gut-on-chip’ devices are providing the tools to better replicate in vivo conditions; adopting and adapting this technology may assist in fish gut research initiatives. This Commentary aims to make fish gut physiologists aware of the various issues in replicating the in vivo conditions and identifies solutions as well as those areas that require further improvement.
The impacts of diet on cardiac performance under changing environments
Authors: Eliason Erika J. , Hardison Emily A. 
Published: October 2024

ABSTRACT
Natural and anthropogenic stressors are dramatically altering environments, impacting key animal physiological traits, including cardiac performance. Animals require energy and nutrients from their diet to support cardiac performance and plasticity; however, the nutritional landscape is changing in response to environmental perturbations. Diet quantity, quality and options vary in space and time across heterogeneous environments, over the lifetime of an organism and in response to environmental stressors. Variation in dietary energy and nutrients (e.g. lipids, amino acids, vitamins, minerals) impact the heart's structure and performance, and thus whole-animal resilience to environmental change. Notably, many animals can alter their diet in response to environmental cues, depending on the context. Yet, most studies feed animals ad libitum using a fixed diet, thus underestimating the role of food in impacting cardiac performance and resilience. By applying an ecological lens to the study of cardiac plasticity, this Commentary aims to further our understanding of cardiac function in the context of environmental change.