bluuebunny/crossref_metadata_2025_split huggingface dataset:
qBiCo: a method to assess global DNA conversion performance in epigenetics via single-copy genes and repetitive elements
Authors: Karkala Faidra , Simons Roy B. , Claessens Floor , Kalamara Vivian , Kayser Manfred , Vidaki Athina 
Published: January 2025

Abstract

Background
Human DNA methylation profiling offers great promises in various biomedical applications, including ageing, cancer and even forensics. So far, most DNA methylation techniques are based on a chemical process called sodium bisulfite conversion, which specifically converts non-methylated cytosines into uracils. However, despite the popularity of this approach, it is known to cause DNA fragmentation and loss affecting standardization, while incomplete conversion may result in potential misinterpretation of methylation-based outcomes.

Results
To offer the community a solution, we developed qBiCo - a novel quality-control method to address the quantity and quality of bisulfite-converted DNA. qBiCo is a 5-plex, TaqMan® probe-based, quantitative (q)PCR assay that amplifies single- and multi-copy DNA fragments of converted and non-converted nature. It estimates four parameters: converted DNA concentration, fragmentation, global conversion efficiency, and potential PCR inhibition. We optimized qBiCo using synthetic DNA standards and assessed it using standard developmental validation criteria, showcasing that qBiCo is reliable, robust and sensitive down to picogram level. We also evaluated its performance by testing decreasing DNA amounts using several commercial bisulfite conversion kits. Depending on the starting DNA quantity, bisulfite-converted DNA recoveries ranged from 8.5 to 100%, conversion efficiencies from 78 to 99.9%, while certain kits highly fragment DNA, demonstrating large variability in their performance. Towards building a prototype tool, we further optimized key functionalities, for example, by replacing the poorest performing single-plex assay and creating a more representative DNA standard. Aiming to scale-up and move towards implementation, we successfully transferred and validated our novel method in six different qPCR platforms from different major manufacturers.

Conclusions
Overall, with the present study, we offer researchers in the epigenetic field a novel long-awaited QC tool that for the first time allows them to measure key quality and quantity parameters of the most popular DNA conversion process. The tool also enables standardization to prevent inconsistent data and false outcomes in the future, regardless of the downstream experimental analysis of DNA methylation-based research and applications across different fields of biology and biomedicine.
Is early use of sodium-glucose cotransporter type 2 inhibitor (SGLT2i) necessary even in diabetic patients without cardiovascular disease: a prospective study regarding the effect of SGLT2i on left ventricular diastolic function
Authors: Jeon Kina , Jang Shin Yi , Lee You-Bin , Kim Jihoon , Kim Darae , Chang Sung-A , Park Sung-Ji , Lee Sang-Chol , Park Seung Woo , Lee Moon-Kyu , Kim Eun Kyoung , Hur Kyu Yeon 
Published: January 2025

Abstract

Background
There are insufficient studies to determine whether sodium-glucose cotransporter type 2 inhibitors (SGLT2i) will help reduce early diabetic cardiomyopathy, especially in patients without documented cardiovascular disease.

Methods
We performed a single center, prospective observation study. A total of 90 patients with type 2 diabetes patients without established heart failure or atherosclerotic cardiovascular disease were enrolled. Echocardiography, cardiac enzyme, and glucose-control data were examined before and 3 months after the administration of SGLT2i (dapagliflozin 10 mg per day). Cardiovascular risk factors included hypertension, smoking, obesity, dyslipidemia, and old age. The primary end point was the change of E/e’ before and after administration of SGLT2i.

Results
Most patients (86.7%) had three or more cardiovascular risk factors, and about 32% had all five risk factors. Although the decrease in E/e’ after the administration of SGLT2i was observed in 20% of enrolled patients, there was no significant difference in average E/e’ value or left atrial volume index before and after the SGLT2i medication. Even in patients with all known risk factors including old age, E/e’ value did not decrease after adding SGLT2i (8.9 ± 2.4 vs. 8.7 ± 3.2). There was a statistically significant difference in E/e’ change after the SGLT2i administration between patients younger than 60 years and those older than 60 years (–0.7 ± 2.2 vs. 1.1 ± 2.8, P = 0.002).

Conclusions
In type 2 diabetes patients without documented cardiovascular disease including heart failure, administration of SGLT2i showed no improvement in diastolic function profile. Further large-scale randomized studies are needed to determine who will benefit from potential cardiovascular events with early addition of SGLT2i.
Survival After Orbital Exenteration for Primary Cutaneous Squamous Cell Carcinoma: A Retrospective Cohort Study
Authors: Murray-Douglass Alexander , Crawford Lachlan , Hunt Justin , Dunn Darryl , Hughes Brett G. M. , Lin Charles , Fox Carly 
Published: January 2025

Abstract

Background
Locally advanced periorbital cutaneous squamous cell carcinoma (cSCC) may require orbital exenteration, which is highly morbid. As immunotherapy develops, orbit preservation may become widespread, and data benchmarking survival with current standard-of-care surgery and radiotherapy are essential to the integration of this emerging method into modern treatment paradigms. This study aimed to determine the survival of patients after orbital exenteration for cSCC and investigate contributing factors. It was hypothesized that postoperative radiotherapy would be associated with improved survival.

Methods
This was a retrospective cohort study of patients with T3 and T4 cSCC undergoing orbital exenteration. Survival analysis was performed using Cox proportional hazards.

Results
The study enrolled 40 patients with a median age of 61.5 years who met the criteria. None of the patients had received preoperative radiotherapy. Age (hazard ratio [HR], 1.09; p = 0.019) and residual disease (HR, 9.00; p = 0.003) were associated with worse survival. Postoperative radiotherapy (HR, 0.003; p < 0.001) was associated with improved survival. Perineural, lymphovascular, and bony invasion and T and N stage were not associated with survival. Survival with postoperative radiotherapy was 94 % at 1 year, 87 % at 2 years, and 84 % at 5 years.

Conclusions
The oncologic outcomes of orbital exenteration with postoperative radiotherapy for locally advanced head and neck cSCC are good. However, amelioration of the morbidity caused by resection of the eye would be ideal. Data to support immunotherapy as a sole therapy are currently limited, but a combination of neoadjuvant immunotherapy and surgical treatment may facilitate orbit-preserving treatment in the future.
O conceito de ação simbólica: Michel de Certeau e a busca de sentido
Authors: Paranhos Clarissa 
Published: January 2025

Este artigo propõe um estudo da obra do intelectual francês Michel de Certeau (1925 - 1986) a partir do entrelaçamento entre sua reflexão acerca da Revolução de Maio de 1968 e seu trabalho enquanto historiador da mística moderna. Dando destaque à noção de “ação simbólica”, que desponta em seus escritos sobre Maio, busca-se iluminá-la pondo-a em relação com os desenvolvimentos acerca do simbólico na passagem do mundo medieval para a modernidade. Examina-se o diálogo do autor com as obras de Michel Foucault, Henri de Lubac e com a psicanálise freudo-lacaniana, a fim não apenas de explorar as ressonâncias da noção de “ação simbólica”, mas também de dar a ver a solidariedade entre seu pensamento teórico e o engajamento espiritual do jesuíta Michel de Certeau.
Multimorbidity patterns and cognitive change among Mexican older adults: findings from the Mexican Health and Aging Study
Authors: Bishop Nicholas J. , Botoseneanu Anda , Newsom Jason T. , Allore Heather G. , Nagel Corey L. , Markwardt Sheila , Samper-Ternent Rafael , Quiñones Ana R. 
Published: January 2025

Introduction:
Mexico faces unique challenges due to the confluence of population ageing, an increasing burden of chronic conditions and limited resources to address these concerns. Substantial evidence links both independent and co-occurring chronic conditions to the risk of cognitive decline, but the association between common multimorbidity patterns and change in cognitive function has not been examined among older adults in Mexico.

Objective:
The objective of our research was to identify the most common multimorbidity patterns among ageing Mexican adults in 2012, then examine the association between these multimorbidity patterns and change in cognitive function with advancing age.

Methodology:
Data from the Mexican Health and Aging Study (2012–21; n = 6,082) was used to identify multimorbidity patterns in 2012 (including hypertension, diabetes, cancer, lung disease, heart attack, stroke, arthritis and depressive symptoms), then latent growth modelling was used to examine associations between the mean cognitive trajectory and the baseline multimorbidity patterns.

Results:
Several baseline multimorbidity patterns were associated with variation in cognitive function. Diabetes and depressive symptoms were present in the majority of multimorbidity patterns associated with lower cognitive function at baseline, and respondents with either lone diabetes or hypertension+diabetes+arthritis at baseline experienced more rapid cognitive decline than those reporting no conditions at baseline.

Conclusion:
Our findings suggest that prevention and management of diabetes may reduce cognitive gaps that manifest prior to older adulthood and protect against rapid cognitive decline among older Mexican adults. Further examination of depressive symptoms as a component of multimorbidity and cognitive change is also warranted.
Sociodemographic and behavioral factors associated with diet quality among low-income community health center patients with hypertension
Authors: Cheng Jessica , Faulkner Katherine C. , Malone Ashlie , Gu Kristine D. , Thorndike Anne N. 
Published: January 2025

Objective
Identify the most important sociodemographic and behavioral factors related to the diet of low-income adults with hypertension in order to guide the development of a community health worker (CHW) healthy eating intervention for low-income populations with hypertension.

Design
In this cross-sectional analysis, dietary recalls were used to assess Healthy Eating Index-2020 (HEI-2020) total (range: 0 to 100 [best diet quality]) and component scores and sodium intake. Self-reported sociodemographic and behavioral data were entered into a Least Absolute Shrinkage and Selection Operator (LASSO) regression model to determine the relative importance of factors related to diet quality.

Setting
Five community health centers in Boston, Massachusetts.

Participants
Adults (>20 years old) with a hypertension diagnosis.

Results
Participants (N = 291) were mostly female (65.0%), on Medicaid (82.8%), food insecure (59.5%), and Hispanic (52.2%). The mean (95% CI) HEI-2020 score was 63.0 (62.3, 65.7) Component scores were low for sodium and whole grains; mean (SE) sodium intake was 2676.9 (45.5) mg/day. The most important factors associated with lower HEI-2020 scores were: not having own housing, male gender, tobacco use, marijuana use, and skipping meals; the most important factors associated with higher HEI-2020 scores were Hispanic ethnicity and receipt of community food resources (5-fold cross-validated R2 = 0.17).

Conclusions
In this population of low-income adults with hypertension, diet quality would be improved by reducing sodium and increasing whole grain intake. Healthy eating interventions among low-income populations should consider providing dietary guidance in the context of behavioral factors (e.g., meal skipping) and substance use (e.g., marijuana) and should address barriers to health eating through referral to community food resources (e.g., food pantries).
Cardiorespiratory demands of firearms training instruction and 15m shuttle tests in British law enforcement
Authors: Warwick Joseph , Cooper Sophie , Ronca Flaminia 
Published: January 2025

Objectives
Law enforcement agencies require minimum fitness standards to safeguard their officers and training staff. Firearms instructors (FI) are expected to maintain the same standards as their operational counterparts. This study aimed to quantify the daily physiological demands placed on FI.

Methods
19 FI (45 ± 5 years) completed occupational tasks whilst wearing heart rate (HR) monitors for a minimum 10 days. Maximal oxygen consumption (VO2max) testing was conducted on FI during a treadmill test (TT) and a multistage shuttle test (ST). Linear regression models were used to model the relationship between VO2 and HR throughout the TT. This model was applied to HR data from occupational tasks to infer oxygen consumption. Repeated Measures ANOVAs were used to compare time spent in VO2max equivalent zones throughout.

Results
The VO2max achieved during ST (45.1 ± 5.6 ml/kg/min) was significantly higher than TT (39 ± 3 ml/kg/min) (p = 0.014). Time to exhaustion (TTE) was sooner on ST (06:26 min) compared to TT (13:16 min) (p < .001). FI spent ~85% of occupational time with an oxygen demand ≤20 ml/kg/min (p < .005). The most intense occupational tasks saw FI achieve VO2max ≥30 ml/kg/min, but <40 ml/kg/min.

Conclusion
Using ST to assess cardiorespiratory fitness resulted in a quicker TTE and a higher VO2max. Predominantly, FI occupational tasks are low intensity with sporadic exposures requiring a VO2max of >40 ml/kg/min. To safeguard FI from occupational-related cardiorespiratory or long-term health issues, it is intuitive to suggest fitness standards should exceed a VO2max of 40 ml/kg/min.
Iron deficiency and fatigue in inflammatory bowel disease: A systematic review
Authors: Sartain Stephanie , Al-Ezairej Maryam , McDonnell Martin , Westoby Catherine , Katarachia Vasiliki , Wootton Stephen A. , Cummings J. R. Fraser 
Published: January 2025

Background
It is unclear what impact iron deficiency has on fatigue in people with inflammatory bowel disease (IBD). This systematic review examined the evidence of whether iron deficiency, with or without anaemia, was associated with fatigue in IBD. Fatigue is a common symptom in patients with IBD that can be difficult to manage and treat. A greater understanding of the role and contribution of iron deficiency to fatigue may help improve the management of this condition.

Methods
The databases searched were MEDLINE, OVID, CINAHL and Web of Science. Inclusion criteria were studies measuring iron status for iron deficiency (ID) and patient-reported outcome measures (PROMs) for fatigue in patients with IBD of any level of disease activity. Assessment of bias was conducted using the Newcastle Ottawa Scale. Studies were grouped for syntheses according to whether exposure was iron deficiency without anaemia (IDWA) or ID regardless of haemoglobin level.

Results
Two hundred and eighty-five individual database results were identified and screened; 32 complete records were reviewed, from which seven studies with 1425 individuals were deemed eligible for inclusion in the results synthesis. Considerable variation in the methods and statistical analysis used to investigate the relationship between ID and fatigue prevented any quantitative synthesis. Studies varied by population disease activity levels, approaches used to define ID and PROMs used to measure fatigue. Three studies directly compared fatigue scores in IDWA to those not iron deficient, two of which showed patients with IDWA had significantly lower fatigue scores. Four studies used ID irrespective of anaemia as the exposure and reported mixed results on fatigue, with only one study reporting a higher prevalence of fatigue in the ID group.

Conclusions
There was marked heterogeneity between studies in this review. Two studies found evidence of a slight increase in fatigue levels in patients with IDWA. Though this does not explain all fatigue in patients with IBD, iron replacement should be considered to improve fatigue in iron-deficient patients.
Association between depression and the prevalence and prognosis of prediabetes: Data from National Health and Nutrition Examination Survey (NHANES) 2013–2018
Authors: Zhou Jin , Yang Xiaojiao 
Published: January 2025

Background
Diagnosis and intervention of prediabetes is an emerging approach to preventing the progression and complications of diabetes. Inflammatory factors and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis have been suggested as potential mechanisms underlying the pathogenesis of both diabetes and depression. However, the relationship between depression levels and the prevalence of prediabetes and its prognosis remains elusive. This study aimed to explore the relationship between depression and the prevalence of prediabetes and to further explore the all-cause mortality of different levels of depression in patients with prediabetes.

Methods
Our study used a data set from the National Health and Nutrition Examination Survey (NHANES). Participants were initially divided into two groups (depression vs. non-depression) and further stratified by different depression severity levels. We used a weighted multiple logistic regression model to analyze the association between depression and prediabetes prevalence and a Cox regression model to assess all-cause mortality in prediabetic patients.

Results
A total of 4384 participants were included, divided into depression group (n = 1379) and non-depression group (n = 3005). Results showed that people with depression were at higher risk of developing prediabetes. After adjusting for covariates, moderate to severe depression was positively associated with prediabetes (moderate to severe depression vs no depression: OR = 1.834, 95%CI: 0.713–4.721; severe depression vs no depression: OR = 1.004, 95% CI 0.429–2.351). In addition, we explored the relationship between all-cause mortality and depressive status in patients diagnosed with prediabetes (n = 2240) and found that moderate to severe depression (HR = 2.109, 95%CI 0.952–4.670) was associated with higher mortality in patients with prediabetes.

Conclusions
Overall, the findings consistently suggest that depression is positively associated with both the prevalence and mortality risk among individuals with prediabetes. This suggests that depression may be a new and valuable indicator of prediabetes risk. Early treatment of depression improves outcomes in prediabetes.
Trends in the levels, causes, and risk factors of maternal mortality in Pakistan: A comparative analysis of national surveys of 2007 and 2019
Authors: Midhet Farid , Khalid Samina Naeem , Baqai Shehla , Khan Shahzad Ali 
Published: January 2025

Background
Maternal mortality ratio (MMR) has decreased worldwide but Pakistan is still striving towards achieving the SDG targets for maternal health. This study highlights the trends in maternal mortality levels and risk factors in Pakistan between 2007 and 2019.

Methods
This study compares the results of secondary data analysis of the Pakistan Maternal Mortality Survey 2019 with the Pakistan Demographic and Health Survey 2007. A nested case-control study was carved to compare maternal deaths with the women who survived a pregnancy, in the same sampling clusters during the same period. Logistic regression was used to estimate odds ratios (OR) for major risk factors of maternal mortality after adjusting for the women’s age, parity, education, and wealth quintile.

Results
In 2019, Pakistan’s MMR was 186 per 100,000 live births, registering a 33% decline from 2007 (rural 42% vs. urban 11%). The leading causes of maternal mortality were postpartum hemorrhage, hypertensive disease of pregnancy, postpartum infection, and post-abortion complications. Women > 35 years and those expecting their first child were more likely to die from childbirth, while those who had ever used family planning had a lower risk according to the data for both years. In 2007, a distance of > 40 kilometers to a hospital significantly increased the risk of mortality but this association was not significant in 2019. In 2019, women who died were more likely to receive antenatal care than those who survived (adjusted OR 9.3); this association was not significant in 2007.

Conclusion
The modest reduction in MMR can be attributed to improved access to maternal health services in rural areas with increased antenatal care and institutional deliveries. However, most maternal deaths were caused by poor accessibility to quality emergency obstetric care. Lack of family planning remains a major risk factor for high maternal mortality in Pakistan.
Rural Roads to cognitive Resilience (RRR): A prospective cohort study protocol
Authors: Besser Lilah M. , Wiese Lisa , Cook Diane J. , Holt Janet , Magzamen Sheryl , Minor Bryan , Mitsova Diana , Park Juyoung , Sablan Olivia , Tourelle Madeleine , Williams Christine 
Published: January 2025

Background
Ambient air pollution, detrimental built and social environments, social isolation (SI), low socioeconomic status (SES), and rural (versus urban) residence have been associated with cognitive decline and risk of Alzheimer’s disease and related dementias (ADRD). Research is needed to investigate the influence of ambient air pollution and built and social environments on SI and cognitive decline among rural, disadvantaged, ethnic minority communities. To address this gap, this cohort study will recruit an ethnoracially diverse, rural Florida sample in geographic proximity to seasonal agricultural burning. We will (1) examine contributions of smoke-related fine particulate matter (PM2.5) exposures to SI and cognitive function; (2) determine effects of built and social environments on SI and cognitive function; and (3) contextualize SI and cognitive function among residents from different ethnoracial groups during burn and non-burn seasons.

Methods
We will recruit 1,087 community-dwelling, dementia-free, ≥45-year-olds from five communities in Florida’s Lake Okeechobee region. Over 36 months, participants will complete baseline visits to collect demographics, health history, and health measurements (e.g., blood pressure, body mass index) and 6-month follow-ups assessing cognitive function and social isolation at each visit. A subsample of 120 participants representative of each community will wear smartwatches to collect sensor data (e.g., heart rate) and daily routine and predefined activities (e.g., GPS-captured travel, frequent destinations) over two months. Ecological momentary assessments (EMA) (e.g., whether smoke has bothered participant in last 30 minutes) will occur over two months during agricultural burning and non-burning months. PurpleAir monitors (36 total) will be installed in each community to continuously monitor outdoor PM2.5 levels.

Discussion
We expect to identify individual- and community-level factors that increase the risk for SI and cognitive decline in a vulnerable rural population.