bluuebunny/crossref_metadata_2025 huggingface dataset:
Season-long microbial dynamics from the cuticle of rice weevil originating at food facilities after dispersal to novel food patches
Authors: Morrison William R , Ponce Marco A , Castaldi Joseph , James Avery , Stoll Ian , Moreland Jenna , Abshire Jennifer , Kim Tania N , Gerken Alison R
Published: February 2025

Stored-product insects may pose food safety concerns due to their capacity to vector harmful microbes. As climate change progresses, the propensity for vectoring may be affected by temperature. Vectoring capacity may also fluctuate over the season. Thus, we evaluated (i) how the area of microbial growth and morphospecies richness vary over the season from field-collected Sitophilus oryzae that were allowed to disperse onto a novel food patch habitat comprised of agar and (ii) whether temperature in the week preceding collection of S. oryzae affected growth and richness. On a weekly basis during 2022 and 2023, we introduced S. oryzae onto agar, and photographed patches at 3 and 5 d, characterizing growth with ImageJ and visually scoring richness. There was 1.4- to 1.6-fold more microbial growth in patches at 5 d compared to 3 d in both years. The greatest microbial growth consistently occurred from S. oryzae collected during the wheat and maize harvest in grain bins, while morphospecies richness increased progressively over time. We observed an 11-fold and 3-fold increase in the number of morphospecies at the end of the season compared to the beginning in 2022 and 2023. There was 2.1- to 316-fold more microbial growth during the wheat (Jun to Jul) and maize harvest (Sep to Oct) compared to early May. We found a positive exponential relationship between temperature in the field and microbial growth in both years. This study expands our understanding of insect–microbe interactions after harvest and highlights variable periods of risk by food facilities over the season.
Individual and Joint Effects of Red Blood Cell Traits on Hypertension: A Longitudinal Analysis
Authors: He Zhen , Chen Zekai , Wang Yuxian , Qin Hailun , Wu Weiqiang , Fu Peng , Chen Shuohua , Wu Shouling , Chen Youren
Published: February 2025

Aim

Previous reports found positive associations between RBC traits (RBC count and hemoglobin) and hypertension, but their individual and joint effects on new-onset hypertension by sex are unclear.

Methods

This longitudinal study involved 51,663 adults from the Kailuan Cohort. We utilized weighted Cox regression models to evaluate the individual and joint effects of RBC count and hemoglobin on new-onset hypertension by sex. Restricted cubic splines regression and Kaplan-Meier curves were employed to evaluate the nonlinear relationships and depict the differential survival probabilities, respectively.

Results

In the longitudinal analysis regarding individual effects, we found positive associations between RBC count and hemoglobin with new-onset hypertension in both men and women. As for joint effects, we discovered that subjects with higher RBC counts than the median but lower hemoglobin values than the median, labeled as RBC (+) & Hemoglobin (-), had a higher risk of hypertension in women (HR = 1.19, 95% CI: 1.02 to 1.39) compared to those categorized as RBC (-) & Hemoglobin (-), yet not in men. Additionally, subjects with lower RBC values than the median but higher hemoglobin values than the median, denoted as RBC (-) & Hemoglobin (+), exhibited an increased risk of hypertension in men (HR = 1.12, 95% CI: 1.06 to 1.18) compared to those classified as RBC (-) & Hemoglobin (-), but not in women. These findings were consistent in sensitivity and cross-sectional analyses.

Conclusions

Our findings suggest that RBC count primarily plays a role in women’s hypertension, while hemoglobin mainly affects hypertension in men.
Prevalence of Human Papillomavirus Genotypes in Unvaccinated 16-20-Year-Old Males in Quebec, Canada
Authors: Wolfe Catherine , Ionescu Iulia Gabriela , Mayrand Marie-Hélène , Coutlée François , Sauvageau Chantal
Published: February 2025

Background

The province of Quebec (Canada) has had a school-based Human Papillomavirus (HPV) vaccination program with high coverage since 2008, with more than 90% of girls having received at least one quadrivalent vaccine (4vHPV) dose by age 15. In 2018, Quebec was the first jurisdiction to switch to a mixed schedule (nonavalent+bivalent), and as such wanted to evaluate it. However, when devising an evaluation strategy for new vaccine schedules, the presence of herd effect needs to be ascertained. With this in mind, this study aimed to measure HPV prevalence among unvaccinated 16-20-year-old sexually active men.

Methods

In 2020-2022, men were recruited from schools and online across the province of Quebec. Participants completed an online questionnaire and provided a self-collected penile swab (surface) for HPV detection and genotyping (Anyplex™ II-HPV28 Detection assay). Risk factors associated with HPV positivity were assessed. Vaccination status (unvaccinated) was verified through the Quebec Vaccination Registry.

Results

Overall, 369 participants provided a sample suitable for HPV testing. HPV prevalence was 18.4% (95%CI:14.6-22.8). Only two participants harbored a 4vHPV-targeted genotype (0.5%; 95%CI:0.1-1.9), both reporting sexual contact with men. In multivariate analysis, age, greater number of lifetime sexual partners and history of other sexually transmitted infections were independently associated with positivity for at least one HPV genotype.

Conclusion

The low 4vHPV-targeted genotypes prevalence (˂1%) among unvaccinated men of the same age as women vaccinated with 4vHPV suggests a strong herd immunity among young adults in Quebec. Evaluation of schedule changes will have to take this finding into account.
Is the microbiome important in celiac disease?
Authors: Galipeau Heather J , Verdu Elena F
Published: February 2025

Celiac disease (CeD) is an autoimmune condition driven by gluten in genetically predisposed individuals. CeD is characterized by small intestinal villous atrophy but presents with a spectrum of gastrointestinal and systemic manifestations. Its only treatment is a strict, life-long adherence to a gluten-free diet, which is difficult to manage and does not always lead to symptomatic or mucosal recovery. About 40% of the population express the CeD-associated risk genes, but only 1%-2% of the worldwide population has CeD. This, along with the rising prevalence of CeD suggests other cofactors in disease pathogenesis. The gut microbiome has been implicated in CeD based on epidemiology studies and clinical associations. Mechanistic studies using relevant in vitro and in vivo preclinical models have begun to elucidate mechanisms through which microbes can influence CeD. Ultimately, a better understanding of these cofactors and their mechanisms will provide rationale intervention strategies and novel therapeutic targets to prevent or treat CeD.
DyS-MPADE: A Novel Multi-population Adaptive Differential Evolution Methodology Based on Dynamic Subpopulation
Authors: Huang Chen , Zhu Junyi , Xu Mingyao
Published: February 2025

Differential evolution (DE) is widely recognized in global optimization. However, it is not immune to the issue of premature convergence. To address this challenge, a dynamic subpopulation-based DE algorithm (i.e., DyS-MPADE) is presented in this paper. In DyS-MPADE, spectral hashing clustering is introduced to adaptively adjust the population structure. The innovative approach enhances SHADE's capacity by balancing exploration and exploitation, thereby improving its convergence properties. The population of DyS-MPADE is decomposed into subpopulations, facilitating independent evolution and emulating geographical separation. The number of subpopulations is dynamically adjusted by clustering analysis of optimal and pessimal individuals. We conducted a thorough evaluation of DyS-MPADE using the CEC 2017 benchmark functions to assess its performance of different dimensions. Compared to DE, JADE, SHADE, BDE, BeSD, ESOA, ARO, SHO, GRO and DO, the average ranks of DyS-MPADE are 1.76 and 1.2 in 50 and 100 dimensions, respectively. The accuracy of DyS-MPADE is superior to SHADE and other state-of-the-art DE variants. Additionally, DyS-MPADE is applied to airport gate allocation problem, where it demonstrated better performance compared to other algorithms, indicating its significance for engineering applications.
Host-feeding behavior of mosquitoes (Diptera: Culicidae) in North Dakota, 2003 to 2006
Authors: Anderson John F , Bransfield Angela , Misencik Michael J , Jones Sydney , Main Andy J , Armstrong Philip M , Andreadis Theodore G , Molaei Goudarz
Published: February 2025

Mosquitoes are abundant near temporary, semipermanent, and permanent water in North Dakota and are associated with human and veterinary diseases. Little is known about the feeding habits of mosquitoes as related to the transmission of arboviruses. We report on the identification of vertebrate hosts of 9 species of mosquitoes collected in 2003 to 2006. Blood meals of 1,223 from 9 mosquito species were identified to vertebrate species by PCR assays using the mitochondrial cytochrome b gene. Aedes dorsalis (Diptera: Culicidae) and Culiseta inornata fed only on mammals, and Aedes vexans fed almost exclusively on mammals. Aedes trivittatus fed significantly more on mammals than on birds. Culex tarsalis acquired blood meals from the most diverse group of vertebrates, frequently fed on American Robins, and did not exhibit a seasonal shift of feeding on birds to mammals. The extensive feeding of Cx. tarsalis on passerine birds and the isolation of West Nile virus (WNV) from 2 specimens that had fed on passerines supports their role in horizontal transmission of WNV. This species also transmits western equine encephalitis virus. Host feeding by Ae. trivittatus, Ae. vexans, Cs. inornata, and Ae. dorsalis in relation to their possible importance in transmission of trivittatus virus, Cache Valley virus, Jamestown Canyon virus, Potosi virus, or snowshoe hare virus is presented. The identification of host feeding behavior pattern of specific species of mosquitoes enhances our understanding of the enzootic and epizootic nature of 7 viruses in North Dakota.
Intelligent design of mechanical metamaterials: a GCNN-based structural genome database approach
Authors: Hao Wenyu , Du Zongliang , Hou Xiuquan , Guo Yilin , Liu Chang , Zhang Weisheng , Gao Huajian , Guo Xu
Published: February 2025

The reciprocal mapping between the geometry and properties of a unit cell is crucial for the intelligent and inverse design of advanced materials and structural systems. Beyond classical homogenization-based numerical methods, this paper presents an efficient and accurate mapping between the geometry and properties of a class of unit cells described by moving morphable components, achieved via a graph convolutional neural network (GCNN). This leads to a structural genome database (SGD) approach for the intelligent design of mechanical metamaterials. Using the SGD approach, metamaterials exhibiting the Hashin-Shtrikman upper bound of bulk modulus, auxetic behavior, and unimodal property have been created, with design efficiency improved by 3-4 orders of magnitude. Additionally, transfer learning and a small amount of training data allow the SGD to predict non-local behaviors beyond a unit cell, such as optimized unit cells with critical buckling strength enhanced by nearly 200% and a bandgap metamaterial with a relative bandgap width of 51%. Experimentally validated optimized metamaterials demonstrate auxetic behavior and superior buckling resistance. The proposed SGD approach holds promise for the advanced design of multi-scale and multi-physics systems.
Rheumatoid factors revisited in the age of biologic therapy
Authors: Avci Ali Berkant , Feist Eugen , Burmester Gerd R
Published: February 2025

The discovery of RF has been instrumental in diagnosing and classifying RA. Various RF isotypes, including IgM-RF and IgA-RF, have been linked to disease severity and treatment responses. The role of RF in RA pathogenesis, primarily through the formation of immune complexes, also carries the potential to influence the response to different medications. Recent progress in biologic therapies has further elucidated the role of RF in RA management. Treatments such as rituximab, abatacept and tocilizumab have shown differential efficacy based on RF status, with RF-positive patients often exhibiting better responses. Recent research also suggests that TNF inhibitors (TNFi) lacking the IgG1-Fc fragment like certolizumab pegol (CZP) may offer advantages over TNFi with an IgG1-Fc fragment, in RF-positive patients by preventing immune complex formation. Since this early observation is predominantly derived from previous multicentre studies with heterogeneous populations and potentially varying RF measurement methods, prospective randomized studies directly addressing this issue are essential for a more thorough and reliable evaluation. This paper is a narrative review outlining the evolving understanding of RF in the context of biologic therapies, emphasizing the need for personalized treatment approaches based on serological profiles and underlying immune mechanisms.
SEPT14 complexes maintain sperm morphogenesis and function
Authors: Wang Han‐Yu , Chen Kuan‐Ru , Yeh Bor‐Chun , Li Wei‐De , Wu Shang‐Rung , Ching Yung‐Hao , Wang Chia‐Yih , Kuo Pao‐Lin
Published: February 2025

Mutations in the septin (SEPT) family lead to male infertility. Septin 14 (SEPT14) is abundantly expressed in the testis, and its expression is significantly reduced in individuals with teratozoospermia, suggesting that SEPT14 may play a role in spermatogenesis. Here, we demonstrated that Sept14 is expressed mainly at the acroplaxome, manchette, neck, and annulus during spermiogenesis. To study the role of SEPT14 in sperm morphogenesis and function, the Sept14 knockout (Sept14−/−) mice were generated. The Sept14−/− male mice were subfertile and presented phenotypes such as irregular acrosomes, DNA damage, disorganized mitochondria, and displaced annuli. These abnormalities contributed to reduced sperm motility and impaired capacitation. Mechanistically, in the sperm head, SEPT14 interacted and colocalized with microtubules and actin during the manchette formation at the sperm metamorphosis phase. In the annulus, SEPT14 interacted with SEPT9, SEPT7, and SEPT2 to form the septin filaments to maintain the localization of the annulus. The GTP‐binding domain (GBD) of SEPT14 interacted with the GBD of SEPT2, whereas the C‐terminus of SEPT14 interacted with the GBD of SEPT7. Thus, our study reveals a role of SEPT14 in mediating sperm morphogenesis.
Speech and Non-Speech Auditory Task Performance by Non-Native English Speakers
Authors: McNamara Bridget , Brungart Douglas S. , Bieber Rebecca E. , Phillips Ian , Davidson Alyssa J. , Gordon-Salant Sandra
Published: February 2025

Objectives:

The goal of this study was to determine if performance on speech and non-speech clinical measures of auditory perception differs between two groups of adults: self-identified native speakers of English and non-native speakers of English who speak Spanish as a first language. The overall objective was to establish whether auditory perception tests developed for native English speakers are appropriate for bilingual Spanish-speaking adults who self-identify as non-native speakers of English. A secondary objective was to determine whether relative performance on English- and Spanish-language versions of a closed-set speech perception in noise task could accurately predict native-like performance on a battery of English language–dependent tests of auditory perception.

Design:

Participants were young, normal-hearing adults who self-identified as either native speakers of American English (n = 50) or as non-native speakers of American English (NNE; n = 25) who spoke Spanish as their first language. Participants completed a battery of perceptual tests, including speech tests (e.g., Quick Speech-in-Noise, time-compressed reverberant Quick Speech-in-Noise, etc.) and non-speech tests (Gaps in Noise, Frequency Pattern test, Duration Pattern test, Masking Level Difference). The English version of the Oldenburg Sentence test (OLSA) was administered to both groups; NNE participants also completed the Spanish version of the OLSA.

Results:

Analyses indicate that the native speakers of the American English group performed significantly better than the NNE group on all speech-based tests and on the two pattern recognition tests. There was no difference between groups on the remaining non-speech tests. For the NNE group, a difference of more than 2 SD on group-normalized scores for the English and Spanish OLSA accurately predicted poorer than normal performance on two or more tests of auditory perception with a language-dependent component either in the instructions or the stimuli.

Conclusions:

The results indicate that a number of English-based tests designed to assess auditory perception may be inappropriate for some Spanish-English bilingual adults. That is, some bilingual adults may perform worse than expected on tests that involve perceiving spoken English, in part because of linguistic differences, and not because of unusually poor auditory perception. The results also support the use of preliminary speech-in-noise screening tests in each of a bilingual patient’s languages to establish if auditory perception tests in English are appropriate for a given individual. If a non-native English speaker’s screening performance is worse in English than in the native language, one suggested strategy is to select auditory perceptual tests that are impacted minimally or not at all by linguistic differences.
Presurgery and Postsurgery Outcomes Following Lower Extremity Torsional Osteotomies
Authors: Gagnon Marianne , Veilleux Louis-Nicolas , Bernstein Mitchell
Published: February 2025

Objective:

Torsional osteotomies of the femur and tibia may be indicated in select individuals with a combination of increased femoral anteversion and external tibial torsion. This study aims to quantify the presurgery and postsurgery levels of pain, function and mobility, and gait patterns in patients with lower extremity torsional abnormalities (LETAs).

Methods:

Patients with LETA who underwent torsional osteotomy of the femurs and/or tibias were recruited. Before and 1 year postsurgery, participants had a gait analysis and completed patient-reported outcomes. CT torsional assessment was performed at baseline. Paired t tests and statistical parametric mapping were used to assess presurgery and postsurgery changes.

Results:

Ten participants (18 ± 2 y) completed the study. Participants had 29 ± 10 degrees of femoral anteversion and 45 ± 11 degrees of external tibial torsion. The hip rotational arc and transmalleolar axis improved towards norms following surgery. The major deviations found in the kinematic were observed in the transverse plane, and they improved towards norms postsurgery. The patient-reported outcomes were below norm presurgery but improved significantly postsurgery.

Conclusions:

Results from this study suggest that LETA can be diagnosed based on radiologic, gait, and physical abnormalities. Postsurgery results showed that torsional osteotomy alleviated pain, restored physical function, and normalized gait patterns.

Level of Evidence:

Level IV.
Pursuing Enterprise Risk Management Excellence in Emergency Preparedness
Authors: dellaBadia Simon Maxine
Published: February 2025

Enterprise risk management (ERM) is a proactive strategy that, when effectively implemented, can support an organization in reducing risk, improving alignment, and building staff trust. An effective program includes leadership transparency and a range of initiatives focusing on regulatory and financial compliance, patient safety, overall risk reduction, information management, and the use of data in the decision-making process. An effective ERM program must include a highly functioning emergency preparedness program if it is to truly support risk reduction. Emergency preparedness is an integral component of ERM, and it is also a clear example of how proactive management within a high-reliability culture catalyzes an organization’s pursuit of excellence. Today’s healthcare challenges have shifted disaster planning from an operational requirement to a foundational imperative. Regardless of an organization’s mission, structure, or size, operational continuity depends on a culture that supports sustained readiness. An organizational planning process that includes potential disruptions to daily activities is an important factor when preparing for and responding to the unexpected. Although operational leaders cannot predict every type of event, all efforts should be made to implement a fiscally sound readiness program that achieves the desired outcomes while minimizing workflow disruptions. Leaders need to ensure that their emergency preparedness program is adaptive enough to support mission-critical components of the organization when faced with unanticipated and potentially unfavorable events. In order for the program to be effective, it is important to holistically assess its necessary elements for excellence and determine how the program should be dynamically aligned with organizational culture.
Cedars-Sinai: Addressing Workforce Risks Through a New School
Authors: Anderson Nicole
Published: February 2025

Located in Los Angeles, a diverse and expensive city of 3.8 million residents, Cedars-Sinai Health System seeks to hire and retain a qualified workforce that reflects its patient population. Research shows that concordance of a person’s ethnicity with their clinical care team improves outcomes and reduces health disparities. Across the nation and at Cedars-Sinai, the pandemic exacerbated already existing workforce shortages and challenges to hiring, training, and retaining allied health workers. In September 2021, leaders at Cedars-Sinai began exploring ways to address these potential workforce risks to its operations. Through interviews with stakeholders and thorough analysis of Cedars-Sinai and local workforce and educational data, the decision was made to launch an allied health school. The goal of the program is to help fill the pipeline to meet the highest areas of need and provide opportunities for community members and existing Cedars staff to upgrade their skills and earning power.
Latent Profile Analysis and Related Factors of Colorectal Cancer Knowledge and Health Beliefs and Their Associations With Screening Behavior and Intention Among Urban Populations in China
Authors: Shi Bingzi , Zhang Jing , Wang Haixin , Rao Xue , Sun Yujing , Cui Wenming
Published: February 2025

Background

Colorectal cancer (CRC) incidence is rising in urban China, and screening participation remains low. Understanding the influence of knowledge and health beliefs on CRC screening behaviors can inform targeted interventions.

Objective

To identify latent profiles of CRC knowledge and health beliefs among average-risk urban adults in China and examine factors influencing profile membership.

Methods

A cross-sectional study was conducted with 500 urban adults, utilizing validated questionnaires on CRC knowledge and health beliefs. Latent profile analysis identified distinct profiles, and multinomial logistic regression assessed sociodemographic predictors.

Results

Three profiles emerged: profile 1, “moderately informed and believing” (48.0%, n = 240); profile 2, “underinformed and skeptical” (18.8%, n = 94); and profile 3, “well-informed and strongly believing” (33.2%, n = 166). Unstable employment and low health literacy predicted membership in profile 2, whereas higher social support and proximity to health centers were associated with profile 3. Profile 2 negatively predicted screening behavior (β = −0.516) and intention (β = −0.786), whereas profile 3 showed positive associations (β = 0.541 and β = 0.969, respectively).

Conclusions

These findings highlight distinct CRC knowledge and health belief profiles, suggesting that tailored interventions addressing subgroup-specific gaps and barriers could enhance CRC screening engagement in urban China.

Implications for Practice

Nurses can efficiently identify at-risk populations through brief assessments of employment status, health literacy, and social support and implement targeted interventions such as patient navigation, simplified health education, and social support enhancement to improve screening uptake.
Intuitive knowing for student nurses
Authors: Ruth-Sahd Lisa A.
Published: February 2025

“Intuitive knowing” is the ability to understand a clinical case instinctively without the need for conscious reasoning. This article examines the critical role of intuitive knowing in clinical decision-making among nurses, particularly in the context of increasingly complex patient care. Furthermore, the article offers recommendations for nursing educators to cultivate this essential skill in nursing students, ensuring they are equipped to effectively navigate the challenges of modern healthcare environments.
Osteomyelitis
Authors: Cadet Myriam Jean
Published: February 2025

Osteomyelitis is characterized by inflammation of the bone tissue, typically caused by microorganisms such as bacteria. It can be challenging to treat and may lead to unnecessary antibiotic therapies. Prompt identification of osteomyelitis and implementation of effective treatments are necessary to eradicate this infection. This article discusses the pathophysiology, clinical presentation, diagnosis, and nursing management of osteomyelitis, focusing on native bone infection.
Building empathy toward older adults using simulation
Authors: Boll Tamara , Gouwens Sarah
Published: February 2025

Empathy is an important skill that needs to be taught in nursing school. This article discusses a project that evaluated the effectiveness of a geriatric simulation suit in enhancing nursing students' empathy toward older adults. In a Community Health course, 48 students participated in a hands-on simulation that replicated the physical and cognitive challenges faced by older adults.
Influence of Reader Expertise on Myocardial Infarction Detection
Authors: Martens Bibi , van der Meulen Lara R. , Crawley Richard J. , van Cauteren Yvonne J.M. , Smulders Martijn W. , Streukens Sebastian , Hendriks Babs M.F. , Houben Ivo P.L. , Gommers Suzanne , Frey Simon M. , Brandts Lloyd , Wildberger Joachim E. , Chiribiri Amedeo , Holtackers Robert J.
Published: February 2025

Objectives

This study aimed to evaluate the influence of reader training and experience on the detection of (small) myocardial infarctions (MIs) and the assessment of ischemic scar transmurality using dark-blood late gadolinium enhancement (LGE) and bright-blood LGE magnetic resonance imaging. It was hypothesized that dark-blood LGE simplifies the detection of (small) MIs for less experienced readers, compared with bright-blood LGE imaging.

Materials and Methods

One hundred patients referred for cardiac magnetic resonance imaging for suspected ischemic scar were retrospectively included. Dark-blood LGE was performed first, followed by bright-blood LGE. Nine clinicians, grouped into three levels based on their training and experience, assessed the LGE images for the presence of MI and ischemic scar transmurality. Their assessment was subsequently compared with a European Association of Cardiovascular Imaging level 3 consultant. Reader confidence was evaluated with a 4-point Likert scale. Multilevel logistic regression was used to compare the 2 LGE methods and assess differences in myocardial infarction detection and transmurality among the 3 experience levels. Wilcoxon signed rank tests were performed to compare the reader confidence between the 2 LGE methods, whereas Friedman omnibus tests were conducted to assess differences in reader confidence among the 3 experience levels.

Results

Dark-blood LGE resulted in increased correct detection of MIs compared with bright-blood LGE for both level 1 (87.3% vs 82.7%, odds ratio [OR]: 1.55 [95% confidence interval (CI): 0.94–2.54], P = 0.083) and level 2 readers (89.7% vs 83.0%, OR: 2.05 [95% CI: 1.20–3.51], P = 0.009). There was no significant difference observed between dark-blood LGE and bright-blood LGE for level 3 readers (88.7% vs 87.0%, OR: 1.20 [95% CI: 0.70–2.06], P = 0.495). Level 2 readers significantly detected more small MIs correctly when using dark-blood LGE compared with bright-blood LGE (66.7% vs 50.8%, OR: 2.40 [95% CI: 1.03–5.60], P = 0.042). All experience levels showed significantly increased confidence in presence of ischemic scar and transmurality with dark-blood LGE.

Conclusions

Readily available dark-blood LGE can assist less experienced readers in correctly detecting and assessing (small) MIs compared with conventional bright-blood LGE. Regardless of experience level, dark-blood LGE improves reader confidence in assessing the presence and transmurality of MIs.
An introduction to propensity score analysis in acute care surgery research: Methodology and pitfalls
Authors: Garwe Tabitha , Zakhary Bishoy L.
Published: February 2025

Observational studies assessing causal effects of interventions are subject to indication (selection) bias, which may be difficult to eliminate using traditional multivariable techniques. When properly specified, propensity score–adjusted analysis may offer an advantage over traditional regression by ensuring that investigators explicitly assess comparability of baseline prognostic factors between the treated and untreated. However, it is important to note that the effectiveness of a propensity score–adjusted analysis depends on the variables selected for the model and the analytic approach. Noninclusion of important prognostic factors and model misspecification among other errors may in fact increase bias; thus, in performing propensity score analysis, these errors must be minimized as much as possible or assessed using sensitivity analysis to ensure validity.
Geographic and age-related variations in mutational processes in colorectal cancer
Authors: Díaz-Gay Marcos , dos Santos Wellington , Moody Sarah , Kazachkova Mariya , Abbasi Ammal , Steele Christopher D , Vangara Raviteja , Senkin Sergey , Wang Jingwei , Fitzgerald Stephen , Bergstrom Erik N , Khandekar Azhar , Otlu Burçak , Abedi-Ardekani Behnoush , de Carvalho Ana Carolina , Cattiaux Thomas , Penha Ricardo Cortez Cardoso , Gaborieau Valérie , Chopard Priscilia , Carreira Christine , Cheema Saamin , Latimer Calli , Teague Jon W , Mukeriya Anush , Zaridze David , Cox Riley , Albert Monique , Phouthavongsy Larry , Gallinger Steven , Malekzadeh Reza , Niavarani Ahmadreza , Miladinov Marko , Erić Katarina , Milosavljevic Sasa , Sangrajrang Suleeporn , Curado Maria Paula , Aguiar Samuel , Reis Rui Manuel , Reis Monise Tadin , Romagnolo Luis Gustavo , Guimarães Denise Peixoto , Holcatova Ivana , Kalvach Jaroslav , Vaccaro Carlos Alberto , Piñero Tamara Alejandra , Świątkowska Beata , Lissowska Jolanta , Roszkowska-Purska Katarzyna , Huertas-Salgado Antonio , Shibata Tatsuhiro , Shiba Satoshi , Sangkhathat Surasak , Chitapanarux Taned , Roshandel Gholamreza , Ashton-Prolla Patricia , Damin Daniel C , de Oliveira Francine Hehn , Humphreys Laura , Lawley Trevor D. , Perdomo Sandra , Stratton Michael R , Brennan Paul , Alexandrov Ludmil B
Published: February 2025

Colorectal cancer incidence rates vary geographically and have changed over time. Notably, in the past two decades, the incidence of early-onset colorectal cancer, affecting individuals under the age of 50 years, has doubled in many countries. The reasons for this increase are unknown. Here, we investigate whether mutational processes contribute to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries. No major differences were found in microsatellite unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases. Multiple signatures, most with unknown etiologies, exhibited varying prevalence in Argentina, Brazil, Colombia, Russia, and Thailand, indicating geographically diverse levels of mutagenic exposure. Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin, had higher mutation loads in countries with higher colorectal cancer incidence rates. SBS88 and ID18 were also enriched in early-onset colorectal cancers, being 3.3 times more common in individuals diagnosed before age 40 than in those over 70, and were imprinted early during colorectal cancer development. Colibactin exposure was further linked toAPCdriver mutations, with ID18 responsible for about 25% ofAPCdriver indels in colibactin-positive cases. This study reveals geographic and age-related variations in colorectal cancer mutational processes, and suggests that early-life mutagenic exposure to colibactin-producing bacteria may contribute to the rising incidence of early-onset colorectal cancer.
Shared and distinct pathways from anxiety disorder and depression to cardiovascular disease: a UK Biobank prospective cohort study
Authors: Nakada Shinya , Celis-Morales Carlos , Pell Jill P , Ho Frederick K
Published: February 2025

Aims

Although anxiety and depression increase the risk of cardiovascular disease, no studies have examined their underlying mechanisms systematically, particularly contrasting the difference between the two of them. Our study aimed to examine the extent to which lifestyle, physical and metabolic factors mediate the associations of anxiety and depression with incident CVD.

Methods

A prospective cohort study was conducted using UK Biobank. Anxiety, depression, and incident CVD were ascertained through linkage to hospital and death records. A causal mediation analysis was performed for anxiety and depression separately examining multiple potential lifestyle, physical, and metabolic mediators. Cox proportional hazard models and log-linear models were used to derive indirect effect estimates and proportions mediated.

Results

A total of 254,695 participants were included. Both anxiety (HR 1.62, 95% CI 1.15–2.13) and depression (HR 2.15, 95% CI 1.75–2.64) were associated with CVD after adjusting for sociodemographic confounders. The strongest mediators were current smoking and higher waist-hip ratio which accounted for 12.2% and 12.8% of the excess risk from anxiety, and 17.2% and 13.8% from depression, respectively. The strongest metabolic mediators were systolic blood pressure for anxiety (10.2%) and CRP (10.7%) for depression. Systolic blood pressure was the weakest mediator for depression (4.0%).

Conclusions

Lifestyle and physical pathways to incident CVD may be common to both anxiety and depression, but shared metabolic pathways seem unlikely. Our findings inform which risk factors to target among people with anxiety or depression in order to reduce their higher risk of developing CVD.

What is already known on this topic

Anxiety disorder and depression are associated with an increased risk of cardiovascular disease.

Some mechanisms were suggested for depression (e.g., obesity and inflammation) but there was no systematic investigation of pathways especially in comparing depression and anxiety disorder.

What this study adds

Our study showed that whilst smoking and central obesity were common mediators of both anxiety disorder and depression, systolic blood pressure was more specific to anxiety disorder and C-reactive protein to depression.

How this study might affect research, practice or policy

Our findings inform how best to target prevention strategies to reduce the higher risk of cardiovascular disease among people with established anxiety disorder or depression.
Type 2 diabetes polygenic risk score demonstrates context-dependent effects and associations with type 2 diabetes-related risk factors and complications across diverse populations
Authors: Guo Boya , Cai Yanwei , Kim Daeeun , Smit Roelof A.J. , Wang Zhe , Iyer Kruthika R. , Hilliard Austin T , Haessler Jeffrey , Tao Ran , Broadaway K Alaine , Wang Yujie , Pozdeyev Nikita , Stæger Frederik F. , Yang Chaojie , Vanderwerff Brett , Patki Amit D. , Stalbow Lauren , Lin Meng , Rafaels Nicholas , Shortt Jonathan , Wiley Laura , Stanislawski Maggie , Pattee Jack , Davis Lea , Straub Peter S. , Shuey Megan M. , Cox Nancy J. , Lee Nanette R. , Jørgensen Marit E. , Bjerregaard Peter , Larsen Christina , Hansen Torben , Moltke Ida , Meigs James B. , Stram Daniel O. , Yin Xianyong , Zhou Xiang , Chang Kyong-Mi , Clarke Shoa L. , Guarischi-Sousa Rodrigo , Lankester Joanna , Tsao Philip S , Buyske Steven , Graff Mariaelisa , Raffield Laura M. , Sun Quan , Wilkens Lynne R. , Carlson Christopher S. , Easton Charles B. , Liu Simin , Manson JoAnn E. , Marchand Loïc L. , Haiman Christopher A. , Mohlke Karen L. , Gordon-Larsen Penny , Albrechtsen Anders , Boehnke Michael , Rich Stephen S. , Manichaikul Ani , Rotter Jerome I. , Yousri Noha A. , Irvin Ryan M. ,   The biobank at the Colorado Center for Personalized Medicine,   VA Million Veteran Program,   The Population Architecture using Genomics and Epidemiology (PAGE) study, Gignoux Chris , North Kari E. , Loos Ruth J.F. , Assimes Themistocles L. , Peters Ulrike , Kooperberg Charles , Raghavan Sridharan , Highland Heather M. , Darst Burcu F.
Published: February 2025

Polygenic risk scores (PRS) hold prognostic value for identifying individuals at higher risk of type 2 diabetes (T2D). However, further characterization is needed to understand the generalizability of T2D PRS in diverse populations across various contexts. We characterized a multi-ancestry T2D PRS among 244,637 cases and 637,891 controls across eight populations from the Population Architecture Genomics and Epidemiology (PAGE) Study and 13 additional biobanks and cohorts. PRS performance was context dependent, with better performance in those who were younger, male, with a family history of T2D, without hypertension, and not obese or overweight. Additionally, the PRS was associated with various diabetes-related cardiometabolic traits and T2D complications, suggesting its utility for stratifying risk of complications and identifying shared genetic architecture between T2D and other diseases. These findings highlight the need to account for context when evaluating PRS as a tool for T2D risk prognostication and potentially generalizable associations of T2D PRS with diabetes-related traits despite differential performance in T2D prediction across diverse populations.
Stress-responsive transcription factor families are key components of the core abiotic stress response in maize
Authors: Pardo Anna C.H. , Pardo Jeremy D. , VanBuren Robert
Published: February 2025

Abiotic stresses, including drought, salt, heat, cold, flooding, and low nitrogen, have devastating impacts on agriculture and are increasing in frequency globally due to climate change. Plants can experience multiple abiotic stresses simultaneously or sequentially within a single growing season, and combinatorial stresses elicit shared or overlapping molecular and physiological responses. Here, we searched for core stress responsive genes in maize across diverse abiotic stressors through meta-analysis of public RNAseq data. Our analysis revealed significant heterogeneity in gene expression across datasets due to factors such as tissue type, genotype, and experimental conditions, which we mitigated through batch correction. Using nearly 1,900 RNAseq samples with both traditional set operations and a novel random forest machine learning approach, we identified a core set of 744 stress-responsive genes across the six stresses. These core genes are enriched in transcription factors, including stress-responsive families such as AP2/ERF-ERF, NAC, bZIP, HSF, and C2C2-CO-like. Co-expression network analysis demonstrated that these core TFs are co-expressed with stress-specific peripheral genes, supporting their role in regulating both generalized and stress-specific responses. Our results suggest that maize employs a conserved yet flexible transcriptional strategy to respond to abiotic stresses, with core TFs acting as potential regulators of both universal and stress-specific pathways. These findings provide a valuable resource for understanding stress tolerance mechanisms and for guiding future breeding and engineering efforts to enhance maize resilience under climate change.
Trajectories of blood-based protein biomarkers in chronic traumatic brain injury
Authors: Hicks Amelia J. , Plourde Jay , Selmanovic Enna , de Souza Nicola L. , Blennow Kaj , Zetterberg Henrik , Dams-O’Connor Kristen
Published: February 2025

Blood-based protein biomarkers may provide important insights into the long-term neuropathology of traumatic brain injury (TBI). This is urgently required to identify mechanistic processes underlying post-traumatic neurodegeneration (PTND); a progressive post-recovery clinical decline experienced by a portion of TBI survivors. The aim of this study was to examine change over time in protein levels in a chronic TBI cohort. We selected six markers (Aβ42/Aβ40, GFAP, NfL, BD-tau, p-tau231, and p-tau181) with known importance in acute TBI and/or other neurodegenerative conditions.

We used a longitudinal design with two time points approximately 3.5 years apart on average (SD 1.34). Proteins were measured in plasma using the ultrasensitive Single molecule array technology for 63 participants with mild to severe chronic TBI (sustained ≥ 1 year ago; M 28 years; SD 16.3 since their first blow to the head) from the Late Effects of TBI study (48% female; current age M 52 years; SD 13.4). Multivariate linear mixed effect models with adjustments for multiple comparisons were performed to examine trajectories in proteins over time with age and age squared as covariates. A series of sensitivity analyses were conducted to account for outliers and to explore effects of key covariates: sex,APOEε4 carrier status, medical comorbidities, age at first blow to the head, time since first blow to the head, and injury severity.

Over an average of 3.5 years, there were significant reductions in plasma Aβ42/Aβ40(β = −0.004, SE = 0.001, t = −3.75, q = .001) and significant increases in plasma GFAP (β = 12.96, SE = 4.41, t = 2.94, q = .01). There were no significant changes in NFL, BD-tau, p-tau231, or p-tau181.

Both plasma Aβ42/Aβ40and GFAP have been associated with brain amyloidosis, suggesting a role for Aβ mis-metabolism and aggregation in the long-term neuropathological consequences of TBI. These findings are hypothesis generating for future studies exploring the diverse biological mechanisms of PTND.
Mitochondrially Transcribed dsRNA Mediates Manganese-induced Neuroinflammation
Authors: Gokhale Avanti , Mendez-Vazquez Hadassah , Sampson Maureen M. , Moctezuma Felix G Rivera , Harbuzariu Adriana , Sing Anson , Zlatic Stephanie A. , Roberts Anne M. , Prajapati Milankumar , Roberts Blaine R. , Bartnikas Thomas B. , Wood Levi B. , Sloan Steven A. , Faundez Victor , Werner Erica
Published: February 2025

Manganese (Mn) is an essential trace element required for various biological functions, but excessive Mn levels are neurotoxic and lead to significant health concerns. The mechanisms underlying Mn-induced neurotoxicity remain poorly understood. Neuropathological studies of affected brain regions reveal astrogliosis, and neuronal loss, along with evidence of neuroinflammation. Here, we present a novel Mn-dependent mechanism linking mitochondrial dysfunction to neuroinflammation. We found that Mn disrupts mitochondrial transcriptome processing, resulting in the accumulation of complementary RNAs that form double-stranded RNA (dsRNA). This dsRNA is released to the cytoplasm, where it activates cytosolic sensor pathways, triggering type I interferon responses and inflammatory cytokine production. This mechanism is present in 100-day human cerebral organoids, where Mn-induced inflammatory responses are observed predominantly in mature astrocytes. Similar effects were observed in vivo in a mouse model carrying mutations in the SLC30A10 gene, which results in Mn accumulation. These findings highlight a previously unrecognized role for mitochondrial dsRNA in Mn-induced neuroinflammation and provide insights into the molecular basis of manganism. We propose that this mitochondrial dsRNA-induced inflammatory pathway has broad implications in for neurodegenerative diseases caused by environmental or genetic insults.
Characterisation of CD4 Th subsets as well as dietary, exercise and lifestyle factors in an established Rheumatoid Arthritis cohort; pilot study
Authors: Venkataraman Shweta , D’Cunha Nathan , Kozlovskaia Maria , Naumovski Nenad , McKune Andrew , Bruestle Anne , Xu Tony , Marie Julien C , Hernandez-Vargas Hector , Raj Anna Dorai , Tsai Ted , Pyne David B. , Goldsmith Chloe
Published: February 2025

Background

Sex disparities in the incidence and severity of Rheumatoid Arthritis (RA) are well-documented, with females experiencing more aggressive disease and different responses to treatment. While underlying mechanisms remain elusive, immune factors and lifestyle components, such as diet and physical activity, could play a role in shaping disease outcomes. Since Th cells are key drivers of RA, this study characterised CD4 Th subset frequencies, including Th1, Th2, Th17 and Th1/17 cells, in a cohort of males and females with established RA. Considering the role of diet and lifestyle in RA development, we also evaluated participant diet and lifestyle patterns.

Methods

An observational cross-sectional cohort study profiling 39 individuals (19 RA and 20 age and sex matched controls) with no major co-morbidities was conducted. Percentages of Th1, Th2, Th17 and Th1/17 cells from peripheral blood were determined by flow cytometry as well as serum levels of RF and cytokines IL17α, IFN-γ, TNF-α, GM-CSF, TGF-β, IL-6, and CRP by ELISA. Dietary intake was assessed by Food Frequency Questionnaire (FFQ), the Dietary inflammatory Index (DII) calculated from nutrient intake. Physical activity levels were evaluated by Global Physical Activity Questionnaire (GPAQ).

Results

Sex-specific differences of Th17, Th1 an Th2 cells were observed in RA groups. Males had lower levels of Th1 cells and higher levels of Th17 cells than control subjects, while females had lower levels of Th2 cells than controls. Female RA subjects had higher ratio of Th1:Th2 cells than controls, while male RA subjects had higher Th17:Th1 ratio than controls. Interestingly, circulating CD4 Th subset levels were predictive of RA in this cohort. No changes in cytokine levels were observed. The male RA group consumed 30% less carbohydrate (RA = 156g +/-57g, Control = 253g +/-59g;p=0.003), 37% less sugar (RA = 74.1g +/-29g, Control = 118g +/-33g;p=0.004) and 30% less dietary fibre (R = 33g +/-8g, Control = 48g +/-13 g;p=0.008) than the male control group. The female RA group had the lowest consumption of alcohol in comparison to female control group (RA = 0.31g, Control = 8.97g;p=0.047). Male subjects had a 4x higher DII than females (p=0.012).

Conclusions

Our findings highlight potential sex-specific differences in CD4+ Th cell subsets in individuals with established RA, indicating that sex may influence immune cell composition in this disease. Furthermore, dietary components showed sex-specific consumption patterns, underscoring the potential role of tailored lifestyle interventions in modulating immune responses in RA. Evaluating immunological sex differences and dietary and lifestyle factors may be important for enhancing management strategies in RA.