bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Features and Treatment Outcomes of Choroidal Osteoma in Asian Indians (80 Patients)
Authors: Ketkar Manasi , Jacob Ninan , Sahoo Niroj , Kaliki Swathi , Raval Vishal
Published: December 2024

Purpose:

To describe the demographic and clinical characteristics, and treatment outcomes of choroidal osteoma in Indian patients.

Methods:

This cross-sectional hospital-based study included 80 patients (100 eyes) between 2nd October 2012 and 15th May 2024.

Results:

Forty-nine (61%) participants were female, and 31 (39 %) were male. The most common age group was the second decade (n=27, 34%). Tumor ossification with intact RPE was observed in 37 (44%) eyes and tumor deossification with/without RPE atrophy was observed in 55 (65%). Associated features observed were choroidal neovascularization (CNV) in 40 (40%) eyes, subretinal fluid without CNV in 4 (4%) eyes, and documented tumor growth in 6 (6%) eyes (mean interval, 4 years). At 4 and 8 years, Kaplan–Meier analysis revealed tumor growth in 18% and 38% of eyes, respectively. Of the 83 eyes, OCT showed the presence of choroidal lamellae in ossified zones in 30 eyes (100%), CNV in 40 (48%) eyes, SRF without CNV or growth in 8 (10%) eyes, and RPE atrophy with deossification in 53 (64%) eyes. Treatment included intravitreal anti-VEGF therapy for CNV in 39 eyes, transpupillary thermotherapy in 3, and focal laser photocoagulation in one eye to the perifoveal leaning edge with SRF without CNV. The mean BCVA changed from 0.4 to 0.6 logMAR units (6/15 to 6/24 Snellen’s equivalent) at a mean follow-up of 19 months (3-149 months).

Conclusion:

Choroidal osteoma is a unilateral condition observed in females. Although benign, the presence of CNV, SRF, or tumor growth requires treatment and periodic surveillance.
Ivermectin 1% Combined With Intense Pulsed Light Treatment for Dry Eye Disease Secondary to Demodex Blepharitis
Authors: Safir Margarita , Rabina Gilad , Arbel Itamar , Sharon Yael , Spierer Oriel , Mimouni Michael , Nahum Yoav
Published: December 2024

Purpose:

To examine the safety and efficacy of combined treatment with topical ivermectin 1% and intense pulsed light (IPL) for dry eye disease (DED) secondary to demodex blepharitis.

Methods:

A retrospective review of medical files of patients treated at a private clinic specializing in DED between November 2022 and February 2024 was performed. Sixty-one patients aged 18 years or older with DED because of demodex blepharitis, who received the IPL and ivermectin 1% combination therapy, were included. IPL was applied to the periocular area 4 times at 2- to 3-week intervals, and ivermectin 1% once daily for 1 to 2 months. Both eyes (n = 122) of each patient were evaluated before and immediately after treatment cessation. Blepharitis, meibomian gland secretion, corneal staining, patient satisfaction, and overall clinical improvement were recorded.

Results:

Mean age was 59.6 ± 17.6 years and 50.8% (n = 31) were males. Meibomian gland secretion grading improved significantly after treatment from 2.74 ± 0.63 to 1.63 ± 0.63 (P < 0.001). Blepharitis was eliminated after treatment in 77.0% of patients (23.0% after treatment vs. 100.0% before, P < 0.001). The patient satisfaction rate was moderate to high (range 0–2, mean 1.54 ± 0.60). Clinical improvement rate was moderate to high as well (range 0–2, mean 1.52 ± 0.50). No significant side effects were observed.

Conclusions:

The combined application of topical ivermectin and IPL to the facial area induced significant improvement of demodex blepharitis and meibomian gland secretion grading along with a high rate of patient satisfaction. Further randomized controlled double-blinded studies are needed.
Effect of Corticosteroid Phobia on Treatment Adherence and Outcome in Women With Lichen Sclerosus: A Prospective Study
Authors: Borghi Alessandro , Flacco Maria Elena , Pacetti Lucrezia , Schettini Natale , Toni Giulia , Corazza Monica
Published: December 2024

Objective

The phenomenon of topical corticosteroid (TC) phobia (TCP) poses a challenge to the adherence of patients requiring prolonged treatments, particularly those with conditions like atopic dermatitis. Nonadherence to treatment significantly contributes to the inadequate control of diseases. This study aimed to evaluate TCP among women suffering from vulvar lichen sclerosus (VLS) and its potential impact on treatment adherence and therapeutic outcomes.

Materials and Methods

This observational, prospective study involved adult patients who received their first histological diagnosis of VLS and underwent a 12-week corticosteroid treatment regimen at the authors’ Vulva Unit between June 2022 and September 2023. All participants completed the validated TOPICOP questionnaire, which assesses concerns, worries, and beliefs regarding TC usage. Baseline and 12-week control visit assessments were conducted to evaluate subjective and objective parameters of VLS. Patient adherence to treatment was monitored through diary entries.

Results

Among the 50 patients included (with a mean age of 64.9 ± 13.5 years), more than half (58%) had prior experience with TC treatments and 10.3% had used corticosteroids for vulvar symptoms without a precise diagnosis. The median global TOPICOP score was 19.4% (interquartile range = 5.6–36.1), with a corresponding median value of 7.0 (interquartile range = 2.0–13.0). A total of 41 patients (82.2%) adhered to the study treatment, which proved highly effective in alleviating symptoms and improving signs of VLS. Multivariate analysis revealed that neither treatment adherence nor effectiveness were significantly associated with the level of TCP.

Conclusions

Among the authors’ VLS patients, TCP was relatively low and did not negatively impact treatment adherence to corticosteroids. Moreover, TCP did not influence the effectiveness of TC therapy, as it did not affect adherence.
Bridging Gaps in Cervical Cancer Care: A Web-Based Intervention to Improve Knowledge and Follow-up
Authors: Kulkarni Amita , Ahsan Muhammad Danyal , LaRosa Taylor , Webster Emily , Ma Xiaoyue , Cantillo Evelyn , Frey Melissa K. , Holcomb Kevin M. , Safford Monika M. , Chapman-Davis Eloise
Published: December 2024

Objectives

Contributors to disparities and worse cervical cancer outcomes include limited education and loss to follow-up after an abnormal Pap smear. Effective interventions are necessary to engage diverse populations. The authors piloted an intervention to assess acceptability, knowledge uptake, and follow-up.

Materials and Methods

This prospective pilot study recruited patients scheduled for colposcopy visits at a government-insured clinic and faculty clinics within an academic medical center to use the Patient Activated Learning System (PALS). The PALS intervention included 5 short educational videos about human papillomavirus and colposcopy. Participants completed a baseline knowledge questionnaire, viewed PALS videos followed by post-intervention knowledge and acceptability surveys. Perceptions of PALS, anxiety, and impact on follow-up were evaluated.

Results

Of 63 (70%) participants completing the intervention, 24 (38%) were from the government-insured clinic and 39 (62%) from faculty clinics. Median age was 36 (range 30–48), 38 (63%) were racial and ethnic minorities, and 21 (33%) were non-Hispanic White. The intervention improved knowledge scores for the entire cohort (60%–75%, p < .01), even when stratified by race/ethnicity (p < .01 for all), income (p < .01), education (p < .01), practice (p < .01), and insurance type (p < .001). Participants found PALS convenient to use (4.6/5), enjoyable (4.2/5), and acceptable (4.6/5); 75% said the videos alleviated colposcopy-related anxiety, and 84% indicated PALS made them more likely to follow up. The guideline concordant follow-up rate among study completers was 73%.

Conclusion

In this pilot study, PALS was effective and acceptable among a diverse cohort. These free, widely viewed videos can successfully engage diverse populations to improve colposcopy knowledge and follow-up.
Multitracer PET/CT Findings in a Case of Behavioral Variant Frontotemporal Dementia With Parkinsonism
Authors: Chen Shuai , Fu Chang , Shao Jing-Yu , Xu Jun-Ling , Zhang Jie-Wen
Published: December 2024

Abstracts

We report the clinical and multimodal PET/CT manifestations in a patient with behavioral variant frontotemporal dementia and parkinsonism. The 18F-FDG PET scan revealed hypometabolism in the left supratentorial cortex. The 18F-fluorodopa PET scan demonstrated decreased uptake in the bilateral striatum, most prominent in the head of caudate nucleus. The 18F-florbetapir PET scan indicated an absence of β-amyloid deposition, whereas the 18F-flortaucipir PET scan showed uptake in the left hemisphere neocortex. The clinical presentation and asymmetric neuroimaging features supported the underlying frontotemporal lobar degeneration-tau pathology.
Diagnosis of Clostridioides difficile infection and impact of testing
Authors: Viprey Virginie F. , Clark Emma , Davies Kerrie A.
Published: December 2024

Diagnosis of Clostridioides difficile infection (CDI) remains challenging as it involves in the first instance recognition (clinical awareness) of the patients’ symptoms for clinical suspicion of CDI to warrant testing, and secondly, different laboratory tests have been described for CDI. Due to the overwhelming amount of information in the literature on CDI tests and their performance, with separately published guidelines, this review aims to provide a comprehensive but concise summary of the current state of CDI diagnostic testing. Current knowledge and the impact of using different laboratory diagnostic procedures for CDI, including the most recommended approach as a two-step algorithm and the concept of diagnostic stewardship, are being discussed. This review provides an updated overview and valuable take-home messages in the field of CDI laboratory testing and highlights that timely diagnosis is important for the clinical management of CDI and that the recommended testing procedures are increasingly becoming more widely accepted.
Toward Holistic Solutions to Undernutrition: A Comprehensive Preclinical Protocol for Novel Ready-to-Use Therapeutic Foods Testing
Authors: Utume Laura Nguoron , Janssen Jerome Nicolas , Akomo Peter , Shaw Daisy , Edwards William Joseph Samuel , Muleya Molly , Nikolaou Charoula Konstantia , Schneider Aviv , Westby Andrew , Reifen Ram , Tsaousis Anastasios D. , Monsonego-Ornan Efrat , Bechoff Aurélie
Published: December 2024

Severe acute malnutrition (SAM) affects over 45 million children under five worldwide. Ready-to-Use Therapeutic Foods (RUTFs), the cornerstone of treatment, reach only 30% of children in need due to high production costs and reliance on imports. RUTF formulations developed from local ingredients have shown varying efficacy levels focusing primarily on weight gain, overlooking critical factors like micronutrient status, skeletal development, and gut health. The presented study establishes a comprehensive protocol for preclinical testing of novel RUTF formulations using a validated juvenile rat model replicating key features of malnutrition in children. Beyond the standard anthropometric measurements (body weight, length, and food consumption), bone quality is assessed through micro-computed tomography and mechanical testing, providing insights into microstructure and functionality beyond standard anthropometric measurements. Concurrently, gut microbiome dynamics are analysed using 16S rRNA sequencing coupled with metabolomic profiling of stool and serum to monitor gut health and systemic recovery.By addressing critical gaps in traditional RUTF evaluations and emphasising locally sourced, cost-effective formulations, this protocol offers a transformative framework for developing accessible and impactful malnutrition treatments. The findings generated through this multidisciplinary approach will guide RUTFs optimisation, strengthen their scientific foundation, and pave the way for evidence-based clinical trials to improve global malnutrition treatment strategies.
Advancing White Blood Cell Detection: A Multi-Domain Dataset for Morphological Analysis and Addressing Sparse Annotation Challenges
Authors: Rehman Abdul , Meraj Talha , Minhas Aiman Mahmood , Imran Ayisha , Ali Mohsen , Sultani Waqas
Published: December 2024

Realistic leukemia analysis on microscopic slides requires a system that localizes, classifies, and performs WBC morphological analysis. While deep learning has advanced medical imaging, leukemia analysis is hindered by the lack of a large, diverse dataset. Our contribution here is twofold. First, we present a large-scale Leukemia dataset collected through Peripheral Blood Films (PBF) from many patients, through multiple microscopes, multi-cameras, and multi-magnification. To enhance explainability and medical expert acceptance, each leukemia cell is annotated with 7 morphological attributes, ranging from Cell Size to Nuclear Shape. Specifically, we used two microscopes from two different cost spectrums (high-cost: HCM and low-cost: LCM) to capture the dataset at three magnifications (100x, 40x,10x) through different sensors (high-end camera for HCM, middle-level camera for LCM, and mobile phone camera for both). Our dataset has 2.4k annotated images per resolution (in both HCM and LCM), with 10.3K cells annotated for 14 WBC types and 7 morphological properties. Secondly, hematologists typically annotate only well-spread, non-overlapping cell regions within small fields of view (FoV), leaving larger FoVs unannotated. Models trained solely on these annotated areas underutilize available information. To overcome this limitation, we present a novel method for training object detectors using sparse annotations. Along with this, we present a second dataset Leukemia-Sparse-Attri dataset. Curated at 40x FoV, this dataset consists of 1546 sparsely annotated microscopic images, and 185 fully annotated images (used for testing). From explainability to overcoming domain-shift challenges, presented datasets could be used for many challenging aspects of microscopic image analysis.
Therapeutic potential of human mesenchymal stromal cell-derived mitochondria in a rat model of post-surgical digestive fistula: towards an energetic nano-biotherapy
Authors: Mariani Antoine , Guichard Augustin , Sebbagh Anna C. , Cronemberger Andrade André , Al Amir Dache Zahra , Ribes Christopher , Ayollo Dmitry , Karoui Mehdi , Lavieu Gregory , Gazeau Florence , Silva Amanda K. A. , Rahmi Gabriel , Mozafari Sabah
Published: December 2024

Background

Tissue regeneration heavily relies on cellular energy production, with mitochondria playing a crucial role. Dysfunctional mitochondria are implicated in various degenerative diseases, driving interest in targeting mitochondrial transplantation for tissue repair. Wound healing is highly compromised in gastrointestinal conditions resulting in fistula development, particularly after sleeve gastrectomy. Human mesenchymal stem/stromal cells (hMSCs) and their cell-free products such as mitochondria offer potential benefits due to their therapeutic properties on cellular energy production. Here we investigated the therapeutic advantage of hMSCs-derived mitochondria nano-biotherapy in a rat model of post-surgical fistula healing.

Methods

Viable and structurally intact mitochondria were isolated from hMSCs before exposure to human colonic epithelial cells (HCEC-1CT) culture or transplantation into a rat model of post-operative fistula.

Results

Our findings reveal significant dose-dependent improvement on cellular metabolic activity and ATP content of the recipient cells. Assessment of the external fistula orifice developed following post sleeve gastrectomy fistula, revealed a substantial healing in all transplanted rats compared to control group.

Conclusion

Our findings highlight the therapeutic potential of hMSCs-derived mitochondria in post-surgical fistula healing. This research contributes to advancing cell-free regenerative strategies for gastrointestinal conditions, offering new insights into mitochondrial-based therapies for enhancing wound healing and tissue repair.
Drosophila’s sensory responses to bacterial peptidoglycan integrates positive and negative signals
Authors: Montanari Martina , Manière Gérard , Masuzzo Ambra , Milleville Romane , Grosjean Yaël , Kurz C. Léopold , Royet Julien
Published: December 2024

Interactions between animals, including humans, and surrounding microbes are governed by a delicate balance, crucial for survival. Animals must distinguish and respond adequately to beneficial and harmful microbes to maintain homeostasis. Recent research suggests that bacterial components such as lipopolysaccharide and peptidoglycan (PGN) influence host behavior by modulating neuronal activity. PGN detection by specific neurons can prompt infected female flies to reduce oviposition or trigger avoidance behaviors via gustatory neurons. Using behavioral assays and calcium imaging, we found that PGNs can also act as attractants, activating the sweet taste circuit in a concentration-dependent manner. Our findings demonstrate that flies integrate PGN-derived positive and negative signals to make ad hoc decisions. This dual response underlines the need forDrosophilato distinguish between different concentrations of compounds in their environment, integrating sensory data to navigate efficiently in microbe-co-inhabited environments.

Highlights

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Bacterial PGN is attractive to flies at high concentrations

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Gr5a sweet gustatory neurons are activated by PGN in an NF-kB independent manner

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PER to high PGN concentrations remains in axenic flies

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Fly gustatory response to PGN integrates both attractive and aversive signals
Genomic Landscape of Thrombosis Recurrence Risk Across Venous Thromboembolism Subtypes
Authors: Munsch Gaëlle , Thibord Florian , Bezerra Ohanna C , Brody Jennifer A. , van Hylckama Vlieg Astrid , Gourhant Lénaïck , Chen Ming-Huei , Germain Marine , Caro Ilana , Suchon Pierre , Olaso Robert , Wiggins Kerri L. , Saut Noémie , Besse Céline , Goumidi Louisa , Bacq Delphine , Harrington Laura B , Boland Anne ,   CHARGE Hemostasis working group,   INVENT consortium, Lemarié Catherine A , Danckwardt Sven , Debette Stéphanie , Deleuze Jean-François , Jacqmin-Gadda Hélène , Rodger Marc A , Gagnon France , Rosendaal Frits R , Johnson Andrew D , Smith Nicholas L , Couturaud Francis , Morange Pierre-Emmanuel , Trégouët David-Alexandre
Published: December 2024

Venous thromboembolism (VT) is a frequent (annual incidence of 1 to 2 per 1,000) and potentially life-threatening (case-fatality rate up to 10%) disease. VT is associated with serious short-term and long-term complications including a recurrence rate of approximately 20% within five years. Anticoagulant therapy, the mainstay of VT treatment, drastically reduces the risk of early VT recurrence, but it exposes patients to a substantial risk of bleeding. We analysed the genomic architecture of VT recurrence using data from 6,571 patients across eight cohorts, 1,816 of whom experienced recurrence, with a particular focus on the clinical manifestation of the type of first VT event. Through genome-wide association studies (GWAS), we identified three loci significantly associated (P<5×10-8) with VT recurrence in the general VT population:GPR149/MME,L3MBTL4, andTHSD7B. Protein Quantitative Trait Locus and Mendelian Randomization analyses further identified elevated plasma levels of coagulation factor XI and GOLM2 as risk factors for recurrence, while decreased levels of PCSK9 and pro-IL16 were linked to reduced VT recurrence risk.

Subgroup analyses revealed 18 loci associated with VT recurrence, with notable differences between pulmonary embolism (PE) and deep vein thrombosis (DVT). For example, the exonic variantSLC4A1p.Glu40Lys was significantly associated with recurrence in PE patients (Hazard Ratio (HR)=3.23, P=9.7×10-12) but showed no effect in DVT (HR=1.00, P=0.98).

These findings emphasize the role of specific genetic loci and protein pathways in influencing VT recurrence and provide valuable insights into potential therapeutic targets. Further research is needed to clarify the biological mechanisms driving these associations.

Key points

29 loci/proteins associated with VT recurrence risk.

The genomic architecture of VT recurrence risk varies based on the initial clinical presentation.
Impact of Trunk Function and Lower Limb Paralysis on Independence in Activities of Daily Living in Patients with Stroke
Authors: Nishida Takato , Sawai Shun , Fujikawa Shoya , Yamamoto Ryosuke , Shizuka Yusuke , Maru Takayuki , Nakagawa Kotaro , Nakano Hideki
Published: December 2024

Stroke is a major global health issue, and many patients experience motor paralysis and sensory impairments that affect their independence in activities of daily living (ADL). Trunk and lower limb functions are crucial in post-stroke ADL independence. Although these two functions are closely related, few studies have evaluated them in combination, and the importance of assessment methods that consider their mutual relationship has not been thoroughly examined. In this study, we aimed to clarify the degree to which trunk function and lower limb paralysis impact ADL independence when evaluated individually versus in combination, through a hierarchical regression analysis, and to verify the significance of the combined assessment of both functions. This cross-sectional study included 51 patients with first-ever stroke and hemiplegia. Trunk function was assessed using the Trunk Impairment Scale, lower limb paralysis was evaluated using the Brunnstrom Recovery Stage for the lower extremities, and ADL independence was measured using the Functional Independence Measure. Hierarchical regression analysis was conducted to examine the impact of trunk and lower limb functions on ADL independence. Across two regression models, the assessment of trunk and lower limb function in combination significantly improved the accuracy in reflecting ADL independence compared with the assessment of each function individually. The findings suggest that a combined assessment of both trunk and lower limb functions is a valuable evaluation method in the rehabilitation of patients with stroke.
Genetically Informed Methods Uncover the Low Polygenicity of Natural Dizygotic Twinning and Highlight Its Role in Female Fertility and Infertility
Authors: Hubers Nikki , Page Christian M. , Pool René , Mbarek Hamdi , Lambalk Nils , Mijatovic Velja , Ligthart Lannie , van Dongen Jenny , Corfield Elizabeth C. , Beck Jeffrey J. , Ehli Erik A. , Martin Nicholas G. , Willemsen Gonneke , Håberg Siri , Harris Jennifer R. , Hottenga Jouke-Jan , Boomsma Dorret I.
Published: December 2024

Natural dizygotic twinning (DZT) results from hyper-ovulation and is often considered an indicator of female fertility. Paradoxically, DZT is associated with factors linked to sub-fertility, such as advanced maternal age. We investigated the association between DZT and female fertility by comparing polygenic scores (PGS) for DZT in mothers of twins and singletons who conceived naturally versus those who conceived after medically assisted reproduction (MAR). We also estimated genetic correlations between DZT and other fertility-related traits.

Using GENESIS and SbayesS, we found that DZT is not highly polygenic, with about 0.20% of SNPs showing a nonzero effect and 17 SNPs contributing to 17.2% of the total predicted SNP heritability of 7.2%. We calculated PGSs for 4,381 twin mothers and 2,797 fathers of twins in the Netherlands Twin Register (NTR) and 1,299 twin mothers versus 64,810 singleton mothers in the Norwegian Mother, Father, and Child Cohort Study (MoBa). The PGS for DZT captured 1.60% of the variance in DZT liability. PGSs were higher in mothers of naturally conceived twins compared to those with MAR-conceived twins, especially for mothers who used hormonal ovulation induction and higher PGSs were associated with a shorted time to pregnancy. High genetic correlations were observed between DZT and anovulatory infertility (rg = -0.698, p = 5.099x10-5), PCOS (rg = -0.278, p = 0.035), and endometriosis (rg = 0.279, p = 0.003).

These findings suggest that the PGS for DZT is a valuable, under-recognized marker of female fertility, meriting further exploration within fertility research to improve reproductive health insights.
Optimizing Student Success: Leaders’ Perspectives on Advising Practices in Graduate Health Professions Education Programs
Authors: Meyer Holly S , Samuel Anita , Cleland Jennifer , Maggio Lauren A. , Artino Anthony R. , Scarlett Emily , Martin Paolo C.
Published: December 2024

Phenomenon

Effective graduate advising is crucial for student success but remains an understudied area, particularly in Health Professions Education (HPE). While the importance of advising is widely recognized, faculty often lack adequate preparation and face competing demands. Current research on advising primarily focuses on other disciplines, neglecting the unique challenges of HPE programs. This study aims to address this gap by exploring leaders’ perspectives on advising practices that optimize student success in HPE graduate programs.

Approach

A qualitative interview study using narrative inquiry was conducted to explore leaders’ perspectives on advising practices in graduate HPE programs globally. Purposive sampling was used to recruit program leaders across six World Health Organization regions. Semi-structured interviews were conducted and analyzed using narrative inquiry and developmental advising theory as a framework.

Findings

Fifteen HPE program leaders described advising practices focused on academic advancement, personal advancement, and community building. Leaders emphasized the importance of clear communication, goal setting, and student support. While advisors valued building strong relationships with students, challenges arose from balancing professional and personal roles. Findings suggest that a developmental advising approach, incorporating academic, personal, and community-building elements, can enhance student success in HPE graduate programs.

Insights

This study underscores the critical role of advisors in graduate HPE programs, revealing that effective advising involves both academic guidance and substantial emotional support. It highlights a gap in the existing literature and advocates for the expansion of developmental advising that addresses not only administrative tasks but also the broader developmental needs of students, such as career advancement and personal growth. The findings suggest that to enhance advising practices, graduate HPE programs should invest in ongoing professional development for advisors, adopt holistic advising models, and allocate resources to support students’ integration into professional communities, thereby preparing them more fully for their future careers.
Utilizing Saliva for Non-Invasive Detection of Exercise-Induced Myocardial Injury with Point-of-Care Cardiac Troponin-I
Authors: Ovchinnikov Aleksandr N.
Published: December 2024

Background

Point-of-care (POC) cardiac troponin-I (cTnI) measurement methods often involve immunoassays, which can provide a momentary view of cTnI levels but the current modality highly restricts access to and frequency of testing in a sports and exercise medicine setting due to the requirement of a blood draw.

Objectives

This study aimed to compare cTnI concentrations in saliva and serum in athletes before (T1), early (T2), 4 h (T3), and 24 h (T4) after exercise.

Methods

82 male runners were recruited and then divided into two groups. 54 participants (group 1) completed a 5-km time-trial, while 28 participants (group 2) did not undergo this exercise. POC testing device was used to quantify salivary and serum concentrations of cTnI in both groups at T1, T2, T3, and T4.

Results

In group 1, salivary and serum concentrations of cTnI increased at T2 (0.41±0.06 ng/mL and 0.48±0.06 ng/mL) compared to T1 (0.18±0.04 ng/mL and 0.22±0.04 ng/mL), reaching the highest values at T3 (0.62±0.05 ng/mL and 0.76±0.05 ng/mL) with the subsequent return to baseline values at T4 (0.16±0.03 ng/mL and 0.22±0.03 ng/mL). In group 2, there were no time-dependent changes in cTnI levels in both saliva (T1: 0.17±0.04 ng/mL, T2: 0.16±0.03 ng/mL, T3: 0.16±0.04 ng/mL, T4: 0.16±0.04 ng/mL) and serum (T1: 0.22±0.04 ng/mL, T2: 0.22±0.04 ng/mL, T3: 0.21±0.03 ng/mL, T4: 0.21±0.04 ng/mL). Salivary and serum concentrations of cTnI were significantly lower in group 2 compared to group 1 at T2 and T3; there was no difference between groups at T1 and T4. Deming regression and Passing–Bablok regression revealed that there was differential bias (at T3), but proportional agreement (at T1, T2, T3, T4) between salivary and serum levels of cTnI in both groups. The Bland–Altman method indicated that there was a negative differential bias but no proportional bias in the data. Recalibration of the new measurement approach (measurement of cTnI levels in saliva) by using the MethodCompare R package was effective in removing existing bias, as evidenced by its similar precision to the reference method (measurement of cTnI levels in serum), particularly at T2, T3, and T4.

Conclusions

In athletic settings, quantification of cTnI levels in saliva utilizing the POC-cTnI-Getein1100 assay may be a useful non-invasive tool in evaluating whether exercise-induced increases in cTnI levels are transient or there are acutely or chronically elevated cTnI concentrations.

Graphical abstract
Long Sleep Duration, Cognitive Performance, and the Moderating Role of Depression: A Cross-Sectional Analysis in the Framingham Heart Study
Authors: Young Vanessa M. , Bernal Rebecca , Baril Andree-Ann , Zeynoun Joy , Wiedner Crystal , Gaona Carlos , Beiser Alexa , Teixeira Antonio L. , Salardini Arash , Pase Matthew P. , Himali Jayandra Jung , Seshadri Sudha
Published: December 2024

INTRODUCTION

We investigated whether depression modified the associations between sleep duration and cognitive performance.

METHODS

Multivariable linear regression models examined the associations between sleep duration and cognition in 1,853 dementia- and stroke-free participants from the Framingham Heart Study. Participants were categorized in four groups: no depressive symptoms, no antidepressants; depressive symptoms without antidepressants use; antidepressant use without depressive symptoms; both depressive symptoms and antidepressant use.

RESULTS

Long sleep was associated with reduced overall cognitive function. Strong associations between sleep duration and cognitive performance were found in individuals with depressive symptoms, regardless of antidepressant use. Weaker but significant effects were observed in those without depressive symptoms. No significant associations were observed in participants using antidepressants without depressive symptoms.

DISCUSSION

These findings provide new evidence that sleep duration may be a modifiable risk factor for cognitive decline, particularly in individuals with depressive symptoms. Future research should elucidate underlying mechanisms and temporal relationships.

RESEARCH IN CONTEXT

Systematic review:We conducted a systematic search on PubMed and Google Scholar for peer-reviewed articles using keyword combinations related to sleep, cognition, and depression. Existing evidence reveals mixed findings on the relationship between sleep duration and cognition, with limited studies examining the role of depression on this association.

Interpretation:We observed that only long sleep duration (≥9h) was associated with poorer global cognition, executive function, visuospatial memory, and verbal learning/memory. Depression moderated this association, showing stronger negative effects of long sleep on cognition in individuals with depressive symptoms, regardless of antidepressant use. This suggests that long sleep duration may serve as an early indicator or risk factor for cognitive decline in those with depressive symptoms.

Future directions:Longitudinal studies with objective and subjective sleep assessments across diverse populations are needed to clarify how depression and its treatment influence the relationship between sleep duration and cognitive decline and support clinical strategies.

HIGHLIGHTS

Sleeping ≥ 9hours/night was associated with worse cognitive performance.

This association was stronger among those with depression.

Long sleepers were more likely to report symptoms of depression.

Sleep may be a modifiable risk for cognitive decline in people with depression.
Patient and Physician Perspectives on Cardiovascular Risk: A Multicenter Study of Communication Gaps
Authors: Górriz-Magaña Juan , Maruri-Sánchez Ramon , Elorriaga Ane , Salterain-González Nahikari , Prieto-Lobato Alicia , Rubia Raúl Gascueña , Sánchez Isabel Monedero , Elvira-Laffond Ana , Reguero Miguel Lapena , Barros Amanda Leandro , Rivas Cristina Villabona , Fernández Alejandro Gutiérrez , Méndez César Jiménez , Prieto-González Silvia , Melendo-Viu María , Durán Blanca Alcón , López Emilio Blanco , Lozano Clara Bonanad , Durante-López Alejandro , Carrasquer Anna , Losas Pedro Martínez , Casas Teresa Alvarado , Merino Pedro Pájaro , Olmos Victor Juárez , Lopez-Pais Javier , Kittleson Michelle M , Díez-Villanueva Pablo , Bañeras-Rius Jordi
Published: December 2024

Background

Effective risk communication is crucial for managing cardiovascular disease, the leading cause of global mortality. Clear communication between patients and physicians is essential for informed decision-making, yet gaps in understanding often persist.

Objective

This study examines the state of risk communication during hospital admissions for cardiovascular events, evaluating both patient and physician perspectives and identifying factors influencing risk perception.

Methods

The SEC-HARIPA study is a multicenter, cross-sectional analysis conducted across 28 Spanish centers from October 2022 to March 2023. It included 943 patients admitted to cardiology departments, either urgently or for scheduled procedures. Patients and their physicians completed parallel questionnaires assessing perceptions of cardiovascular risk, procedural complications, and overall communication. Statistical analysis focused on agreement between patient and physician perceptions and the impact of demographic and clinical variables.

Results

The mean age of participants was 68.2 years, with ischemic heart disease being the most common cause of admission (41.3%). While 76.9% of patients felt adequately informed about procedural risks, 69.3% of those experiencing adverse events reported a lack of information on potential complications. A significant discrepancy was found between patients’ and physicians’ perceptions of future cardiovascular risk, with patients often underestimating their risk (weighted kappa index of 0.29). Key factors influencing risk perception included prior cardiovascular history, age, gender, and diabetes mellitus.

Conclusions

This study reveals significant gaps in risk communication in cardiovascular care, particularly regarding future risks and complications. Tailoring communication strategies to individual patient characteristics could improve understanding and align perceptions with clinical realities, enhancing health outcomes.
Sex-specific disruptions in the developmental trajectory of anxiety due to prenatal cannabidiol exposure
Authors: Iezzi Daniela , Cáceres-Rodríguez Alba , Chavis Pascale , Manzoni Olivier J.
Published: December 2024

Many pregnant women use cannabidiol (CBD) as a natural remedy to alleviate symptoms such as nausea, insomnia, anxiety, and chronic pain. As much as 20% of pregnancies in the USA and Canada may involve the use of CBD-only products. CBD crosses the placenta and may affect fetal development, potentially leading to neuropsychiatric conditions later in life. Given the limited understanding of the effects of CBD during pregnancy, we adopted a longitudinal approach to investigate the neurodevelopmental trajectory associated with prenatal CBD exposure.

Pregnant mice were administered 3 mg/kg CBD from gestational days 5 to 18. At early adolescence, offspring displayed sex-specific behavioral changes. Females, but not males, exhibited a complex anxiety-like phenotype during the elevated plus maze task. This phenotype persisted into adulthood in the open field test and was accompanied by altered reward responsiveness. Throughout post-natal life, female offspring demonstrated heightened stretch-attend postures, a risk-assessment behavior reflecting approach-avoidance tendencies and anxiety. Finally, prenatal CBD exposure increased repetitive behaviors in adult animals of both sexes, as evidenced by the marble burying task. These results provide strong evidence of sex-specific disruptions in the developmental trajectories of anxiety associated with prenatal CBD exposure. They challenge the perception that CBD is universally safe and highlight vulnerabilities linked to gestational CBD exposure.
Dynamic evolution of satellite DNAs drastically differentiates the genomes ofTriboliumsibling species
Authors: Veseljak Damira , Despot-Slade Evelin , Volarić Marin , Horvat Lucija , Vojvoda Zeljko Tanja , Meštrović Nevenka , Mravinac Brankica
Published: December 2024

Tandemly repeated satellite DNAs (satDNAs) are among the most abundant and fastest-evolving eukaryotic sequences, but the way they model genomes is still elusive. Here, we investigated the evolutionary dynamics of satDNAs in the extremely satDNA-rich genomes of two closely relatedTriboliuminsects that produce sterile hybrids. InTribolium freemani, we identified 135 satDNAs, accounting for 38.7% of the genome. Comparative analysis with theTribolium castaneumsatellitome revealed that the drastic difference happened in their centromeric regions, which share orthologous organization hallmarked by totally different major satDNAs but related minor satDNAs. TheT. freemanimale sex chromosome, which lacks the major satDNA but contains a minor-like satDNA, further heightened the question of which satDNA is centromere-competent. By analyzing the long-range organization of the centromeric regions, we revealed that both the major and minor satDNA arrays exhibit a strong tendency toward macro-dyad symmetry, suggesting that the secondary structures in the centromeres may be more important than the primary sequence itself. We found evidence that the centromeric satDNAs ofT. freemanioccur in extrachromosomal circular DNAs, which may contribute to their expansion and homogenization between non-homologous chromosomes. We also identified numerous low-copy-number satDNAs that are orthologous between the siblings, some of which are associated with transposable elements, highlighting transposition as a mechanism of their spreading. The dynamic evolution of satDNAs has clearly influenced the differentiation ofTriboliumgenomes, but the question remains whether the differences in their satDNA profiles are a cause or consequence of speciation.
PDGFRα+Mesenchymal Stromal Cells Contribute to Epithelial Lineages during Prostate Development
Authors: Maiti Dibyo , Tien Hsin-Jung , Joshi Purna A.
Published: December 2024

Organ development is attributed to stem/progenitor cells which self-renew and differentiate into mature cells critical for tissue form and function. The prostate is an epithelial organ that participates in the production of seminal fluid. Bipotent and unipotent stem/progenitor cells resident in prostatic epithelia are shown to support its development. While the stroma is crucial for prostate organogenesis, precise stromal cells including immature stromal subsets involved in prostate biology are unknown. Utilizing genetic reporter and lineage tracing mouse models, we identify a PDGFRα+mesenchymal population in the fibromuscular stroma that harbors progenitors which undergo a mesenchymal-to-epithelial transition, generating prostatic luminal and basal epithelial lineages during postnatal development. Further, these mesenchymal progenitors and their epithelial progeny persist in the adult, demonstrating their self-renewal potential. Our findings unveil a prostatic progenitor beyond the epithelium, laying down a framework for probing the contribution of stromal progenitors to the normal and diseased prostate.

Graphical Abstract
An ancient origin of the naked grains of maize
Authors: Fairbanks Regina , Ross-Ibarra Jeffrey
Published: December 2024

Adaptation to novel environments requires genetic variation, which may either predate the novel environment or arise as new mutations. The relative importance of standing genetic variation vs.de novomutations in adaptation remains a fundamental question in evolutionary biology. Selection during domestication has been long used as a model to understand evolutionary processes, providing information not only on the phenotypes selected but also, in many cases, an understanding of the causal loci. Of the multiple causal loci that have been identified in maize, the selected allele can be found segregating in natural populations, consistent with their origin as standing genetic variation. The sole exception to this pattern is the well-characterized domestication locustga1, which has long been thought to be an example of selection on ade novomutation. Here, we use a large dataset of maize and teosinte genomes to reconstruct the origin and evolutionary history oftga1. We first estimated the age oftga1-maizeusing a genealogy-based method, finding that the allele arose approximately 41,000-49,000 years ago, predating the beginning of maize domestication. We also identify, for the first time,tga1-maizein teosinte populations, indicating the allele can survive in the wild. Finally, we compare observed patterns of haplotype structure and mutational age distributions neartga1with simulations, finding that patterns neartga1in maize better resemble those generated under simulated selective sweeps on standing variation. These multiple lines of evidence suggest that maize domestication likely drew upon standing genetic variation attga1and cement the importance of standing variation in driving adaptation during domestication.
Human mitochondrial RNA polymerase structures reveal transcription start-site and slippage mechanism
Authors: Shen Jiayu , Goovaerts Quinten , Ajjugal Yogeeshwar , Wijngaert Brent De , Das Kalyan , Patel Smita S.
Published: December 2024

Human mitochondrial RNA polymerase (POLRMT) and protein factors TFAM and TFB2M assemble on mitochondrial DNA promoters to initiate promoter-specific transcription. We present cryo-EM structures of two initiation complexes, IC3 and slipped-IC3, with fully resolved transcription bubbles containing RNA transcripts starting from +1 and −1 positions, respectively. These structures reveal the mechanisms of promoter melting, start site selection, and slippage synthesis. Promoter melting begins at −4 with base-specific interactions of −4 and −3 template guanines with POLRMT and −1 non-template adenine with TFB2M, stabilizing the bubble and facilitating initiation from +1. Slippage occurs when a synthesized 2-mer RNA shifts to −1; the −1 position is not an alternative start-site. The conserved non-template sequence (-1)AAA(+2) is recognized by a non-template stabilizing loop (K153LDPRSGGVIKPP165) and Y209 from TFB2M and W1026 of POLRMT. The initiation complex on cryo-EM grids exist in equilibrium with apo and dimeric POLRMTs, whose relative concentrations may regulate transcription initiation.

HIGHLIGHTS

Cryo-EM structures of active human mitochondrial transcription initiation complexes

De novo RNA synthesis begins at +1, linking +1 and +2 NTPs

Synthesized 2-mer RNA anneals at −1, initiating RNA slippage synthesis

POLRMT fingers’ motion alters TFB2M interactions with non-template strand
Is calcium intake associated with sleep quality? : a systematic review
Authors: Isoda Ami , Kiriya Junko , Jimba Masamine
Published: December 2024

As the prevalence of sleep disorders has grown worldwide, studies on sleep quality are increasingly required. Recent evidence suggests that calcium intake may influence sleep quality and duration, but few studies have investigated factors associated with sleep quality. This systematic review aimed to examine and synthesize existing evidence on the association between calcium intake and sleep quality and sleep duration. We included randomized controlled trials, case-control studies, cohort studies, and cross-sectional studies from multiple databases, including PubMed, Web of Science, Cochrane Library, Scopus, and CINAHL Plus, followed by keywords search at Google Scholar and reference review of included articles. A total of seven independent studies presented in nine reports met the inclusion criteria. Six of them were cross-sectional studies. The studies suggested a positive association between calcium intake and sleep quality, although the results were not statistically significant in some cases. Studies also indicated that lower calcium intake was associated with inappropriate sleep duration. We decided not to conduct meta-analysis because of the insufficient number of studies. The findings suggest a positive relationship between calcium intake and sleep quality. To test the effectiveness of calcium intake on sleep quality, a randomized controlled trial is required across different ethnicity and culture.
Few-to-many-particle crossover of pair excitations in a superfluid
Authors: Resare Fabian , Hofmann Johannes
Published: December 2024

Motivated by recent advances in the creation of few-body atomic Fermi gases with attractive interactions, we study theoretically the few-to-many-particle crossover of pair excitations, which for large particle numbers evolve into a mode that describes amplitude fluctuations of the superfluid order parameter (the “Higgs” mode). Our analysis is based on the hypothesis that salient aspects of the excitation spectrum are captured by interactions between time-reversed pair states in a harmonic oscillator potential. Microscopically, this assumption leads to a Richardson-type pairing model, which is integrable and thus allows a systematic quantitative study of the few-to-many-particle crossover with only minor numerical effort. We first establish a parity effect in the ground-state energy, i.e., a spectral convexity in the energy of open-shell configurations compared to their closed-shell neighbors, which is quantified by a so-called Matveev-Larkin parameter discussed for mesoscopic superconductors, which generalizes the pairing gap to mesoscopic ensembles and which behaves quantitatively differently in a few-body and a many-body regime. The crossover point for this quantity is widely tunable as a function of interaction strength. We then compute the excitation spectrum and demonstrate that the pair excitation energy shows a minimum that deepens with increasing particle number and shifts to smaller interaction strengths, consistent with the finite-size precursor of a quantum phase transition to a superfluid state. We extract a critical finite-size scaling exponent that characterizes the decrease of the gap with increasing particle number.

Published by the American Physical Society
2024
Stabilizer Tensor Networks: Universal Quantum Simulator on a Basis of Stabilizer States
Authors: Masot-Llima Sergi , Garcia-Saez Artur
Published: December 2024

Efficient simulation of quantum computers relies on understanding and exploiting the properties of quantum states. This is the case for methods such as tensor networks, based on entanglement, and the tableau formalism, which represents stabilizer states. In this Letter, we integrate these two approaches to present a generalization of the tableau formalism used for Clifford circuit simulation. We explicitly prove how to update our formalism with Clifford gates, non-Clifford gates, and measurements, enabling universal circuit simulation. We also discuss how the framework allows for efficient simulation of more states, raising some interesting questions on the representation power of tensor networks and the quantum properties of resources such as entanglement and magic, and support our claims with simulations.

Published by the American Physical Society
2024