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Development and validation of a multienzyme isothermal rapid amplification and lateral flow dipstick combination assay for HTLV-1 proviral DNA detection

J Transl Med. 2025 Jun 11;23(1):646. doi: 10.1186/s12967-025-06642-9.

ABSTRACT

BACKGROUND: Human T-cell lymphotropic virus-1(HTLV-1) infection may lead to adult T-cell leukemia, HTLV-associated myelopathy/tropical spastic paraplegia, and various neurological diseases. Therefore, developing a rapid and accurate detecting method is crucial for preventing and controlling HTLV-1 infection. This study aims to develop and validate a detection assay for HTLV-1 proviral DNA by combining multienzyme isothermal rapid amplification(MIRA) and lateral flow dipstick(LFD) techniques.

METHODS: Primers and probes were designed based on the conserved sequence of the HTLV-1 Tax gene, and the MIRA-LFD method was established and optimized. Different concentrations of HTLV-1 plasmids were tested by the MIRA-LFD assay to verify the limit of detection(LOD) of the method. To evaluate the cross-reactivity, viral pathogens were detected by this assay, including hepatitis B virus(HBV), hepatitis C virus(HCV), hepatitis E virus(HEV), cytomegalovirus(CMV), herpes simplex virus-1/2(HSV-1/2), Epstein-Barr virus(EBV), Parvovirus B19(B19V), and human T-cell lymphotropic virus-2(HTLV-2). 500 clinical samples were simultaneously detected using real-time PCR(qPCR) and MIRA-LFD methods, and the consistency between the two methods was statistically analyzed. The qPCR was used as the reference method to determine the diagnostic sensitivity and specificity of the MIRA-LFD method.

RESULTS: The MIRA-LFD method can detect HTLV-1 within 20 min at 37℃. The LOD for HTLV-1 using this method was 200 copies/µL. This method had no cross-reaction with the other eight viruses, with good specificity. Using qPCR as the standard, the diagnostic sensitivity and specificity of the MIRA-LFD method for 500 clinical samples were 100%. The MIRA-LFD and qPCR methods had 100% consistency(kappa value = 1.00).

CONCLUSIONS: This study established a method based on MIRA-LFD for detecting HTLV-1 proviral DNA, which has the advantages of fast, accurate, good sensitivity, strong specificity, simplicity, and portability. This method meet the needs of rapid on-site detection and is easy to promote and use in grassroots medical institutions or blood stations.

PMID:40500737 | DOI:10.1186/s12967-025-06642-9

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Suppression effect of folate on poly- and perfluoroalkyl substance-induced alterations in lipids and the atherogenic index of plasma in adolescents

Lipids Health Dis. 2025 Jun 11;24(1):213. doi: 10.1186/s12944-025-02638-y.

ABSTRACT

BACKGROUND: The specific mechanisms by which poly – and polyfluoroalkyl substances (PFAS) influence the particular lipid levels of adolescents and the progression of early subclinical atherosclerosis remain unclear. A certain degree of correlation exists between folate and the exposure of adolescents to PFAS, the maintenance of lipid homeostasis, as well as cardiovascular health status. This study investigated the role and mechanisms of folate in the process through which PFAS can influence the blood lipid profiles of adolescents.

METHODS: We used data from the National Health and Nutrition Examination Survey 2005-2018. Weighted generalized linear regression analysis, Bayesian kernel machine regression, weighted quantile sum regression, mediation analysis, and network toxicology were employed to investigate the association between mixed exposures to perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate, and perfluorononanoic acid (PFNA) and lipids, as well as the atherogenic index of plasma (AIP), and to determine the impact of red blood cell folate or serum folate in the body.

RESULTS: A positive association was detected between low density lipoprotein cholesterol (LDL-C) and PFOS; between total cholesterol (TC) and both PFOS and PFOA; between triglycerides (TG) and PFNA, PFOS, and PFOA; and between AIP and PFNA, PFOS, and PFOA. Analysis identified a positive correlation between mixed PFAS and LDL-C, TC, TG, and AIP. Red blood cell folate suppressed the associations of PFOA, PFOS, PFNA, and total PFAS with TG, as well as PFOA, PFOS, and total PFAS with AIP. The suppression effect of red blood cell folate was more pronounced in female adolescents. PFAS was associated with certain targets, including albumin, peroxisome proliferator-activated receptor γ, and interleukin-10, and may influence lipid metabolism and atherosclerosis. PFAS and folate share caspase-1 and carbonic anhydrase 2 as targets for mechanisms associated with atherosclerosis.

CONCLUSIONS: PFAS exposure may be associated with dyslipidemia and impaired cardiovascular health in adolescents, while folate could potentially attenuate the direct association between PFAS exposure and these health outcomes. In the future, maintaining normal levels of folate in the body could be a key strategy in preventing disruptions to lipid metabolism and potential threats to cardiovascular health in adolescents caused by PFAS.

PMID:40500729 | DOI:10.1186/s12944-025-02638-y

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Digital learning resource use among Swedish medical students: insights from a nationwide survey

BMC Med Educ. 2025 Jun 11;25(1):849. doi: 10.1186/s12909-025-07446-7.

ABSTRACT

BACKGROUND: Medical students navigate a complex landscape of digital tools with potential to enhance learning. The main objectives of the current study were to investigate which digital resources are being used, which background factors are associated with utilization, perceived advantages and disadvantages of different digital resources, and explore future directions.

METHODS: Cross-sectional, nationwide, online 25-item multiple-choice question survey and one free-text question enabling qualitative data analysis. Medical students at all seven universities with medical school programs in Sweden were invited to participate. Data were collected October – December 2024.

RESULTS: One thousand seven hundred sixty-six students responded to the survey, with an average response rate of 20.2% across sites. The five most frequently used digital resources were (percentage using at least on a weekly basis): University study platform (75.3%), videos (68.0%), flashcards (66.4%), student notes (53.4%) and external study platforms (47.3%). Flashcards were perceived to have a large to very large positive impact on development and maintenance of theoretical knowledge by 63.7% of students. Younger age (≤ 25 years) was strongly associated with higher use of flashcards (OR 1.98 (95% CI 1.54-2.54)) and generative artificial intelligence (AI) (OR 1.66 (1.29-2.15)), whereas having children at home was associated with more frequent use of videos (OR 2.32 (1.32-4.08)) and university digital platforms (OR 2.62 (1.26-5.45)), in multivariable logistic regression analyses. Most students (74.8%) reported finding their digital resources based on recommendations from more senior medical students. Perceived key advantages of digital resources in general were availability (90.9%), flexibility (80.6%), and more effective learning compared to traditional modalities (59.0%), while possible disadvantages included risk for distraction (49.6%) and uncertainty regarding reliability of content (45.4%). Qualitative data highlighted several areas of interest, including calls for universities and lecturers to provide high-quality, updated video material and flashcard decks tailored to the curriculum, and review and recommend third-party digital resources (e.g., YouTube channels).

CONCLUSIONS: Medical students extensively use digital resources, with perceived large positive learning effects and benefits. Several background factors influence usage patterns. These data may support institutions, program directors and teachers in their efforts to guide and improve use of digital learning tools in medical schools.

PMID:40500719 | DOI:10.1186/s12909-025-07446-7

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Complications of 3D printed dentures: A systematic review

J Prosthet Dent. 2025 Jun 10:S0022-3913(25)00455-X. doi: 10.1016/j.prosdent.2025.05.019. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: Computer-aided manufacturing and computer-aided design (CAD-CAM) has been implemented less in complete removable prosthodontics because various factors affect the results and quality of complete dentures. Some clinical studies and systematic reviews have compared digitally fabricated complete dentures (DCDs) with conventional complete dentures (CCDs), but few have focused on the complications and number of postinsertion visits.

PURPOSE: The purpose of this systematic review was to compare CCDs and DCDs in terms of complications and postinsertion visits by evaluating outcomes that included occlusion, retention, and patient discomfort. The goal was to provide insights into the clinical implications of using digital versus conventional techniques for denture fabrication.

MATERIAL AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the question: “Is there a difference in complications and postinsertion visits when CCDs are compared with digitally printed complete dentures?” was addressed. Two independent electronic searches up to March 2024 were done in the PubMed, Google Scholar, and Embase databases. The risk of bias in each study was assessed by using the Cochrane risk of bias tool and the Newcastle-Ottawa scale.

RESULTS: Of 63 articles, 11 were included. Outcomes were grouped into different kinds of complications: occlusion, retention or stability, pain, and number of postinsertion visits. In terms of all 4 complications, some statistically significant differences were reported.

CONCLUSIONS: The manufacturing technique for complete dentures influenced the number and type of complications. The digital technique showed a similar or greater number of follow-up visits, depending on the method used and the study design.

PMID:40500684 | DOI:10.1016/j.prosdent.2025.05.019

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Safety concerns and speak-up in patient care from the perspective of nursing assistant trainees in Tyrol – a multicenter exploratory quantitative cross-sectional study

Z Evid Fortbild Qual Gesundhwes. 2025 Jun 10:S1865-9217(25)00126-6. doi: 10.1016/j.zefq.2025.05.002. Online ahead of print.

ABSTRACT

BACKGROUND: ‘Speak up’ refers to the act of raising safety concerns, which can greatly influence patient safety outcomes. In healthcare, hierarchical structures may inhibit nursing assistant trainees from voicing their concerns effectively. This study explored the speak-up behavior and perceptions of safety culture among nursing assistant trainees in Tyrol (Austria). It also investigated the reasons and barriers for speaking up, as well as potential differences in speak-up behavior based on macro-social characteristics.

METHODS: Between May and July 2023, a multicentric, exploratory quantitative cross-sectional study was conducted involving 508 trainees in nursing assistance and advanced nursing assistance across seven training institutions in Tyrol. Data were collected using the “Speaking Up about Patient Safety Questionnaire” (SUPS-Q). Descriptive statistics along with the Mann-Whitney U test were employed for data analysis.

RESULTS: A total of 358 nursing assistant trainee participated in the study. Most trainees reported perceiving safety concerns, actively speaking up about them, and experiencing a generally positive safety culture during their internships. However, common barriers to speaking up included fear of negative repercussions for their training (45.6%) and uncertainty about how to articulate their concerns (31.8%). The primary motivations for addressing safety concerns were the desire to prevent harm (71.3%) and a strong sense of duty (62.5%).

DISCUSSION: Compared to existing studies with nursing students, trainees in the nursing assistant professions seem to express their safety concerns more often. The reasons for this could be primarily intradisciplinary communication and a higher average age.

CONCLUSION: Trainees in nursing assistance professions tend to be more willing to voice their safety concerns than nursing students. Further multicenter studies should be undertaken to improve the transferability of results.

PMID:40500646 | DOI:10.1016/j.zefq.2025.05.002

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Nevin Manimala Statistics

Imaging the orientation of hydroxyapatite crystallites across full mouse femora

Faraday Discuss. 2025 Jun 11. doi: 10.1039/d5fd00009b. Online ahead of print.

ABSTRACT

Imaging the orientations of crystallites in bone requires the usage of synchrotron X-ray radiation, which is a limited resource for researchers. Thus scans have historically been limited to either small regions or few samples. In the present study, we scan 16 full frontal cross sections of mouse femora. This makes it possible to study structure, orientation, and composition, statistically across many different bones and animals, while preserving the structural context. From the following analysis, we can deduce that while the trabecular bone in the shaft has a larger fraction of oriented crystallites than other regions in the bone, the oriented fraction is more well aligned in the cortical bone in the shaft compared to other regions in the bone. We also see that the crystallites in the cortical and trabecular bone are longer than those in the femoral head and the condyle. The study also shows a larger Sr content in the cortical bone compared to other regions, and a larger Zn content in the femoral head compared to other regions of the bones. This study shows the need for and possibility of scanning larger regions to understand bioinorganic materials.

PMID:40498542 | DOI:10.1039/d5fd00009b

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The Jugular Foramen is Rather a Canal With Distinctive Morphological Configuration Concerning Its Clinical Anatomy and Surgical Implications: Morphological Analysis

Oper Neurosurg (Hagerstown). 2025 Jun 10. doi: 10.1227/ons.0000000000001654. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The jugular foramen (JF) is rather a complex anatomical structure with internal configuration. Its osteomorphology was assessed to redefine this rather long bony passage as a jugular canal (JC) based on its morphometric data.

METHODS: The JF was endocranially and exocranially observed and measured by a digital Vernier caliper bilaterally in 402 dry skulls with opened cranial cavity. The following parameters were measured and analyzed statistically: (1) external and internal widths in the mediolateral dimension, (2) external and internal lengths in the anteroposterior dimension, and (3) depth between the external and internal planes of the foramen. The JF/canal was classified based on its appearance and its morphometric features.

RESULTS: The mean length of the JC was approximately 12 mm (12.25 mm-right, 11.76 mm-left) and was longer on the right side (P = .05, 95% CI). Its external opening was found to be slightly larger than the internal opening (P = .07-right, P = .06-left). The JC took 3 distinctive course patterns of straight (47.6%), curved (45.5%), and angulated (6.9%). Its openings exhibited 3 types based on their morphometric analysis: 14.4% Type-I (width = length ±1 mm), 9.8% Type-II (width > length), and 75.9% Type-III (width < length). The size of the external opening into the JC was larger than its internal opening (straight: P = .08-right and P = .07-left), (curved: P = .03-right and P = .03-left), (angulated: P = .03-right and P = .04-left).

CONCLUSION: The JF should be regarded clinically as a canal. It is composed of internal and external openings where the jugular fossa resides in between. The provided osteomorphological variations of the JC would enhance the diagnostics and surgical planning in JF syndromes radioimaging and surgical interventions.

PMID:40498516 | DOI:10.1227/ons.0000000000001654

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Scenario Projections of Respiratory Syncytial Virus Hospitalizations Averted Due to New Immunizations

JAMA Netw Open. 2025 Jun 2;8(6):e2514622. doi: 10.1001/jamanetworkopen.2025.14622.

ABSTRACT

IMPORTANCE: In 2023, new immunization strategies became available for preventing respiratory syncytial virus (RSV) hospitalizations in infants and older adults. Modeling studies to understand the population-level impact of their use are important for public health planning.

OBJECTIVE: To estimate the number of hospitalizations averted in 2023 to 2024 due to new RSV immunization strategies and provide scenario projections for future seasons.

DESIGN, SETTING, AND PARTICIPANTS: This decision analytical model examined RSV hospitalizations in King County, Washington, from October 7, 2023, through April 26, 2025. The population of King County was disaggregated into infants younger than 6 months, infants aged 6 to 11 months, children aged 1 to 4 years, children/adults aged 5 to 59 years, adults aged 60 to 74 years, and adults aged 75 years or older.

EXPOSURES: Respiratory syncytial virus vaccination for adults aged 60 years or older, maternal RSV vaccination, and long-acting monoclonal antibodies (nirsevimab) for infants younger than 8 months.

MAIN OUTCOMES AND MEASURES: The proportion of RSV hospitalizations averted in adults aged 60 years or older and infants younger than 1 year were estimated using an RSV transmission model calibrated to RSV hospitalizations.

RESULTS: The RSV transmission model simulated the population of King County, which includes approximately 2.3 million individuals, with 23 700 infants younger than 1 year and 446 500 adults aged 60 years or older. During the 2023 to 2024 RSV season, 21.2% of adults aged 60 to 74 years, 32.7% of adults aged 75 years or older, and 33.0% of infants were protected through active or passive immunization. A total of 125 (95% projection interval [PI], 77-192) RSV hospitalizations were averted, with most of the benefit observed in infants younger than 6 months (28.6% [95% PI, 26.9%-30.5%] reduction from baseline) and adults aged 75 years or older (14.8% [95% PI, 14.3%-15.5%] reduction from baseline). For the 2024 to 2025 season, optimistic scenarios of high immunization coverage (50% in older adults and 80% in infants) projected reductions of 29.8% (95% PI, 29.1%-30.8%) in adults aged 75 years or older and 68.8% (95% PI, 66.0%-71.7%) in infants younger than 6 months compared with a counterfactual scenario with no immunizations. Targeting infants eligible for catch-up doses of nirsevimab early in the season increased the proportion of RSV hospitalizations averted in infants aged 6 to 11 months from 31.7% (95% PI, 29.4%-33.9%) to 40.4% (95% PI, 39.0%-42.1%). If vaccine protection in adults aged 75 years or older waned by 50% in the second year after immunization, the proportion of RSV hospitalizations averted was projected to decrease to 22.2% (95% PI, 21.7%-23.0%).

CONCLUSIONS AND RELEVANCE: In this decision analytical model of RSV immunizations, the results suggest a modest reduction in RSV-diagnosed hospitalizations during the 2023 to 2024 season due to limited availability of immunization products, particularly for infants. A higher uptake earlier in the season may lead to substantial reductions in RSV hospitalizations in the 2024 to 2025 season.

PMID:40498487 | DOI:10.1001/jamanetworkopen.2025.14622

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Resistance Training and Lymphedema in Breast Cancer Survivors

JAMA Netw Open. 2025 Jun 2;8(6):e2514765. doi: 10.1001/jamanetworkopen.2025.14765.

ABSTRACT

IMPORTANCE: Lymphedema is a common treatment-related adverse effect among breast cancer survivors that can limit activity and mobility. Although exercise is associated with improved outcomes after breast cancer treatment, data are limited on the association of intense physical activity, including strength training, with lymphedema.

OBJECTIVE: To examine the association between resistance training and lymphedema among breast cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study conducted between September 15, 2022, and March 26, 2024, women from 3 prospective studies (EXERT-BC, EXERT-BCN, and EXERT-C) underwent thrice-weekly, dose-escalated resistance training for 3 months to promote strength, mobility, and hypertrophy.

MAIN OUTCOMES AND MEASURES: Lymphedema was assessed at baseline and completion using bioimpedance analysis to evaluate fluid and body composition metrics, distinguishing among intracellular water, extracellular water, and total body water.

RESULTS: A total of 115 women completed the exercise regimen (median age, 54 years; range, 24-71 years). Ninety-six participants (83%) underwent sentinel lymph node biopsy, whereas 14 (12%) underwent axillary lymph node dissection. At baseline, 15 women (13%) had clinical lymphedema: 8 (8%) in the sentinel lymph node biopsy group and 7 (37%) in the axillary lymph node dissection group. No participants experienced subjective or clinical worsening of lymphedema after completing the exercise regimen. Bilateral arm lean mass significantly increased after resistance training (affected arm: median [IQR], 5.64 [4.98-6.20] lb; 95% CI, 5.40-5.84 lb) vs baseline (median [IQR], 5.45 [4.92-6.08] lb; 95% CI, 5.34-5.67 lb) (s = 1789.5; P < .001). The edema index (extracellular water to total body water ratio) significantly improved in all patients, signifying a reduction in lymphedema at the completion of exercise (mean, 0.383; 95% CI, 0.382-0.385) compared with baseline (mean, 0.385; 95% CI, 0.384-0.386) (t110 = 4.05; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study of breast cancer survivors, intense resistance training did not exacerbate lymphedema and was associated with improvements in fluid balance and lean mass in the upper extremities. These findings suggest support for the inclusion of structured resistance exercise as part of breast cancer treatment and survivorship care.

PMID:40498485 | DOI:10.1001/jamanetworkopen.2025.14765

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Alcohol-Associated Liver Disease Mortality

JAMA Netw Open. 2025 Jun 2;8(6):e2514857. doi: 10.1001/jamanetworkopen.2025.14857.

ABSTRACT

IMPORTANCE: Alcohol-associated liver disease (ALD) is a major public health concern, accounting for one-quarter of cirrhosis-related deaths and becoming the leading indication for liver transplantation in the US, with concerning increases in mortality during and following the COVID-19 pandemic onset.

OBJECTIVE: To evaluate comprehensive national trends in ALD mortality in the US from 1999 to 2022, with a particular focus on disparities related to sex, race, ethnicity, and age.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional analysis used the Centers for Disease Control and Prevention Wide Ranging Online Data for Epidemiologic Research mortality database from 1999 to 2022, examining death certificates across all 50 states and the District of Columbia. The study included individuals aged 25 years and older. Data analysis was performed from September to November 2024.

EXPOSURE: ALD mortality was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (K70.xx) for both alcohol-associated hepatitis (K70.1x) and alcohol-associated cirrhosis (K70.3x).

MAIN OUTCOMES AND MEASURES: Primary outcomes included age-adjusted annual mortality rates per 100 000 population, stratified by sex, age groups (25-44, 45-64, 65-84, and ≥85 years), race and ethnicity, and geographic regions. Joinpoint regression analysis was used to calculate average annual percentage changes (AAPCs) and to identify significant trend changes.

RESULTS: In this study, a total of 436 814 ALD deaths were recorded (308 923 men [70.7%]), with ALD mortality increasing from 6.71 to 12.53 deaths per 100 000 between 1999 and 2022 and significant acceleration during 2018 to 2022 (annual percentage change [APC], 8.94%; 95% CI, 6.27% to 14.51%; P = .001). Women showed more rapid increases than men (AAPC, 4.29% [95% CI, 3.09% to 5.51%] vs 2.50% [95% CI, 1.51% to 3.51%]), whereas young adults (aged 25-44 years) demonstrated concerning trends (AAPC, 4.23%; 95% CI, 3.47% to 4.83%; P = .001). American Indian and Alaska Native populations experienced the highest mortality rates, increasing from 25.21 to 46.75 deaths per 100 000 (AAPC, 4.93%; 95% CI, 3.45% to 5.96%; P = .001). Alcohol-associated hepatitis mortality increased from 0.47 to 0.76 deaths per 100 000 (AAPC, 2.08%; 95% CI, 1.27% to 3.05%; P = .001), with women showing steeper increases than men (AAPC, 3.94% [95% CI, 2.58% to 5.46%] vs 1.56% [95% CI, 0.73% to 2.42%]). Alcohol-associated cirrhosis mortality increased from 4.09 to 9.52 deaths per 100 000 (AAPC, 4.00%; 95% CI, 3.63% to 4.40%; P = .001), with particularly concerning trends among women (APC from 2011 to 2022, 8.32%; 95% CI, 7.40% to 9.82%; P = .01) and adults aged 25 to 44 years (APC from 2018 to 2022, 19.51%; 95% CI, 15.00% to 28.53%; P = .001).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study using data from the Centers for Disease Control and Prevention Wide Ranging Online Data for Epidemiologic Research database, ALD mortality increased significantly across demographic groups, with particularly concerning trends among women, younger adults, and American Indian and Alaska Native populations. These findings highlight the urgent need for targeted public health interventions and enhanced surveillance, especially given the sustained impact of COVID-19 pandemic-related changes in alcohol consumption patterns.

PMID:40498484 | DOI:10.1001/jamanetworkopen.2025.14857