Category: Nevin Manimala

Genome Biol. 2025 Jun 11;26(1):161. doi: 10.1186/s13059-025-03635-1.

ABSTRACT

BACKGROUND: G-quadruplexes (G4s) are non-canonical DNA structures that can form at approximately 1% of the human genome. They facilitate genomic instability by increasing point mutations and structural variation. Numerous G4s participate in telomere maintenance and regulating transcription and replication, and evolve under purifying selection. Despite these important functions, G4s have remained under-studied in human and ape genomes due to incomplete assemblies.

RESULTS: Here, we conduct a comprehensive analysis of predicted G4s (pG4s) in the recently released, telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, and Sumatran orangutan. We annotate 41,232-174,442 new pG4s in these T2T compared to previous ape genome assemblies (5%-21% increase). Analyzing inter-species whole-genome alignments, we identify pG4s shared across apes (approximately one-third of all pG4s) and thousands of species-specific pG4s. pG4s accumulate and diverge at rates consistent with divergence times between species, following molecular clock. pG4s shared across apes are enriched and hypomethylated at regulatory regions-enhancers, promoters, UTRs, and origins of replication-suggesting their conserved formation and functions. Species-specific pG4s (constituting 11-27% of all pG4s) are located in regulatory regions, potentially contributing to adaptations, and in repeats, likely driving genome expansions.

CONCLUSIONS: Our findings illuminate the evolutionary dynamics of G4s, conservation of their role in gene regulation, and their contributions to ape genome evolution. Our study highlights the utility of high-resolution T2T genomes in revealing elusive yet likely functionally relevant genomic features previously hidden by incomplete assemblies.

PMID:40500762 | DOI:10.1186/s13059-025-03635-1

Breast Cancer Res. 2025 Jun 11;27(1):102. doi: 10.1186/s13058-025-02062-1.

ABSTRACT

PURPOSE: Based on improved survival, the 2017 ASCO and Cancer Care Ontario clinical guidelines (ACGD) recommended consideration of adjuvant bisphosphonates for postmenopausal women with early-stage breast cancer (EBC). However, small survey-based studies suggest inconsistent prescribing. This study evaluated receipt of adjuvant bone modifying agents (BMAs) in the United States before and after publication of the 2017 ACGD.

METHODS: This nationwide retrospective cohort study used a deidentified electronic health record-derived database to identify patients diagnosed with stage I-III EBC treated at health care practices from 2012 to 2019. We defined adjuvant BMA (bisphosphonates or denosumab) use as first dose received within 24 months of EBC diagnosis. We used Chi-squared and multivariable logistic regression analyses to compare the proportion of patients receiving adjuvant BMAs pre- and post-ACGD and identify factors associated with receipt of any BMA as well as bisphosphonates alone.

RESULTS: Our cohort included 11,470 patients. Most patients were 50 years of age or older (82%), and had stage I (57%), node-negative (70%) and estrogen receptor (ER)-positive (76%) breast cancer. Patients diagnosed post-ACGD (2017-19) were more likely to receive adjuvant BMAs (9%) than patients diagnosed in earlier years (7.4%; odds ratio [OR] 1.23; 95% confidence interval (CI) 1.08-1.42; p = 0.002). Post-menopausal status, age ≥ 50, receipt of adjuvant chemotherapy and endocrine therapy, and coexisting bone loss diagnoses were significantly associated with increased receipt of adjuvant BMAs. Among BMA recipients, 65.8% received denosumab only, 32.6% received bisphosphonates only, and 1.4% received both.

CONCLUSIONS: Even after release of the ACGD guidelines, adjuvant BMA prescribing was low, and the majority of patients who received BMA did not receive bisphosphonates.

PMID:40500761 | DOI:10.1186/s13058-025-02062-1

Chiropr Man Therap. 2025 Jun 11;33(1):25. doi: 10.1186/s12998-025-00585-0.

ABSTRACT

BACKGROUND: Manual therapy, including high-velocity low-amplitude spinal manipulation (HVLA-SM), is a complex motor task performed by trained individuals. The ability to modulate the magnitude of applied forces is an attribute of proficiency that is challenging for providers and students. Adopting different biomechanical strategies may facilitate force modulation by practitioners performing HVLA-SM. This study evaluated the efficacy of different biomechanical strategies on force-time characteristics of prone thoracic HVLA-SM.

METHODS: A randomized crossover experimental design was used. Data were collected between October 2022 and May 2023 from chiropractic students at the Canadian Memorial Chiropractic College who performed HVLA-SM targeted to the thoracic spine of a prone-lying manikin using as much force as possible in each of six different strategies. Strategies (S1 to S6) were specifically developed to successively increase a person’s ability to produce force while performing HVLA-SM. Force-time parameters for the HVLA-SM trials were recorded. Peak force was the primary outcome of interest while preload force, load rate, and time to peak force were analyzed as secondary measures.

RESULTS: Data were collected from 97 participants (51 female). Peak force increased successively from S1 to S5 with moderate effects (- 0.45 ≤ effect size ≤ -0.72). There was no statistical difference in either peak force or load rate between S5 and S6. Load rate also did not statistically increase between S3 and S4 where different muscle groups were targeted to produce force. The strategy with the highest peak force (S6) also demonstrated the lowest preload force.

CONCLUSIONS: Strategies used in this study effectively facilitated modulation of force-time characteristics of prone thoracic HVLA-SM. Thus, training approaches may consider introducing people to different biomechanical strategies to enhance HVLA-SM force modulation.

PMID:40500758 | DOI:10.1186/s12998-025-00585-0

Thyroid Res. 2025 Jun 12;18(1):26. doi: 10.1186/s13044-025-00242-x.

ABSTRACT

OBJECTIVE: Graves’ disease (GD) patients treated with radioactive iodine may face health risks from potential radiation exposure, both for themselves and their offspring. This systematic review aims to comprehensively evaluate the association between prior radioactive iodine (RAI) therapy for GD and subsequent pregnancy outcomes in women of childbearing age.

METHODS: A search of the bibliographic databases PubMed/MEDLINE and Web of Science was conducted up to December 2024 to identify relevant studies.

RESULTS: The final systematic review included 1055 patients from 5 articles, all of which were retrospective cohort studies. Two studies reported the incidence of miscarriage after RAI treatment of 2.3% (3/130) and 22.2% (6/27). One study indicated that the miscarriage rate in the RAI group was not significantly different from that in the control groups, while the other did not provide a statistical comparison between groups. Two studies reported the incidence of neonatal hyperthyroidism (NH) after RAI therapy of 11.3% (5/44) and 5.5% (8/145). Both studies indicated that high levels of serum TRAb during late pregnancy were significantly associated with NH (P < 0.05). One study reported the incidence of postpartum thyrotoxicosis (PT) after RAI therapy of 2.1%. Compared with surgical treatment and ATD treatment, patients with RAI therapy had a significantly lower incidence of PT (P < 0.05).

CONCLUSION: Based on the limited evidence from retrospective studies, current data does not demonstrate a statistically significant increase in the risk of miscarriage or postpartum thyrotoxicosis following RAI therapy, compared to ATDs or surgical treatment. Elevated maternal TRAb levels in late pregnancy were strongly associated with neonatal hyperthyroidism. However, the small sample sizes and heterogeneity in study designs preclude definitive conclusions. Further prospective studies are required to establish more comprehensive and reliable conclusions and to evaluate more pregnancy outcomes.

PMID:40500752 | DOI:10.1186/s13044-025-00242-x

BMC Palliat Care. 2025 Jun 11;24(1):164. doi: 10.1186/s12904-025-01777-4.

ABSTRACT

BACKGROUND: Palliative sedation is the monitored use of medications intended to reduce consciousness to relieve the burden of otherwise intractable suffering. Since 2016, the French Leonetti-Claeys law has granted patients the right to receive continuous deep sedation until death (CDSUD) for some indications. There are relatively few data in the literature assessing sedation practices in palliative care units (PCUs).

METHODS: This study aimed to compare sedation practices in six French PCUs, analyzing the frequency, types of sedation (CDSUD vs. proportional sedation), and use of sedative medications during the last 72 h of life. This retrospective study examined the data of patients who died in these units between July and December 2021.

RESULTS: The results revealed statistically significant variability in sedation practices. The overall prevalence of sedation practices (all types) was 22%. The prevalence for CDSUD was 12%. Some units had much higher or lower rates of sedation, suggesting differences in the interpretation of guidelines and regulations, possibly because of cultural or individual factors within the units. The study also found important variability in the use of sedative medication in terms of molecules and dosage. Midazolam was the most commonly used benzodiazepine but the dosage varied significantly depending on the units.

CONCLUSIONS: Further qualitative research is needed to understand the reasons for the observed variability in sedation practices and improve the standardization and clarity of palliative sedation.

PMID:40500746 | DOI:10.1186/s12904-025-01777-4

J Neuroeng Rehabil. 2025 Jun 11;22(1):132. doi: 10.1186/s12984-025-01665-1.

ABSTRACT

BACKGROUND: The practicality of implementing digital cognitive screening tests in primary health care (PHC) for the detection of cognitive impairments, particularly among populations with lower education levels, remains unclear. The aim of this study is to assess the validity and usability of digital cognitive screening tests in PHC settings.

METHODS: We utilized a randomized crossover design, whereby 47 community-dwelling participants aged 65 and above were randomized into two groups. One group completed the paper-based Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) first, followed by the tablet-based digital version after a two-week washout period, while the other group did the reverse. Validity was assessed by Spearman correlation, linear mixed-effects models, sensitivity specificity, and area under the curve (AUC). Usability was assessed through the Usefulness, Satisfaction, and Ease of Use (USE) questionnaire, participant preferences and assessment duration. Regression analyses were conducted to explore the impact of usability on digital test scores, controlling for cognitive level, education, age, and gender.

RESULTS: Regarding validity, digital tests showed moderate correlations with paper-based versions and superior AUC performance. The AUC was 0.65 for the MMSE versus 0.82 for the electronic MMSE (eMMSE), and 0.45 for the CDT compared to 0.65 for the electronic CDT (eCDT). Regarding usability, while older participants gave positive feedback on digital tests (P < 0.001), they preferred paper-based versions. The eMMSE took significantly longer to complete than the MMSE, averaging 7.11 min versus 6.21 min (P = 0.01). Notably, digital test scores were minimally affected by subjective attitudes but strongly linked to test duration (β = -0.62, 95% CI: -1.07 to -0.17).

CONCLUSIONS: Digital cognitive tests are valid and feasible in PHC settings but face implementation challenges, especially in usability and adaptability among individuals with lower education levels.

PMID:40500744 | DOI:10.1186/s12984-025-01665-1

J Neuroeng Rehabil. 2025 Jun 11;22(1):133. doi: 10.1186/s12984-025-01647-3.

ABSTRACT

OBJECTIVES: To determine the evolution of lower-limb joint power values during walking across the lifespan.

DESIGN: Series of cross-sectional studies.

SETTING: This was a pooled analysis of the individual participant joint power data from six datasets, resulting in a sample size of 629 participants, between the ages of three to 91 years old.

MAIN OUTCOME MEASURES: Three function-on-scalar regression models were fitted on the outcome measures of joint hip, knee, and ankle power. The covariates of this analysis included sex, age, walking speed, stride length, height, the interaction between age and speed, and a random intercept for different studies.

RESULTS: Ankle push-off (A2) power peaked with a value of 2.46 (95%CI 2.41 to 2.50) W/kg in the 3rd decade of life. Hip early-stance power (H1) peaked in the 1st decade, which followed a sharp decline with age till the 3rd decade. Hip pull-off power (H3) increased sharply to 0.86 (95%CI 0.84 to 0.88) W/kg in the 5th decade and stabilised thereafter with older age.

CONCLUSION: Ankle push-off power appears to reach maturity in the 3rd decade of life. A strict temporal correspondence between a decline in ankle push-off power (A2) with age and a compensatory increase in hip pull-off power (H3) was not observed, challenging the distal-to-proximal alteration in propulsion strategy commonly attributed to the ageing process.

PMID:40500742 | DOI:10.1186/s12984-025-01647-3

BMC Public Health. 2025 Jun 11;25(1):2164. doi: 10.1186/s12889-025-22844-8.

NO ABSTRACT

PMID:40500740 | DOI:10.1186/s12889-025-22844-8

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

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