Nevin Manimala

Ann Hum Genet. 2025 Jun 27:e12606. doi: 10.1111/ahg.12606. Online ahead of print.

ABSTRACT

We review three areas of human genetics that have been developed in the past few decades, in which statistical innovation has made a crucial contribution with recent important advances and the potential for further rapid progress. The first topic is the development of mathematical models for the genealogy underlying samples of genome-wide genetic data. Coalescent theory emerged in the 1980s, leaped ahead in the past decade and is now burgeoning into new application areas in population, evolutionary and medical genetics. The second is the development of statistical methods for genome-wide association studies which has made great strides over two decades, including exciting recent developments for association testing based on coalescent theory and improved methods for trait prediction. Finally, we review the statistical ideas that helped resolve the controversies surrounding the introduction of forensic DNA profiling in the early 1990s. Big advances in interpretation of the predominant autosomal DNA profiles have set a benchmark for other areas of forensic science, but the statistical assessment of uniparentally inherited profiles (derived from the mitochondrial DNA or the Y chromosome) remains unsatisfactory.

PMID:40579738 | DOI:10.1111/ahg.12606

BMC Nurs. 2025 Jun 27;24(1):670. doi: 10.1186/s12912-025-03416-y.

ABSTRACT

BACKGROUND: Insufficient knowledge among assistant nurses (ANs) in nursing homes (NHs) on medicines and drug-related problems (DRPs) in older people causes difficulties in acknowledging the side effects of medications, which can be harmful to the individual and endangers patient safety. The aim of this study was to explore the ANs’ thoughts on their professional role in preventing DRPs in NH residents, their self-perceived knowledge about medicines, DRPs and physiological conditions in older people, and their wishes concerning further medical education.

METHODS: This mixed methods study took place in Sweden, in 2022. First, a survey was conducted at nine NHs, with a total of 112 respondents. Data were analysed using descriptive statistics and groups were compared using t-tests. Thereafter, semi-structured interviews were performed at four NHs and included 20 participants. A qualitative content analysis was performed.

RESULTS: In the survey, a generally good self-perceived knowledge of medicines was reported. In the interviews, three main categories were identified: “Professional role of the AN”, “Perspectives on pharmacotherapy in older people” and “Approaches to knowledge”. Their professional role entailed different aspects, including the central assignment of observing the residents whilst having delimited responsibilities and knowledge. Regarding pharmacotherapy, the self-perceived knowledge was generally good, but more specific questions regarding DRPs proved a lack of widespread competence. An approach to obtain more knowledge was found in the possibility for ANs to attend ward rounds. A latent theme emerged in the professional role of the AN in preventing DRPs by being the nurse’s eyes and ears for patient safety.

CONCLUSIONS: The AN’s perceived their professional role in preventing DRPs in NHs as being the nurse’s eyes and ears for patient safety. Generally, the ANs’ self-perceived knowledge of medicines was good, although self-perceived knowledge regarding DRPs, and the physiology of older people, was sparser. A positive attitude towards attending ward rounds to contribute firsthand information on the residents, as well as the opportunity to receive knowledge, existed among the respondents. We propose a working model within the framework of doctor’s ward rounds at NHs to increase the knowledge of ANs and utilise their knowledge of patients’ well-being for safe medication follow-up.

PMID:40579728 | DOI:10.1186/s12912-025-03416-y

Neurol Res Pract. 2025 Jun 27;7(1):46. doi: 10.1186/s42466-025-00404-0.

ABSTRACT

BACKGROUND: Acute stroke care has evolved markedly in recent decades, yet long-term trends across stroke subtypes remain understudied. This study analyzed national trends in inpatient stroke care for ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in Germany from 2000 to 2021.

METHODS: We conducted a retrospective analysis of nationwide hospital administrative data, assessing annual case counts, age-standardized rates, mean length of stay, and annual inpatient case days (AICD). Stroke unit (SU) treatments were analyzed from 2005 onward. Joinpoint regression identified changes in trends over time.

RESULTS: IS case rates, length of stay, and AICD declined significantly until 2005/2006, after which they stabilized at remarkably high levels. Paralleled by a rapid expansion of SU care, in-hospital mortality from IS decreased significantly. Coding of unspecified stroke (I64) declined steeply, suggesting shifts in diagnostic precision. In contrast, ICH and SAH showed falling case rates but increasing lengths of stay, particularly among deceased patients. SU treatments rose continuously from 2005 to 2021, with age-standardized rates increasing by 7.1% annually.

CONCLUSIONS: Over two decades, total inpatient burden from stroke has declined, primarily due to reductions in IS admissions and mortality. However, longer hospital stays in SAH and ICH and an overall rising SU care indicate shifting but consistently high resource requirements. Thus, continued efforts in optimizing healthcare infrastructure seem reasonable and should consider a subtype-specific resource allocation in acute stroke care.

PMID:40579722 | DOI:10.1186/s42466-025-00404-0

Eur Geriatr Med. 2025 Jun 27. doi: 10.1007/s41999-025-01251-7. Online ahead of print.

ABSTRACT

PURPOSE: Frailty, a state of increased vulnerability to adverse health outcomes, impacts individuals and healthcare systems. The cumulative deficit model provides a flexible frailty measure but its application across diverse data remains underexplored. This study compares frailty indices derived from survey and routine data.

METHODS: Frailty indices in the Clinical Practice Research Datalink (CPRD) Aurum (N = 1,625,677) and the English Longitudinal Study of Ageing (ELSA) (N = 5190) were compared for adults aged 65 + in England. Deficits were categorised as “one-to-one”, “one-to-many”, and “one-to-none”. Age-sex-standardised deficit prevalence, frailty distribution and associations with demographics were analysed using summary statistics and regression.

RESULTS: Mean frailty index scores were similar (CPRD: 0.13 ± 0.10; ELSA: 0.13 ± 0.12) but differences were observed in the capture of specific deficits. The majority of deficits had a “one-to-none” or “one-to-many” mapping. Among 14 comparable deficits, visual impairment, fractures and heart failure were more common in CPRD, while falls, sleep disturbance and arthritis were more frequent in ELSA. Severe frailty and greater fitness were more prevalent in ELSA than CPRD. Sex and age influenced frailty similarly in both datasets, with frailty index scores increasing more rapidly with age in CPRD.

CONCLUSION: Differences in the number and types of deficits measured offset each other overall, supporting the cumulative deficit model’s premise that including a sufficient range of deficits does not significantly alter population-level frailty measures. This interchangeability may alleviate concerns about deficit selection, supporting more flexible approaches to population frailty assessment across both survey and routine data.

PMID:40579683 | DOI:10.1007/s41999-025-01251-7

Psychon Bull Rev. 2025 Jun 27. doi: 10.3758/s13423-025-02717-2. Online ahead of print.

ABSTRACT

Are left-handers more creative than right-handers? In both popular belief and scientific literature, left-handedness is linked with higher creativity. In a qualitative review supported by meta-analyses, here we evaluated whether left- or mixed-handers are more creative than right-handers, as measured by tests of divergent thinking, and evaluated whether left- or mixed-handers are overrepresented in creative professions. We argue that plausible mechanisms for a link between creativity and handedness can be found within influential theories of the neural basis of creativity. However, we found no evidence that left- or mixed-handers are more creative than right-handers; on the contrary, right-handers scored statistically higher on one standard test of divergent thinking (the Alternate Uses Test). Additionally, although left- and mixed-handers may be overrepresented in Art and Music, they are underrepresented in creative professions, in general. Both right and left-handers tend to believe that left-handers are more creative, but this belief is not supported by the available empirical evidence.

PMID:40579679 | DOI:10.3758/s13423-025-02717-2

Insights Imaging. 2025 Jun 27;16(1):137. doi: 10.1186/s13244-025-02023-4.

ABSTRACT

OBJECTIVES: To compare the image acquisition time, total examination time, image quality, and technical reliability of three free-breathing MRCP techniques: BioMatrix-triggered (BM-MRCP), respiratory-gating triggered using respiratory bellows (RG-MRCP), and navigator-triggered (NT-MRCP).

METHODS: A prospective intra-individual comparison was performed in 47 patients undergoing 3.0-T MRCP for suspected pancreatic and biliary diseases. Two patients with technique adaptability limitations were included in the reliability analysis as “technical failures.” For primary analyses, data from 45 patients completing all three techniques were used. Image quality was evaluated by three blinded radiologists (experience: 5, 10, 16 years). Statistical analysis included Friedman tests with Bonferroni correction (p < 0.0167).

RESULTS: Median total examination times were significantly shorter for BM-MRCP (218 [48] seconds) compared to RG-MRCP (228 [56] seconds) and NT-MRCP (259 [53] seconds) (p < 0.05). BM-MRCP and RG-MRCP had comparable image acquisition times, both significantly faster than NT-MRCP (p < 0.05). BM-MRCP provided superior image quality for key anatomical structures (p < 0.05), higher SNR, and CNR compared to RG-MRCP and NT-MRCP (p < 0.05). Image contrast showed no significant differences (p > 0.05). Two patients experienced failures with RG-MRCP or NT-MRCP due to breathing issues, while BM-MRCP had no failures.

CONCLUSION: BM-MRCP significantly reduces examination times while achieving superior image quality and technical reliability. Its integration into clinical workflows enhances efficiency, reduces technician workload, and improves patient-centered imaging.

CRITICAL RELEVANCE STATEMENT: BioMatrix-gating 3D-MRCP enhances imaging efficiency and diagnostic accuracy for the biliary and pancreatic duct systems. By reducing scan times and improving workflow, it supports patient comfort and compliance. Its simplicity and reliability also make it ideal for high-throughput clinical settings.

KEY POINTS: BioMatrix-triggered (BM)-MRCP shortens examination time, aiding patients with compliance or limitations. BM-MRCP offers superior image quality with reduced motion artifacts and higher clarity. BM respiratory sensors streamline workflows, boost reliability, and enhance patient comfort.

PMID:40579676 | DOI:10.1186/s13244-025-02023-4

Odontology. 2025 Jun 27. doi: 10.1007/s10266-025-01136-y. Online ahead of print.

ABSTRACT

The aim of the present study was to investigate the efficiency of pH cycling models to induce enamel experimental subsurface lesions and to enhance enamel remineralization in vitro. Enamel blocks (n = 50) were obtained from the buccal surface of human permanent incisors and canines and assigned to five independent groups (n = 10/gp). In Group D1, enamel blocks were subjected to a demineralizing solution, and in Group D2 a demineralization pH cycling model was used to induce an experimental subsurface lesion. In Group R, enamel blocks with subsurface-induced lesions were treated with fluoride varnish and submitted to a remineralization pH cycling model. Enamel blocks were investigated with scanning electron microscope-energy-dispersive X-ray (SEM-EDX) and Fourier transform infrared spectroscopy (FTIR). Quantitative data were statistically analyzed (repeated measures ANOVA, Bonferroni, p < 0.05). EDX revealed significant differences with respect to atomic percentage (At%) of calcium, phosphate, fluorine (F), carbon, and oxygen between groups (p < 0.05; repeated measures ANOVA). Group R revealed the highest F (At%) on the enamel surface (0.71 ± 0.2) (p < 0.05). FTIR revealed variations in PO₄^3- and CO₃^2- characteristic bands between groups in correlation with enamel surface demineralization and remineralization. In this study, the demineralization pH cycling model (Group D2) investigated with SEM-EDX and FTIR simulated chemical and structural characteristics of enamel natural subsurface carious lesions. Surface demineralization was created in enamel when a demineralization solution was used for induction of a caries-like lesion (Group D1), without any subsurface created lesion. Remineralization pH cycling model tested in Group R revealed an effective enamel remineralization in SEM-EDX and FTIR.

PMID:40579674 | DOI:10.1007/s10266-025-01136-y

Stem Cell Rev Rep. 2025 Jun 28. doi: 10.1007/s12015-025-10929-1. Online ahead of print.

ABSTRACT

BACKGROUND: The limited regenerative capacity of epidermal cells following tissue injury impairs wound healing in diabetic foot ulcers (DFUs), contributing to elevated rates of amputation and mortality. Recent advances have demonstrated that somatic cells can be reprogrammed into diverse cell types through the application of defined reprogramming factors. This study aims to develop a safe, efficient, and clinically translatable strategy for skin regeneration via direct lineage reprogramming.

METHODS: We established a novel reprogramming approach using a combination of two factors, BMI1 and FGFR2b (termed B2), to induce fibroblast-to-keratinocyte-like cells (iKCs) conversion in vitro and delivered via adeno-associated virus 9 (AAV9) in vivo. Molecular and functional characteristics of iKCs were evaluated by qRT-PCR, Western blot, immunofluorescence, transcriptomic analysis, and in vitro differentiation assays. A diabetic (db/db) mouse skin wound model was used to assess the regenerative potential and therapeutic effects. Statistical significance was determined using Student’s t-test or one-way ANOVA.

RESULTS: iKCs-B2 (Keratinocyte-like cells form from B2-infected L929) exhibited both morphological and functional characteristics comparable to primary keratinocytes. In vivo, AAV9-mediated delivery of B2 factors significantly promoted wound closure, reconstructed stratified epithelium, restored barrier function, and markedly reduced the mortality rate.

CONCLUSIONS: This study presents a safe and effective direct reprogramming strategy for skin regeneration, bypassing the pluripotent stage and avoiding cell transplantation. The B2 combination provides a novel molecular tool for wound repair and offers translational potential for treating non-healing wounds such as DFUs.

PMID:40579673 | DOI:10.1007/s12015-025-10929-1

Geroscience. 2025 Jun 27. doi: 10.1007/s11357-025-01777-5. Online ahead of print.

ABSTRACT

Dysregulation of lipid metabolism is increasingly recognized as a key factor in the pathogenesis of Alzheimer’s disease (AD). Unfortunately, an accurate lipidomic fingerprints in AD patients’ biofluids remains challenging. A comprehensive analysis of plasma samples from 26 patients with AD and 30 healthy individuals was performed using untargeted and targeted lipidomics techniques with strict lipid annotation criteria. By monitoring characteristic fragments per precursor, we achieved precise lipid characterization and quantification for approximately 270 lipid species. Multivariate statistical analysis revealed a distinct lipid profile between AD patients and controls, with 72 lipids significantly altered (FC > 1.5 or < 0.667, VIP > 1, P < 0.05). Notably, a biomarker analysis based on the multivariate exploratory receiver operating characteristic (ROC) curve identified a comprehensive panel consisting of 10 novel lipids as potential markers for AD, achieving 98.2% accuracy with a favorable auxiliary diagnostic value (area under curve of 0.995). Additionally, the higher levels of SM(d18:1/16:0), SM(d18:1/18:1), and LPE 18:0 were strongly correlated with the clinical dementia rating (CDR) and mini-mental state examination (MMSE) scores, underscoring the therapeutic potential of lipid modulation in AD. These findings reveal the intricate relationship between lipid alterations and AD pathology and emphasize the necessity for LC-MRM/MS lipidomics with rigorous criteria in the discovery of reliable biomarkers, enriching our understanding of lipid roles in neurodegenerative processes and informing future mechanistic investigations and drug target development.

PMID:40579668 | DOI:10.1007/s11357-025-01777-5

World J Pediatr. 2025 Jun 27. doi: 10.1007/s12519-025-00932-4. Online ahead of print.

ABSTRACT

BACKGROUND: The risk-benefit balance and safety of postnatal corticosteroid use for chronic lung disease (PNCSCLD) in preterm infants is a controversial matter. Our objective was to determine the trends in the use of PNCSCLD over eleven years and to analyze the neurodevelopmental consequences of PNCSCLD in preterm infants at 18-42 months of corrected age.

METHODS: The data for this retrospective population-based cohort study were obtained from ten tertiary neonatal intensive care units across New South Wales and the Australian Capital Territory, Australia. Preterm infants < 29⁺⁰ weeks’ gestation born between January 1, 2007, and December 31, 2017, who were alive at discharge, without any major congenital anomalies were included and analyzed based on their PNCSCLD status.

RESULTS: Over eleven years, 611 (14.3%) out of 4258 infants received PNCSCLD. Among the 3386 eligible infants, 2636 (77.8%) underwent neurodevelopmental follow-up and were included in the final analysis. The rate of PNCSCLD use increased from 12.4% in 2007 to 19.6% in 2017. Similarly, the rate of moderate to severe functional disability (MSFD) increased from 8.8% in 2007 to 16.1% in 2017. Propensity-adjusted analysis revealed a greater odds ratio (OR) for MSFD in the PNCSCLD group than in the control group [average treatment effect: OR = 1.252, 95% confidence interval (CI) = 1.185-1.322, P ≤ 0.001; average treatment effect on the treated group: OR = 1.104, 95% CI = 1.031-1.184, P = 0.005].

CONCLUSIONS: PNCSCLD use was associated with a greater incidence of MSFD. Clinicians should exercise caution when using PNCSCLD.

PMID:40579659 | DOI:10.1007/s12519-025-00932-4