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PubMed2026

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (χ2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans↗

PubMed1978

Graphic representation of the distribution of acetylcholinesterase in cat dorsal root ganglion neurons.

Acetylcholinesterase (AChE) activity of primary sensory neurons of the cat has been quantitated and correlated with cell size. Dorsal root ganglia of the fourth and fifth thoracic spinal levels were studied. Frozen longitudinal and cross-sections were collected serially and stained with Cresyl Violet for total cell counts of the ganglia on the left; the average count was 3375 cells. Ganglia from the right were stained for AChE after the method of Karnovsky & Roots (1964) as modified by El Badawi & Schenk (1967), and counterstained with Haematoxylin. Cells were counted in every fourth section and the diameter of each was recorded. AChE-positive cells were classified as brown (B1, B2, B3) and AChE-negative ones as blue (BL). An inverse correlation exists between cell size and AChE activity. High activity was demonstrated in 29% of the cells (B1), moderate activity in 52% (B2), minimal activity in 15% (B3) and 4% were classified as AChE-negative (BL). Small cells with high activity were centrally located in the ganglia whereas large AChE-negative cells were peripherally distributed. Chi-Square analysis revealed that the size of the cell was not independent of the enzyme colour category.

Acetylcholinesterase↗

PubMed1975

Cytomegalovirus infection: a seroepidemiologic comparison of nuns and women from a venereal disease clinic.

A seroepidemiologic study of prevalence of antibody to cytomegalovirus (CMV) was simultaneously done in four populations: group I, nuns working as nurses or school teachers; group II, women admitted to a upper socioeconomic private hospital; group III, women admitted to a lower socioeconomic county hospital, and group and IV women attending a veneral disease clinic. Groups II, III and IV, were not statistically different and showed an abrupt rise in antibody prevalence during your adulthood. Group I, however, did not show the expected abrupt rise in antibody prevalence during young adulthood, and the prevalence in this group was singificantly lower than that in the other three groups at all but the oldest age range. These differences could not be accounted for by race, socioeconomic status or respiratory exposure to CMV. The data suggest that there may be more than one mechanism of CMV transmission and that venereal or intimate salivary contact may be a significant mode of spread in adults.

Adolescent↗

PubMed2026

A profile of suspected female homicide cases at the Johannesburg and Diepkloof Forensic Pathology Service Medico-legal Mortuaries for 2020-2022.

This study profiles suspected female homicide victims in Johannesburg, South Africa, during the COVID-19 period marked by socio-environmental changes from lockdown restrictions. Guided by the Socio-Ecological Model, a retrospective case series of 369 victims was reviewed using medico-legal mortuary records from Johannesburg and Diepkloof Forensic Pathology Service facilities. Descriptive analyses were conducted, supplemented by a chi-square test to assess whether distributions of causes of death among women differed between COVID-19 and non-COVID-19 periods. No statistically significant association was found, χ2 (6, N = 339) = 6.68, p = 0.35. Key findings highlight that Black, unemployed, unmarried women aged 21-40 were at greatest risk. Cause of death was established in 97.0% (358/369) of cases, with firearm injuries predominating (43.9%), followed by sharp‑force (24.5%) and blunt‑force trauma (13.1%). Approximately 90% of victims were suspected to have been killed by males, with half of deaths attributed to intimate partner violence. Homicide frequency decreased during strict lockdowns but rose as restrictions eased, suggesting that movement and alcohol controls may reduce risk. Despite temporary disturbance caused by COVID‑19 restrictions, the underlying risk profile of female homicide victims remained unchanged. These findings inform multi-level prevention and intervention strategies in South Africa.

Humans↗

PubMed2026

PIK3CA Polymorphisms in Cervical Cancer: Differential Impact of rs6443624 and rs141178472.

BACKGROUND: Cervical cancer remains a major cause of mortality in low- and middle-income settings. We assessed whether two PIK3CA single-nucleotide polymorphisms (SNPs) rs6443624 (A/C) and rs141178472 (C/T) are associated with disease risk, clinicopathological features, and survival. MATERIALS AND METHODS: In a prospective case control study at a tertiary center, 154 participants were enrolled (77 cases, 77 controls). Genomic DNA was isolated from FFPE cervical tumors (QIAamp DNA FFPE Tissue Kit) and genotyped using TaqMan allelic discrimination. Clinicopathological variables (FIGO stage, histology, grade, treatment, tumor-infiltrating lymphocytes [TILs]) were abstracted from records. Genotype distributions were compared by Pearson chi-square. Associations with clinicopathological features used chi-square/Fisher's exact as appropriate; ANOVA compared age across genotypes. Overall survival (OS) was estimated by Kaplan-Meier and compared with the log-rank test; mean OS with SE and 95% CI is reported. RESULTS: Cases were predominantly locally advanced at presentation and squamous histology; most were moderately differentiated. rs6443624 differed significantly between cases and controls (χ²=21.1, p<0.001), with CC over-represented in cases and CA less frequent. rs141178472 showed no significant case control difference (χ²=2.9, p=0.086). For OS, rs6443624 showed a significant genotype effect (log-rank χ²=23.45, p=0.001): AA had the poorest survival, CA the longest, CC intermediate. rs141178472 was not associated with OS (χ²=1.06, p=0.588). Genotype clinicopathological correlations for stage group, grade, TILs, and treatment were non-significant or inconsistent, with some comparisons limited by small sample sizes. CONCLUSION: The PIK3CA rs6443624 variant appears to influence both susceptibility and prognosis in cervical cancer, highlighting its potential as a biomarker for molecular risk stratification. Validation in larger, multi-center cohorts incorporating HPV/p16 assessment and extended follow-up is warranted to confirm its clinical relevance.

Humans↗

PubMed2026

Low Prevalence of the HBB c.20A > T (HbS) Allele in a Turkish Cypriot Cohort: A Molecular Screening Study.

Sickle cell disease is caused by the HBB c.20A > T (p.Glu6Val; HbS) variant. Although Cyprus has a long-standing hemoglobinopathy prevention program, current population-specific data on HbS among Turkish Cypriots remain limited. Two hundred unrelated Turkish Cypriot adults were included. The HBB c.20A > T variant was genotyped by PCR-RFLP and confirmed by allele-specific real-time PCR. Genotype distribution was evaluated for Hardy-Weinberg equilibrium. No homozygous HbS genotype was detected. Three individuals were heterozygous carriers (AS), corresponding to a carrier frequency of 1.5%. The HbS allele frequency was 0.7%, and the genotype distribution was consistent with Hardy-Weinberg equilibrium (p = 0.916; chi-square = 0.011). HbS was uncommon in this Turkish Cypriot cohort. These findings support continued hemoglobinopathy surveillance and the integration of HbS counseling into existing premarital and population screening strategies, particularly as migration may alter local carrier frequencies over time.

Humans↗

PubMed1977

Temporal patterns, their distribution and redundancy in trains of spontaneous neuronal spike intervals of the feline hippocampus studied with a non-parametric technique.

A modification of the non-parametric technique for the analysis of temporal patterns in long trains of single neuronal spike intervals has been described and tested empiracally. The technique is based on inequality testing of sequential pairs of intervals. If the second interval in a pair is longer or shorter than or equal to the first interval, a(+), a(-), and a (0) is recorded respectively in sequential bins of the computer memory. Subsequently, the long sequences of signs are arranged into transition frequency matrices which are then converted into transition probability matrices of various complexity. In this manner, the sign permutations composed of 4, 5, 6, etc. signs were studied. First of all, the theoretical distribution of various sign permutations was derived, assuming that the arrangement of intervals that generate the signs is totally independent. The theoretical distribution of signs permutations in tetragrams, pentagrams and hexagrams constitute the 'controls' with which the empirical data can be compared. In this manner, using the chi-square test, the total deviation of a studied neuronal output from an independent state can be quantified. The empirical data showed a consistent deviation from the theoretical distribution of sign permutations during REM sleep, as compared to slow wave sleep which was characterized by an almost perfect theoretical distribution of sign permutations. This indicates that slow wave sleep is associated with relaxation of constraints that are responsible for the emergence of specific patterns. In addition, redundancies in the occurrence of sign permutations, and the linear relationships between them, have been defined and tested empirically. The apparent discrepancies between the redundancies, based on theoretical symmetry in sign distribution and the linear redundancy that fits the empirical data, have been defined and discussed.

Action Potentials↗

PubMed1979

Perceptions of the school nurse's role.

This study identifies and compares perceptions of school personnel (principals, teachers, counselors and school nurses) about the nurse's role in secondary school settings. A two-art questionnaire was utilized. Part one elicited descriptive data, while part two consisted of 50 Likert-type items related to the school nurse's role. Mean perception scores on the 50 items were obtained by job category and compared using a one-way ANOVA. Chi-square analyses were performed on the frequencies of scale values to determine if their distributions, by item, were the same for all job categories. Correlation coefficients were utilized to determine relationships between training levels, experience, direct contact and perceptions. Analyses revealed: (1) Significant differences in perceptions of the school nurse's role between each group of educators and school nurses. (2) No significant relationship between training level, experience, number of contacts with the nurse and perceptions of the school nurse's role.

Administrative Personnel↗

PubMed2026

Three-Dimensional Fracture Mapping of the Terrible Triad of the Elbow: Morphological Characteristics and Clinical Implications.

BACKGROUND: The morphology of fractures in the terrible triad of the elbow (TTE) is complex, and precise management relies on a profound understanding of this morphology. This study aims to systematically analyze, for the first time, the distribution and morphological characteristics of TTE fracture lines using three-dimensional (3D) imaging technology. METHODS: Clinical data and thin-slice CT scans of 112 patients with TTE from January 2021 to December 2024 were retrospectively included. 3D fracture models were reconstructed using Mimics software. Virtual reduction and standardized alignment were performed using 3-matic software. Fracture lines were mapped onto standard ulnar and radial templates, and 3D fracture heat maps were generated using the E-3D software to demonstrate the high-frequency distribution zones of the fracture lines visually. Statistical analysis was performed using SPSS software (version 21.0, IBM Corp., Armonk, NY, USA). Continuous variables were compared using one-way analysis of variance (ANOVA), and categorical variables were compared using the chi-square test (χ2 test). A two-tailed p < 0.05 was considered statistically significant. RESULTS: The study revealed distinct patterns in the distribution of TTE fracture lines. In the coronoid process, the fracture "hot zone" presented as an annular high-density band extending from the lateral middle aspect to the tip. In the radial head, an oblique high-density band was observed in the anterolateral quadrant of the articular surface. The radial neck exhibited a circumferential high-density zone, which was most prominent in the anterolateral aspect. Statistical analysis indicated a significant correlation between age and fracture complexity; the proportion of Regan-Morrey type III coronoid fractures and Mason type III radial head fractures was significantly higher in elderly patients (> 60 years) (p < 0.05), suggesting that advanced age is a significant risk factor for complex fractures. CONCLUSION: This study is the first to visually reveal the Collaborative Distribution Patterns of TTE fracture lines using 3D fracture mapping technology. This model provides morphological evidence for understanding the injury mechanism of TTE and offers an anatomical framework that may assist surgeons in individualizing surgical approaches and fixation strategies.

Humans↗

PubMed2026

Distinct mutational landscapes for germline and somatic cancer variants in forty tumor suppressor genes.

Germline and somatic cancer variants in tumor suppressor genes (TSGs) share loss-of-function mechanisms, but studies of a few genes (DICER1 and CEBPA) have demonstrated differences in variant consequence and location. To systematically assess whether TSGs display distinct mutational patterns, we leveraged large public genetic databases and compared 32,941 high-quality pathogenic/likely pathogenic (P/LP) germline variants in ClinVar, with 12,907 oncogenic/likely oncogenic (O/LO) somatic tumor variants from cBioPortal across 40 TSGs. Only 3,863 (9.2%) variants were shared. Eighteen TSGs showed significantly different distributions of variant occurrences by molecular consequence, replicated with non-overlapping somatic data from the COSMIC database (chi-squared tests, false discovery rate = 5%). DICER1, TP53, and SMAD4 displayed excess somatic missense events, while nine TSGs (e.g., RB1 and APC) contained excess somatic stop-gain events throughout the coding sequence. Analysis by tumor type revealed excess stop-gain events in tissues exposed to environmental mutagens with corresponding mutation signatures. For several TSGs (WT1), germline variants predispose to tumors (Wilms' tumor) distinct from the majority source of somatic data (myeloid leukemia). Germline and somatic events are also distributed unevenly across cDNA locations, with 103 regions of preferential clustering in 39 TSGs (78 somatic and 25 germline). Twenty somatic clusters contained recurring frameshifts in homopolymer runs, many in tumors with microsatellite instability. Germline clusters contain more germline-exclusive variants, some driving non-cancer phenotypes reflecting genetic pleiotropy. Altogether, germline and somatic variants of TSGs represent unique sets with substantially different patterns shaped by selection pressures from gene-specific and somatic mutational mechanisms. Characterizing these distinctions enables more accurate clinical interpretation of TSG variants.

Humans↗

PubMed1977

Caries experience in orthodontically treated individuals.

The caries ecperience in 26 girls and 26 boys living on an island outside. Bergen, who had received orthodontic treatment with fixed appliances, was examined 1.5 to 2 years after the end of treatment. The children were then between 1l and 17 years old. The remaining children of the same age group, 58 girls and 53 boys, served as controls. The orthodontic patients had received repeated hygiene instructions during the treatment period and were expected to rinse their mouth with 0.05% sodium fluoride daily. The percentage distribution of DMF-surfaces indicated somewhat less caries experience in the treated group. A chi-square test showed significantly more intact surfaces on the maxillary first molars, second premolars, canines and central incisors, and mandibular molars and second premolars in treated than in untreated children, and also demonstrated significantly fewer new lesions in the upper second molars at the time of examination in the treated groups. A comparison of the caries experience of the different surfaces revealed significantly more intact surfaces in the treated group and significantly fewer new lesions on the mesial and distal surfaces in treated in untreated children at the time of examination.

Adolescent↗

PubMed1979

Influence of a between-run component of variation, choice of control limits, and shape of error distribution on the performance characteristics of rules for internal quality control.

A computer-stimulation study has been performed to determine how the performance characteristics of quality-control rules are affected by the presence of a between-run component of variation, the choice of control limits (calculated from within-run vs. total standard deviations), and the shape of the error distribution. When a between-run standard deviation (Sb) exists and control limits are calculated from the total standard deviation (St, which includes Sb as well as the within-run standard deviation, Sw), there is generally a loss in ability to detect analytical disturbances or errors. With control limits calculated from Sw, there is generally an increase in the level of false rejections. The presence of non-gaussian error distribution appears to have considerably less effect. It can be recommended that random error be controlled by use of a chi-square or range-control rule, with control limits calculated from Sw. Optimal control of systematic errors is difficult when Sb exists. An effort should be made to reduce Sb, and this will lead to increased ability to detect analytical errors. When Sb is tolerated or accepted as part of the baseline state of operation for the analytical method, then further increases in the number of control observations will be necessary to achieve a given probability for error detection.

Chemistry, Clinical↗

PubMed2025

Association of Calpain-10 gene polymorphisms with Type 2 diabetes mellitus: a case-control study from a tertiary care hospital in Pakistan.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major public health challenge, with rising prevalence in low- and middle-income countries such as Pakistan. Genetic susceptibility plays a critical role in its pathogenesis. Calpain-10 (CAPN-10), a gene implicated in insulin secretion and glucose homeostasis, has been studied for its potential involvement in T2DM. This study aimed to evaluate the association of CAPN-10 polymorphisms-SNP44 (rs2975760) and SNP43 (rs3792267)-with T2DM in a Pakistani cohort. METHODS: This case-control study included 164 T2DM patients and 164 healthy controls (mean age ± SD: 57.2 ± 8.2 vs. 53.9 ± 6.3 years; age range: 41-82 years). The male-to-female ratio was 41.4-58.6% in cases and 37.2-62.8% in controls. Participants were enrolled using non-probability convenience sampling. Genomic DNA was extracted from whole blood, and genotyping of CAPN-10 SNPs (rs3792267 and rs2975760) was performed using PCR-RFLP. Genotype distributions were assessed for Hardy-Weinberg equilibrium. Associations with T2DM were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) via logistic regression. Chi-square tests were used for categorical comparisons, with p < 0.05 considered statistically significant. Analyses were conducted using SPSS version 26. RESULTS: For SNP44, no significant association with T2DM was observed under dominant, heterozygous, or recessive models after Bonferroni correction (adjusted p > 0.05). Similarly, SNP43 showed no statistically significant association with T2DM in either dominant or recessive models (adjusted p > 0.05), although the AA genotype appeared more frequently among T2DM cases. These findings suggest no significant role of CAPN-10 polymorphisms in T2DM susceptibility in this population. CONCLUSION: CAPN-10 polymorphisms SNP44 and SNP43 showed no significant association with T2DM in this population, suggesting limited predictive value for disease susceptibility.

Humans↗

PubMed2026

Are we Prepared? Genetic Counseling for Stillbirth in the Sequencing Era.

Stillbirth affects approximately 1 in 175 pregnancies annually in the United States. Although the American College of Obstetricians and Gynecologists recommends genetic testing as part of the stillbirth evaluation, families often face barriers to obtaining a complete evaluation. Expansion of the diagnostic evaluation of stillbirth is expected to include exome/genome sequencing, with preliminary studies demonstrating its diagnostic utility. Consequently, genetic counselors (GCs) are expected to play an expanding role in post-stillbirth care. This study explored current genetic counseling practices for stillbirth and GCs' preparedness to support patients in this setting. A cross-sectional survey was distributed across four channels. Eligible participants included GCs in the United States and Canada with at least 1 year of prenatal experience. The survey assessed GC frequency and timing in stillbirth counseling, genetic testing practices, comfort addressing psychosocial needs, and perceived barriers to care. Responses were analyzed using descriptive statistics. Group comparisons were performed using Chi-square and Fisher's exact tests. Open-ended responses were coded for themes. Seventy-one responses were analyzed. Approximately half of respondents (49.3%, n = 36) reported "never/very rarely/rarely" counseling patients postpartum, despite this being the optimal time to offer genetic testing. Delivering providers (46.5%, n = 33) were often responsible for informing patients about testing and obtaining consent, compared to GCs (11.3%, n = 8). Although chromosomal microarray (CMA) is recommended as the standard of care (SOC), 12.7% (n = 9) of GCs reported not offering CMA for anomalous and non-anomalous stillbirths. Perceived barriers to SOC testing included reported lack of obstetrician awareness (91.5%, n = 65) and challenges coordinating specimen collection (90.1%, n = 64). These findings highlight barriers to SOC genetic evaluation and underscore the need to strengthen institutional protocols, enhance provider education, and develop stillbirth-specific genetic counseling guidelines. GC involvement in these efforts will be essential to promoting equitable access to comprehensive post-stillbirth care as sequencing becomes integrated into practice.

Humans↗

PubMed2026

Analysis of genetic polymorphisms and mRNA expression of DRD3 and HTR2A in bruxism.

BACKGROUND: Bruxism, characterized by the involuntary grinding or clenching of teeth, is influenced by genetic, psychological, and environmental factors. This study aimed to evaluate the role of DRD3 (rs6280) and HTR2A (rs6313) polymorphisms in bruxism and to investigate the expression of these genes to better understand their biological significance. METHODS: This case-control study included 82 bruxism patients and 87 controls. Diagnosis was based on clinical examination and non-instrumental criteria from the 2018 international consensus. Genotyping of HTR2A rs6313 and DRD3 rs6280 was performed using PCR-RFLP, and gene expression in peripheral blood was assessed by qPCR. Statistical analyses included chi-square tests, logistic regression, and mRNA expression analysis using the ΔΔCt method. RESULTS: A significant association was identified between bruxism and the rs6313 polymorphism of the HTR2A gene (p = 0.004; OR = 1.89 [1.23-2.92]), with the C allele associated with increased risk. Moreover, HTR2A mRNA expression was upregulated in individuals with bruxism. While no significant differences were observed in DRD3 rs6280 genotype distribution between cases and controls, the presence of the C allele appeared to increase susceptibility to sleep bruxism. In addition, DRD3 mRNA expression was downregulated in bruxism patients. CONCLUSIONS: These findings highlight a significant association between bruxism and the rs6313 polymorphism of the HTR2A gene. Furthermore, increased HTR2A and decreased DRD3 expression support the involvement of serotonin and dopamine pathways in bruxism etiology, underscoring its multifactorial and complex nature. CLINICAL SIGNIFICANCE: This study elucidates the genetic basis of bruxism, indicating a potential role of serotonin and dopamine signaling in its pathogenesis. Understanding genetic predisposition could aid in early detection, risk assessment, and targeted treatment development. TRIAL REGISTRATION: Clinicaltrials.gov ; trial registration number: NCT06457646 (13/06/2024).

Adult↗

PubMed2026

Genomic determinants of fluoroquinolone resistance in Escherichia coli in Nigeria: dominance of QRDR mutations and limited contribution of PMQR in a cross-sectional study.

BACKGROUND: Fluoroquinolone-resistant Escherichia coli is a major global clinical threat, particularly in low- and middle-income countries like Nigeria. However, the full genomic landscape, including the relative contributions of chromosomal mutations, plasmid-mediated resistance, and the role of high-risk clones, remains poorly characterized in this setting. This study aimed to define the genomic mechanisms, clonal distribution, and genotype-phenotype relationships of fluoroquinolone resistance in clinical E. coli isolates from Nigeria. METHODS: A cross-sectional study of 107 clinical E. coli isolates was conducted. Phenotypic susceptibility to ciprofloxacin and nalidixic acid was determined using VITEK 2 and broth microdilution. Whole-genome sequencing was performed, and analysis included detection of quinolone resistance determining region (QRDR) mutations (gyrA, parC, parE) and plasmid-mediated quinolone resistance (PMQR) genes, multilocus sequence typing (MLST), and phylogenetic analysis. Statistical associations were evaluated using chi-squared tests or Fisher's exact tests. RESULTS: Ciprofloxacin non-susceptibility was high at 86.0%. Resistance was primarily driven by a conserved chromosomal mutation profile; the combination of gyrA S83L, gyrA D87N, and parC S80I was present in 85 isolates and was associated with ciprofloxacin non-susceptibility in all affected isolates in this cohort. Isolates with only gyrA mutations were resistant to nalidixic acid but susceptible to ciprofloxacin, consistent with a stepwise resistance pathway. In this cohort, the triple QRDR signature (gyrA S83L + gyrA D87N/Y + parC S80I) was a perfect positive predictor of ciprofloxacin non-susceptibility (85/85; 100%). The ST131 lineage dominated, accounting for 21.5% of isolates and universally carrying the complete triple QRDR profile; notably, no ST131 isolate carried a PMQR determinant. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 15.0% of isolates but were not independently associated with ciprofloxacin non-susceptibility in this cohort in the absence of concomitant QRDR mutations. Efflux pump genes were ubiquitous and non-predictive. Notably, six isolates, all from urine, were non-susceptible (R/I) despite lacking all known QRDR and PMQR determinants, pointing to uncharacterized mechanisms. In a multivariable logistic regression model that included ST131 status, PMQR carriage, and parE mutation status, ST131 was associated with ciprofloxacin non-susceptibility (adjusted OR 5.96, 95% CI 1.21-29.4, p = 0.028), whereas PMQR carriage was not (adjusted OR 0.94, 95% CI 0.18-4.85, p = 0.94). The triple QRDR signature was not included in this model because it perfectly predicted ciprofloxacin non-susceptibility in this cohort. Resistance patterns varied by clinical source, with the highest burden in bloodstream and wound infections. This stepwise hierarchy from first-step gyrA mutations to the classic triple QRDR profile is summarised in the graphical abstract, Fig. 1. CONCLUSIONS: Fluoroquinolone resistance in Nigerian clinical E. coli is predominantly driven by chromosomal QRDR mutations within successful clones like ST131. PMQR genes and efflux pumps appeared to play a supplementary role rather than being independent drivers of ciprofloxacin resistance in this cohort. These data support prioritising key QRDR mutations in genomic reporting and local stewardship decisions, while the QRDR-negative resistant urine isolates require further investigation.

Escherichia coli↗

PubMed2026

Genetic Correlation Between Brain Imaging Phenotypes and Externalizing Behavior: A Large-Scale LDSC Analysis of UK Biobank IDPs.

Externalizing has been associated with differences in brain structure and function; however, it remains unclear whether these associations reflect shared common-variant genetic influences. Cross-trait linkage disequilibrium score regression was used to estimate genome-wide genetic correlations between externalizing genome-wide association study (GWAS) results and 3,935 brain imaging-derived phenotypes from the UK Biobank BIG40 resource. The imaging phenotypes covered structural magnetic resonance imaging (MRI), diffusion MRI, susceptibility-weighted imaging, resting-state functional MRI, and task-based functional MRI. Results were included in the primary analysis when the imaging phenotype had positive single-nucleotide polymorphism (SNP) heritability, a heritability Z statistic of at least 1.96, a mean GWAS chi-square statistic of at least 1.02, at least 200,000 regression SNPs, and a complete LDSC result without a fatal error. Technical imaging quality-control phenotypes were excluded from biological inference. Individual results were corrected using the Benjamini-Hochberg false discovery rate procedure. Aggregated Cauchy association tests (ACATs) were used to evaluate evidence across all imaging phenotypes and within predefined imaging categories. Statistical power, simultaneous confidence bounds, and alternative quality-control definitions were examined in sensitivity analyses. Of the 3,935 imaging phenotypes, 3,716 produced estimable genetic correlations, 2,980 met the primary LDSC quality-control criteria, and 2,967 were classified as biological imaging phenotypes. No individual phenotype survived false discovery rate correction. The smallest unadjusted P value was 0.0005, and the minimum adjusted q value was 0.486. The distribution of genetic correlations was centered near zero, with a median genetic correlation of 0.0014 and a median absolute genetic correlation of 0.0338. ACAT provided no evidence of an aggregate association across all biological imaging phenotypes (P = 0.302), and no predefined imaging category survived multiple-testing correction. The median minimum detectable genetic correlation at 80% power was 0.216. Bonferroni-adjusted simultaneous confidence intervals were fully contained within the interval [-0.30, 0.30] for 80.0% of phenotypes in the primary analysis and 88.0% under the stringent heritability quality-control definition. Broad and stringent sensitivity analyses produced the same overall conclusions. In this study, no statistically robust evidence of genome-wide genetic correlations between externalizing and individual UK Biobank brain imaging phenotypes was found. Nevertheless, small, localized, mixed-direction, or developmentally specific genetic effects remain possible.

Journal Article↗

PubMed2026

Comparative Analysis of Potential Clinical Actionability of Genomic Alterations in Early-Onset Versus Later-Onset GI Cancers.

PURPOSE: As biomarker-directed therapy increasingly shapes GI oncology, it remains unclear whether early-onset (EO) and later-onset (LO) GI cancers harbor comparable opportunities for clinically actionable targeting. We compared the landscape of potentially actionable genomic alterations in EO versus LO GI cancers using American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange v19.0. METHODS: GI tumor samples were assigned to 10 prespecified tumor groups using OncoTree codes. Samples were annotated with OncoKB therapeutic levels and classified as potentially actionable if they harbored at least one level 1-3B alteration. EO and LO disease were defined as age at sequencing <50 years and ≥50 years, respectively. Group-wise comparisons used Wilcoxon rank-sum, chi-square, or Fisher exact testing as appropriate and with false discovery rate correction. Multivariable logistic regression evaluated age group associations overall and within tumor groups. RESULTS: Among 53,945 GI tumor samples, 10,573 (19.6%) were EO and 43,372 (80.4%) were LO. EO tumors had lower prevalence of potentially actionable alterations in colorectal (71% v 78.1%, q < 0.001), esophagogastric (53.3% v 57.9%, q = 0.0097), GI stromal tumor (GIST) (75.1% v 90.9%, q < 0.001), liver (25.4% v 35.4%, q = 0.0021), and pancreatic tumors (82.9% v 90.7%, q < 0.001). In the overall model, LO status was associated with higher odds of potential actionability (odds ratio, 1.39 [95% CI, 1.33 to 1.47]; P < .001). Tumor group-specific associations persisted in colorectal, GIST, liver, and pancreatic tumors after multivariable adjustment. CONCLUSION: Potential clinical actionability differs between EO and LO GI cancers in a tumor lineage-specific manner. Several major EO GI tumor groups appear relatively depleted of potentially actionable alterations, suggesting that the expanding therapeutic reach of precision oncology may not be distributed evenly across age-defined GI cancer populations and underscoring the need for EO-focused biomarker discovery and therapeutic development.

Humans↗