Real‐time fault detection in multicomponent nuclear‐waste slurries through data fusion of spectroscopic sensors

Abstract Three instruments–Raman spectroscopy, attenuated total reflectance–Fourier transform infrared spectroscopy, and focused beam reflectance measurement–were used to detect sensor faults, mixing faults, and unanticipated chemistry in a system of multicomponent slurries. Data from the three instruments were combined via a data fusion scheme utilizing principal component analysis, Hotelling T   2, and squared prediction error. Uncertainty was quantified yielding a three‐sigma region of normal operation to identify faults. The three instruments allowed for the detection of a variety of process faults that may appear in either phase of a slurry. This work represents a major step forward in (1) monitoring radioactive slurry processes by reducing the need for offline monitoring, (2) accurately detecting faults in the presence of probe fouling, and (3) enabling the use of commercially available spectroscopic sensors to detect a variety of faulty process states in real‐time and remotely.

Dimorphic enantiostyly and its function for pollination by carpenter bees in a pollen‐rewarding Caribbean bloodwort

Abstract Premise Flowers that present their anthers and stigma in close proximity can achieve precise animal‐mediated pollen transfer, but risk self‐pollination. One evolutionary solution is reciprocal herkogamy. Reciprocity of anther and style positions among different plants (i.e., a genetic dimorphism) is common in distylous plants, but very rare in enantiostylous plants. We investigated the pollination and reproductive system of the enantiostylous Caribbean plant Cubanicula xanthorrhizos (Haemodoraceae). Methods We assessed stylar orientation of flowers and conducted controlled pollination experiments. We used videography of flower visitors and pollen load analysis to determine the pollination mechanism. We also measured floral morphology, pollen production, spectral reflectance, and volatile emissions. Results Cubanicula xanthorrhizos exhibits dimorphic enantiostyly with c. 50:50 left‐ to right‐styled morphs. Plants are self‐compatible, but pollinator dependent for seed production. Intra‐ and intermorph crosses are equally fertile. The nectarless flowers are pollinated by female carpenter bees ( Xylocopa cubaecola ) that collect pollen, often by sonication, from two centrally positioned yellow feeding anthers. An inconspicuous deflected pollinating anther deposits pollen on the side of the bee thorax, which contacts the stigma of the mirror‐image morph. A yellow‐orange “guide” on the white tepals appears to be a visual attractant. Flowers emit methoxy benzenoid volatiles that may also attract bees. Conclusions Reciprocity of the style with a single pollinating stamen in C. xanthorrhizos appears to promote intermorph pollen export via “safe sites” on pollen‐collecting bees. This novel case of dimorphic enantiostyly contributes to understanding of the evolution of floral polymorphisms.

Phylogenomics reveals the evolution of floral traits associated with pollinators and pollinator–prey conflict within the carnivorous Pinguicula subgenus Temnoceras

Abstract Premise The carnivorous plant genus Pinguicula (Lentibulariaceae) exhibits remarkable floral diversity associated with pollination, particularly in the largest subgenus Temnoceras , which spans Mexico and Central America. Despite this diversity, the relationships between species and the evolution of key floral traits remain unresolved. Here, we employed whole‐genome sequencing to reconstruct a robust phylogeny and examine the evolution of pollination syndromes and potential pollinator–prey conflicts. Methods We generated nuclear and plastid genomic data for 32 Pinguicula species. Phylogenetic relationships were inferred using 2189 BUSCO loci analyzed through ASTRAL. Morphological traits associated with pollination and carnivory were assessed with ancestral state reconstruction, principal component analysis, and phylogenetic linear models. Loss and pseudogenization of ndh genes implicated in potential shifts in trophic strategies were evaluated in both nuclear and plastid genomes. Results Our genome‐scale phylogeny resolved six monophyletic clades within Temnoceras , refining infrageneric classification. Most ndh genes are either lost or pseudogenized across both genomic compartments. Floral morphology strongly clusters by pollinator type, with fly‐pollinated species forming a distinct clade characterized by cylindrical spurs and tubes. Ancestral reconstructions indicate multiple independent transitions in spur and tube morphology. Phylogenetic linear modeling revealed a significant evolutionary correlation between scape length and carnivorous leaf area, suggesting that spatial separation may represent an adaptive response to mitigate pollinator–prey conflict. Conclusions This study provides a refined phylogenetic framework for Pinguicula subgenus Temnoceras and highlights how pollinator specialization and carnivory‐related traits contribute to floral evolution.The repeated loss of ndh genes implies relaxed selective pressure on photosynthesis‐related pathways in these carnivorous species.

Venetoclax or Pirtobrutinib in Relapsed/Refractory Waldenström Macroglobulinemia: Clinical and Molecular Predictors and Sequencing Implications

ABSTRACT Venetoclax and pirtobrutinib have emerged as two chemotherapy‐free options for relapsed or refractory Waldenström macroglobulinemia (WM). However, evidence to guide treatment sequencing or identify molecular subsets most likely to benefit from each agent remains limited. We retrospectively evaluated consecutive WM patients treated with venetoclax or pirtobrutinib. Major response rate (MRR) and progression‐free survival (PFS) were assessed for each agent, with predictors of response and PFS analyzed using logistic and Cox regression. Comparative efficacy was examined in unmatched analyses and in a 1:1 matched cohort. Among 91 treatment exposures (64 venetoclax and 27 pirtobrutinib) across 80 unique patients, treatment discontinuation due to adverse effects occurred in 12 of 64 patients (19%) treated with venetoclax and in none treated with pirtobrutinib. In the venetoclax cohort, TP53 alterations were associated with shorter PFS (10.0 vs. 35.6 months; p  < 0.001). In the pirtobrutinib cohort, CXCR4 mutations predicted lower MRR (40% vs. 91%; p  = 0.01) and shorter PFS (8.3 months vs. not reached; p  = 0.02). When transitioning from a cBTKi, IgM rebound occurred in 62% (8/13) of patients initiating venetoclax without overlap, whereas no rebound was observed with cBTKi‐venetoclax overlap (0/5) or with pirtobrutinib initiation (0/15). In the matched cohort ( n  = 42), venetoclax and pirtobrutinib demonstrated comparable outcomes for MRR ( p  = 0.91) and PFS ( p  = 0.83). Despite the retrospective design and limited sample size, these findings indicate comparable efficacy between venetoclax and pirtobrutinib with distinct molecular vulnerabilities and support consideration of pirtobrutinib sequencing when transitioning from a cBTKi, as well as further exploration of combination strategies that may exploit complementary vulnerabilities.

The Association of Current Asthma With and Without Exacerbation With Products Used and Tasks Performed by Healthcare Workers

ABSTRACT Background Results from a 2014 survey of 2030 healthcare workers (76% female, mean age 48.6 years) in New York City included the association of current asthma and asthma exacerbation with the general activities of cleaning fixed surfaces and administering aerosolized medications. We extended that analysis to determine if specific products and tasks for these and other activities were associated with the same outcomes. Methods The survey instrument inquired about asthma‐related outcomes, products used, and tasks performed. Polytomous logistic regression was used to model a three‐category outcome for current asthma without and with exacerbation and no current asthma (referent). Inverse probability weights were applied in all regression models to adjust for selection and participation bias that may have resulted from a low response of 11.1% of invitees. A separate model was fit for each exposure variable and yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results For cleaning fixed surfaces, two products and eight tasks had increased odds of at least one adverse outcome. Enzymes had an OR = 3.01 (95% CI 1.50, 6.04) for current asthma with exacerbation, and bleach had an OR = 1.92 (95% CI 1.22, 3.01) for current asthma without exacerbation. The eight general cleaning tasks included three (cleanup blood/spills, wipe furniture, wipe equipment) associated with both adverse outcomes, and five tasks associated only with current asthma without exacerbation. For aerosolized medication tasks, the small‐volume nebulizer was associated with current asthma with (OR = 1.89, 95% CI 1.06, 3.34) and without (OR = 1.66, 95% CI 1.01, 2.72) exacerbation, and two other tasks (continuous delivery system, metered dose inhaler) were associated only with current asthma without exacerbation. Conclusions Products and tasks in healthcare were associated with current asthma and asthma exacerbation. Future analyses will explore quantitative exposure‐assessment strategies for specific chemicals and mixtures.

Occupational Medical Surveillance Reduces Mortality: Who Knew?

Identification of a Non‐Coding Causative Variant Underlying Warsaw Breakage Syndrome Using Long‐Read Based Genomic Sequencing and Transcriptome Analysis

ABSTRACT Currently, exome and genome sequencing achieve a diagnostic rate of 30%–50% for rare genetic diseases. With multi‐modal technologies profiling the genome, transcriptome, and epigenome, interrogation of genomic elements outside of protein‐coding regions shows potential to improve this as demonstrated herein. Siblings with sensorineural hearing loss, microcephaly, intellectual impairment, and growth restriction were seen in consultation. Following extensive clinical testing, long‐read whole genome and cDNA‐based transcriptome sequencing on the Oxford Nanopore platform identified a homozygous 1.6 kb deletion of the 5′ UTR and promoter region of DDX11 , a gene associated with Warsaw breakage syndrome. The deletion included the hypomethylated CpG island regulating DDX11 , led to a loss of expression of DDX11 mRNA and protein, and resulted in the characteristic “railroad chromosome.” Identifying a causal variant for this family required expanding the search space for genomic variants beyond protein‐coding regions, and multi‐modal data integration enabled a more holistic approach to variant prioritization and classification prior to pursuing targeted protein and functional assays. This multi‐modal genome‐wide approach heralds promise for patients on the diagnostic odyssey and who have exhausted standard of care testing.

Cover Image, Volume 200A, Number 4, April 2026

The cover image is based on the article Identification of Compound Heterozygous CYP11A1 Variants via Reanalysis of Clinical Sequencing Data by Ana Acosta Bedón et al., https://doi.org/10.1002/ajmga.70008 .

The rs11150601 Intron Variant of SETD1A Is Associated With Female Schizophrenia in the UK Biobank Cohort

ABSTRACT Schizophrenia is a complex psychiatric disorder with an estimated heritability of 80%. SETD1A, a gene encoding a histone methyltransferase critical for transcriptional regulation, has been identified as a significant risk factor for schizophrenia. Loss‐of‐function mutations in SETD1A confer up to a 35‐fold increased risk, implicating its role in neurodevelopment and synaptic plasticity. Using data from the UK Biobank cohort (468,998 participants), we investigated the association of SETD1A variants with schizophrenia, obesity, and hypertension. Schizophrenia cases were identified using ICD‐10 codes, while obesity and hypertension were assessed using specific data fields. Genome‐wide association analysis was performed using PLINK, and statistical analyses utilized SPSS v26. Logistic regression assessed the impact of the SETD1A intron variant (rs11150601) alongside age, obesity, and hypertension on schizophrenia risk. Among 1063 individuals diagnosed with schizophrenia, obesity ( p  < 0.001) and hypertension ( p  < 0.001) were significantly more prevalent. The rs11150601 GG genotype was associated with an increased risk of schizophrenia in women (OR 1.6, p  < 0.001) but not in men. Logistic regression revealed that obesity, hypertension, and age were independent risk factors for schizophrenia in women. SETD1A genotype exerted a significant sex‐specific effect, highlighting its potential role in the biological mechanisms underlying schizophrenia. Our findings emphasize the role of SETD1A in the genetic architecture of schizophrenia and its comorbidities, particularly in women. The sex‐specific effects of SETD1A variants underscore the importance of incorporating biological sex into studies of psychiatric genetics. Further research is warranted to elucidate the mechanisms by which SETD1A influences neurodevelopment and identify therapeutic strategies targeting its epigenetic functions.

Identification of Compound Heterozygous CYP11A1 Variants via Reanalysis of Clinical Sequencing Data

ABSTRACT A molecular diagnosis is currently achievable in approximately 50% of patients assessed by clinical geneticists at tertiary care centres. Next‐Generation Sequencing Panels contain a defined group of genes associated with a clinically defined set of phenotypes. Most clinical sequencing providers streamline their wet‐bench workflows by sequencing the entire exome or genome, followed by targeted bioinformatic extraction of variant data from a pre‐specified gene set. Thus, additional data on these patients remain available but are only reviewed by special request. We interrogated clinical‐grade sequencing data on two out of three affected members of a family with childhood‐onset adrenal insufficiency in whom an autosomal recessive condition was suspected. Review of clinome data identified heterozygosity for CYP11A1 variants c.644T>C; p.(Phe215Ser) and c.1187G>A; p.(Arg396Lys) in both affected sibs. Long‐read whole genome sequencing of the proband showed these variants were in trans , confirming compound heterozygosity and resolving the molecular etiology of the clinical diagnosis.