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Androgenetic alopecia (AGA) is the most common cause of progressive hair thinning in adults and has traditionally been viewed as an androgen-driven inherited condition. Genomic research now demonstrates that AGA is a complex polygenic disorder involving multiple biological pathways, including androgen signaling, hair follicle development, cell survival, and extracellular matrix remodeling. Genome-wide association studies have identified numerous susceptibility loci, revealing that follicle miniaturization arises from interacting molecular mechanisms rather than a single pathogenic process. Genetic risk and predictive value vary across populations, with many loci identified in European cohorts showing limited transferability to other ancestries, highlighting the need for more diverse genetic studies. In women, genetic studies remain underpowered, and emerging data suggest partially distinct risk architecture compared with male AGA. Pharmacogenetic findings indicate that genetic variation may influence response to commonly used therapies, although no markers are currently validated for routine clinical use. Advances in single-cell and multi-omic approaches are improving understanding of how genetic risk translates into follicular dysfunction, supporting the development of more personalized and mechanism-based treatment strategies.

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The intramolecular π-polarization induced upon binding the bichromophoric ligand L1 to lanthanide ions produces intermolecular hetero-π-stacked pyrene-terimine organization in the resulting complexes as ascertained by ground state supramolecular aggregations leading to dimeric [L1Ln(hfac)3]2 (Ln = Y, Eu) units both in the solid state (X-ray crystal structure determination) and in dichloromethane solution (1H NMR titrations). Photoexcitation engenders additional polarization changes which further complicate/extend interaromatic aggregation processes via the formation of light-driven excimers and exciplexes. The various π-stacking intermolecular interactions operating in the [L1Y(hfac)3] host are probed by reaction with three competitive aromatics guests: electron-poor nitrobenzene, neutral benzene and electron-rich methoxybenzene.

There is a lack of direct comparative studies evaluating the long-term efficacy of the approved biologic therapies bimekizumab, secukinumab and adalimumab for moderate-to-severe hidradenitis suppurativa (HS) beyond Week 16. To address this evidence gap, this study uses matching-adjusted indirect comparisons (MAIC) to assess and compare their sustained efficacy. To assess the long-term relative efficacy of bimekizumab 320 mg every 2 weeks/every 4 weeks (Q2W/Q4W) in moderate-to-severe HS compared with biologic therapies (secukinumab 300 mg Q2W and Q4W and adalimumab 40 mg every week [QW]) at Week 48-52. Relevant trials were identified as part of a systematic literature review. Individual patient data for bimekizumab trials (BE HEARD I/II; Week 48) were combined and subsequently weighted to match aggregate baseline characteristics of trials for secukinumab (SUNRISE/SUNSHINE; Week 52) and adalimumab (PIONEER I/II; Week 48). Weights for patients receiving bimekizumab were determined using a propensity score model. Unanchored comparisons of reweighted bimekizumab and comparator data for key HS efficacy outcomes were analysed. Bimekizumab Q2W/Q4W demonstrated significantly higher odds of response for all HS Clinical Response (HiSCR) and HS Severity Score System (IHS4) outcomes compared with secukinumab Q4W, including HiSCR50 (odds ratio [OR]: 2.68; 95% confidence interval [CI]: 1.71, 4.19), HiSCR75 (OR: 2.20; 95% CI: 1.48, 3.26) and IHS4-55 (OR: 2.27; 95% CI: 1.48, 3.48); and for HiSCR50/75 compared with adalimumab QW (OR: 2.57; 95% CI: 1.48, 4.44/OR: 1.84; 95% CI: 1.08, 3.13, respectively). Compared with other approved biologics, bimekizumab showed favourable efficacy across the majority of outcomes assessed at Week 48-52, indicating its potential as a durable long-term therapeutic option for patients with moderate-to-severe HS.

Organic light-emitting diodes (OLEDs) featuring circularly polarized (CP) electroluminescence (EL) are gaining tremendous attention for their potential in advanced display and photonic applications. Chiral organic molecules and 4d and 5d metal complexes have been extensively studied for their role in the emissive layer of these devices. Here, pioneering work demonstrating EL emission from a chromium(III) complex is presented. Notably, by leveraging the highly polarized spin-flip transitions of enantiopure CrIII complexes, a proof-of-concept device showcasing near-infrared (NIR) CP EL with peaks at 726 and 747 nm and corresponding dissymmetry values up to 0.015 and -0.029 is developed. These findings highlight the potential of earth-abundant CrIII complexes for cutting-edge chiral optoelectronic applications in medicine, security, and quantum communications.

Emotion processing deficits are common in Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), yet few studies have examined how specific cognitive domains relate to emotion processing in these syndromes. This study investigated these relationships using network psychometrics. A total of 209 participants (56 AD, 55 bvFTD, 98 healthy controls) completed neuropsychological testing. Cognitive functions were assessed with the Addenbrooke's Cognitive Examination-III and the Sydney Language Battery, while emotion processing was measured with the Facial Affect Selection Task. Network models were estimated for each group and compared using the Network Comparison Test (NCT). Both patient groups showed impaired emotion recognition versus controls. Network density was highest in bvFTD (.62), followed by AD (.44), with controls showing the sparsest network (.16). In AD, emotion processing was associated with semantic comprehension and semantic knowledge, whereas in bvFTD, emotion processing related more closely to verbal fluency. Centrality indices supported these syndrome-specific patterns. NCT results showed no significant global differences in overall strength (St = .55, p = .411) or structure (Mt = .34, p = .529) between AD and bvFTD networks, indicating comparable overall organization despite differing functional roles of specific nodes. These findings suggest disease-specific cognitive-emotion associations: semantic mechanisms in AD and fluency-related mechanisms in bvFTD. Importantly, however, contributions of other cognitive processes, not measured here, are also plausible. Overall, the study highlights both shared and distinct patterns characterizing emotion processing impairments across dementias, offering insights for developing tailored interventions targeting syndrome-specific cognitive profiles.

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Anxiety is an aggravating comorbidity of many psychiatric disorders that is often underdiagnosed and undertreated, and little is known on the mechanisms underlying its regulation. Here, we find that serum LPA16:0 abundance increases with trait anxiety in both humans and mice; while high LPA16:0 levels are sufficient to reduce the in vitro proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor LPA1, bears single nucleotide polymorphism variants associated with anxiety. In mice, LPA16:0 decreases hippocampal neurogenesis and stress resilience, whereas LPA1 antagonism or the reduction of platelets, the main source of circulating LPA16:0, increases adult neurogenesis and resilience to acute stress. Conditional knockdown of LPA₁ receptor in neural stem cells is sufficient to enhance cell proliferation in the dentate gyrus. Finally, the inhibition of adult neurogenesis abolishes the beneficial effect of LPA1 antagonism on resilience against both acute and chronic stress. Together, these findings identify circulating LPA16:0 as a biomarker of trait anxiety and LPA16:0-LPA1 signaling as a regulation mechanism of mood-related behavior through the decrease of adult neurogenesis.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease primarily affecting apocrine gland-bearing areas. Although T helper (Th) 17-mediated inflammation is well-described in advanced HS (Hurley II-III), the immune mechanisms driving early disease remain unclear. To characterize the cellular and molecular environment of early HS lesions and identify potential early drivers of disease, full-thickness skin biopsies from papular inflammatory HS lesions in patients with Hurley stages I-II were analyzed using spatial RNA sequencing and imaging mass cytometry. Distinct immune phenotypes were identified, including B cells, T cells, macrophages, plasma cells, and neutrophils. Early HS lesions showed a marked increase in plasma cells and memory B cells within dermal infiltrates, with high expression of Ig genes and plasma cell markers. T cells aggregated around blood vessels in ectopic lymphoid structures but lacked expression of canonical Th1, Th2, or Th17 cytokines. Early HS is characterized by B-cell activation and plasma cell differentiation, preceding full Th17 pathway activation. These findings highlight B cells and plasma cells as potential early therapeutic targets before the transition to Th17-driven chronic inflammation.

Engaging in conversational and story-telling discourse involves an interplay of language and cognitive skills, including working memory, attention, and inference-making. Primary progressive aphasia (PPA) provides a model for exploring discourse, as both language and cognitive abilities change over time with changes in cortical atrophy. Here, associations between morphosyntactic discourse skills and patterns of cortical atrophy are measured over time in nonfluent (nfv), logopenic (lv) and semantic (sv) variants of PPA. Participants were 27 individuals with nfvPPA (M = 66.6 years ± 8.3), 30 lvPPA (M = 66.7 ± 7.3), 33 svPPA (M = 64.8 ± 6.7), and 36 healthy controls (HC; M = 65.5 ± 6.8). Picture descriptions were analysed for word density and diversity, sentence complexity, well-formedness, and fluency annually for up to three timepoints. Associations between language measures and cortical thickness on structural MRI scans were analysed. At timepoint 1, nfvPPA performed below other groups on most measures; lvPPA were differentiated from svPPA on fluency measures only. Longitudinally, utterance length declined in all variants. For nfvPPA, this was linked with reduced sentence complexity and cortical atrophy in regions engaged by higher attentional demand. For lvPPA, it was linked with increasing grammatical errors and atrophy extending into perisylvian language network. No associations were identified for svPPA. Findings provide insight into how discourse production is underpinned by a network that extends beyond classic language regions, with morphosyntactic elements of discourse associated in part with regions involved in domain-general cognitive skills such as error-monitoring and elaborative encoding. Findings can also inform assessment, prognosis, and intervention for communication through the PPA disease course.

Autoimmune hemolytic anemia (AIHA) with an isolated C3d+ direct antiglobulin test is a rare and understudied condition in children. It typically encompasses cold agglutinin syndrome and paroxysmal cold hemoglobinuria, both transient, infection-triggered disorders collectively referred to as cold AIHA. We report a national cohort of 142 pediatric patients with isolated C3d+ AIHA, representing 21.6% of all childhood AIHA cases enrolled in the French OBS'CEREVANCE cohort over a 32-year period. The median age at diagnosis was 3.2 years (male-to-female ratio, 1.3), and median follow-up was 2.8 years. Infectious symptoms were present in 63.4% of cases. At diagnosis, median hemoglobin was 6.4 g/dL; 69.7% of patients had inadequate reticulocytosis (bone marrow responsiveness index of <121), and 90.4% required transfusions. Eighteen patients (12.7%) had or developed immunopathological manifestations (IM) including 5 diagnosed with primary immunodeficiency (4 with autoimmune lymphoproliferative syndrome). Among 8 (5.6%) patients with relapsing disease, 6 had no IM at diagnosis but 4 developed IM at relapse. Nine patients were antinuclear antibodies (ANA) positive; none progressed to systemic lupus over a median follow-up of 4.9 years. Corticosteroids were administered to 82.4% of patients (median duration, 4.5 months), with no clear benefit over untreated patients regarding hospital stay or transfusion needs. No deaths were reported. In conclusion, pediatric isolated C3d+ AIHA generally follows a favorable course. However, a minority of patients may reveal underlying immune disorders, highlighting the importance of tailored evaluation at diagnosis. Cold agglutinin testing with thermal amplitude and Donath-Landsteiner testing, rarely performed in this cohort, warrant further study for their impact on diagnosis and clinical management.

The physical and social exposome affects human aging, and brain clocks may track its effects. However, most studies neglect multidomain exposures (physical, social and political) across diverse settings globally and their associations with brain aging. In this study, we characterized the associations between 73 country-level physical and social exposomal factors and multimodal brain age in 18,701 participants from 34 countries (healthy individuals and those with Alzheimer's disease, frontotemporal lobar degeneration or mild cognitive impairment). Exposome effects were assessed using generalized additive models and meta-analytic frameworks. Aggregated exposome models explained up to 15.5-fold more variance than individual exposures (delta Akaike information criterion (&#x394;AIC): 2,034-3,127). Physical exposome was primarily associated with accelerated structural brain aging (limbic, subcortical and cerebellar regions), whereas social exposome was more strongly associated with functional brain aging (frontotemporal and limbic networks). Exposome burden accounted for 3.3-9.1-fold higher risk of accelerated aging, exceeding effects of clinical diagnoses. Findings were out-of-sample validated in cross-sectional and longitudinal designs, remained consistent across clinical subgroups and persisted after adjustment for demographics, age correction bias, cognition, scanner type and data quality. The exposome accelerates brain aging in health and disease, underscoring the need to address physical, social and political inequities.

This study aims to identify circulating cellular immune cell endotypes in psoriatic arthritis (PsA), assess their association with treatment response, and explore key biological pathways linked to these immune profiles. Using mass cytometry, we analysed CD3+ immune cell populations in patients with PsA initiating targeted therapies. Hierarchical clustering identified immune cell endotypes, and their associations with clinical features and treatment response were assessed using generalised estimating equation models. Proteomic profiling via an aptamer-based assay compared differentially expressed proteins across clusters, followed by pathway analysis. Imaging mass cytometry analysis was performed to characterise T cell subsets in synovial tissue samples. We analysed blood samples from 40 treatment periods involving 34 patients and identified 3 immune clusters (C); C1: 'memory CD4+ T cell endotype' - associated with higher sonographic musculoskeletal inflammation and peri-articular bone formation, and poorer response to therapy; C2: 'Nonclassical T cell endotype'-exhibited lowest levels of musculoskeletal inflammation; and C3: 'Terminal effector/Th1 cell endotype'-linked to higher sonographic peri-articular inflammation. The immune endotypes remained relatively stable 3 months posttreatment. The 'memory CD4+ T cell endotype' was characterised by deregulation of immune-related biological pathways, including several intracellular signalling pathways, the most notable being WNT signalling. CD4+ cells with memory and effector phenotypes were abundant in the synovial tissue sample from patients with PsA. Heterogeneity in circulating immune cell profiles is associated with PsA clinical features and therapeutic response. The results underscore the potential of immune cell phenotyping to improve prognosis in PsA, which could inform personalised treatment strategies.

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease characterized by painful nodules, abscesses, tunnels, and scarring, with substantial clinical and psychological burden. Genetic studies have revealed that HS has a complex and heterogeneous architecture, encompassing rare monogenic mutations, intermediate-frequency variants, and polygenic risk distributed across multiple loci. Familial aggregation, twin studies, and genome-wide association studies collectively demonstrate that inherited factors contribute substantially to disease susceptibility. Different genetic profiles influence disease onset, severity, and clinical phenotype. Monogenic &#x3b3;-secretase mutations are associated with early-onset, severe, and extensive disease, whereas polygenic risk shapes heterogeneous presentations and may modify disease trajectory. Genetic variants implicated in HS also intersect with systemic comorbidities including inflammatory bowel disease, spondyloarthritis, coronary artery disease, and diabetes, highlighting shared pathogenic pathways. Mechanistic insights indicate that dysregulated Notch and Wnt/&#x3b2;-catenin signaling; keratinization and epithelial differentiation are central drivers of genotype-informed clinical trials. Despite advances, many variants remain uncharacterized, and polygenic risk scores currently have limited predictive power. Integration of genetic findings with clinical, environmental, and longitudinal phenotypic data is therefore essential to inform risk assessment, patient stratification, and early intervention. This review synthesizes current knowledge on HS genetics, emphasizing genotype-phenotype correlations, comorbidity associations, and translated opportunities, and outlines research priorities needed to advance toward precision medicine approaches for HS.

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The absorption spectra of lanthanide trihalide complexes were calculated using the multiconfigurational SO-CIS(PT2) method, which accounts for spin-orbit coupling, dynamic electron correlation, and the dynamic coupling with the ligands. These complexes exhibit well-characterized hypersensitive transitions whose oscillator strengths depend sensitively on the nature of the ligands. The good agreement among the calculated transition energies, absorption intensities, and experimental spectra highlights the potential of this method for predicting absorption spectra of lanthanide complexes with larger ligands from first principles. Judd-Ofelt parameters were derived from the spin-free manifolds (i.e., without spin-orbit coupling) to avoid state mixing arising from intermediate coupling. Only transitions between manifolds with &#x394;L = -2 exhibit hypersensitivity. The Judd-Ofelt parameters display a decreasing trend across the lanthanide series and, as expected, an increasing trend along the halide series. In this work, the dynamic coupling model is not expressed in terms of polarizability but is formulated in an orbital framework, facilitating a microscopic rationalization of the observed results.