Blau syndrome, a granulomatous autoinflammatory disease, is a rare condition that is typically characterized by a triad of polyarthritis, uveitis, and dermatitis. It is caused by either an autosomal dominantly inherited or a de novo pathogenic variant in the NOD2 gene. In this report, we present a case of an 11-month-old male with Blau syndrome who presented with calcitriol-mediated hypercalcemia at an early stage. Severe hypercalcemia was controlled by intravenous fluid therapy, diuretics, calcitonin and a short course of corticosteroids. Following resolution of the hypercalcemic episode, the patient gradually developed the full clinical spectrum of Blau syndrome, including symptoms of the classic triad, along with hepatosplenomegaly, lymphadenopathy, and bone marrow involvement. Trio-genome sequencing reported a de novo pathogenic heterozygous variant in the NOD2. Following the genetic testing result, corticosteroids and methotrexate were introduced to control the disease. This is the first reported case of Blau syndrome presenting with hypercalcemia as an initial manifestation, preceding the development of the classic triad of symptoms. This case underscores the importance of considering Blau syndrome in the differential diagnosis of early-onset hypercalcemia of unknown etiology. Molecular genetic testing should be pursued in such cases to facilitate accurate and timely diagnosis, enabling appropriate management.
To describe the long-term ocular and systemic course of a pediatric patient with Blau syndrome carrying aNOD2p.Arg587Cys mutation, and to report the therapeutic response to infliximab after inadequate disease control with adalimumab. Single-case report of a girl with genetically confirmed Blau syndrome managed at a tertiary referral center for pediatric uveitis in Japan. Clinical findings, multimodal imaging, treatment course, and long-term outcomes were reviewed from infancy through late childhood. Ocular inflammation was assessed by slit-lamp biomicroscopy, fundus examination, fluorescein angiography, and optical coherence tomography. Systemic therapy comprised methotrexate and tumor necrosis factor-alpha (TNF-α) inhibitors. The patient developed recurrent fever and urticaria-like rash at 7months of age, followed by bilateral granulomatous uveitis with optic disc edema at 9months. Genetic testing at 14months identified a heterozygousNOD2p.Arg587Cys mutation, confirming Blau syndrome. Methotrexate combined with adalimumab achieved only partial control: ocular inflammation recurred despite normalization of C-reactive protein and erythrocyte sedimentation rate, and recurrent hypopyon developed even after dose escalation to the standard pediatric maximum. After switching to infliximab at 4years and 6months of age, sustained remission was maintained for more than four years, with stable visual acuity, stable intraocular pressure, and no further ocular or systemic relapses. In this patient, systemic inflammatory markers did not reliably reflect intraocular disease activity, and infliximab achieved durable remission of Blau-associated uveitis refractory to adalimumab. Although limited to a single observation, the long-term outcome supports infliximab as a salvage option in refractory pediatric Blau-associated uveitis and underscores the value of ophthalmologic-rather than serological-monitoring of disease activity.
Blau syndrome is a rare autoinflammatory disorder caused by NOD2 mutations, characterized by granulomatous arthritis, uveitis, and dermatitis. While type I interferon signatures are biomarkers in several autoinflammatory diseases, their role in Blau syndrome remains unclear. We assessed the interferon score in 11 patients with Blau syndrome and correlated it with disease activity. Our results demonstrate that type I interferon signatures were detected in only a minority of patients and showed no significant correlation with clinical disease activity, inflammatory markers, or treatment response. These findings suggest that type I interferon signatures are not useful biomarkers for disease monitoring in Blau syndrome, highlighting the need to identify alternative biomarkers reflecting NOD2-mediated inflammatory pathways.
Autoinflammation typically arises from mutations affecting molecules such as inflammasome backbones that give rise to gain-of-function (GOF) pro-inflammatory activity requiring little or no normal ligand stimulation. This has been assumed to be the case in the auto-inflammation known as Blau syndrome wherein mutations usually present in the nucleotide oligomerization domain of the CARD15 gene encoding NOD2 result in widespread granulomatous inflammation, seemingly in the absence of NOD2 stimulation by its canonical ligand, muramyl dipeptide (MDP); moreover, despite such lack of ligand stimulation, NOD2 bearing a Blau mutation is thought to cause inflammation by initiating conventional downstream signaling that ultimately results in NF-κB activation. However, newer data concerning Blau syndrome pathogenesis suggest a more complex picture in which Blau CARD15 mutations cause inflammation by unconventional and/or loss of conventional signaling and which depend, at least in part, from a genetic defect which arises from loss-of-function pro-inflammatory activity. In this review, we present and analyze these newer data with the aim of defining a further pathway to the understanding and treatment of this disease.
Blau syndrome is a rare autosomal dominant autoinflammatory disorder characterized by granulomatous dermatitis, arthritis, and uveitis resulting from gain-of-function mutations in the NOD2 gene. In India, the condition is frequently underrecognized or misdiagnosed due to significant clinical overlap with juvenile idiopathic arthritis associated uveitis and early onset sarcoidosis. Reports of familial Blau syndrome are rare. This report describes familial granulomatous uveitis suggestive of Blau syndrome, with emphasis on ocular manifestations, diagnostic challenges and treatment outcomes in the absence of genetic testing. A mother and her two children presenting with variable combinations of arthritis, cutaneous lesions and ocular inflammation were evaluated. Detailed ophthalmic examination, systemic assessment, laboratory investigations, tuberculosis screening, and histopathologic analysis were performed. Diagnostic reasoning was based on clinicopathologic correlation and familial clustering. Granulomatous uveitis was identified in the mother and the elder child, with the mother exhibiting advanced disease likely due to delayed diagnosis and treatment. Skin biopsy in the elder child demonstrated well-formed non-caseating epithelioid granulomas with negative acid-fast bacilli staining. All three patients were treated with methotrexate, with adjunct corticosteroids as required. Ocular inflammation remained quiescent on follow-up, with stabilization of visual function in the affected eyes. This family illustrates the classic yet variably expressed ocular phenotype suggestive of Blau syndrome. The report highlights the role of ophthalmologists in early recognition of the disease, particularly in tuberculosis-endemic regions. Early diagnosis and prompt immunomodulatory therapy are essential to prevent irreversible visual morbidity, especially when genetic testing is not readily available.
BACKGROUND AND OBJECTIVES: Blau syndrome (BS) is a rare autosomal dominant autoinflammatory disease with limited treatment options, driven by the nucleotide-binding oligomerization domain containing 2 (NOD2) mutations that constitutively activate RIP2-mediated nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling. We have reported the potent anti-inflammatory activity of carboxyamidotriazole (CAI), originally developed as a non-cytotoxic anticancer drug. In this study, we investigated the therapeutic potential and possible mechanism of CAI for BS. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with BS. Various BS-specific cellular models and animal models were established. Immunoblot, immunofluorescence and immunohistochemistry were utilized to examine the NOD2-mediated inflammatory signaling pathways. NF-κB activity was measured with a dual-luciferase reporter assay system, and cytokines were detected by ELISA. RESULTS: In BS patient-derived PBMCs, CAI did not affect RIP2 activation under unstimulated conditions or following stimulation with muramyl dipeptide (MDP) plus lipopolysaccharide (LPS), but it suppressed NF-κB activation by reducing IKK phosphorylation and p65 nuclear translocation, ultimately leading to a marked attenuation of pro-inflammatory cytokines production. In cellular models, CAI inhibited MDP-induced activation of both NF-κB and MAPKs pathways in RAW264.7 cells, as well as the production of cytokines triggered by MDP alone or in combination with LPS. This anti-inflammatory activity was also confirmed in immortalized bone marrow-derived macrophage (iBMDM) and THP-1 cell models. Furthermore, CAI effectively suppressed constitutive NF-κB activity driven by two prevalent BS-associated NOD2 mutants (R334W and R334Q) in HEK293T cells. Finally, in animal models, CAI treatment effectively alleviated L18-MDP-induced systemic inflammation in a mouse BS model. In a rat model of BS-associated uveitis, CAI’s efficacy was further validated by its ability to ameliorate ocular pathological damage, inhibit the overactivation of NF-κB and MAPKs, and decrease the levels of pro-inflammatory cytokines in ocular tissues. CONCLUSIONS: Our findings suggest that CAI may have therapeutic value in BS by targeting the core pathogenic NF-κB/MAPK signaling axes and reducing cytokines production, which highlights CAI as a new potential medication for BS.
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Mosaicism is a recognised cause of systemic autoinflammatory diseases (SAIDs). Initially described in Cryopyrin-Associated Periodic Syndromes (CAPS), it has since been reported in several dominantly inherited SAIDs, including Blau syndrome, TNF Receptor-Associated Periodic Syndrome (TRAPS), STING-Associated Vasculopathy with Onset in Infancy (SAVI), NLRC4 inflammasomopathies, and familial Mediterranean fever (FMF). Recently, somatic variants underlying Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome have extended this to late-onset disease. This study aimed to characterize the prevalence, spectrum, and clinical significance of acquired variants in SAIDs. 5530 patients referred to a national SAIDs reference centre between 2017-2025 underwent deep next-generation sequencing autoinflammatory gene panel testing to detect low-level mosaicism. Results underwent multidisciplinary review and correlation with clinical data from electronic medical records. SAIDs diagnosis was made in 403/5530 patients (7.3%, 95% CI 6.6-8.0%). Among these, mosaic variants were identified in 83 patients (20.6%, 95% CI 16.9-24.8%), including VEXAS (69%), CAPS (24%), TRAPS (5%), Blau syndrome (1%), and NLRC4 inflammasomopathies (1%). Twenty-three distinct mosaic variants were identified across different SAIDs genes; in eight, the minor allele frequency was ≤5%. We report the first case of vertical transmission of TRAPS due to gonosomal mosaicism. AA amyloidosis complicated the disease course in 20% of patients diagnosed with late-onset mosaic CAPS. Somatic mosaicism is a frequent mechanism underlying late-onset SAIDs, which are often diagnosed late and carry a high risk of AA amyloidosis. To our knowledge, this represents the largest genetically heterogeneous single-centre cohort of mosaic SAIDs reported to date.
Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease that is influenced by environmental and genetic factors. Linkage studies and genome-wide association studies have identified genes that contribute to the risk of developing JIA but are limited in their ability to identify disease-risk variants of large effect. Penetrant, heritable risk variants can be detected in high-risk families, but such cases are uncommon due to the low prevalence of JIA. This study utilizes whole-genome sequencing of 23 multiplex families, the largest such cohort to date, to discover variants and genes relevant to JIA pathogenesis. Pathogenic variants in NOD2 associated with Blau syndrome, an ultra-rare Mendelian inflammatory disorder, are the most recurrent variants in the cohort, consistent with previous reports that milder presentations of Blau syndrome are oftentimes misdiagnosed as JIA. For the first time, however, rare variants in ACVR1 and SMAD6, integral components of the Bone Morphogenic Protein (BMP) pathway, are found to be associated with JIA. Identified ACVR1 variants map to critical protein domains. AlphaFold modeling predicts that the ACVR1 interaction with its inhibitor OGT is disrupted by these variants, indicating that the patient-mutated protein has a gain-of-function phenotype. Drosophila melanogaster expressing either a wild-type or patient-mutated version of ACVR1 exhibit embryonic lethality, with the mutant exhibiting 1.4-fold greater lethality than wild-type. The combination of family-based cohorts for gene discovery, AI-based computational tools, and animal model studies for tests of variant function underscores shared disease pathogenesis between JIA and monogenic disorders of immunity and connective tissue.
Childhood-onset sarcoidosis (COS) is a rare granulomatous autoinflammatory condition characterised by arthritis, dermatitis, and uveitis which includes early-onset forms (sporadic or Blau syndrome) and a later-onset form resembling adult sarcoidosis. Ocular involvement often occurs early and may be a prominent, sight-threatening feature. Despite this, COS is sparsely described in the literature. This case series aims to characterise the ocular manifestations, complications, and outcomes in COS. A review of patients diagnosed with COS under a tertiary paediatric uveitis service. Data collected included age at onset, clinical findings, diagnostic methods, treatments, ocular complications, and visual acuity (VA) at presentation and last follow-up. Six patients were identified, all of whom presented with granulomatous uveitis. Four had posterior segment involvement including choroiditis and optic disc swelling. The mean age of ocular disease onset was 7 years. Diagnosis was supported by elevated serum angiotensin converting enzyme (ACE) followed by lymph node biopsy (n = 3), skin biopsy (n = 2), and/or NOD2 mutation (n = 3). All received systemic immunosuppression: methotrexate (n = 6), adalimumab (n = 5), mycophenolate (n = 2), oral corticosteroids (n = 3), and infliximab (n = 1). Complications included uveitic glaucoma (n = 2), cataract (n = 3), and chorioretinal scarring (n = 1). VA improved or remained stable in most, with one case of persistent visual impairment. COS-related uveitis demonstrates an aggressive, chronic course with early onset, bilateral involvement, and frequent complications with potential to cause visual loss. Careful ophthalmic screening in children with known or suspected sarcoidosis is critical.
Healthcare service delivery considers ethnic diversity as an essential factor in its operations. There's however, limited empirical evidence from Kenyan public hospitals. The study aimed to determine how ethnic diversity affects service delivery results, which included staff performance, teamwork, and patient satisfaction. An analytical cross-sectional study was conducted, including 182 healthcare workers and 210 outpatients. Blau's Index (1 - Σpi2) was used to measure ethnic diversity, divided into three groups: low ethnic diversity at 0.3 level or below, moderate ethnic diversity between 0.3 and 0.6 level, and high ethnic diversity above 0.6 level. The researchers obtained data through three instruments: the Team Climate Inventory and the Individual Work Performance Questionnaire and a 5-point patient satisfaction scale. Multivariable regression analysis was used to examine results while controlling for demographic and professional variables. The average ethnic diversity index across departments showed high diversity with a value of 0.64 ± 0.12. The relationship between ethnic diversity and staff performance showed a positive connection with a correlation coefficient of 0.35 (p < 0.001) and a 95% confidence interval of 0.22 to 0.47. The research results showed that ethnic diversity accounted for 18.9% of staff performance variations (Adjusted R 2 = 0.189, p < 0.001). Public healthcare facilities experience improved service delivery results when they adopt ethnic diversity as a positive factor. The positive effects of diversity management require the effective implementation of diversity management initiatives.
Nursing team research has focussed primarily on staffing ratios and skill mix; however, even when staffing levels are comparable, patient and staff outcomes can vary substantially. Team composition factors beyond professional roles may fundamentally shape performance through demographic diversity and team stability mechanisms identified in organisational behaviour theory. To examine whether ward-level nursing team demographic diversity, stability, and educational composition are associated with patient and team outcomes across multiple healthcare systems. We conducted a cross-sectional observational study across 48 adult medical and surgical nursing units in six hospitals across Belgium, Germany, Luxembourg, and the Netherlands from October 2022 to September 2023. Team composition variables included demographic diversity (age, tenure, employment rate), team stability (workforce retention) metrics, and educational composition. Patient outcomes were falls with injury and mortality rates; staff outcomes included turnover, overtime hours, and absenteeism. We employed a two-stage analytical approach: Elastic Net regularisation for variable selection followed by Bayesian ridge regression for effect estimation with comprehensive uncertainty quantification. Teams demonstrated substantial demographic diversity with high age heterogeneity (mean Blau index = 0.92; SD = 0.04) and variable stability (60-100% retention rates). Age dispersion within teams showed the strongest association with patient safety, with one standard deviation increase in age dispersion associated with a 0.50 standard deviation reduction in fall rates (95% equal-tails credible interval (CrI): -0.74 to -0.26). Within-team variation in work percentages (employment rate dispersion) was associated with higher fall rates (0.31; 95% CrI: 0.08 to 0.55). Team stability was associated with lower absenteeism, but also with increased overtime hours by 0.34 standard deviations (95% CrI: 0.05 to 0.65). Higher team educational levels were associated with reduced fall-rate (-0.28; 95% CrI: -0.50 to -0.06) and lower overtime (-0.34; 95% CrI: -0.62 to -0.04). All mortality predictors were eliminated during the variable selection process, indicating insufficient power, or absence of any effects. Greater age dispersion and higher educational levels within nursing teams were associated with better patient safety outcomes. Employment rate dispersion (differences in full-time versus part-time employment within teams) showed associations with poorer outcomes. Team stability presents a trade-off, reducing absenteeism but increasing overtime. Given the observational design and exploratory nature of this multi-country analysis, these findings generate hypotheses about team composition effects that warrant further investigation through longitudinal and interventional research designs.
Modern image restoration and super-resolution methods utilize deep learning due to its superior performance compared to traditional algorithms. However, deep learning typically requires large labeled training datasets, which are rarely available in astrophotography. Deep Image Prior (DIP) bypasses this constraint by performing unsupervised optimization on a single image without training data; however, DIP often suffers from overfitting, artifact generation, and instability. This work proposes DIPLI - a framework designed specifically for resolved, high-contrast astronomical targets that shifts from single-frame to multi-frame processing using the Back Projection technique, combined with dense optical flow estimation via the TVNet model, and replaces deterministic predictions with Monte Carlo estimation obtained through Stochastic Gradient Langevin Dynamics (SGLD). A comprehensive evaluation compares the method against the original DIP, the transformer-based model RVRT, and the diffusion-based model DiffIR2VR-Zero on synthetic data with ground truth, while comparing qualitatively against Lucky Imaging on real astronomical data. On synthetic datasets, DIPLI achieves the best perceptual fidelity scores (LPIPS in 12/12 and DISTS in 10/12 scenarios), while the diffusion-based DiffIR2VR-Zero achieves the best pixel-level distortion scores (PSNR in 9/12 and SSIM in 8/12 scenarios), consistent with the well-known perceptual-distortion trade-off in image restoration (Blau and Michaeli In Proceedings of the IEEE Conference on Computer Visionand Pattern Recognition 6228-6237 2018). Compared to classical Lucky Imaging, the model requires far fewer input frames (7-13 versus thousands) and avoids the need for early stopping that limits standard DIP. Qualitative evaluation on real-world data of resolved solar-system objects, where ground truth is unavailable and domain shifts typically hinder generalization, suggests that the method appears to preserve fine detail while suppressing noise and artifacts.
A molecular-level understanding of electrolyte solvation structure and ion-ion correlations is critical to developing next-generation battery chemistries. Atomistic simulation capabilities with sufficient accuracy, speed, and transferability to deliver reliable structural insights while avoiding arduous system-specific reparameterization are thus highly desirable. Machine learning interatomic potentials (MLIPs) trained on large, chemically diverse data sets are revolutionizing computational chemistry, enabling molecular dynamics simulations of battery electrolytes with near-DFT accuracy over 10,000× faster than DFT. While previous MLIP training data sets with suitable elemental coverage for electrolytes have been based on inorganic materials, the Open Molecules 2025 (OMol25) data set provides large-scale molecular DFT MLIP training data with broad elemental coverage and specifically samples tens of millions of electrolyte configurations. Here, we integrate computational modeling with experimental validation to systematically assess the ability of large-scale MLIPs pretrained on materials data or on OMol25 to accurately resolve nanoscale structural organization and ion-solvation characteristics in Na-ion battery electrolytes across diverse physicochemical conditions and compositional regimes. We find that the OMol25-trained Universal Model of Atoms (UMA-OMol) predicts experimentally measured densities and X-ray structure factors in substantially better agreement compared to state-of-the-art models trained only on inorganic materials data. Using UMA-OMol, we further analyze systematic trends in solvation structure as a function of cation identity, anion chemistry, salt concentration, and solvent topology. We observe that increasing system temperature amplifies the heterogeneity within the solvation environment, perturbing cation-solvent interactions and promoting the formation of contact ion pairs (CIPs). Moreover, subtle variations in the solvent topology of glyme-based electrolytes cause pronounced changes in ion correlations and solvation structure. The experimental agreement and microscopic insights shown here position OMol25-trained MLIPs as a practical route to predictive, high-throughput electrolyte simulations beyond the limits of classical force fields and direct DFT molecular dynamics, serving as a powerful tool for accelerating the design of next-generation Na-ion battery electrolytes and beyond.
This paper examines the effect of the 1984 Hatch-Waxman Act and its 2003 amendment - the Medicare Prescription Drug, Improvement, and Modernization Act - on the level of innovation in pharmaceutical firms. In part, the purpose of these policies was to balance the exclusivity rights of pioneer drug manufacturers with generic drug competition, which would allow for more consumer affordability. Using difference-in-difference regression analysis, we analyze how, relative to innovation in other industries, pharmaceutical innovation changes surrounding the implementation of the two laws. Results from several difference-in-difference tests show that, relative to non-pharmaceutical firms, research and development (R&D) in pharmaceutical firms markedly increased during the post-Hatch-Waxman period. We do not find, however, that the 2003 amendment directly influenced pharmaceutical innovation. If anything, the latter policy was associated with a reduction in innovation. These findings seem to suggest that the level of pharmaceutical innovation is highly sensitive to changes in policy that might change the incentives for firms to innovate.
Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited. We analyzed 3,301 serum samples from 617 patients enrolled in the phase III GMMG-HD7 trial to characterize the analytical performance and clinical relevance of MS-based measurable residual activity. MS reliably distinguished therapeutic antibodies, tracked diagnostic M proteins longitudinally, and demonstrated strong prognostic value across defined time points. MS negativity was associated with superior progression-free survival (PFS), with the greatest separation at later time points (12 months of maintenance: hazard ratio, 0.25 [95% CI, 0.15 to 0.43]; adjusted P < .001). Combined assessment with bone-marrow measurable residual disease (MRD) further refined risk stratification: MS/MRD double-positive patients exhibited the worst PFS, whereas all other groups showed comparably favorable outcomes. MS/MRD concordance increased over time and was influenced by immunoglobulin isotype, with expected immunoglobulin G-recycling-associated early discordance. MS provided accurate M-protein detection and outperformed serum protein electrophoresis at low concentrations, reliably quantifying low-level residual disease. These findings establish serum MS as a sensitive, reproducible, and practical biomarker that complements MRD and supports minimally invasive disease monitoring in MM, with potential integration into future response assessment and risk-adapted treatment strategies.
Bioelectronic devices benefit from materials that have tissue-like levels of softness and good conductive coupling to biological structures. Conventional conjugated polyelectrolyte complexes such as poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) have favorable levels of mixed ionic-electronic conductivity, but have high elastic stiffness, typically reflected in Young's moduli in the GPa range. Soft ionic conductors, such as ionogels, offer extreme deformability but generally lack the semiconducting mixed ionic-electronic transport required for signal transduction and amplification. Here, we report the first room-temperature liquid semiconducting block copolymer (L-SBCP) that functions as an organic electrochemical transistor (OECT) and enables solvent-free processing. The synthesis of L-SBCP involves the covalent linkage of two unlike polymers: a π-conjugated block bearing glycol side chains and a PEGMEMA bottlebrush acrylic block. This architecture combines mixed ionic-electronic conductivity with the mechanical properties of a viscoelastic liquid. The result is a phase-stable, free-flowing single-component material with a deformability comparable to that of biological cells (1-100 Pa) and a substrate-limited stretchability of 800%. Its liquid rheology supports direct injection and vacuum filling of microchannels without additives or thermal processing. The L-SBCP exhibits p-type accumulation-mode behavior in an organic electrochemical transistor (OECT), with a threshold voltage of +0.08 V, comparable to that of state-of-the-art soft semiconductors. Importantly, L-SBCP supports robust cell viability (>97%). The cellular compatibility opens opportunities for bioelectronic signal amplification at cell-material interfaces enabled by a semiconducting material with cell-scale softness. By uniting biorelevant softness, extreme deformability, electronic performance, and solvent-free processability, L-SBCP establishes a new material composition and form factor for semiconducting polymers and bioelectronic devices.
Glucagon-like peptide-1 receptor agonists, including long-acting semaglutide, are transformative anti-obesity therapies. However, emerging evidence indicates that weight loss may come at the expense of skeletal muscle mass, a tissue essential for mobility, metabolic regulation, and overall health. Here, we show that inhibition of the gerozyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme that increases with injury and aging, improves muscle repair and strength recovery in the presence of semaglutide. In a high fat diet-induced mouse model of obesity, semaglutide alone caused significant loss of muscle mass, while preserving contractile function. Following injury, obese mice exhibited pathological calcifications previously reported for the heritable myopathy, Duchenne Muscular Dystrophy. Semaglutide had both beneficial and deleterious effects, reducing calcific remodeling, but causing reduced regenerated myofiber sizes. This impaired regenerative myofiber growth in semaglutide-treated mice was surmounted by cotreatment with a 15-PGDH inhibitor (PGDHi), which stimulated muscle stem cell function and myofiber growth, leading to enhanced strength. Importantly, PGDHi synergizes with semaglutide to boost postinjury muscle quality and muscle force without compromising weight loss.
Dark matter particles with sufficiently large interactions with ordinary matter can scatter in the Earth's atmosphere and crust before reaching an underground detector. This Earth-shielding effect can induce a directional dependence in the dark matter flux, leading to a sidereal daily modulation in the signal rate. We perform a search for such a modulation using data from the SENSEI experiment, targeting MeV-scale dark matter. We achieve nearly an order-of-magnitude improvement in sensitivity over previous direct-detection bounds for dark-matter masses below ∼1  MeV, assuming the standard halo model with a Maxwell-Boltzmann velocity distribution, and restrict the amplitude of a general daily modulation signal to be below 6.8  e/g/d.