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Quaternary carbon centers, especially those bearing nitrogen, are highly valued in drug discovery, imparting three-dimensionality, selectivity, and metabolic stability. Yet, accessing α-tertiary, primary amines (α-TPAs) remains challenging due to steric congestion and the intrinsic basicity of amine nucleophiles. Although classical nucleophilic α-amination, α-C-H functionalization, and photocatalytic α-NH2 radical strategies offer useful platforms, they often suffer from limited functional-group tolerance and poor stereocontrol. Here, we report a streamlined electrochemical difunctionalization strategy that directly transforms 1,1-disubstituted alkenes into C(sp3)-rich α-TPAs using inexpensive and bench-stable ammonium surrogates. This metal- and oxidant-free aminochalcogenation employs thiophenols as the most user-friendly thiolating agents, avoiding pre-activated sulphur reagents and enabling efficient aminosulfenylation and aminoselenylation in a single operation. The strategy accommodates diverse N-sources, including ammonia surrogate, amino acids, dipeptides, aliphatic amines, and N-heterocycles, enabling the synthesis of α-tertiary, primary as well as secondary amines and facilitating late-stage functionalization of pharmaceutically relevant scaffolds (> 71 examples and up to 82% yield). The robustness of the strategy was further demonstrated by an efficient gram-scale electrolysis. This work provides a modular, sustainable route to free alkyl amines that remain difficult to access by conventional methods.

Uterine tumour resembling ovarian sex cord tumour (UTROSCT) is an uncommon neoplasm associated with recurrent gene fusions involving NCOA1-3, with ESR1 and GREB1 being the most frequent fusion partners. Fusions are not present in all cases and there have been few reports of gene mutations in these neoplasms. We report an index case of a UTROSCT (classic morphology with supportive immunophenotype) in a 58-year-old woman with no demonstrable fusions on RNA next generation sequencing (NGS) but with CTNNB1 and PTEN gene mutations. We reviewed a large series (n = 28) of UTROSCT from a single institution which had undergone RNA and DNA NGS. A total of 26 gene mutations were found in 12 of 28 (43%) cases, although no highly recurrent mutations were present. In 8 of these 12 cases, there were also characteristic gene fusions of UTROSCT. We stress that, especially in cases of UTROSCT with no fusions identified on RNA sequencing, it may be useful and informative to undertake DNA testing to look for underlying mutations.

Supercritical water (SCW) is a promising green solvent, yet optimizing its performance requires a fundamental understanding of the thermodynamic behavior and solvation mechanisms. Here, molecular dynamics simulations are used to investigate the thermodynamic responses, cohesive-strength evolution, and cavity-formation behavior of SCW along isobars, with the NIST benchmark data serving as a reference for the classical Widom line (WL) behavior. The origin of the high-pressure WL divergence is analyzed from the perspective of statistical fluctuations and intermolecular interactions. Furthermore, cohesive energy density and the state-dependent mean-radius cavity-formation free energy, together with their corresponding thermal response coefficients, are introduced to establish a thermodynamic connection with the classical WL. Building on this connection, the high-pressure "Widom region" is delineated, and the thermodynamically driven evolution sequence along the isobaric heating path is revealed. This work provides a thermodynamic framework for understanding the evolution of the Widom region and its relevance to the solvation behavior of SCW.

Parkinson's disease (PD) is increasingly recognized as a neurological disorder characterized not only by neurodegeneration but also by chronic immune dysregulation across the lifespan. Although the initiating events underlying PD remain unclear, accumulating evidence suggests that inflammatory processes may contribute to disease susceptibility and progression. Mutations in leucine-rich repeat kinase 2 (LRRK2), particularly the gain-of-function G2019S variant, represent the common genetic cause of familial PD and have been implicated in immune regulation and infection susceptibility. To date, most research has focused on the effect of LRRK2 mutation in neurons and the contributions of G2019S-mediated kinase activity to neuronal toxicity, leaving the role of G2019S-mediated kinase activity in immune cell homeostasis and its contribution to PD pathogenesis largely unresolved. Here, we used murine overexpression models of wildtype and G2019S variant of mouse Lrrk2 to examine how Lrrk2 G2019S shapes host defense across viral and bacterial infection models. We tested systemic sepsis and Escherichia coli infection to examine bacterial clearance. We followed up by testing macrophage responses to intracellular (Listeria monocytogenes) or primarily extracellular (Pseudomonas aeruginosa) bacteria. Finally, tested antibody-mediated immunity using influenza and cytotoxic T cell-mediated immunity using lymphocytic choriomeningitis virus (LCMV) infection. We found that Lrrk2 G2019S overexpression enhanced survival and bacterial clearance during P. aeruginosa lung infection, whereas the same genotype worsened outcomes in polymicrobial sepsis, with increased mortality, pulmonary myeloid infiltration and a hematopoietic cell-intrinsic phenotype. During L. monocytogenes infection, Lrrk2 G2019S selectively reduced non-classical monocytes without altering disease progression. In influenza and LCMV infection, G2019S altered antigen-specific CD8+ T cell distribution without major changes in cell memory responses clinical severity. Together, these data show that Lrrk2 G2019S selectively reprograms innate and adaptive immunity in a pathogen- and tissue-dependent manner, uncoupling inflammatory magnitude from effective host defense. These results and previous work support a model in which the G2019S LRRK2 variant contributes to maladaptive inflammatory responses to specific infection challenges, providing insight into how lifetime immune perturbations may intersect with genetic susceptibility to influence lifetime infection risk.

Papillary renal neoplasm with reverse polarity (PRNRP) is an emerging entity with an indolent clinical course. It is histologically characterized by a low-grade papillary neoplasm with apically located nuclei and frequent KRAS mutation. With the limited amount of literature, there is no established association between PRNRP and other diseases. Herein, we report four patients of PRNRP in Hong Kong. The neoplasms are discovered incidentally by radiographic investigations and diagnosed by their classical histopathological features. All patients are noted to have underlying hyperglycaemia en passant. This preliminary observation provides insight into the pathogenesis of this specific type of renal neoplasm.

Diffuse midline gliomas (DMGs) are highly aggressive, WHO grade 4 glial tumors that arise in midline central nervous system structures and are defined by K27M mutations in histone H3 genes. These K27M mutations shape intratumoral myeloid cell composition in DMG. In H3.1K27M DMGs, genetic ablation of monocyte recruitment reshapes the tumor microenvironment (TME) by reducing monocyte-derived macrophages (MDMs) and increasing microglia and neutrophil presence, with overall survival remaining unchanged, indicating compensatory myeloid remodeling is occurring. Here, by using CRISPR/Cas9-based genome editing, we generated a mouse model deficient for CCR1/CCR2/CCR3/CCR5 (Δ1235). Using this strain, we effectively abolished monocyte and MDM infiltration and reversed compensatory recruitment of CCR1+ neutrophils. Abolishing MDMs in tumors skewed remaining neutrophils and microglia toward a homeostatic state, reduced expression of immune checkpoint molecules on T cells, and extended the survival of H3.1K27M DMG-bearing mice. In contrast, H3.3K27M DMG showed independence from MDM recruitment, suggesting reliance on other TME-driven signaling. Last, H3.1K27M DMGs exhibited reduced microglia presence and a dose-dependent increase in MDM infiltration postirradiation. MDM depletion did not further enhance radiation efficacy, potentially due to compensatory recruitment of classical neutrophils. Collectively, these data reveal histone mutation-specific myeloid dependencies in DMG, highlighting MDM-independent mechanisms in H3.3K27M tumors and MDM-dependent pathways in H3.1K27M tumors.

Null geometric algebra (NGA) refers to a basis-free version of Clifford algebra where the base vector space is spanned by vectors whose inner product with itself equals zero. It provides powerful tools for manipulating expressions in conformal geometric algebra (CGA) when making symbolic reasoning in classical geometry. This paper develops several new techniques in NGA and uses them to explore the geometric interpretations of basic algebraic objects in NGA-null monomials, their scalar parts and pseudo-scalar parts, centred null binomials-and illustrates how these objects are used in making geometric reasoning for problems in classical geometry. This article is part of the theme issue 'Modern applications of geometric algebra'.

The kidney thick ascending limb (TAL) is typically viewed as comprising a single cell type that expresses a Na-K-2Cl transporter and potassium channel at the apical membrane and a basolateral chloride channel. Together, these generate a lumen-positive transepithelial voltage. This review summarizes recent work revising this view substantially. Very early work suggested that not all TAL cells express potassium channels at the apical membrane. More recently, it became clear that paracellular transport pathways for monovalent and divalent cations exhibit a mosaic pattern, suggesting further diversity. By combining transcriptomics with more established approaches, it has become clear that there are 3 types of TAL cells. One type resembles the classic model. A second type, in the cortex and parts of the outer medulla, however, does not express apical potassium channels and is ringed by claudins that transport calcium and magnesium. A third type, in the inner stripe of the outer medulla, also lacks apical potassium channels but exhibits sodium-permeable claudins within the tight junctions. Previously unrecognized distinct cell types along the TAL mediate sodium transport and calcium/magnesium transport separately. Each type expresses regulatory pathways to permit differential regulation thereby preserving homeostasis.

KIF1A-associated neurological disorder (KAND) encompasses recessive and dominant variants with wide clinical variability. Several de novo variants in the KIF1A gene have been reported to cause a complicated form of hereditary spastic paraplegia (HSP), frequently accompanied by peripheral neuropathy, cerebellar ataxia, and cognitive impairment. Instrumented three-dimensional (3D) gait analysis is underutilized in this population, and comparative data between KAND and pure HSP remain limited. We performed a comprehensive instrumented 3D gait analysis in a 19-year-old woman with KAND caused by a heterozygous de novo KIF1A variant c.773C>T (p.Thr258Met) in the motor domain (exon 8), presenting with progressive spastic paraparesis. Assessment included spatiotemporal parameters; 3D kinematics of the hip, knee, and ankle; kinetic analysis of ground reaction forces; joint moments and powers; baropodometry; surface dynamic telemetric electromyography (EMG) of the lower limb muscles bilaterally; and fine-wire EMG of the left flexor digitorum longus and flexor hallucis longus. Walking speed, stride length, and cadence were within normal limits for age and sex. Kinematic analysis revealed bilateral deficits in hip and knee extension during stance, hip internal rotation and adduction during swing, reduced knee flexion in swing, and bilateral ankle dorsiflexion deficit during swing. Clinically, maintained flexion of all toes bilaterally was observed and filmed. Ankle push-off power was markedly reduced bilaterally (32.5%-42.5% of normative values). EMG demonstrated out-of-phase activation of the adductor longus, gracilis, semimembranosus, and biceps femoris, and continuous co-contraction throughout the gait cycle of the extensor digitorum longus, flexor digitorum longus, and flexor hallucis longus. Brief high-amplitude bursts compatible with possible myoclonic activity were identified in the right gastrocnemius and soleus during swing phase. This case illustrates a KAND phenotype in which gait speed is preserved, but kinematic, kinetic, and EMG profiles are substantially abnormal, a pattern that differs from classical HSP, where speed reduction is typically a hallmark finding. The combination of spastic, ataxic, and peripheral neuropathy components produces a distinct and complex gait signature. Quantitative gait analysis may provide clinically useful information to guide targeted interventions, including botulinum toxin injections, orthotic management, and physiotherapy, in this heterogeneous population.

In this study, we propose a novel optical sensor architecture based on two-dimensional photonic crystals for the early detection of cervical cancer (HeLa). The structure consists of a central hollow-disk micro-cavity designed to accommodate biosamples, surrounded by a periodic array of GaAs rods. The detection principle relies on variations in the biosample refractive index, inducing a spectral shift in the resonance. To overcome the limitations of conventional 2D-FDTD method parametric sweeps, an artificial intelligence framework was developed to optimize the geometric parameters of the proposed photonic crystal optical sensor. First, a Random Forest algorithm was employed to identify promising regions of the geometric design space. Next, a multilayer artificial neural network (ANN-MLP) was trained as a high-fidelity surrogate model (R2 = 98.58%) and coupled with a Particle Swarm Optimization (PSO) algorithm to determine the optimal structural configuration. The optimized sensor geometry subsequently achieved an average sensitivity of 5512.91 nm/RIU, a quality factor of 6139.15 and a detection limit of 5.64×10-5 RIU, demonstrating the effectiveness of the proposed AI-assisted design strategy. The optimized design reduces classical performance trade-offs and exhibits high tolerance to nanometric fabrication deviations below ±20 nm.

The rising prevalence of infertility has substantially increased the demand for in vitro fertilization (IVF). While various controlled ovarian stimulation (COS) protocols exist, the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol is valued for its efficacy in preventing premature luteinizing hormone (LH) surges. However, it involves high medication costs and requires frequent injections, which impose a significant burden on patients. Clomiphene citrate (CC), a classic oral ovulation induction agent, offers advantages such as low cost and convenient administration. With the widespread adoption of the "freeze-all" strategy, its potential adverse impact on the endometrium can be mitigated. Recent modifications to the CC protocol, combining it with adequate-dose gonadotropins, aim to balance efficacy and cost. However, well-designed studies directly comparing this modified CC protocol with the conventional GnRH-ant protocol in a general IVF population are lacking, particularly those incorporating comprehensive cost-effectiveness analyses. 3,157 patients undergoing IVF or intracytoplasmic sperm injection (ICSI) cycles using either the CC protocol or the GnRH-ant protocol were matched 1:1 using propensity score matching (PSM) based on female age, basal follicle-stimulating hormone (FSH), anti-M&#xfc;llerian hormone (AMH), antral follicle count (AFC), body mass index (BMI), fertilization method, and sperm source. A total of 1,858 patients (929 per group) were included after matching. Embryological parameters and pregnancy outcomes were compared between the two groups, along with cost-effectiveness and sensitivity analyses. Baseline characteristics were well-balanced after PSM (with almost all standardized mean differences (SMD) < 0.1). The clinical pregnancy rate was comparable between the CC group and the GnRH-ant group (46.26% vs. 41.07%, P =&#xa0;0.113), and the cumulative clinical pregnancy rate was also similar (51.60% vs. 51.79%, P&#xa0;=&#xa0;1.000). The live birth rate (35.48% vs. 31.95%, P&#xa0;=&#xa0;0.268) and cumulative live birth rate (35.48% vs. 38.29%, P&#xa0;=&#xa0;0.398) were also comparable between the two groups. Compared to the GnRH-ant group, the CC group exhibited a higher Day 3 embryo formation rate (66.67% vs. 62.50%, P&#xa0;=&#xa0;0.012), despite having lower numbers of follicles on the day of hCG trigger and retrieved oocytes (9.00 vs. 10.00 and 6.00 vs. 8.00, P&#xa0;<&#xa0;0.0001). No significant differences were observed in the oocyte retrieval rate, oocyte maturation rate, fertilization rate, and blastulation rate between two groups. The cost of COS in the CC group was significantly lower than that in the GnRH-ant group (1,414.70 [741.50-2,915.50] CNY [~198 USD] vs. 7,266.24 [5,747.64-9,011.05] CNY [~1,017 USD], P <&#xa0;0.0001), representing a saving of approximately 5,851.54 CNY (~819 USD; 80.53%). Cost-effectiveness analysis indicated that the CC protocol was superior across all outcome measures, including incremental cost-effectiveness ratios (ICERs) for oocyte, embryo, and clinical pregnancy. One-way sensitivity analysis (OWSA) indicated that the clinical pregnancy rate between the two groups was the most critical factor influencing the ICER for clinical pregnancy. Probabilistic sensitivity analysis (PSA) also suggested that in 98.50% of simulations, the CC protocol was more cost-saving. The modified CC protocol was associated with ovarian stimulation effects and clinical outcomes comparable to those of the GnRH-ant protocol. Furthermore, it represented a more cost-effective ovarian stimulation strategy, significantly reducing treatment costs while maintaining a clinical pregnancy rate comparable to that of the GnRH-ant protocol.

Complete blood count (CBC) discrimination indices are widely used as low-cost triage tools for microcytosis, but their diagnostic utility in population-based samples with ferritin-defined iron status is uncertain. We evaluated whether commonly used indices distinguish ferritin-defined iron-deficient from noniron-deficient microcytosis among women aged 18-49&#x2009;years. We analyzed the National Health and Nutrition Examination Survey (NHANES) 2015-2016, 2017-2018, and August 2021-August 2023 data among nonpregnant women aged 18-49&#x2009;years with CBC, serum ferritin, and survey design variables. Among microcytic (MCV <&#x2009;80&#x2009;fL) women, iron-deficient microcytosis was defined as ferritin <&#x2009;15&#x2009;ng/mL and noniron-deficient microcytosis as ferritin &#x2265;&#x2009;15&#x2009;ng/mL. Mentzer, England-Fraser, Srivastava, and red cell distribution width (RDW) indices were evaluated at conventional cutoffs. Sensitivity analyses used ferritin <&#x2009;30&#x2009;ng/mL and C-reactive protein (CRP) restrictions of &#x2264;&#x2009;5 and &#x2264;&#x2009;3&#x2009;mg/L. All estimates were survey-weighted. Among 3991 women, 507 had microcytosis. Ferritin-defined noniron-deficient microcytosis comprised 40.8% (95% CI, 35.5-46.2) and remained 37.0% and 33.6% after CRP restrictions of &#x2264;&#x2009;5 and &#x2264;&#x2009;3&#x2009;mg/L. With ferritin &#x2265;&#x2009;30&#x2009;ng/mL, the corresponding proportions were 26.5%, 22.6%, and 20.2%. All four indices showed high sensitivity (92.9%-97.6%) but poor specificity (6.7%-35.3%). RDW had the highest specificity but still misclassified most noniron-deficient cases. Classic CBC indices had limited utility as standalone triage tools for ferritin-defined microcytosis. Ferritin-based assessment, interpreted in the relevant clinical and inflammatory context, should remain central. Persistent microcytosis without evidence of reduced iron stores should prompt diagnostic reconsideration and, when appropriate, hemoglobinopathy-aware evaluation.

Androgen excess in polycystic ovary syndrome (PCOS)/polyendocrine metabolic ovarian syndrome (PMOS) is classically attributed to ovarian steroids, yet adrenal-derived 11-oxygenated androgens are potent contributors whose regulation and treatment responsiveness in PMOS remains poorly characterized. To quantify classic and 11-oxygenated androgens across PMOS phenotypes versus controls and to evaluate their responses to oral contraceptive pills (OCPs), metformin, or lifestyle modification (LSM). Secondary analysis of residual serum samples from three trials: OWL-PCOS (16-week OCP vs LSM), COMET-PCOS (24-week OCP vs metformin), and AMIGOS (controls). Two academic medical centers. 276 with Rotterdam-defined PMOS and 97 controls. Low dose OCPs (4-6 months), metformin (2000mg/day for 6 months), or LSM (4 months). Serum concentrations of 11&#x3b2;-hydroxytestosterone (11-OHT), 11-ketotestosterone (11-KT), 11-ketoandrostenedione (11-KA4), and 11&#x3b2;-hydroxyandrostenedione (11-OHA4) measured by LC-MS/MS, and total testosterone (TT), at baseline and end of study. Adjusting for age and BMI, women with PCOS/PMOS had higher median 11-OHT (11.0 vs 7.8&#x2005;ng/dL; P&#x2009;=&#x2009;0.01) and 11-KT (31.9 vs 25.6&#x2005;ng/dL; P&#x2009;=&#x2009;0.03) than controls. Elevations were phenotype-specific: biochemical hyperandrogenism showed broad increases, whereas clinical hyperandrogenism with normal TT found no significant differences compared to controls. OCPs suppressed 11-KT, 11-KA4, and 11-OHT (all P&#x2009;<&#x2009;0.001), comparable to TT reductions. Metformin produced modest reductions in 11-OHT and 11-KT (P&#x2009;<&#x2009;0.05), while LSM had no effect. Changes were independent of BMI, glycemia, and HOMA-IR. 11-oxygenated androgens are elevated in PMOS in a phenotype-specific manner and are strongly suppressed by OCPs, with modest response to metformin and no short-term effect from LSM, supporting their utility in phenotyping and treatment monitoring.

Steroid 5&#x3b1;-reductase type II (SRD5A2) is an enzyme that plays a significant role in steroid metabolism. It is mainly located in the endoplasmic reticulum membrane and can convert testosterone (T) into more active dihydrotestosterone (DHT). It plays a critical role in gender differentiation and androgen physiology, and is implicated in tumorigenesis and progression. It has been reported in various types of tumors. Among the most common gastrointestinal malignancies, colorectal cancer (CRC) imposes a significant global health burden. Nevertheless, the expression profile and clinical significance of SRD5A2 in CRC are poorly characterized, and its precise functional role requires further investigation. This study aimed to investigate the expression profile, prognostic significance, biological functions, and potential mechanisms of SRD5A2 in CRC. This retrospective cohort study included 180 patients with CRC. Tissue microarrays (TMAs) were constructed and subjected to SRD5A2 immunohistochemistry (IHC), and H-scores were used to stratify patients into high- and low-expression groups for clinicopathological and overall survival (OS) analyses. Univariate and multivariate Cox regression analyses, as well as subgroup Kaplan-Meier analyses, were performed to evaluate the prognostic value and stability of SRD5A2. In vitro, SRD5A2 knockdown was performed in CRC cells, followed by assays of cell viability, migration, invasion, and apoptosis. Epithelial-mesenchymal transition (EMT)-related proteins, classical oncogenic signaling pathways, and metabolic homeostasis were further evaluated by western blotting (WB), glucose consumption, adenosine triphosphate (ATP), and reactive oxygen species (ROS) assays. SRD5A2 expression was significantly upregulated in CRC tissues compared with paired distal normal mucosa (P<0.001). High SRD5A2 expression was associated with adverse clinicopathological features and significantly shorter OS (P<0.001). Multivariate Cox regression analysis further showed that high SRD5A2 expression remained independently associated with poorer OS. Subgroup Kaplan-Meier analyses demonstrated that this adverse prognostic association was generally maintained across several T-, N-, and M-based strata. In vitro, SRD5A2 knockdown suppressed cell proliferation, migration, and invasion, while promoting apoptosis. Mechanistically, SRD5A2 silencing reversed EMT-related molecular changes, suppressed the MAPK/ERK, JNK, NF-&#x3ba;B, and AKT/mTOR pathways, reduced glucose consumption and intracellular ATP levels, and increased intracellular ROS levels. SRD5A2 is upregulated in CRC tissues, and its high expression is related to aggressive clinicopathological features and poor OS. Multivariable survival analysis further suggests that SRD5A2 may serve as an independent prognostic factor in CRC. Functional experiments suggest that SRD5A2 has a pro-tumorigenic effect. Preliminary mechanistic analyses further suggest that SRD5A2 may exert its pro-tumorigenic effects through EMT-related molecular changes, activation of classical oncogenic signaling pathways, and maintenance of metabolic homeostasis.

With the rapid development of quantum computing, in response to its disruptive threats to traditional cryptosystems and the urgent demand for lightweight and highly scalable secure group communication among resource-constrained devices in large-scale Internet of Things (IoT) scenarios, this paper proposes a lightweight anonymous group authentication scheme that integrates Physical Unclonable Functions (PUFs), distributed Gossip algorithms, and quantum key distribution. By exploiting the uniqueness and unclonability derived from the inherent physical characteristics of PUF hardware, the scheme fundamentally eliminates attack vectors against quantum computers without requiring devices to pre-store any secret keys in their memory, while the QKCS pre-provisions CRPs and key seeds, which is the standard enrollment procedure in PUF-based systems. Combined with information-theoretically secure quantum keys as session keys, it forms a dual protection mechanism: anti-forgery at the physical layer and anti-quantum attack at the cryptographic layer. Innovatively, the Gossip algorithm is deeply integrated with group key agreement, converting global broadcast into local iterative interactions between nodes, which effectively alleviates broadcast storms and improves the scalability and fault tolerance of the protocol. Meanwhile, a pseudonym mechanism is introduced to achieve anonymous identity protection, and a dynamic key update strategy guarantees forward and backward security when members join or leave the group. Formal verification based on BAN logic and security analysis show that the proposed protocol can resist typical attacks such as replay attacks, man-in-the-middle attacks, and impersonation attacks. Performance evaluations demonstrate that our scheme outperforms existing comparable schemes in terms of computational cost, communication overhead, and dynamic group management efficiency, demonstrating its potential for resource-constrained IoT environments, pending further validation on real hardware platforms.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder characterized by high-spiking fever, arthritis, rash, and systemic inflammation. Because there is no single diagnostic test, diagnosis relies on compatible clinical features, fulfillment of classification criteria, and exclusion of infectious, malignant, and autoimmune conditions. Atypical cutaneous manifestations may further delay recognition, particularly in resource-limited settings. We report the case of a 22-year-old Ethiopian woman who presented with a five-month history of inflammatory polyarthritis, daily spiking fever, sore throat, and a persistent hyperpigmented scaling rash rather than the classic evanescent salmon-colored eruption. Laboratory evaluation demonstrated marked neutrophilic leukocytosis, elevated inflammatory markers, abnormal liver enzymes, and hyperferritinemia (1,675 &#x3bc;g/L). Echocardiography revealed mitral valvulitis with mild pericardial effusion. Infectious, autoimmune, and rheumatologic conditions, including acute rheumatic fever, rheumatoid arthritis, systemic lupus erythematosus, viral hepatitis, HIV infection, and other competing diagnoses, were excluded through clinical assessment and laboratory investigations. The patient fulfilled the Yamaguchi classification criteria for AOSD, while markedly elevated serum ferritin provided supportive evidence for the diagnosis. She was treated with intravenous pulse methylprednisolone followed by oral prednisolone and methotrexate, resulting in rapid resolution of fever, marked improvement in joint symptoms, fading of the skin lesions, and complete resolution of the pericardial effusion at one-month follow-up. This case highlights the diagnostic challenges of AOSD when atypical dermatologic manifestations occur, particularly in resource-limited settings where infectious diseases are frequently prioritized in the differential diagnosis. Persistent hyperpigmented scaling lesions should not exclude consideration of AOSD when accompanied by characteristic systemic features. Although elevated serum ferritin is not diagnostic, it can provide valuable supportive evidence when interpreted alongside clinical findings and after exclusion of alternative diagnoses.

Alzheimer's disease (AD) is a major neurodegenerative disorder affecting more than 7 million Americans. Extensive studies have identified various factors associated with the development of AD, but the actual cause remains unknown. Transgenic mouse model and human studies strongly indicate that oxidative stress precedes amyloid-&#x3b2; plaque formation and tau phosphorylation in AD. GSH loss itself raises the Abeta42/Abeta40 ratio and promotes tau aggregation [5], placing GSH depletion upstream of classical AD pathology. Subsequently, the role of the master antioxidant, glutathione (GSH), came into focus for brain GSH level enrichment through supplementation with &#x3b3;-glutamylcysteine (GGC), the immediate precursor of GSH. We present that GGC has an excellent safety record and bioavailability. GGC is a strong candidate to investigate for brain GSH enrichment (target engagement hippocampus, anterior cingulate cortex etc.) and subsequent cognitive enhancement for patients with mild cognitive impairment (MCI).

Ultrasound risk stratification systems for thyroid nodules worldwide describe different types of echogenic foci, including punctate echogenic foci (microcalcifications), coarse internal calcifications, and peripheral (rim) calcifications (complete or incomplete), with different levels of association with malignancy. We identified a previously undescribed pattern of small, discontinuous peripheral punctate echogenic foci&#xa0;(DPEF) associated with papillary thyroid carcinoma (PTC). This multicenter retrospective case series included thyroid ultrasound images from five countries (Brazil, United States, Italy, France, and Romania) between January 2020 and September 2025. Cases were included solely based on the presence of discontinuous peripheral punctate hyperechoic foci, defined as small echogenic dots arranged along the nodule periphery, regardless of nodule echogenicity or morphology. Each nodule underwent comprehensive evaluation by a multidisciplinary team, including experienced radiologists, endocrinologists, head and neck surgeons, and pathologists. The final diagnosis was confirmed by histopathological examination after surgical resection. Twenty-three thyroid nodules from 22 patients met the inclusion criteria across all participating centers. Patient demographics included 17 women and 5 men, with ages ranging from 17 to 57 years (mean age, 36.1 years; median age, 37.5 years). Nodule size ranged from 0.4 cm to 4.8 cm in maximum diameter. All nodules exhibited the characteristic discontinuous peripheral arrangement of punctate echogenic foci on high-resolution ultrasonography. Histopathological examination confirmed PTC in 100% of the sample (n = 23), including 16 classical variants, 1 "hobnail" subtype, and 3 cases of papillary carcinoma not otherwise specified. In this hypothesis-generating case series, DPEF was strongly associated with PTC. Further studies are needed to determine the sensitivity and specificity of this new sign. Recognition and reporting of this pattern, which was consistently observed in PTC, are important for raising awareness among thyroid radiologists and sonographers.

Sclerosing angiomatoid nodular transformation (SANT) is a benign non-neoplastic splenic lesion, well described in adults but rarely reported in children. Its clinical and imaging features in pediatric patients remain poorly characterized, and the optimal management-surgical versus non-operative-is uncertain, especially given the risks of splenectomy in children (e.g., overwhelming post&#x2011;splenectomy infection). This case series of four pediatric patients aims to describe the imaging-pathology correlation of SANT and generate a hypothesis regarding potential non-operative management in selected cases. Four male children (age range 36-156 months) presented with solid splenic masses and underwent partial splenectomy. All four had preoperative ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Postoperative pathology confirmed isolated splenic SANT in three patients; one patient had synchronous splenic SANT and a separate pancreatic calcifying fibrous tumor. Imaging features varied: the characteristic "spoke&#x2011;wheel" enhancement pattern was present in only two of four cases. MRI better delineated fibrous septa, hemosiderin deposition, and nodular boundaries than CT. All patients recovered uneventfully after surgery. Follow&#x2011;up ranged from 52 to 132 months, with no recurrence or metastasis. Pediatric splenic SANT should be considered in the differential diagnosis of a well-circumscribed solid splenic mass, even without the classic spoke-wheel sign. Because SANT is benign and splenectomy carries risks, a hypothesis-generating alternative is close observation after percutaneous core&#x2011;needle biopsy confirmation. However, this approach requires prospective validation; When imaging findings are atypical or malignancy cannot be excluded, surgical resection remains the definitive intervention, surgical resection remains the definitive intervention.