Neonatal antiphospholipid syndrome (APS) is an exceptionally rare but clinically significant thrombotic disorder associated with antiphospholipid antibodies (aPL) in the neonatal period. Two principal pathogenic mechanisms have been proposed: passive transplacental transfer of maternal antiphospholipid antibodies and de novo neonatal production of aPL. Although approximately 30% of neonates born to aPL-positive mothers exhibit detectable antibodies at birth, thrombotic complications remain exceedingly uncommon. A "second-hit" model involving additional prothrombotic triggers such as infection, perinatal stress, inherited thrombophilia, or vascular catheters likely contributes to thrombogenesis. Available evidence from case reports and small series indicates that arterial thrombosis predominates, particularly neonatal arterial ischemic stroke, while venous thrombosis is less frequent. Diagnosis remains challenging because no validated neonatal-specific classification criteria exist, and interpretation of laboratory findings is confounded by transient maternal antibody transfer. Current diagnostic approaches rely on clinical suspicion, thrombosis confirmation, maternal antibody testing, serial neonatal aPL measurements, and exclusion of other prothrombotic conditions. Management strategies are extrapolated from pediatric and adult APS guidelines, with low-molecular-weight heparin representing the mainstay of anticoagulant therapy in affected neonates. Neonatal APS remains a diagnostic challenge due to its rarity and atypical presentations. Establishing age-specific criteria and long-term neurodevelopmental follow-up is critical for improving clinical outcomes and understanding the prognosis of this early-onset autoimmune condition. This narrative review aims to summarize current evidence regarding the pathophysiology, clinical manifestations, diagnostic challenges, and management of APS-associated thrombosis regarding the distinct neonatal population.

Studies have shown promising results using bone graft as a carrier for local administration of antibiotics to reduce the risk of prosthetic joint infection (PJI). The objective of this clinical trial is to determine if tobramycin and vancomycin-impregnated bone graft is safe and effective in reducing the rate of PJI after total hip arthroplasty (THA).

Adequate protection of adjuvanted vaccines against accidental freezing is of utmost importance to prevent loss of potency of the Drug Product, and in turn ensure adequate efficacy and safety when injected into patients. In this lessons learned we present two cases, at large- and small-scale manufacturing level, where a loss of potency was observed for an adjuvanted vaccine. By successful application of a shake-test protocol this loss of potency was traced back to atypical transport conditions, leading to accidental freezing of multiple drug product syringes. Controlled experiments show a consistent trend indicating faster settling with an increasing numbers of freeze-thaw cycles. Additionally, we observe an apparent inversely proportional relationship between the freezing speed and the settling rate. The observations further suggest that severe freeze-thaw damage, by for example slow freezing and/or multiple freeze-thaw cycles, can lead to reduced turbidity of the drug product right after resuspension, providing a clear signature of severe freeze-thaw damage. Finally, we show that inspection of the sedimentation layer thickness may provide semi-quantitative information on the severity of freeze-thaw damage. The cases presented in this lessons learned support the effectiveness of a shake test in a manufacturing setting as an additional tool to understand and investigate potential freezing impact during root cause investigations.

Pycnodysostosis (PYCD) is a rare genetic bone disease characterized by impaired osteoclastic bone resorption. The inability to resorb bone leads to sclerosis, with increased bone mineral density (BMD) but paradoxically increased bone fragility. We report a case of a young female with PYCD with multiple fragility fractures including bilateral atypical femur fractures (AFF). Areal and volumetric bone density were supranormal, measured by dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), respectively. However, bone disorganization was prominent, observed on visual assessment of HR-pQCT images, with microfractures and sclerotic intramedullary lesions. ALIGNOGRAM1.0 is an artificial intelligence (AI) powered disorganization quantifier. It detected femoral lesions (including microfractures) on femoral radiographs up to two years prior to atypical femoral fractures at those sites. These microcracks were not visible on routine hip radiographs without the ALIGNOGRAM1.0 software. We postulate that disorganized bone, including microfractures, may be an underrecognized mechanism of bone fragility in patients with PYCD that could contribute to complications such as delayed fracture healing. Visual assessment via HR-pQCT may detect gross abnormalities but may miss subtle, subclinical changes - e.g., early sclerotic changes - that predate severe lesions and are not visible on routine HR-pQCT analysis. Quantitative tools such as ALIGNOGRAM1.0 may be particularly valuable in disorders characterized by paradoxical skeletal fragility despite normal or elevated bone density and apparently preserved microarchitecture. By quantifying bone disorganization on standard radiographs, these approaches may provide complementary information beyond conventional assessments of bone mass and structure. The paradox of severe fragility despite supranormal bone density has long remained unexplained. This diagnostic paradox is not unique to pycnodysostosis and is encountered across a range of genetic, metabolic, and treatment-related skeletal disorders in which fracture risk appears disproportionate to conventional measures of bone density or structure. Consequently, there is a need for complementary approaches capable of identifying abnormalities that are not captured by standard assessments. In genetic and metabolic bone disorders (e.g., pycnodysostosis or hypophosphatasia) that evade conventional assessments of bone health (e.g., DXA and HR-pQCT), we demonstrate how disorganization may act as a causative mechanism as an independent biomarker of fragility.

Galectin-3, a β-galactoside-binding lectin, is a driver and regulator of inflammation and fibrosis, and its levels are elevated in some heart and lung diseases. It also serves as a biomarker for the risk and severity of some forms of heart failure and, potentially, for various other pathological conditions. These observations make galectin-3 a promising potential therapeutic target. Both genetic and pharmacological inhibition of galectin-3 have been shown to ameliorate renal dysfunction and exert protective effects against liver fibrosis in animal models. Several galectin-3 inhibitors have been developed for therapeutic application in various pathological conditions. This review examines the progress of the development of 161 galectin-3 inhibitors, including monosaccharides, oligosaccharides, natural polysaccharides and their derivatives, carbohydrate polymers, antibody-drug conjugates, and non-carbohydrate compounds. Structure-activity relationships are emerging for these inhibitors, and the atypical binding pockets of galectin-3 have informed the development of a pharmacophore model that is expected to guide the design and discovery of potent, selective inhibitors for treatment of cancer, inflammation, and fibrosis.

Current clinical methods for detecting low-abundance PML::RARα fusion and drug-resistant single-base mutations face significant challenges, highlighting the urgent need for a rapid, sensitive, cost-effective genetic detection method for diagnosing acute promyelocytic leukemia. The CRISPR/Cas12a system has emerged as a revolutionary tool in nucleic acid detection. However, its applications are frequently constrained by the requirement for protospacer adjacent motifs (PAMs). In this study, we demonstrated that a moderate temperature increase enhanced CRISPR/Cas12a activity while allowing the use of atypical suboptimal PAMs. Utilizing a PCR-driven, suboptimal PAM-dependent CRISPR/Cas12a cascade, we sensitively detected the BCR1-type PML::RARα fusion with a detection limit of 0.1 aM. This method effectively identified low-abundance mutant cells in the presence of wild-type cells and demonstrated its efficacy in detecting minimal residual disease samples from patients with relapsed acute promyelocytic leukemia. Additionally, we developed a sensitive approach for detecting L217F single-base mutations using a cascade strategy of polymerase chain reaction, ligase chain reaction and CRISPR/Cas12a, achieving a detection limit of 10 aM in various wild-type DNA samples. Consequently, these methods hold considerable promise for the rapid diagnosis of acute promyelocytic leukemia, the sensitive detection of and the low-abundance drug-resistance nucleic acid mutations.

Online preconcentration in capillary electrophoresis (CE) is severely limited by the high ionic strength of biomatrices, which eliminates the conductivity gradient required for field-amplified stacking. pH-Mediated stacking overcomes this problem by injecting a strong acid plug to neutralize matrix anions, thereby restoring field amplification for efficient on-column enrichment. In this work, a pH-mediated stacking CE method was developed for the simultaneous determination of the atypical antipsychotics clozapine and amisulpride in plasma, achieving sensitivity enhancement factors of approximately 114-fold for clozapine and 220-fold for amisulpride over conventional capillary zone electrophoresis. Upon coupling with MS detection, the method was fully validated. Both analytes exhibited good linearity over 5 to 400 ng/mL (R² ≥ 0.9926), with LODs of 1 ng/mL and LOQs of 5 ng/mL. Intra- and inter-day precision (RSD) were below 10% for peak areas and below 1.34% for migration times, and accuracy (RE) was within ±10%. Analysis of patient plasma samples yielded relative differences of 0.9% (clozapine) and 2.8% (amisulpride) compared with UHPLC-MS/MS, confirming good agreement between the two methods. These results indicate that pH-mediated stacking CE-MS provides a practical alternative to UHPLC-MS/MS for therapeutic drug monitoring, with comparable sensitivity, minimal sample consumption, and requiring only liquid-liquid extraction without additional offline enrichment.

Embodied cognition assumes that language processing involves sensory, motor, and affective representations. However, further empirical research is required to reveal how embodied representations are used in language processing. This study investigated whether readers could represent the color of an object and whether the color was influenced by context. Thirty-five native English speakers performed a semantic Stroop task in which a sentence was presented (e.g., Joe was excited to see a bear in the woods/at the North Pole) to them. They were then presented with a word from the sentence (bear) in colored font. A series of linear mixed-effects modeling was performed to determine the reaction times under the following three-color conditions: typical (brown), atypical (white: polar bear), and an unrelated color (green). The results showed that regardless of the sentence (implying a typical brown bear or atypical white bear), typical colors received significantly faster reaction times than atypical and unrelated colors. These results were also observed when participants read context phrases (in the woods/at the North Pole) before the keywords. The findings thus suggest that readers represent typical colors of objects, regardless of context.

This case report highlights the diagnostic challenges associated with PHL and outlines corresponding diagnostic strategies, underscoring the importance of clinicians being vigilant for PHL in patients with HCC, particularly when clinical presentations and imaging features are atypical. Instead of making a decision based only on a positive ICG result, it is advised that clinicians thoroughly assess the features of the newly discovered lesions found through ICG imaging during the procedure, the patient's general condition, and the surgical risks before deciding whether to resect them. We conducted a retrospective analysis of a confirmed case of PHL complicated by HCC. indicates that even when HCC is suspected, the possibility of PHL should not be ruled out when diagnosing liver lesions; therefore, active screening is necessary. ICG imaging can serve as an adjunctive tool to improve the detection rate of lesions during surgery; however, its clinical value is limited for small-volume lesions that are not considered for surgical resection.

Liposarcomas of the spermatic cord are rare malignant soft-tissue tumors, representing a small fraction of adult sarcomas and an even smaller proportion of para-testicular neoplasms. These tumors often present as slow-growing, painless inguinoscrotal masses and may be mistaken for benign conditions such as inguinal hernias or lipomas. We present the case of a man in his mid-60s who presented with a progressively enlarging right hemi-scrotal mass. Imaging revealed a large fat-containing lesion involving both the spermatic cord and testicular parenchyma, suspicious for fat-containing hernia. The patient underwent right radical inguinal orchiectomy with high ligation of the cord. Histopathologic evaluation demonstrated a well-differentiated liposarcoma without lymphovascular or perineural invasion, with negative surgical margins and no evidence of dedifferentiation. The tumor measured approximately 18 cm in total, involving both cord and testicular tissue. The post-operative course was uneventful, and surveillance imaging has shown no recurrence to date. This case highlights the importance of maintaining a high index of suspicion for malignant etiologies in atypical scrotal masses, the role of radical orchiectomy with wide resection in management, and the necessity for long-term follow-up given the potential for late recurrence even in well-differentiated tumors.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition characterized by sterile platelet-fibrin vegetations on cardiac valves in the absence of systemic infection. The pathogenesis of marantic endocarditis is driven by endothelial dysfunction and a systemic hypercoagulable state. In contrast to infective endocarditis, vegetations in NBTE lack significant inflammatory infiltrates and do not yield positive blood cultures. NBTE typically comes to clinical attention via systemic embolic events, with cerebrovascular accidents serving as a clinical hallmark and constituting over 50% of cases. While NBTE is commonly associated with mucin-producing adenocarcinomas of the lung, pancreas, and gastrointestinal tract, its occurrence secondary to hematological malignancies or precursor plasma cell dyscrasias like monoclonal gammopathy of undetermined significance (MGUS) is exceedingly rare, particularly in young individuals. We report the case of a previously healthy 35-year-old woman who presented with acute-onset blurred vision. Neuroimaging via magnetic resonance imaging (MRI) revealed an acute left occipital infarct along with multiple chronic infarcts, raising a strong suspicion of a recurrent embolic process. A transesophageal echocardiogram (TEE) demonstrated two vegetations on the aortic valve with moderate transvalvular regurgitation; in the context of persistent negative blood cultures, these findings supported the diagnosis of NBTE. The patient was managed with systemic anticoagulation. A comprehensive hypercoagulable and autoimmune workup revealed an elevated lambda free light chain level with a decreased kappa/lambda ratio. Subsequent bone marrow biopsy and cytogenetic analysis established a diagnosis of MGUS featuring high-risk genomic aberrations, specifically an immunoglobulin heavy chain/musculoaponeurotic fibrosarcoma (IGH/MAF) rearrangement and the loss of chromosome 13 in a polyploid (3n, 4n) background, findings consistent with plasma cell neoplasia. The prevalence of MGUS in individuals under the age of 40 is exceptionally low, estimated at less than 0.3%. This case underscores NBTE as a critical finding that can unmask underlying, atypical plasma cell neoplasms. It highlights the necessity of an exhaustive diagnostic evaluation for occult hematological disorders and high-risk cytogenetic features in young patients presenting with multi-territory embolic strokes.