Faculty Bibliography

BackgroundX-linked myotubular myopathy (XLMTM) and autosomal dominant centronuclear myopathy (ADCNM) are rare neuromuscular disorders characterized by severe weakness and respiratory impairment and have recently been the focus of therapeutic development. Robust baseline data are essential to understand disease trajectories and enable trial readiness. We present baseline clinical, functional, and biomarker findings from the terminated Unite-CNM trial (NCT04033159), a basket study of the antisense oligonucleotide DYN101, designed to modulate DNM2 expression in adolescents and adults with XLMTM or ADCNM.MethodsScreening and baseline evaluations included medical history, patient-reported outcomes, quantitative muscle strength and motor function, respiratory testing, muscle ultrasound and histology, and biomarker analyses (DNM2 protein, creatinine, creatine kinase, cystatin C, myostatin, and microRNAs) in plasma and muscle.ResultsTwenty-six patients were screened (15 DNM2, 11 MTM1); 14 entered the study. Patient-reported measures highlighted swallowing challenges and variable personal goals. Baseline respiratory impairment was variable in DNM2 and female MTM1 patients but consistently reduced in males with MTM1 (FVC% and FEV1% stable over follow-up to 78 weeks). MFM32 scores were similar across genotypes and sexes, while Myogrip strength was reduced versus age norms yet stable longitudinally. Muscle pathology was comparable across groups. Biomarker analyses showed altered DNM2 protein, reduced myostatin, and specific abnormalities in creatinine, creatine kinase, cystatin C, and microRNAs.ConclusionThis dataset provides valuable phenotypic, functional, and biomarker characterization of adult XLMTM and ADCNM, emphasizes the importance of baseline data for ultrarare disease trials, and highlights the need for protocol flexibility in response to safety signals and disruptions (e.g. COVID-19).

INTRODUCTION/UNASSIGNED:Although hypoxic interventions are increasingly explored as non-pharmacological modulators of stress-related pathology, their ability to benefit PTSD remains poorly understood. We compared behavioural and molecular outcomes of three hypoxic regimes - intermittent normobaric hypoxia (IHT), hypobaric hypoxia (Bar), and chemical hypoxia (CH) via cobalt chloride (CoCl₂) - in rats with PTSD induced by single prolonged stress (SPS). METHODS/UNASSIGNED:= 105; eight groups) received one of the three treatments after control or SPS conditioning. Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM), Open Field Test (OFT), and Dark-Light Box (DLB); HIF-1α, HIF-2α, HIF-3α, PACAP, and PAI-1 mRNA were quantified in the medial prefrontal cortex (mPFC) and hippocampus by real-time qPCR. RESULTS/UNASSIGNED:= 0.039); HIF-2α and HIF-3α showed a similar, non-significant upward trend (both ns after FDR correction, reflecting wide between-animal variability). Group means for all three HIF subunits converged toward the control range under all three interventions. HIF-3α responses to IHT or Bar were consistently blunted in PTSD animals across both regions, while PACAP was uniformly suppressed with stronger trauma-dependent attenuation under Bar. DISCUSSION/UNASSIGNED:As protein-level and canonical HIF target-gene readouts were not assessed, the reported transcript changes should be interpreted as a downstream feedback signature rather than a direct index of functional HIF activity. Hypoxic modality, not hypoxia per se, determines behavioural and molecular responses in PTSD; mild IHT uniquely normalised both in traumatised animals, supporting its development as a state-dependent non-pharmacological intervention for trauma-related conditions.

BACKGROUND AND STUDY AIMS/UNASSIGNED:Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is emerging as a minimally invasive alternative for benign gastric outlet obstruction (GOO). This study evaluated its safety, efficacy, and long-term outcomes. PATIENTS AND METHODS/UNASSIGNED:This international, multicenter retrospective study included 72 patients who underwent EUS-GE for benign GOO across 13 centers. Clinical success was defined as ability to tolerate solid food based on the GOO scoring system. Secondary outcomes included technical success and adverse events (AEs). RESULTS/UNASSIGNED:< 0.00001). Mean time to oral intake was 20.1 hours. AEs were mild,occurring in 6% intra-procedurally and 10% post-procedurally. Mean follow-up duration was 426.3 days. CONCLUSIONS/UNASSIGNED:EUS-GE demonstrates high technical and clinical success rates with a favorable safety profile for benign GOO, offering a promising alternative to traditional surgical approaches.

Environmental pollution, particularly water contamination, continues to be a critical global challenge, thereby necessitating the development of sustainable and high-efficiency catalytic systems for wastewater treatment. In this study, silver nanoparticles (AgNPs) were synthesized via a green chemistry approach and embedded on a biocomposite, cellulose-chitosan aerogel integrated with hydroxyapatite (HCCA) derived from Basa (Pangasius bocourti) fish bones. Notably, the synthesis route is straightforward, eco-friendly, and minimizes the use of hazardous chemicals. Durian shell (DS) extract was utilized as a natural reducing and stabilizing agent, while residual biomass was treated to obtain high-purity cellulose, highlighting the effective valorization of agricultural waste. The resulting HCCA aerogel biocomposite, fabricated through crosslinking and freeze-drying, exhibits high porosity (>97%) and ultralow density (about 0.03 g cm^-3), facilitating uniform dispersion and stabilization of AgNPs. The optimized 1.25Ag@HCCA sample achieved nearly complete conversion (about 99%) of p-nitrophenol (PNP) to p-aminophenol (PAP) within 15 minutes and retained approximately 98% efficiency after seven reuse cycles. Additionally, strong antibacterial activity against Escherichia coli and Salmonella paratyphi was observed. Overall, the Ag@HCCA sample demonstrates high potential as a multifunctional, sustainable material for wastewater treatment and waste valorization in circular economy applications.

Apicomplexan parasites, including Toxoplasma gondii and Plasmodium falciparum, reside within a specialized compartment known as the parasitophorous vacuole (PV) during their intracellular life cycle. The PV membrane (PVM), which derives from the host plasma membrane upon invasion, serves as a selective barrier that permits nutrient acquisition while shielding the parasite from host defense mechanisms. Although the protein composition of the PVM has been studied extensively, its lipid organization remains poorly understood. Using the quick-freeze, freeze-fracture replica labeling (QF-FRL) method, we quantitatively analyzed the transbilayer distribution of phosphatidylserine (PtdSer), phosphatidylethanolamine (PtdEtn), and GM3 ganglioside in the PVM of T. gondii and P. falciparum. Unlike host cell plasma membranes, where these lipids exhibit strict asymmetry-PtdSer and PtdEtn confined to the cytoplasmic leaflet and GM3 to the exoplasmic leaflet-we found that all three lipids were symmetrically distributed across both leaflets of the PVM. This striking loss of lipid asymmetry suggests that the PVM undergoes profound remodeling during infection. The presence of PtdSer and PtdEtn in the luminal leaflet may facilitate the binding of perforin-like proteins (PLP1s) during egress. These findings reveal a unique feature of the PVM that redefines our understanding of host-parasite membrane biology.

Stem diameter distributions underpin forest planning and inventory practice worldwide, yet permanent sample plot inventories are routinely truncated by merchantability limits and diameter caps. Truncated densities are the standard remedy, but those forms are seldom documented or supported in common software, so practitioners default to biased complete-form fits. We introduce a two-stage weighted least-squares workflow that retains the familiar complete-form implementation while recovering truncated-fit accuracy. Stage one estimates a scaling factor alongside the density parameters; stage two freezes that normaliser to deliver unbiased shape and scale estimates. Applied to fixed-area plots from Québec, Canada, the two-stage estimator tracks truncated Weibull and gamma fits across 32 species-group/cover-type combinations (root-mean-square error between one-stage truncated and two-stage complete fits:

To address the deterioration of expansive soil in seasonally frozen regions subjected to freeze-thaw cycles, this study investigated the effects of fiber modification by incorporating polypropylene fiber (PP) and lignin fiber (LF) on the swelling behavior, mechanical properties, and freeze-thaw durability of expansive soil. Using expansive soil as the base material, the modification effects of individual fiber incorporation were evaluated through free swell ratio, no-load swell ratio, and direct shear tests. Freeze-thaw cycle tests were then conducted on the composite fiber-modified soils, and the microscopic mechanism was analyzed in combination with SEM observations. The main conclusions are as follows: (1) For single-fiber modification, lignin fiber (LF) at a dosage of 1.2% exhibited the best overall performance, producing the greatest reduction in free swell ratio and the largest increase in shear strength. The incorporation of polypropylene fiber (PP) also significantly improved these parameters, although its effect was weaker than that of lignin fiber (LF). (2) Based on the results of single-fiber modification, the addition of 1.2% polypropylene fiber (PP) on the basis of 1.2% lignin fiber (LF) further improved the mechanical properties of expansive soil, under which the shear strength and unconfined compressive strength of the modified expansive soil were both enhanced. (3) In terms of freeze-thaw durability, the composite fiber-modified soil subjected to freeze-thaw cycles showed significantly lower attenuation rates of shear strength and unconfined compressive strength than the untreated specimens. SEM results showed that local overlapping and bridging structures formed between the fibers and soil particles, which helped delay crack propagation and weaken freeze-thaw damage. Through physical restraint and reinforcement effects, lignin fiber (LF) and polypropylene fiber (PP) jointly improved the mechanical performance and frost resistance of expansive soil, thereby providing an experimental reference for research on fiber modification of expansive soils in seasonally frozen regions.

With the rapid development in cell therapy and biopharmaceutical production in recent years, safe cryopreservation technologies are required to ensure product quality and safety. Dimethyl sulfoxide (DMSO), which is widely used as a conventional cryoprotectant, raises concerns owing to its cell permeability and consequent cytotoxicity. In this study, we focused on non-cell-permeable zwitterions that exhibit low cytotoxicity. We synthesised 21 zwitterions and systematically evaluated the relation between their molecular structures and cryoprotective effects. Elongation of the cationic side chain or spacer decreases the cryoprotective effects, which are associated with cytotoxicity and freezing of the unfrozen fraction. In contrast, ammonium/sulfonate-type zwitterions exhibited strong cryoprotective effects. This suggests their involvement in the modulation of membrane properties and the suppression of ice crystal formation. Notably, one of the synthesized ammonium/sulfonate-type zwitterions achieved cell recovery comparable with that of a commercial DMSO-containing cryoprotectant for human mesenchymal stem cells. This study deepens understanding of cryoprotective mechanisms based on the molecular design of zwitterions and provides guidelines for safe cellular cryoprotectants.

Tumor vaccines represent promising strategies for cancer immunotherapy. However, their application remains restricted in HER2-positive breast cancer due to poor immunogenicity and inefficient antigen presentation. Herein, a multitargeting HER2 nanoparticle vaccine, HER2_aHPF, is developed by co-displaying the HER2 extracellular domain and AE37 T-cell epitope on a Helicobacter pylori ferritin nanoparticle via SpyTag/SpyCatcher conjugation. The nanoparticle vaccine exhibits structural homogeneity, enhanced lymphatic drainage, and high stability during freeze-thaw cycles and long-term storage, with retained immunogenicity after repeated freeze-thaw treatment. WH peptide-mediated DC targeting, in combination with the ferritin scaffold, enhances antigen uptake and DC maturation. In BALB/c mice, CpG and fullerenol dual-adjuvanted HER2_aHPF elicits robust HER2-specific humoral and cellular immunity, characterized by high-titer antibodies, polyfunctional CD4⁺ and CD8⁺ T cells, and expanded effector-memory T cells. Prophylactic and therapeutic vaccination markedly inhibits primary tumor growth and lung metastasis in mouse and human HER2-positive 4T1 models. Mechanistically, HER2_aHPF reduces myeloid-derived suppressor cells and regulatory T cells, increases cytotoxic T-cell infiltration, and maintains a favorable in vivo safety profile. Combination with anti-PD-1 and anti-CD47 antibodies further enhances T-cell activity and tumor control, demonstrating strong synergy between active vaccination and dual immune checkpoint blockade. These findings establish HER2_aHPF as a versatile nanoparticle vaccine platform with clinical translation potential for HER2-positive cancer immunotherapy.

INTRODUCTION/UNASSIGNED:Autologous serum eye drops (ASEDs) are used to treat patients with dry eye syndrome. ASED is manufactured by fractionation of autologous whole blood of concerned patients and usually stored under home freezing conditions. METHODS/UNASSIGNED:We analyzed sterility, particle number, protein concentration, and stability of 14 growth factors in ASED for 148 days at -10°C. RESULTS/UNASSIGNED:Total protein concentration was constant showing no significant degradation as assessed by 1D-SDS-PAGE. Slightly increased concentrations of angiopoietin-2, vascular endothelial growth factor, platelet-derived growth factor, and hepatocyte growth factor were observed, while stem cell factor concentration showed only a modest decrease. CONCLUSION/UNASSIGNED:Our data support the feasibility to store ASED for patient use under usual home freezing conditions for up to 148 days.