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FUSION: a web-based application for in-depth exploration of multi-omics data with brightfield histology
No full textSpatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, and skin in the Human BioMolecular Atlas Program. FUSION is cloud-based, open-source, and accessible at https://fusion.hubmapconsortium.org/ , hosting over 50 paired datasets and tutorials. In a series of use cases, we show its capacity to distinguish renal glomeruli injury states, quantify morphometric changes, and characterize fibrosis with immune infiltration
Decoding Secondary Motor Cortex Neuronal Activity During Cocaine Self-Administration: Insights From Longitudinal In Vivo Calcium Imaging
No full textBackground: We recently reported that cocaine relapse risk is linked to hyperexcitability in the secondary motor cortex (M2) after prolonged withdrawal following intravenous self-administration (IVSA). However, the neuronal mechanisms underlying drug-taking behaviors and the response of M2 neurons to contingent drug delivery remain poorly understood.
Methods: Mice received cocaine as reinforcement (reinforcers [RNFs]) following active lever presses (ALPs) but not inactive lever presses (ILPs). Using miniScopes for in vivo calcium imaging during cocaine IVSA, we tracked M2 neuronal activity with single-cell resolution. Then we analyzed Ca2+ transients in the M2 at the early versus late stages during the 1-hour daily sessions on day 1 and day 5.
Results: M2 neurons adapted to both operant behaviors and drug exposure history. Specifically, saline mice showed a reduction in both saline-taking behaviors and Ca2+ transient frequency with the 1-hour session. In contrast, cocaine mice maintained high ALP and RNF counts, with increased Ca2+ transient frequency and amplitude on day 1, persisting through day 5. Compared with saline control mice, cocaine mice exhibited a lower percentage of positively responsive neurons and a higher percentage of negatively responsive neurons before ALPs and after RNFs, a difference not seen before ILPs. Furthermore, as drug-taking behaviors progressed during the daily session, cocaine mice showed greater neuronal engagement with a larger population, particularly linked to ALPs and RNFs, with reduced overlap in neurons associated with ILPs.
Conclusions: The M2 undergoes dynamic neuronal adaptations during drug-taking behaviors, supporting its role as a potential substrate mediating the persistence of drug-seeking behaviors in cocaine relapse
The plot thickens: A pediatric cases series on collagenous gastritis
No full textObjective: Collagenous gastritis (CG) is a rare gastrointestinal disorder characterized by the deposition of collagen in the sub-epithelium of the gastric mucosa. CG can cause a variety of symptoms including iron deficiency anemia, abdominal pain, dyspepsia, vomiting, and weight loss. We present four cases of pediatric CG, and the first known reported case of identical twins with collagenous gastritis.
Methods: This is a retrospective chart review of four cases of CG.
Results: Four male patients all presented with anemia, three of which were initially diagnosed with eosinophilic gastritis. They were all eventually diagnosed with CG and most did not respond to medication management.
Conclusions: CG is a rare disorder that is difficult to diagnosis and manage
The protein degradation system encoded by hslUV (ClpYQ) is dispensable for the virulence of Haemophilus ducreyi in human volunteers
No full textHaemophilus ducreyi causes cutaneous ulcers in children who live in yaws-endemic countries and the genital ulcer disease chancroid. In the human host, H. ducreyi resides in an abscess and may need to resist both heat and oxidative stress, which result in aggregation and misfolding of bacterial proteins. In Escherichia coli, the hslUV (clpYQ) operon encodes a proteasome-like complex that degrades misfolded proteins and is upregulated during heat shock. In previous studies, we showed that hslUV transcripts are upregulated in experimental lesions caused by H. ducreyi in human volunteers, suggesting that HslUV may help H. ducreyi adapt to the abscess environment. Here, we constructed an unmarked hslUV operon deletion mutant, 35000HPΔhslUV, in H. ducreyi. Whole-genome sequencing showed that compared to its parent (35000HP), the mutant contained only the deletion of interest. Six volunteers were inoculated at three sites on skin overlying the deltoid on opposite arms with 35000HP and 35000HPΔhslUV. Within 24 h, papules formed at 88.9% (95% CI [69%, 100%]) at both parent and mutant-inoculated sites (P = 1.0). Pustules formed at 44.4% (95% CI [25.6%, 64.3%]) at parent-inoculated sites and 33.3% (95% CI [2.5%, 64.1%]) at mutant-inoculated sites (P = 0.17). Thus, the proteosome-like complex encoded by hslUV was dispensable for H. ducreyi virulence in humans. In the absence of hslUV, H. ducreyi likely utilizes other systems such as the Lon protease, ClpXP, and ClpB/DnaK to combat protein aggregation and misfolding, underscoring the importance of the functional redundancy of such systems in gram-negative pathogens
IMTRC 2025 Continues to Bridge the Research/Practice Gap in the Massage Therapy Field
No full textMunk, N. (2025, Fall). IMTRC 2025 Continues to Bridge the Research/Practice Gap in the Massage Therapy Field. Massage Therapy Journal (AMTA), issue 4, pp. 80-84
Decentralized Biobanking Pathway to Precision Medicine: Futures Study
No full textBackground: Biobank privacy policies remove identifiers from donated specimens, siloing patients, discounting multimodal data, and hindering precision medicine. Decentralized biobanking is a new paradigm that unlocks value by uniting patients, specimens, scientists, and physicians in a blockchain-backed platform with robust incentives, governance, and ethical oversight. Informed by a real-world pilot, this mixed methods futures study explores how we advance decentralized biobanking from theory to practice.
Objective: This study aimed to define the implementation strategy, synthesize pilot experiences into future vision, and highlight the implications and potential roadblocks.
Methods: We applied backcasting from 2021 to 2024 through ethnography, alignment exercises, surveys, interviews, site visits, and futures workshops to map biospecimen supply chains and define principles for decentralized biobanking, using a breast cancer biobank for prototyping and software development. A decentralized biobanking app was piloted to engage breast cancer biobank members in participatory visioning. Thematic analysis of pilot experiences revealed a technology-enabled future vision. We systematically analyzed the pilot event via a Futures Wheel, organizing participant quotes as first-order effects, indirect effects, and anticipated implications.
Results: Backcasting unveiled a pathway for designing an initial app for patients to track their biospecimens within institutional databases. We defined the "rails, rules, and tools" for a long-term, effective, and structurally just Biomediverse. Pilot enrollment was robust, and concurrent biobank enrollment was increased. Qualitative themes revealed impact on dignity, recognition, understanding, belonging, ownership, and empowerment. A vision for the future emerged from user journeys: "From 'Lab Rat' to Research Partner," vividly depicted as a path transitioning from sterile graveyard to flourishing community garden. Primary themes were matched to first-order effects, indirect effects, and future implications, culminating in gratitude and unity, network effects reinforced by reciprocity, as well as potential for compensation and precision medicine.
Conclusions: Reconnecting patients with their donated biospecimens via decentralized biobanking apps unlocks value for patients and aligns incentives across the Biomediverse. We illuminate the future person-centered biomedical data economy and put forward the goal of enabling all US biospecimen donors with decentralized biobanking by 2030
Accelerated model‐based T1, T2* and proton density mapping using a Bayesian approach with automatic hyperparameter estimation
No full textPurpose: To achieve automatic hyperparameter estimation for the model-based recovery of quantitative MR maps from undersampled data, we propose a Bayesian formulation that incorporates the signal model and sparse priors among multiple image contrasts.
Theory: We introduce a novel approximate message passing framework "AMP-PE" that enables the automatic and simultaneous recovery of hyperparameters and quantitative maps.
Methods: We employed the variable-flip-angle method to acquire multi-echo measurements using gradient echo sequence. We explored undersampling schemes to incorporate complementary sampling patterns across different flip angles and echo times. We further compared AMP-PE with conventional compressed sensing approaches such as the l1 norm minimization, PICS and other model-based approaches such as GraSP, MOBA.
Results: Compared to conventional compressed sensing approaches such as the l1 -norm minimization and PICS, AMP-PE achieved superior reconstruction performance with lower errors in T*2 mapping and comparable performance in T1 and proton density mappings. When compared to other model-based approaches including GraSP and MOBA, AMP-PE exhibited greater robustness and outperformed GraSP in reconstruction error. AMP-PE offers faster speed than MOBA. AMP-PE performed better than MOBA at higher sampling rates and worse than MOBA at a lower sampling rate. Notably, AMP-PE eliminates the need for hyperparameter tuning, which is a requisite for all the other approaches.
Conclusion: AMP-PE offers the benefits of model-based recovery with the additional key advantage of automatic hyperparameter estimation. It works adeptly in situations where ground-truth is difficult to obtain and in clinical environments where it is desirable to automatically adapt hyperparameters to individual protocol, scanner and patient
Inhibition of IFNAR-JAK signaling enhances tolerability and transgene expression of systemic non-viral DNA delivery
No full textLipid nanoparticles (LNPs) have demonstrated significant therapeutic value for non-viral delivery of mRNA and siRNA. While there is considerable interest in utilizing LNPs for delivering DNA (DNA-LNPs) to address a broad range of genetic disorders, acute inflammatory responses pose significant safety concerns and limit transgene expression below therapeutically relevant levels. However, the mechanisms and immune signaling pathways underlying DNA-LNP-triggered inflammatory responses are not well characterized. Through the use of gene-targeted mouse models, we have identified cGAS-STING and interferon-α/β receptor (IFNAR) pathways as major mediators of acute inflammation triggered by systemic delivery of DNA-LNPs. cGAS-STING activation induces expression of numerous JAK-STAT-activating cytokines, and we show that treatment of mice with the JAK inhibitors ruxolitinib or baricitinib significantly improves tolerability to systemically delivered DNA-LNPs. Furthermore, specific inhibition of IFNAR signaling enhances both DNA-LNP tolerability and transgene expression. Utilization of JAK inhibitors or IFNAR blockade represent promising strategies for enhancing the safety and efficacy of non-viral DNA delivery for gene therapy
Familial complete pachydermoperiostosis presenting with vertebral hypertrophy and myelopathy
No full textPachydermoperiostosis (PDP) is a rare, male-predominant (9:1) primary hypertrophic osteoarthropathy of the skin and bone, commonly called the acromegaly mimic. Clinical diagnosis of PDP is based on a triad of digital clubbing, pachydermia with coarse facial features, and radiographic evidence of long bone periostosis. It can manifest in a complete or incomplete form, with skin involvement distinguishing the complete subtype. The etiology of PDP remains uncertain, though it has been associated with pathogenic variants in genes involved in prostaglandin E2 metabolism genes (HPGD) in autosomal recessive primary hypertrophic osteoarthropathy-1 and SLCO2A1 in autosomal dominant primary hypertrophic osteoarthropathy. We present a 31-yr-old male with complete PDP with atypical clinical features of vertebral involvement, severe myelopathy and radiculopathy, mild digital clubbing, and frontal pachydermia. IGF-1 and HGH levels were normal despite the acromegalic features. Genetic testing did not identify variants in HPGD or SLCO2A1. The patient exhibited elevated bone-specific alkaline phosphatase levels and increased BMD, supporting the diagnosis of PDP. Iliac crest bone biopsies were technically difficult and contained only dense cortical bone. Dermatologic manifestations were managed with glycopyrrolate, dupilumab, and topical treatments. His bone disease was treated with intravenous bisphosphonates, yielding a marked decrease in bone-specific alkaline phosphatase levels. This case reveals the necessity of considering PDP in differential diagnoses for patients with atypical acromegalic features and highlights the potential for vertebral involvement in PDP, expanding the understanding of its clinical presentation