Search Results (251)

Background/Objectives: Pulmonary artery (PA) dilatation and slow-flow are imaging features of pulmonary hypertension (PH), but their quantitative assessment on routine cardiovascular magnetic resonance (CMR) remains limited. This study aimed to develop and evaluate an automated CMR pipeline for quantifying PA size-based and slow-flow metrics from routine white-blood (WB) and black-blood (BB) acquisitions. Methods: A total of 205 CMR acquisitions (106 WB and 99 BB) were used for model development and independent testing. Separate deep learning nnU-Net-based segmentation models were developed for WB and BB acquisitions using a two-stage cascaded framework. Automated measurements included PA volume and PA slow-flow. The trained models were subsequently applied to a larger cohort of 1471 patients using available WB and BB acquisitions to assess automated measurement extraction and agreement with clinical reports. Results: Automated PA volumetric measurements demonstrated excellent agreement with manual reference measurements for both the WB and BB models (ICC 0.94 and 0.93, respectively), with high segmentation accuracy (Dice 0.86 and 0.80, respectively). Automated slow-flow measurements also demonstrated excellent volumetric agreement (ICC 0.94), despite lower spatial overlap (Dice 0.61). Automated slow-flow classification demonstrated 83% agreement with qualitative clinical reporting (κ = 0.58). Conclusions: Automated PA volumetric quantification from routine CMR is feasible. Automated slow-flow quantification showed promising performance but requires validation across scanner vendors and BB acquisition protocols before broader clinical application. Full article

Background/Objectives: The frog skin peptide raniseptin-PL (GVFDTVKKIGKAVGKFALGVAKNYLNS.NH₂) is active against a range of antibiotic-resistant bacteria including ESKAPE⁺ pathogens, but its therapeutic potential is limited by high cytotoxicity against mammalian cells. The study aimed to determine the effects of selective amino acid substitutions by L- and D-lysine residues on the biological activity of the peptide. Methods: Conformational analysis of raniseptin-PL and its analogs was accomplished using circular dichroism spectroscopy. Antimicrobial activity was determined using reference strains and antibiotic-resistant strains of ESKAPE⁺ bacteria, and cytotoxicity against human neoplastic and non-neoplastic cells was evaluated. Results: Raniseptin-PL adopts an extended helical conformation in membrane-mimetic environments. Replacement of the Asp-4 residue by either L-Lys or D-Lys or the Leu-18 residue by L-Lys produced only modest changes in antimicrobial potency but high cytotoxicity against human-derived cells was retained. In contrast, substitution at Leu-18 by D-Lys attenuated potency against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis (MIC ≥ 50 µg.mL⁻¹), but high potency against the antibiotic-resistant Gram-negative ESKAPE⁺ pathogens Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli was either maintained or increased (MIC 3.1–12.5 µg.mL⁻¹; approx.1–4 µM). Importantly, [L18k]raniseptin-PL and [D4k,L18k]raniseptin-PL lacked cytotoxic activity against human-derived HaCaT keratinocytes, A549 non-small cell lung adenocarcinoma cells, PC-3 prostate cancer cells and erythrocytes at concentrations up to 100 µM. Conclusions: [L18k]raniseptin-PL and [D4k,L18k]raniseptin-PL show therapeutic potential as templates for development of a non-toxic antimicrobial agent for use against systemic infections by Gram-negative bacteria, particularly ESKAPE⁺ pathogens. Full article

Understanding how vaccination-event characteristics relate to doses administered can inform public health delivery strategies. This study examined associations between modifiable characteristics of community-based COVID-19 vaccination events and doses administered per event. We conducted a retrospective analysis of 631 vaccination events coordinated by the Louisville Metro Department of Public Health and Wellness (LMPHW) in Jefferson County, Kentucky, between March 2021 and May 2022. The outcome was the number of COVID-19 vaccine doses administered per event. Multivariable regression models assessed associations between event characteristics and doses administered per event. Across all events, 27,767 COVID-19 vaccine doses were administered. Each additional hour of event duration was associated with 21.6% more doses administered per event (95% CI: 14.0–29.8%). Weekend events were associated with 87.8% more doses administered per event than weekday events (95% CI: 45.7–142.0%). Compared with government-hosted events, 44.7% more doses were administered at non-profit organizations, 110.0% more at business organizations, and 57.8% more at medical service providers. LMPHW-only events were associated with 198.4% more doses administered per event than partnered events (95% CI: 120.1–304.6%). Principal findings were generally consistent across sensitivity analyses. These findings may help inform planning of future community vaccination and other immunization initiatives. Full article

Introduction: Osteoporosis is a debilitating bone disease that affects a large segment of the population. Currently, pharmacological treatment options for osteoporosis, including antiresorptive drugs and those that prevent bone loss, are limited. Multiple studies have shown that the endocannabinoid system and cannabis may play a significant role in bone remodeling. As both the use of cannabis and high-quality research on its effects continue to grow, novel medicinal uses of selected components, such as tetrahydrocannabinol (THC), are being investigated. The present study examined the potential effect of chronic THC inhalation during early adulthood on an ovariectomized rodent model of post-menopausal osteoporosis. Materials and Methods: Young (26-week-old) adult female rats received daily either THC or air inhalation for 8 weeks. The rats then underwent an ovariectomy (OVX) or sham surgery (Sx) when they were 34 weeks old. They were then euthanized 4 weeks post-OVX, and skeletal tissues were collected for analysis. Results: MicroCT analysis of femora showed that THC + OVX rats showed a significant decrease (45%) in trabecular bone volume compared to Air + Sham Sx rats. As expected, the Air + OVX rats also showed a 17% reduction in trabecular bone volume. Discussion: Overall, early adulthood THC exposure increased susceptibility to osteoporosis following ovariectomy-induced menopause. This suggests that THC exerts long-lasting effects on bone health, which may exacerbate post-menopausal bone loss. Full article

Background: Osteoporosis, a debilitating bone disease characterized by low bone mineral density, poses a large burden on the population. Current pharmacological treatment options are limited, with antiresorptive drugs being the current first-line option. Recent research has shown that the endocannabinoid system, modulated by endocannabinoids and phytocannabinoids, may influence bone remodeling. As the prevalence of cannabis use and research into its medicinal potential continues to increase, its therapeutic potential has emerged. Objective: To investigate the role of Δ9-tetrahydrocannabinol (THC) inhalation in treating osteoporosis in a rodent model. Methods: Adult female Sprague–Dawley rats underwent ovariectomy (OVX) to induce osteoporosis. Four weeks post-OVX, rats received either THC or Air treatment via inhalation for 8 weeks. A control group of age-matched rats received sham surgery. Rats were then euthanized at 38 weeks old, and hindlimb samples were collected for caliper, microCT, and biomechanical analyses. Results: OVX Air-treated rats showed significantly decreased trabecular bone volume, trabecular bone volume fraction, trabecular separation, trabecular tissue mineral density, trabecular number, and connective density compared to sham surgery controls. Compared with Air controls, OVX rats treated with THC showed increased endosteal volume (20%; p < 0.05). THC-treated rats also showed decreased trabecular bone mineral density (2%; p < 0.005) and trabecular thickness (14%; p < 0.05). Conclusions: Chronic inhaled THC worsened key aspects of trabecular bone microarchitecture. Results do not support use of THC vapor as a therapeutic agent for osteoporosis and suggest THC may adversely affect bone quality in estrogen-deficient states. Further research is needed to evaluate dose-dependent effects and to distinguish the skeletal impacts of different cannabinoid components. Full article

Background/Objectives: Germ cell tumors (GCTs) are thought to arise from primordial germ cells that fail to appropriately differentiate and instead retain pluripotency programs. PRDM14 is a key regulator of pluripotency and primordial germ cell specification and is aberrantly expressed in multiple GCT subtypes. However, the role of PRDM14 in GCT malignancy remains unclear. In this study, we investigated whether PRDM14 functions in GCTs through CBFA2T2, a transcriptional corepressor previously identified as a PRDM14-interacting partner in pluripotent stem cells and developmental models. Methods: To determine the presence and level of PRDM14 and CBFA2T2 in GCT, a panel of GCT lines were assessed for RNA and protein expression and interaction. Then, to better understand the biological effects of PRDM14 and CBFA2T2 within GCTs, PRDM14 and CBFA2T2 knockdowns were employed. Results: We show that PRDM14 and CBFA2T2 are expressed across GCT cell lines, colocalize predominantly in the nucleus, and cooperate as a complex in GCT cell lines. Knockdown of either PRDM14 or CBFA2T2 resulted in reduced expression of key pluripotency genes and a significant impairment of cell proliferation, indicating a shared role in maintaining an undifferentiated, proliferative state. Transcriptomic analysis following PRDM14 or CBFA2T2 depletion revealed extensive overlap in differentially expressed genes and convergent alterations in developmental and metabolic signaling pathways. Conclusions: Together, these findings suggest that PRDM14 and CBFA2T2 form a functional complex that sustains pluripotency and proliferation in GCT cells. This supports a model in which persistence of germline regulatory mechanisms contributes to GCT malignancy, highlighting this interaction as a novel component of GCT biology. Full article

We study semi-classical particle production in non-singular bouncing cosmologies by employing the Unruh–DeWitt model of a particle detector. Rather than approximating the scale factor in different regimes of energy domination, the scale factor for the bouncing cosmology is obtained numerically by solving a modified Friedmann–Lemaître equation obtained from the semi-classical limit of a loop quantum cosmology model. We examine how the detector response varies with the energy density at the bounce and the energy gap of the detector, and we also compare our exact numerical results with analytical approximations in the literature. Full article

Several factor analytic investigations question whether the 20-item Toronto Alexithymia Scale (TAS-20) discriminates alexithymia from general psychological distress, with some researchers concluding that the difficulty identifying feelings (DIF) subscale measures distress rather than alexithymia. This debate has focused almost exclusively on structural discriminant validity (i.e., factor analytic analyses) while neglecting predictive discriminant validity, or whether alexithymia predicts clinically relevant outcomes relatively independent of distress. The present study addressed this issue using hierarchical multiple regression in a community sample enriched with participants having psychiatric histories (N = 661). Emotion regulation was assessed across three domains: global emotion dysregulation (DERS), maladaptive and adaptive cognitive strategies (CERQ), and behavioral strategies (BERQ). After controlling for depression, anxiety, and stress (DASS-21), the TAS-20—entered as its three subscales (DIF, DDF, EOT)—retained statistically significant incremental prediction across all five emotion regulation outcomes. Increments were largest for global emotion dysregulation (ΔR² = 0.11) and behavioral regulation (ΔR² = 0.10 adaptive, 0.09 maladaptive), and smallest for cognitive regulation outcomes (ΔR² = 0.02 adaptive, 0.03 maladaptive); none reached the 0.15 heuristic for a clinically meaningful incremental validity, but all were statistically reliable and obtained against a deliberately conservative test in which alexithymia–distress overlap was partialed prior to entry. Among the subscales, difficulty describing feelings (DDF) and externally oriented thinking (EOT) emerged as the most consistent unique predictors across outcomes after distress control, whereas DIF showed greater attenuation. Notably, a domain-level dissociation emerged whereby alexithymia was the stronger unique predictor of behavioral regulation outcomes while distress showed comparatively greater unique prediction of cognitive strategies, suggesting the two constructs contribute to emotion regulation impairment through partially distinct pathways. These findings support the predictive discriminant validity of the TAS-20: the instrument captures incremental variance in emotion regulation that is statistically reliable across domains and theoretically coherent in its facet-level patterning, even as the construct shows some understandable overlap with concurrent psychological distress. Full article

Background: Patients with limited English proficiency (LEP) in the United States face significant barriers to safe and equitable healthcare despite federal protections guaranteeing access to qualified interpreter services at no cost. Many patients with LEP remain unaware of these rights, relying instead on informal learning through clinical encounters and community networks which are unreliable pathways that may perpetuate language access disparities. Point-of-care educational interventions grounded in just-in-time and situated learning theory represent a promising but understudied approach to bridging this gap. Objective: The aim was to examine Spanish-speaking emergency department patients’ interpreter access patterns, baseline knowledge of federal language rights, and immediate responses to a brief multilingual point-of-care educational video intervention. Methods: A pre–post survey design was used with a convenience sample of 40 Spanish-speaking adult patients presenting to a large, level 1 trauma center ED in the Southeastern United States between February and April 2025. Participants completed a 22-item iPad-administered Spanish-language survey that included baseline knowledge questions, an embedded 2 min educational video about federal language access rights, and post-video response questions. Descriptive statistics were calculated for quantitative data and thematic analysis was conducted for open-ended responses, with two independent coders achieving substantial inter-rater agreement (κ = 0.75, p < 0.001). Fisher’s exact tests examined associations between interpreter access mode and patient demographic characteristics. Results: Most participants (70%) accessed interpreters passively rather than by self-request, a pattern that did not vary significantly by patient status, age, or length of time in the United States. At baseline, 57.5% knew that federal laws prohibit language discrimination in healthcare and 77.5% knew they were entitled to a free qualified interpreter. Most participants (80%) reported learning something new from the video, with responses centering on rights awareness and anti-discrimination protections. Most participants (70%) reported that knowing their federal rights was helpful, describing increased confidence and reduced anxiety. All participants (100%) reported difficulty communicating without an interpreter and nearly all (97.5%) felt more confident asking questions when one was present. Conclusions: Significant knowledge gaps persist even among patients with some baseline rights awareness; a brief culturally appropriate point-of-care video may meaningfully increase awareness and confidence. The consistently passive pattern of interpreter access across all demographic subgroups underscores the need for proactive institutional practices and patient-facing education that empowers LEP patients to advocate for themselves in healthcare settings. Full article

Sickle cell disease is the most common monogenetic disease worldwide and affects millions of children and adults. While supportive care practices have improved life expectancy, particularly in high income countries, sickle cell disease typically has adverse impact on quality of life and reduced life expectancy. As a result, patients and providers are increasingly seeking information regarding curative and transformative therapies and advocating for improved global access. This review will describe allogeneic hematopoietic cell transplantation eligibility, approaches to transplant, short and long-term outcomes and key supportive care considerations for providers who care for patients with sickle cell disease. Full article

Collagen V is a minor fibrillar collagen that regulates type I collagen fibrillogenesis; however, its time-dependent role during the stages of adult tendon healing remains unclear. We investigated the stage-specific effects of inducible Col5a1 knockdown during tendon repair in a murine injury model. Collagen V expression was transiently suppressed during either the late inflammatory phase (tamoxifen-induced knockdown at 5 days post-injury; TM5) or early remodeling phase (tamoxifen-induced knockdown at 21 days post-injury; TM21), with outcomes assessed using gene expression, ultrastructural, and mechanical analyses. Early knockdown at 5 days post-injury, TM5, was associated with increased fibril diameter, greater fibril heterogeneity, and reduced structural mechanical properties, including decreased stiffness and maximum load. In contrast, delayed knockdown at 21 days post-injury, TM21, imposed after initial fibril organization, resulted in minimal changes in quasi-static mechanics but altered viscoelastic behavior and late-stage gene expression. An allele dose-dependent response was observed, with complete Col5a1 knockdown producing greater structural disorganization and mechanical deficits. Transcriptional changes suggested time-dependent effects on extracellular matrix regulation, including proteoglycans, remodeling enzymes, and tenogenic markers. Collectively, these findings indicate that collagen V may function as a time- and dose-sensitive contributor to tendon healing, with a critical role during early fibril organization. Disruption during this time window has lasting effects on tendon structure and mechanics, informing stage-specific therapeutic strategies for tendon repair. Full article

Background/Objectives: Alexithymia is a potential transdiagnostic risk factor for psychiatric and medical disorders involving affect dysregulation. But there is debate over whether a constricted imaginal capacity constitutes a core component of the construct or is a separable correlate. Our aim was to further explore this controversy as any revision to the construct has implications for clinical formulation, neurobiological models of associated default mode network dysfunction, and the coherence of the original psychiatric conceptualization. Methods: To replicate and extend previous factor analytic work, we conducted a two-stage exploratory factor analysis in a community sample that included individuals with a psychiatric history (N = 681). Using most of the subscale indicators employed in two prior factor analytic studies, we used a two-stage procedure: Stage 1 re-employed the general design of those studies. Stage 2 re-specified the analytic space by removing emotional reactivity and fantasizing-for-regulation variables that form their own separable latent dimensions. Results: Stage 1 yielded a conceptual replication of structural separation between alexithymia and imaginal processes. Stage 2 revealed meaningful cross-loadings obscured in the full set, most notably positive constructive daydreaming loading negatively on an externally oriented thinking factor, providing empirical support for the pensée opératoire construct. Additional cross-loadings linked dysphoric daydreaming and poor attentional control with negative emotion appraisal. Conclusions: The structural independence of alexithymia and imaginal processes is partly contingent on indicator set composition. Construct revision should be grounded not on two factor analytic studies using abbreviated self-report measures, but in convergent evidence across methods, including neuroimaging, electroencephalography, structured interview, performance-based assessment, and clinical observation. Full article

Regenerative medicine aims to restore the structure and function for improved tissue health; reduced tissue health can arise from causes such as aging, which results in the ongoing degradation of the extracellular matrix (ECM) of the skin. Replacement of a single biological component is not sufficient for an esthetic treatment to be described as regenerative; it is the relative amounts, ratios, types and organization of stimulated components that are important in a treatment’s regenerative potential. Regenerative aesthetics aims to recapture the youthful structure and function of tissue by exploiting the body’s own systems. Poly-L-lactic acid (PLLA-SCA; Sculptra^®), an injectable, biodegradable, non-permanent biostimulator, induces a combination of mechanotransductional/mechanical stimulation and foreign body reaction response and promotes ECM remodeling via the production of collagen through the upregulation of cytokines interleukin-1b and CXCL6, elastin, proteoglycans and multiadhesive glycoproteins. In addition, PLLA-SCA stimulates adipocyte rejuvenation/adipogenesis and increases the thickness of the dermis and adipose layers. Hence, PLLA-SCA stimulates endogenous pathways, and the array of biostimulatory effects should not be considered individually but as interlinked with the overall goal of improvement in skin health. These effects manifest clinically as long-term improvements in the mechanical properties of the skin, the restoration of volume and elasticity, improvements in skin quality and thickness, and dermal remodeling. Full article

Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs—including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)—emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks. Full article

Background: An emerging tool to better simulate the complexity of tumour biology in vitro is 3D culture models. Several approaches have been introduced, yet many face challenges such as technical complexity or limited ability to reproduce critical tumour traits. Modular tissue engineering is a well-known method in tissue transplantation, where it has been used to develop various healthy tissue constructs. In this study, we set out to adapt this established approach to fabricate cancer microtissues and to assess their effectiveness as a tumour model that can capture essential features of cancer biology and drug-treatment response. Methods: Two triple-negative breast cancer (TNBC) cell lines, HCC1806 and MDA-MB-231, were cultured in microtissues and assessed for viability, cell death, generation of hypoxia and response to chemotherapy. To benchmark our model, we utilized flow cytometry to analyze the CD44⁺/CD24⁻ cancer stem cell (CSC) phenotype across microtissues, 2D monolayers, and established 3D models, including spheroids, collagen domes, and laminin-rich domes. Results: The cells showed sustained cell viability with minimal cell death, along with natural development of tumour properties, such as hypoxia. Crucially, flow cytometry revealed a cell-line-dependent regulation of the CD44⁺/CD24⁻ phenotype, underscoring the complex influence of the 3D microenvironment on stem cell regulation. Furthermore, by screening the model with standard anti-breast cancer chemotherapeutics, we observed drug resistance at concentrations comparable to those used in the clinic. Conclusions: Our model offers the unique ability to spontaneously reproduce fundamental features of tumours in vitro, capturing the cellular heterogeneity and reprogramming that drive clinical drug resistance. Full article