S. aureus intestinal colonization elevates infection risk, underscoring decolonization as a key prevention target. SEB is a key target for the development of neutralizing antibodies against toxins to prevent and treat S. aureus infection. B. subtilis is used as a probiotic for human health. To investigate the efficacy of recombinant mSEB B. subtilis spores for reducing S. aureus intestinal colonization in mouse. Mice were orally immunized with recombinant mSEB spores three times a week for three weeks. After immunization, mice were challenged via oral gavage with 1 × 109 CFU of S. aureus (ATCC 14458). Fecal specific IgA and serum IgG1 and IgG2a were analyzed by ELISA. Peritoneal macrophages were isolated for qRT-PCR analysis of TNF-α, IL-6 and IL-1β mRNA expression. Colon contents samples underwent 16S rRNA sequencing for microbiota profiling. Intestinal RNA was extracted for transcriptome sequencing (RNA-seq), and differential pathways were analyzed using KEGG enrichment. Body weight and fecal viable S. aureus burden were monitored. Oral mSEB spores correlated with elevated systemic and mucosal SEB-specific IgG1, IgG2a and fecal sIgA (P < 0.01). After S. aureus challenge, peritoneal macrophages from mSEB mice showed lower pro-inflammatory TNF-α, IL-6 and IL-1β transcripts, consistent with attenuated systemic inflammation. mSEB immunization also altered gut microbiota and increased the relative abundance of Barnesiella. Intestinal RNA-seq identified enriched antigen presentation and B cell receptor signaling gene sets in the mSEB group. On day 3 post-challenge, fecal S. aureus loads were 24.20 ± 3.967 × 104 CFU (Control), 8.081 ± 3.614 × 104 CFU (CotC) and 3.6 ± 1.030 × 104 CFU (mSEB), showing a pathogen-clearing phenotype linked to mSEB treatment. Immunization with mSEB-displaying Bacillus subtilis spores correlates with SEB-specific mucosal and systemic antibody responses, blunted systemic inflammation, modified gut microbiota, and reduced intestinal S. aureus burdens post-challenge. The causal mechanisms underlying these changes remain to be clarified.
Severe hemorrhage remains a leading cause of preventable death in trauma and surgical settings, underscoring the ongoing need for topical hemostats that offer rapid coagulation, robust retention, and a favorable safety profile. Here we report a calcium-releasing silica-modified cellulose nanofiber (Ca-SCNF) aerogel fabricated via a Pickering emulsion-templated approach. In this design, carboxymethyl cellulose nanofibers function both as the scaffold-forming matrix and as the template for silica-based surface modification, with Ca2+ incorporated as a releasable pro-coagulant component. The resulting Ca-SCNF aerogel exhibits a lightweight, highly porous structure, with negligible hemolysis (<1%), minimal heat generation and limited particle detachment. When exposed to platelet-poor plasma, Ca-SCNF aerogel increases detectable Ca2+ availability and promotes plasma coagulation under direct material contact. In a rat femoral artery transection model, Ca-SCNF aerogel significantly reduces hemostasis time and blood loss relative to cotton and QuikClot Combat Gauze. These findings establish Ca-SCNF aerogel as a safe and effective hemostatic agent that outperforms natural inorganic mineral-based counterparts.
The efficacy and effectiveness of the human papillomavirus (HPV) vaccine in reducing the risk of invasive cervical cancer in females and head and neck cancer (HNC) in males have been demonstrated. However, the relationship between HPV vaccination in males and the subsequent risk of other potentially HPV-associated cancers are lacking. We used the TriNetX United States Collaborative Network to conduct a retrospective cohort study. Males aged 9 to 45 years who did or did not receive the HPV vaccine between 2006 and 2024 were included. We assessed the association between HPV vaccination and the risk of cancer, carcinoma in situ, and precancerous lesions at: penis, anus, head and neck cancer (HNC), lungs, esophagus, stomach, prostate, colorectum. Males with HPV vaccination (n = 397,856) have lower hazard ratio (HR) for HNC. Some other potentially HPV-associated cancers also have lower HR in HPV-vaccinated males, including lung cancer, prostate cancer, and colorectal cancer. Vaccinated males were less likely to develop some precancerous lesions of anus, head and neck, esophagus, and stomach. Among males ages 9 to 45, HPV vaccination significantly reduces the risk of certain cancers and precancerous lesions. Further studies are needed to evaluate the protective mechanisms of HPV vaccination against various cancers.
Accurate segmentation of head and neck organs-at-risk remains a critical challenge in radiation therapy planning, where current single-modality approaches often fail to address the inherent complexity of soft-tissue differentiation and interpatient anatomic variations. This study aims to develop a clinically robust auto-segmentation framework that synergistically integrates multimodal imaging features while optimizing computational efficiency. We present multimodality multimask and multitask auto-segmentation network (M3-Net), a triple-interlocked deep learning architecture featuring: (1) cross-modality fusion modules with attention-guided feature recalibration between computed tomography density maps and magnetic resonance imaging soft-tissue contrast; (2) a hierarchical multimask generator producing organ-specific, regional, and global masks through parallel encoding pathways; and (3) a dual-task learning mechanism combining segmentation with deformable image registration to establish voxel-level modality correspondence. The model was trained on 200 retrospective cases (160/20/20 split) with expert-reviewed contours from a tertiary cancer center, supplemented by 10 prospective cases for clinical validation. M3-Net demonstrated significant improvements across 3 key dimensions: Efficiency: reduced inference time by 63.6% (548 ± 23 seconds vs 198 ± 15 seconds; P < .001) through dynamic mask prioritization. These strategies improved the performance of M3-Net. Sixty percent of the organs achieved a Dice similarity coefficient >0.88. M3-Net performed best in 93.3% of all organs. It achieved the best average surface distance for all organs. For independent test cases, the speed and precision can meet clinical requirements. M3-Net establishes new state-of-the-art performance for head and neck organs-at-risk segmentation, by simultaneously addressing accuracy-efficiency tradeoffs and modality discordance. The clinically validated workflow reduces contouring time by 75% while maintaining dosimetrically significant precision, enabling rapid adoption in adaptive radiation therapy protocols.
Coronary artery embolism (CAE) is an underrecognized cause of myocardial infarction, particularly in patients with limited coronary atherosclerosis. Pulmonary vein thrombosis (PVT) as an embolic source of CAE has rarely been described. A 48-year-old woman with active cocaine use and Factor V Leiden mutation presented following out-of-hospital ventricular fibrillation cardiac arrest. Coronary angiography revealed thrombotic left circumflex artery occlusion without atherosclerosis. Computed tomography identified a nonocclusive left superior pulmonary vein thrombus as a possible embolic source. Drug-eluting stent implantation and apixaban were initiated; ticagrelor was de-escalated to clopidogrel given anticoagulation. Thrombus resolved at 12 weeks. Cocaine-provoked PVT causing CAE in inherited thrombophilia is a rare mechanism requiring embolic source evaluation and tailored management. In young patients with cryptogenic CAE, cocaine use with inherited thrombophilia should prompt PVT evaluation. When post-percutaneous coronary intervention antiplatelet therapy requires anticoagulation, P2Y12 de-escalation to clopidogrel reduces bleeding risk.
Complex congenital heart disease (CHD) is associated with reduced brain volumes, but little is known about the brain developmental trajectory in CHD beyond childhood, which is a critical period for brain maturation. This study reports alterations in brain volumes from a large cross-sectional dataset of patients with CHD and controls, with an age range from childhood to young adulthood. Patients and controls underwent 3 T cerebral MRI and overlapping cognitive assessments. Images were processed using Freesurfer 5.3. The dataset comprised 311 participants, 128 CHD and 183 controls aged between 9 and 32 years (male: 52.1%). Associations between the total brain and grey matter, white matter, and cerebrospinal fluid (CSF) volumes and age, sex, group (CHD vs. controls) and maternal education were analysed using linear mixed models. Global and total grey/white matter volumes were smaller in patients with CHD compared to controls (p < 0.001), whereas CSF volumes did not differ significantly between groups (p = 0.23). No significant interaction between the group, sex and age was found. Larger global brain volume was associated with higher maternal education (p < 0.001) and higher IQ (p < 0.001). Consistent lower brain volume in CHD than in controls throughout childhood and young adulthood suggests that there is no convergence towards healthy peers in CHD brain volumes over time. Functional correlates of smaller brain volumes underscore the importance of longitudinal studies in better understanding the evolution and determinants of impaired brain development in CHD populations.
This study aimed to identify personal, occupational, and health-related factors associated with lung function among farmers. A total of 102 farmers were recruited. Participants were assessed for personal characteristics (sex, age, height, weight, body mass index; BMI), occupational characteristics (pesticide use and duration of pesticide use), and health-related information, including exercise habits, underlying medical conditions, history of coronavirus disease 2019 (COVID-19) infection (timing and duration), and COVID-19 vaccination history. Lung function outcomes included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC ratio. For FVC (% predicted), increasing age was associated with lower FVC (B = -0.302, p = 0.033). For FEV1 (% predicted), female sex was associated with lower FEV1 compared with male sex (B = -6.167, p = 0.037), and a history of COVID-19 infection was associated with reduced FEV1 (B = -8.573, p = 0.002). For FEV1/FVC (% predicted), a history of COVID-19 infection was associated with a lower ratio (B = -7.320, p = 0.026). A history of COVID-19 infection is associated with reduced lung function, reflected in both lung volume (FVC) and airflow (FEV1), and it may also be related to a lower FEV1/FVC ratio. In addition, age and BMI were contributors to lower.
Reactive oxygen species (ROS) generated by NADPH oxidase 2 (NOX2) are essential for antimicrobial defense but also for the resolution of inflammation. NOX2 deficiency, as observed in chronic granulomatous disease (CGD), predisposes to persistent sterile inflammation. Current therapeutic strategies largely rely on nonspecific immunosuppression or require residual NOX2 activity, while systemic ROS-inducing therapies are limited by toxicity. Here, we present a NOX2-independent approach to restore inflammation-resolving ROS signaling using N-alkylaminoferrocene-based prodrugs (pro-NAAFs), which amplify pre-existing ROS rather than generating ROS indiscriminately. Among several candidates, prodrug 1 emerged as the most potent and well-tolerated ROS amplifier. In human neutrophils, prodrug 1 induced strong ROS production and neutrophil extracellular trap (NET) formation. These responses occurred independently of NOX2 and were maintained in CGD-derived neutrophils. Similar NOX2-independent ROS induction and NET formation were observed in immune cells from wild-type and NOX2-dysfunctional Ncf1∗∗ mice. Prodrug 1-induced NETs aggregated into high-density structures (aggNETs) capable of degrading pro-inflammatory mediators in vitro. Prodrug 1 also inhibited neutrophil inflammasome activation. In vivo, subcutaneous administration of prodrug 1 reduced inflammatory mediator levels in air pouches, promoted resolution of chronic arthritis in Ncf1∗∗ mice, and protected from bone destruction. Transcriptomic analyses indicated early suppression of inflammatory pathways and restoration of neutrophil maturation trajectories towards a wild-type-like state. While prodrug 1 increased protein oxidation markers, it shifted systemic oxysterol profiles towards an inflammation-resolving phenotype. These findings identify pro-NAAFs as NOX2-independent ROS amplifiers capable of restoring inflammatory resolution and highlight their therapeutic potential for chronic inflammatory conditions linked to NOX2-dysfunction.
Leptospirosis is a global zoonotic disease caused by pathogenic Leptospira species, predominantly Leptospira interrogans. Transmission to humans typically occurs via mucosal or percutaneous exposure to water contaminated by the urine of reservoir hosts, such as rodents and livestock. We report a case of a 67-year-old male admitted with a 2-day history of fever and a 1-day history of altered mental status, complicated by jaundice and hepatorenal failure. A definitive diagnosis of leptospirosis (icterohemorrhagic phenotype) was established by correlating the patient's clinical manifestations and history of occupational exposure in rice paddies with the detection of Leptospira species via cerebrospinal fluid (CSF) targeted next-generation sequencing (tNGS).After treatment with meropenem, corticosteroids to prevent the Jarisch-Herxheimer reaction, and therapy to protect the liver and reduce jaundice, the patient's organ function and mental status improved.This case suggests that for febrile patients with epidemiological exposure, neurological symptoms, and multi-organ involvement, early use of CSF tNGS can improve the diagnosis of leptospirosis, providing a critical basis for early and precise treatment.
This systematic review and meta-analysis aimed to characterize etiological patterns of uveitis in individuals aged 60 years or older. Following the PRISMA 2020 and MOOSE reporting guidelines, we searched PubMed/MEDLINE, Scopus, PubMed Central (PMC), and Web of Science (January 1, 2005-January 1, 2025). Data extraction focused on study characteristics, sample size, uveitis location, and reported causes. Random-effects models were used to pool proportions across studies, heterogeneity assessed by the I2 statistic. Methodological quality was evaluated via the Newcastle-Ottawa Scale for cohort studies and the JBI Critical Appraisal Checklist for cross-sectional studies. Out of 10,829 retrieved citations, 16 studies met the inclusion criteria. Idiopathic uveitis constituted the largest proportion, with a pooled proportion of 41.45% (95% CI 30.63-53.16%). Infectious etiologies included herpetic uveitis (pooled proportion 11.40%, 95% CI 7.45-17.04%), cytomegalovirus (3.09%, 95% CI 1.01-9.06%) and tuberculosis (5.10%, 95% CI 2.58-9.83%). Non-infectious causes, such as sarcoidosis (5.21%, 95% CI 2.78-9.55%) and HLA-B27-associated uveitis (6.05%, 95% CI 3.35-10.71%), also contributed substantially. High heterogeneity (I2 > 75%) was noted across most etiologies, likely reflecting variable study populations, diagnostic criteria, and geographic factors. Our meta-analysis underscores the diverse etiological landscape of uveitis in the elderly, with over 40% of cases remaining idiopathic. High heterogeneity highlights regional variations and diagnostic challenges. Standardized evaluation protocols and improved access to advanced investigations may help reduce the burden of undiagnosed cases. Within Asia, the only continent contributing multiple studies, subgroup analysis reduced heterogeneity for some etiologies, suggesting that regional factors contribute to the observed variability.
Rare breast cancers represent a clinically important but underrepresented group of malignancies. In this Perspective, rare breast cancers are considered within the broader rare cancer definition of an annual incidence below 6 cases per 100,000 persons, while also recognizing breast-specific rarity based on uncommon histology, molecular hallmarks, clinical presentation or sex-specific occurrence. These conditions are characterized by limited case numbers, biological heterogeneity, reduced clinical trial inclusion and fragmented evidence. These constraints challenge artificial intelligence (AI) development because many systems depend on large, balanced and externally validated datasets. AI may support diagnosis, histopathology, molecular interpretation, prognostic stratification and precision oncology decision support, but its use in rare breast cancers requires evidence standards adapted to small cohorts. This Perspective proposes an evidence-informed clinical governance framework organized around five domains: intended clinical use, small-cohort validation, synthetic data governance, human oversight and lifecycle monitoring. Its distinctive contribution is to translate general AI reporting and governance principles into rare breast cancer-specific safeguards, including objective data-quality checks, leakage prevention, uncertainty-aware validation, synthetic data plausibility scoring, pan-rare model reporting, patient involvement and post-deployment surveillance. Synthetic data may support development and simulation, but should not replace validation on real clinical cases. By linking small-cohort methodology with clinical oversight, regulatory alignment and lifecycle monitoring, the framework offers a practical roadmap for safe AI-enabled rare breast cancer precision oncology. Rare breast cancers are difficult to study because they occur infrequently and are often missing from large clinical datasets. This creates problems for artificial intelligence because AI usually needs large and diverse data to work reliably. Synthetic data may help with training and simulation, but it can also create misleading results if it is not carefully reviewed and separated from validation data. This article proposes a stepwise governance approach for using AI safely in rare breast cancers, with emphasis on clear clinical purpose, careful validation in small cohorts, responsible synthetic data use, expert human oversight and continuous monitoring after implementation.
Cognitive biases are implicated in the maintenance of obsessive-compulsive disorder (OCD), yet findings from reaction-time paradigms remain mixed. Eye-tracking offers a direct window into these attentional processes. We examined symptom-specific attentional patterns in university students selected for high vs. low contamination fear (HCF n = 10, LCF n = 10) and high vs. low checking (HC n = 10, LC n = 10) from a screened sample (N = 774). Participants viewed symptom-matched (disgust or checking) and general threat pairs against neutral images. Attentional bias was indexed as vigilance (first fixation and latency), disengagement (first-fixation duration), and maintenance (fixation count and total duration). Results indicated that attentional biases were primarily evident during the maintenance stage rather than early orienting. For the contamination dimension, significant interaction emerged for maintenance. Specifically, HCF participants demonstrated significantly reduced gaze maintenance for disgust images compared to threat and neutral images, consistent with a vigilance-avoidance pattern suggestive of attentional avoidance. For the checking dimension, while significant main effects for image type indicated rapid orienting to checking cues and sustained viewing of checking and threat-related images across all participants, these effects were not significantly moderated by symptom group. Findings indicate that attentional bias in OCD is heterogeneous and partially distinct across symptom subtypes. These results underscore the value of symptom-matched stimuli and gaze metrics, support cognitive bias modification to symptom dimensions, and highlight eye-tracking as a useful tool for parsing vigilance, disengagement, and maintenance. Limitations, clinical implications, and future directions are discussed.
Preventive tests and procedures (PTPs) help to reduce disease burden. However, patient expectations often differ from current guidelines, resulting in overuse or underuse of PTPs. Shared decision making can bridge this gap but requires clear, evidence-based information. This study aimed to develop and conduct an initial evaluation of prototype fact sheets designed to support informed decisions about PTPs. We selected 11 PTPs based on their potential for over- or underuse. For each, we developed a fact sheet following guideline recommendations. These summarised key benefits, risks and relevance using verbal, numerical and graphical formats. User experience and comprehensibility were assessed through a survey among a university population. Participants rated comprehensibility, content and design on a 5-point scale. Approval was defined as the proportion of 'very good' or 'rather good' ratings. Participants giving poor ratings were invited to provide free-text comments. Subgroup analyses were performed by age and educational level. A total of 2,082 individuals answered all relevant questions to fact sheets. The median fact sheet approval score was 77% (interquartile range: 55%, 91%). Six of the 11 fact sheets received an approval of greater than 80% for comprehensibility in general. Lower approval was reported for risk descriptions, usefulness in doctor-patient conversations and visuals. Cancer screening sheets scored the lowest. Subgroup analyses showed lower approval in younger age groups and among individuals with higher levels of education. Initial user testing of the fact sheets showed generally positive ratings regarding comprehensibility and user experience. However, the presentation of specific risks and the use of visuals needed to be adapted, especially for cancer-related topics. The findings highlighted the importance of tailoring informational materials to effectively support shared decision making.
Mineral carbonation of industrial by-products is a promising strategy for carbon capture and storage, contributing to carbon emission reduction in the construction industry. Previous studies have mainly focused on carbonation under high CO2 concentration above 99% to maximize carbon storage, whereas efficient carbonation under low CO2 concentration is more meaningful for practical engineering applications. In this study, high-moisture concrete slurry waste (CSW) was carbonated by wet-grinding carbonation under 25% CO2 concentration. The changes in CSW properties were characterized by pH, conductivity, XRD, TG, and SEM-EDS. Moreover, carbonated CSW with different carbonation degrees was incorporated into foam concrete to evaluate its effects on compressive strength, hydration behavior, hydration products, and microstructure. The results showed that the CO2 uptake and carbonation degree reached 21.0% and 57.2%, respectively, after 60 min of carbonation. Incorporating 10% and 20% CSW carbonated for 15 min significantly accelerated early hydration kinetics, and the 1-day compressive strength increased by more than two times compared with samples containing uncarbonated CSW. This enhancement was attributed to the heterogeneous nucleation effect of ultrafine CaCO3 and the pozzolanic reactivity of silica gel, although later-age strength decreased. In contrast, deeper carbonation reduced CSW reactivity and weakened foam concrete strength. Furthermore, carbonated CSW reduced CO2 emissions by 32.5%, demonstrating its environmental benefits and potential for sustainable foam concrete production.
Disruption of intestinal barrier integrity contributes to inflammation, infection, and chronic disease. Tormentil rhizome ethanolic extract (TR-EtOH), traditionally used in functional alcoholic beverages, is rich in polyphenols that undergo extensive gut microbiota metabolism. This study evaluated the phytochemical composition, total phenolic content, antioxidant activity, and barrier-protective effects of TR-EtOH and its gut-derived metabolites (TREMs). Microbiota metabolism markedly reduced phenolic content and antioxidant activity, consistent with the degradation of polymeric tannins. Biological activity was investigated in a Clostridioides difficile toxin-induced Caco-2 model using TEER, qPCR, Western blot, and cytokine secretion assays. TR-EtOH preserved epithelial integrity and reduced inflammatory responses, whereas TREMs showed donor-dependent effects on barrier stabilization and cytokine modulation. These findings indicate that native tormentil polyphenols and microbiota-derived metabolites may protect the intestinal barrier through complementary mechanisms, supporting their potential use in functional food and beverage development.
As drought impacts on forests intensify, evaluating the potential for adaptation is critical for predicting forest responses and the impacts of management strategies. We assessed phenotypic and genomic variation in western larch (Larix occidentalis Nutt.) populations to evaluate the potential for drought adaptation across its range. First, we established a seedling common garden experiment outside the natural range with 52 populations subjected to two drought treatments. Second, we analyzed pooled targeted exome-sequence capture data from 44 populations of an adult provenance trial to evaluate the relative ability of climate, geography, and neutral genetic structure to predict landscape genomic variation. We found that population differentiation for drought resistance was low. Drought reduced population differentiation for growth and bud set, and weakened clinal associations for growth. We found no antagonistic correlations between drought resistance and growth or phenology, indicating that trade-offs are unlikely to constrain adaptation. Further, landscape genomic variation was primarily explained by neutral genetic structure, with little additional variation explained by climate or geography. Together, these findings demonstrate weak local adaptation to drought and reduced genetic variation in traits under drought indicate that natural populations of western larch may have limited potential to adapt to future drought conditions.
Medical education is globally recognized as a high-stress environment, yet localized data regarding final-year students in Northern Sudan remain scarce. This study investigated the prevalence, independent predictors, and coping mechanisms of stress among final-year medical students at the University of Dongola. A descriptive, cross-sectional study was conducted in (2025) at the University of Dongola, Sudan. The study population comprised 120 final-year medical students. A total of 100 students completed the questionnaire, representing a response rate of 83.3%. Perceived stress was quantified using the Perceived Stress Scale (PSS-10), while a structured 22-item checklist was utilized to identify specific academic/non-academic stressors and coping behaviors. The questionnaire was administered in English to align with the medium of instruction. Data were analyzed using Chi-square tests (X2) and Binary Logistic Regression to identify independent predictors of stress (aOR; 95% CI). A total of 100 students participated (83.3% response rate). The findings revealed that 77% of respondents experienced moderate-to-high stress levels (67% moderate; 10% high), with a mean PSS score of 18.17 ± 6.56. Exam pressure (73%) and academic workload (61%) were the dominant stressors. Multivariable analysis confirmed that exam pressure (aOR = 4.82, 95% CI:} 1.95-11.84, p < 0.001) and academic workload (aOR = 2.54, 95% CI:} 1.12-5.76, p = 0.026) were the primary independent predictors of stress. Regarding coping, prayer (67%) and social interaction (46%) were the most utilized strategies. Notably, physical exercise (aOR = 0.28, p = 0.008) and social support (aOR = 0.35, p = 0.024) were independently associated with a significantly reduced likelihood of high stress. A significant majority of final-year students at the University of Dongola operate under high levels of psychological distress, primarily driven by structural curriculum demands. While religious and social buffers are utilized, the high prevalence of stress suggests that students have surpassed the optimal "eustress" threshold. Institutional interventions, including examination reform and the establishment of formal counseling services, are urgently required to safeguard student well-being and clinical competence.
Disruptions of the superior shoulder suspensory complex (SSSC) represent an uncommon and heterogeneous spectrum of shoulder girdle injuries. Because the available literature is largely limited to case reports, small case series, and technical descriptions, management decisions remain challenging, particularly for double, triple, and quadruple disruption patterns. A clinically oriented synthesis is needed to translate fragmented evidence into practical diagnostic and treatment guidance. The purpose of this narrative review was to synthesize the available literature on SSSC disruptions into a practical diagnostic and treatment framework, supplemented by institutional illustrative cases. Emphasis was placed on injury pattern recognition, stepwise imaging assessment, instability markers, operative decision-making, and patient-specific modifiers, including age, bone quality, comorbidities, and functional demand. A narrative review of the literature was performed, including original articles, case reports, case series, technical notes, review articles, and book chapters addressing single, double, triple, and quadruple SSSC disruptions. Evidence was synthesized according to clinically relevant domains, including mechanism of injury, number of disrupted sites, radiographic and computed tomography (CT) findings, instability markers, operative versus nonoperative indications, fixation principles, and reported outcomes. Institutional cases were included as illustrative examples of the proposed framework rather than as a comparative outcome cohort. Single SSSC disruptions generally preserve ring stability and are commonly suitable for nonoperative management, unless substantial displacement, intra-articular extension, glenoid or scapular neck involvement, or mechanical compromise is present. Double disruptions require careful assessment of ring instability; fixation of one or more dominant unstable components should be considered when there is significant displacement, reduced glenopolar alignment, medial or lateral translation, angulation, persistent acromioclavicular/coracoclavicular instability, or functional instability. Triple and quadruple disruptions are rare and traditionally associated with high-energy trauma and concomitant injuries; however, complex disruption patterns may also occur after low-energy trauma in elderly or osteoporotic patients. CT, particularly with multiplanar and 3-dimensional reconstruction, is central for defining bony injury patterns, instability markers, and surgical planning, whereas magnetic resonance imaging has a selective role in suspected ligamentous injury, occult fracture, or associated soft tissue pathology. SSSC disruptions should be approached as ring injuries rather than as isolated fractures or ligamentous lesions. The practical contribution of this review is a structured diagnostic and treatment algorithm that integrates disruption number, radiographic and CT-based instability markers, selective magnetic resonance imaging, patient physiology, bone quality, functional demand, and selective restoration of stability. This framework may help clinicians avoid missed instability, delayed diagnosis, and undertreatment of complex shoulder girdle injuries.
The development of local circular feed systems has increased interest in protein hydrolysates (PHs) derived from processed animal proteins (PAPs), which can upcycle protein-rich streams into functional aquafeed ingredients. This study evaluated novel PHs sourced from insect meal (Hermetia illucens), fish by-products and swine by-products as replacements for a high-quality fish PH (CPSP90) in diets for gilthead seabream (Sparus aurata). A control diet, containing 20% fish meal, 22% plant proteins, 23% PAPs and 3% CPSP90, was compared with three experimental diets in which CPSP90 was replaced by 3% of each alternative PH, resulting in the INSECT, FISH and SWINE diets. Seabream juveniles (11 g) were reared in triplicate tanks and fed the experimental diets three times per day over 88 days. A parallel digestibility trial was also conducted. All diets were well accepted across treatments (voluntary feed intake [VFI] = 1.7-1.8 g 100 g-1 average body weight day-1). Nutrient digestibility, fish final body weight (FBW; 60-65 g), feed conversion ratio (FCR; 1.1-1.2) and anterior intestine histomorphology remained similar across treatments. Fish fed the SWINE diet showed upregulation of mrf4, mlc2a and mlc2b, suggesting modulation of myogenic differentiation and muscle structural pathways, although this was not reflected in improved growth. Fish fed the INSECT diet showed reduced faecal lipid losses, together with downregulation of capn3, which may reflect metabolic adjustments related to lipid utilisation. Fish fed the FISH diet exhibited muscle gene expression patterns and growth performance similar to those of the control group. Alternative PHs showed potential to replace CPSP90 in gilthead seabream diets, supporting circular aquafeed formulations while sustaining feed efficiency and fish growth.
Multiple groups have reported on the impact of hydrogel stiffness on vascular network formation in vitro, with overall findings indicating that hydrogels with lower stiffness better support vasculogenesis. However, most of this research utilizes hydrogels with static stiffness, even though vasculogenesis occurs in tandem with changes in extracellular matrix stiffness. To that end, we hypothesized that dynamic modulation of hydrogel stiffness during vasculogenesis would improve vascular network formation. Using a Collagen I/Norbornene-modified hyaluronic acid hydrogel system, we diffused additional crosslinker and photoinitiator into the hydrogel and initiated further UV crosslinking at predetermined time points, while maintaining high cell viability (>90%). We observed that in situ stiffening at early time points, prior to the completion of cell elongation, increased vascular network connectivity and volume fraction relative to unstiffened controls, while stiffening at later time points was associated with reduced network formation. Consistent with these findings, cell-laden hydrogels stiffened at early time points implanted subcutaneously in nude mice showed increased blood perfusion, while late-stiffened hydrogels did not improve perfusion relative to controls. Mechanistically, we found that these time-dependent differences were associated with changes in vinculin volume fraction, suggesting differential mechanotransductive signaling. Consistent with this, Rho kinase inhibition suppressed vinculin volume fraction in stiffened hydrogels and partially rescued vascular network formation following in situ stiffening. These findings indicate that the timing of stiffness modulation is a critical factor in determining vasculogenic outcome, and that early-stage stiffening can enhance vascular network formation beyond what is achieved in static hydrogel systems.