Agarose gels are frequently utilized to simulate tissue. This study aimed to find an appropriate agarose concentration that matches the mechanical characteristics of pig kidney at the micro length scale and compare these to macro-scale properties. For all agarose samples and porcine kidneys, the shear storage modulus and loss modulus were measured at the micro-length scale using nanoindentation measurements with a 100μm diameter probe, for frequencies from 10Hz to 110Hz. Measurements at the macro-length scale were carried out with a rheometer from 0.1Hz to a maximum of 9.5Hz at a shear strain amplitude of 0.1% and fit to a fractional derivative mechanical model. The storage modulus at the micro-length scale was higher by factor of 1.2-70 than the storage modulus at macro-length scale in kidney samples and agarose (depending on agarose concentration), which was linked to gel and tissue microstructure. An agarose concentration of 1.2% best fitted the kidney tissue properties at microscale.

Abstract Introduction Machine learning (ML) models are increasingly being developed to predict outcomes in patients undergoing kidney transplantation. Little attention has been paid to assessing their performance across diverse patient subgroups, with risk of bias in predictive performance in subgroups of patients with protected characteristics. This study aimed to evaluate and address potential underperformance of a graft and patient survival prediction model in clinically relevant patient subgroups. Methods We assessed the predictive accuracy of a DeepHit survival analysis model, trained on over 25 years of transplant outcome data. The model's performance was evaluated across subgroups defined by patient ethnicity, sex, age, and pre-transplant sensitization status. To mitigate identified performance disparities, we applied several strategies to re-balance the model's training process to ensure all patient populations were adequately considered. Results Analysis revealed that the model's performance for graft survival was consistent across all investigated subgroups. However, a significant disparity was observed in patient survival predictions. The model demonstrated notably worse predictive accuracy for Black patients and patients over 70 years old, indicating a clear underperformance in these specific populations. Using bias mitigation strategies, we were able to partially close this performance gap. Conclusions This study highlights the critical importance of evaluating ML models for subgroup-specific underperformance in a clinical context. Our findings underscore that while overall model performance may appear strong, it can mask significant disparities. The application of mitigation strategies is essential for developing equitable and reliable decision support tools to ensure fair outcomes for all patients.

Musculoskeletal (MSK) injuries pose a significant health burden across sub-Saharan Africa (SSA). Despite this, regional research output is limited, constrained by insufficient infrastructure, limited funding, and underdeveloped research capacity. This bibliometric analysis examined research outputs and collaboration patterns in MSK injury research across three SSA countries, representing a spectrum of income levels: low, lower-middle, and upper-middle income. MSK injury research articles from Malawi (MLW), South Africa (SA), and Tanzania (TZN), published between January 2014 and April 2024, were identified using Web of Science and Scopus databases, and cross-referenced with ResearchGate. Data were analyzed descriptively in Excel, and institutional coauthorship and collaboration networks were mapped using VOSviewer. A total of 329 articles were published across MLW (n = 98), SA (n = 141), and TZN (n = 90) between January 2014 and April 2024. We report a steady increase in the number of publications from 2014, with a research focus on fracture management, outcomes, and lower limb injuries. Most of the research was published in partnership with high-income countries (HICs) (SA: 51%, MLW: 98%, TZN: 87%), with high-income country (HIC) institutions dominating first and last authorship in MLW (68% and 61%) and TZN (59% and 69%) publications. Most studies were descriptive and based on secondary records. Institutional networks showed strong regional collaboration in SA, international focus in MLW, and limited connectivity in TZN. MSK injury research is increasing across MLW, SA, and TZN, but remains largely HIC-led and descriptive, particularly in lower-income countries. Strengthening local leadership, regional collaboration, and research capacity is essential for more sustainable and context-specific evidence generation.

Abstract Background Ischaemia–reperfusion injury (IRI) is a key factor in early morbidity and graft loss after pancreas transplantation. Oxygenated hypothermic machine perfusion (HMPO₂) has been shown to mitigate the consequences of IRI in liver and kidney preservation and is promising preclinically in pancreas preservation. The metabolic mechanisms underlying the benefit of HMPO₂ are poorly defined. This study aimed to highlight the key metabolites and pathways involved using metabolomic profiling. Methods 18 porcine pancreases, with 19 min of warm ischaemia, were preserved in three groups (n = 6): 8h static cold storage (SCS), 6 h SCS followed by 2 h HMPO2 and 8 h HMPO2, and then assessed by 60-minute normothermic reperfusion (NR) with whole blood. Human validation cohort: seven pancreases declined for transplantation arrived in SCS, underwent 2h HMPO₂ followed by 60-minute NR. Tissue samples were collected at start and end of cold preservation, and end of NR for untargeted metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Results Key porcine tissue metabolic findings included:Succinate, a mitochondrial marker of ischaemia, increased during SCS and decreased during HMPO₂.Malate, a TCA metabolite, was consumed during HMPO₂ relative to SCS.S-adenosylmethionine was lower in continuous HMPO₂ than SCS, indicating methylation demand.L-cystine, a glutathione precursor, was lower in HMPO₂ than SCS.Human graft metabolite trends mirrored the porcine HMPO₂ groups, supporting translational relevance. Conclusions Compared with SCS, HMPO₂ was associated with changes in key metabolites involved in energy metabolism and respiration. This supports that oxygen delivery during HMPO₂ sustains residual metabolism under hypothermia and may mitigate IRI.

Hepatitis A virus (HAV) is an unusual picornavirus with two types of extracellular virions: nonenveloped particles (nHAV) shed in feces and quasi-enveloped particles (eHAV) circulating in blood. Both enter cells by clathrin-dependent endocytic pathways merging in late endolysosomes with capsid binding to ganglioside receptors. Phosphatidylserine receptors facilitate eHAV endocytosis, but no protein receptor has been identified for nHAV. Here, we show low-density lipoprotein receptor (LDLR) is such a receptor. LDLR knockout did not alter viral attachment to cells, but restricted cellular uptake of nHAV (not eHAV). Soluble LDLR ectodomain blocked nHAV entry, as did antibody to LDLR. Recombinant LDLR-related protein-associated protein 1, a pan-LDLR family chaperone, also inhibited nHAV entry, including residual entry into knockout cells, suggesting other LDLR family members may similarly facilitate endocytosis. Reconstituting full-length LDLR expression restored nHAV entry in knockout cells, whereas LDLR mutants lacking LA repeats 4 to 7 or the EGF-like/propeller domain did not. ELISAs confirmed LDLR binds nHAV, optimally above pH7, without destabilizing the capsid. A 1.7Å resolution cryoelectron microscopy (cryo-EM) structure revealed LDLR interacts with VP1 at the fivefold vertex of the capsid. Extreme blurring of the LDLR density prevented detailed identification of LDLR interactions, and suggested binding does not follow particle symmetry, being either flexible or to multiple LDLR regions. Additional cryo-EM studies show ganglioside GD1a binds to a similar region of the capsid. Collectively, these data reveal the LDLR to be an important entry factor, shuttling nHAV from the extracellular environment to endolysosomes where it is likely released at low pH to bind gangliosides.

Abstract Aims Free tissue transfer is a common plastic surgical procedure with a wide array of applications. There is limited consensus on how free flap ischaemia time impacts flap survival. This systematic review aims to evaluate the association between free flap ischaemia time and acute flap failure rate. Methods A systematic review and meta-analysis in compliance with PRISMA statement standards was conducted following registration on the PROSPERO Register (CRD420251052841). A search strategy was developed and the search conducted in September 2024. Studies eligible for inclusion reported length of ischaemia time for free flap surgery and acute flap failure rate. 78 articles were eligible for inclusion and were published between 1997 and 2024. Study populations ranged from 7 to 3926 patients, with a pooled total of 26 374 free flaps in 23 615 patients. The meta-analysis showed overall risk of flap failure was 3.5% (95% c.i. 3%–4.1%). Meta-regression using ischaemia time as a continuous variable showed an increasing risk of acute flap failure from 3% (2.3%–3.9%) at 30 min ischaemia time to 7.5% (4.4%–12.5%) at 240 min. The variables study type, flap type, indication and risk of bias did not account for between study heterogeneity which was substantial. Conclusions This study has systematically assessed existing literature to show a significant association between prolonged ischaemia time and acute free flap loss. This association can guide microsurgical training as carrying out microsurgery in a time efficient manner has a positive impact on free flap survival.

Abstract Background Surgical site infection (SSI) is a common complication following major thoracic and abdominal surgery, associated with increased morbidity, prolonged hospitalisation, and is costly. Negative pressure wound therapy (NPWT) has been proposed as a prophylactic strategy to reduce wound complications, but trial evidence has been inconsistent. Methods This meta-analysis was carried out using the Preferred Reporting Items in Systematic Reviews and Meta-Analysis (PRISMA). A literature search was carried out March 2025, and titles/abstracts screened against our pre-defined inclusion criteria. Summary statistics for outcomes of interest underwent meta-analyses to a confidence interval (c.i.) of 95% and are presented as Forest Plots for Odds Ratio (OR) or mean difference (MD). Results 12 157 patients across 42 randomised trials in abdominal and thoracic surgery were included for analysis. NPWT significantly reduced SSI compared with standard dressings (OR = 0.54; 95% c.i.:0.43–0.69). The effect was consistent across commercial devices (PICO™and Prevena™). NPWT was associated with shorter length of hospital stay (MD = –1.21 days; 95% c.i., –1.61 to –0.80) but not with reduced risk of organ/space infection, wound dehiscence, or reoperation. Publication bias was detected; trim-and-fill analysis attenuated but did not eliminate the benefit (adjusted OR = 0.73; 95% c.i.:0.54–0.98). Discussion NPWT was associated with a nearly 50% reduction in SSI and shorter hospital stay after open abdominal surgery, with consistent benefit across device types. However, evidence of publication bias and limited long-term and patient-reported outcome data suggest that effect size may be overestimated. Selective use in high-risk patients and further investigator-led pragmatic trials are warranted.

Many terms have been invented to describe different types of hallucinogenic drugs, sometimes based on an analogy with the symptoms of schizophrenia, such as “psychotomimetic” and “phrenotropic.” “Psychedelics” refers to drugs that act as agonists at serotonin 5-HT_2A receptors in the brain; they include psilocybin, 5-methoxydimethyltryptamine, and N,N-dimethyltryptamine (tryptamine derivatives), mescaline (a phenethylamine derivative), and lysergic acid diethylamide (LSD, a lysergamide). “Entactogens” refers to drugs that are supposed to touch you within your mind; they act by increasing release of 5-hydroxytryptamine from presynaptic serotonergic neurons and include amfetamine, methylenedioxymetamfetamine (ecstasy, E, MDMA), 5-methoxy-2-aminoindane, and the cathinones methylone and 3-methylmethcathinone. “Oneirogens” refers to drugs that induce a dream-like state similar to the oneirophrenia that is sometimes seen in schizophrenia; they include ibogaine and harmaline alkaloids. “Entheogens” refers to drugs that are used in religious rituals or to elicit a spiritual experience; they include peyote and psilocybin. However, despite the introduction of these and other terms to describe all kinds of hallucinogenic or mind-altering substances, we still don’t understand the pathophysiology of schizophrenia.

To systematically review the anatomical and functional outcomes of vitreoretinal surgery for familial exudative vitreoretinopathy (FEVR)-associated retinal detachment (RD). A systematic review and meta-analysis were conducted following a PROSPERO-registered protocol. The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Ovid, and Medline databases were searched for cohort studies and case series evaluating scleral buckling (SB), pars plana vitrectomy (PPV), or combined procedures for FEVR. Primary outcomes were retinal reattachment rates and postoperative best-corrected visual acuity (BCVA). Secondary outcomes included complication and reoperation rates. Nineteen studies involving a total of 682 eyes were included. The overall pooled primary retinal reattachment rate was 0.77 (95% Confidence Interval (CI): 0.71-0.83; I2 = 59.8%). Subgroup analysis demonstrated a pooled primary reattachment rate for SB of 0.90 (95% CI: 0.70-1.00; I2 = 12.7%) and for PPV of 0.71 (95% CI: 0.60-0.80; I2 = 49.1%). The pooled reoperation rate was 0.24 (95% CI: 0.08-0.45). Qualitative analysis showed that while BCVA outcomes were heterogeneously reported, they generally improved postoperatively. Surgical success was highly dependent on disease stage. Surgical management of FEVR-associated RD achieves high primary reattachment rates. While both SB and PPV yield favourable outcomes, the choice of procedure should be tailored to disease severity and patient characteristics. The evidence suggests SB may be preferred for uncomplicated rhegmatogenous detachments, while PPV is often necessary for more advanced and complex cases.