[This corrects the article DOI: 10.3389/fpsyt.2025.1584719.].

Regulation of sialic acids is important to many biological processes and involves both biosynthesis and catabolism. The human neuraminidase enzymes (hNEU) regulate many sialosides in human health and disease. Polysialic acid (polySia) is a polyanion of α(2 → 8) linked sialic acids with roles in nervous, reproductive, and immune systems and is dysregulated in some malignancies and mental disorders. The unique chemical properties of this polymer, which include an enhanced susceptibility to acid-catalyzed hydrolysis, have hampered its study. Herein we describe the first systematic study of hNEU isoenzyme activity towards polySia in vitro. Our experimental design allowed us to study the impact of several factors that may influence polysialic acid degradation including pH, polymer size, and the relative ionic strength of the media. We report that short chains of polySia (oligoSia, degree of polymerization, DP 3-8) were substrates of NEU3 and NEU4 at acidic pH, but not at neutral pH. We were unable to detect hNEU-catalyzed hydrolysis of longer polymers (polySia, DP 10-20) over background hydrolysis. These findings suggest that longer polySia oligomers may be degraded through neuraminidase-independent mechanisms, such as internalization or degradation in endosomes and lysosomes.

The paper reflects on a Wellcome-funded project led by the Medicines and Healthcare products Regulatory Agency (MHRA) in collaboration with the National Institute for Health and Care Excellence (NICE). Initiated in 2023, the project aimed at developing guidance and regulatory frameworks for digital mental health technologies (DMHTs), emphasising meaningful lived experience involvement throughout the process to ensure accessibility, inclusivity, and accountability. It details methods of engagement, key insights on best practices for lived experience involvement, challenges such as overcoming technical jargon and provides recommendations for broader adoption of lived experience integration, improved public awareness, cross-sector collaboration, and equitable digital futures in mental health regulation and innovation. The paper offers a hybrid narrative approach in which the details of the project are presented and are followed by the lived experience insights of the contributing authors. This highlights the collaborative nature of the project itself and the outputs but gives space for the considered reflections of what it felt like to be part of this initiative. The paper considers recommendations for how lived experience should be incorporated into similar projects in future. The paper articulates the benefit of lived experience for projects that have an impact on the way in which DMHTs are regulated. In this instance the outputs, informed by lived experience, help ensure that DMHTs are safe and effective and will be reflected in what technologies are integrated into mental health nursing practice. It is also important to note that DMHTs are often accessed outside of mental health service settings, and so practitioner awareness of their risks and benefits should be encouraged.

For older adults with non-small cell lung cancer (NSCLC), the choice of resection must balance durable cancer control against physiological reserve and postoperative recovery. We combined population-level long-term survival data with granular real-world perioperative data to examine this trade-off.

The Surveillance, Epidemiology, and End Results (SEER) cohort included 2,630 patients aged ≥ 70 years with NSCLC ≤ 3 cm diagnosed in 2010-2015 (855 lobectomy, 1,421 wedge resection, and 354 segmentectomy). Optimal 1:1 propensity-score matching retained 809 patients per group. The two-center cohort included 223 patients treated by video-assisted thoracoscopic surgery in 2017-2020 (145 lobectomies and 78 sublobar resections: 73 wedge resections and five segmentectomies). Overlap weighting used age, sex, tumor size, clinical stage, consolidation-to-tumor ratio, smoking, and recorded cardiopulmonary comorbidities. The primary real-world survival analysis was restricted to tumors ≤ 2 cm and 36 months.

In SEER, matched sublobar resection was not associated with a statistically significant OS difference for tumors ≤ 2 cm (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.93-1.51; P = 0.177), whereas OS was lower after sublobar resection for tumors > 2-3 cm (HR 1.31, 95% CI 1.03-1.66; P = 0.028). Procedure-specific models showed no significant difference between segmentectomy and lobectomy for tumors ≤ 2 cm (HR 1.03, 95% CI 0.83-1.26), while wedge resection was associated with lower OS (HR 1.32, 95% CI 1.14-1.53). In the real-world cohort, patients selected for wedge-dominant sublobar resection were older and had more recorded comorbidities. After overlap weighting, wedge-dominant sublobar resection was associated with shorter chest-tube duration (mean difference - 2.49 days, 95% CI - 3.56 to - 1.37) and less hypoproteinemia (risk difference - 14.4% points, 95% CI - 27.6 to - 1.7). The composite in-hospital complication risk was 16.4% points lower (95% CI - 34.7 to 1.3), whereas total hospital stay did not differ significantly (mean difference - 1.60 days, 95% CI - 4.62 to 2.04). For tumors ≤ 2 cm, adjusted 3-year OS was 93.0% after lobectomy and 88.5% after wedge-dominant sublobar resection (HR 1.73, 95% CI 0.19-15.63; P = 0.558).

In routine practice, wedge-dominant sublobar resection was selected for older adults with greater comorbidity burden and was associated with shorter chest drainage and less hypoproteinemia, while total hospital stay was similar after adjustment. Among patients with tumors ≤ 2 cm, the real-world cohort showed no statistically significant 3-year OS difference. In the longer-term SEER analysis, segmentectomy showed no significant adjusted OS difference from lobectomy for tumors ≤ 2 cm, whereas wedge resection warrants greater oncologic caution.

Large language models (LLMs) may assist in the prevention of diabetes-related foot ulcers; however, their performance in classification may not translate effectively to context-dependent decisions.

This study aimed to evaluate the accuracy, clinical actionability, reproducibility, and safety of five public LLM web interfaces in the context of the International Working Group on the Diabetic Foot (IWGDF) 2023 risk stratification and preventive management.

A prespecified, paired, blinded, noninterventional pilot benchmark was conducted using 20 translated, de-identified, curated cases structured in a fixed clinical sequence and evenly distributed across the four IWGDF risk categories. These input conditions represent an idealized, best-case benchmark rather than routine clinical documentation. Each interface assessed all cases under standardized no-search conditions. The primary outcome was exact agreement with a frozen multidisciplinary consensus risk category. Additional outcomes included screening frequency, need for referral, specialty and urgency of referrals, completeness, interreviewer reliability, repeated-generation stability, and safety.

Each interface classified 20/20 cases in concordance with the frozen IWGDF reference (100%; Wilson 95% CI 83.9%-100.0%). The 16.1-percentage-point interval below the observed ceiling indicates limited precision and remains compatible with clinically meaningful error in new cases. Of 100 primary outputs, agreement was observed in 89/100 (89.0%) for referral need, 68/75 (90.7%) for referral specialty, and 92/100 (92.0%) for urgency. Median information-item and mandatory-measure coverage was 100.0% for both measures; however, completeness scoring had limited inter-reviewer reliability and should be interpreted cautiously. In an exploratory, hypothesis-generating four-case repeated-generation substudy, all-three-generation consensus concordance was observed in 16/20 interface-case combinations for referral need, 14/15 eligible combinations for specialty, and 19/20 combinations for urgency. These descriptive counts are not estimates of failure probability or tail behavior. Under the prespecified curated no-search benchmark conditions, no major safety errors were observed among 140 outputs; this absence of observed events does not establish safety in routine clinical use.

Performance was highest for structured guideline mapping, though reliability diminished in referral and individualized management across repeated generations. These findings highlight the necessity for auditable, clinician-supervised decision support instead of autonomous deployment.

Prevalent radiographic vertebral fracture is frequently clinically unrecognized in older adults, and areal bone mineral density does not fully characterize its distribution. Whether coexisting type 2 diabetes mellitus (T2DM) and objectively measured low muscle mass identify a subgroup in which this burden is concentrated remains unclear.

This community-based cross-sectional analysis included 1,642 adults aged 65 years or older recruited through 16 community health service centers covering 36 administrative communities in Changchun, China, between July 2021 and March 2023. Participants were classified into four mutually exclusive groups: neither condition, T2DM alone, dual-energy X-ray absorptiometry (DXA)-defined low muscle mass alone, or both conditions. The primary outcome was prevalent radiographic vertebral fracture (Genant grade ≥ 1), with Genant grade ≥ 2 fracture as the key secondary outcome. Modified Poisson models estimated prevalence ratios (PRs). The primary model included age and body mass index as restricted cubic splines, sex, and current smoking, with covariance estimation accounting for 36 community clusters. Missing covariates were handled using 50 datasets generated by multiple imputation by chained equations, and marginal standardization was used to estimate prevalence differences.

The analytic cohort included 343 participants (20.9%) with prevalent radiographic vertebral fracture. The coexisting phenotype comprised 14.1% of the cohort but accounted for 31.5% of all Genant grade ≥ 1 events and 35.2% of all Genant grade ≥ 2 events. Observed prevalence was 11.5, 20.7, 24.2, and 46.6% in the neither-condition, T2DM-alone, low-muscle-mass-alone, and coexisting groups, respectively. Primary-model PRs versus neither condition were 1.66 (95% CI, 1.30-2.12), 1.92 (95% CI, 1.42-2.59), and 3.63 (95% CI, 2.81-4.68), respectively. The coexisting phenotype had a standardized prevalence of 44.1% (95% CI, 38.3-49.9%) and a prevalence difference of 31.9 percentage points (95% CI, 25.3-38.5) versus neither condition. Results were similar in the femoral-neck-BMD-context, complete-case, Genant grade ≥ 2, and no-prior-fracture analyses.

In this analytic sample, coexisting T2DM and DXA-defined low muscle mass defined a relatively small subgroup with a disproportionate share of prevalent radiographic vertebral fracture events and the highest fracture prevalence. These cross-sectional findings do not establish causality, future fracture prediction, screening performance, or an indication for vertebral imaging.

Diabetic peripheral neuropathy (DPN) is a leading cause of neuropathic pain, disability and lower-limb amputation, and the pharmacological options currently available do little to reverse established nerve injury. Compound traditional Chinese medicine preparations that activate blood circulation and unblock the collaterals have shown promise as add-on therapy to neurotrophic treatment, improving nerve conduction and relieving symptoms, but head-to-head comparisons between individual formulas are lacking.

PubMed, Embase, the Cochrane Library, CNKI, Wanfang and other databases were searched to July 2026 for randomised controlled trials comparing a blood-activating, collateral-unblocking formula plus mecobalamin with mecobalamin alone in adults with type 2 diabetes and peripheral neuropathy. The primary outcome was the Toronto Clinical Scoring System (TCSS); secondary outcomes were motor and sensory conduction velocity (MCV, SCV) of the median and common peroneal nerves, together with adverse events. Mean differences (MD) and 95% credible intervals were estimated in a Bayesian random-effects model, and ranking distributions were summarised as the surface under the cumulative ranking curve (SUCRA). Risk of bias was assessed with RoB 2 and certainty of evidence with CINeMA (Confidence in Network Meta-Analysis).

Nineteen randomised controlled trials (2,090 participants) were included. All were conducted in China, and most nodes were informed by a single trial. Relative to mecobalamin alone, most add-on regimens improved TCSS and nerve conduction velocity. Credible intervals excluded zero for 9 of 12 formulas for TCSS, 7 of 14 for median nerve MCV, 3 of 14 for median nerve SCV, 5 of 14 for peroneal nerve MCV and 8 of 9 for peroneal nerve SCV. By SUCRA, Yiqi Huashi Tongbi Formula ranked first for TCSS (90.3%; MD -3.49, 95% CrI -5.17 to -1.81), Shengyang Sanhuo Decoction for median nerve MCV (85.6%; MD 4.16, 95% CrI 1.58 to 6.78), Xiaoma Zhitong Capsule for median nerve SCV (84.4%; MD 4.19, 95% CrI 0.88 to 7.58), Modified Buyang Huanwu Decoction for peroneal nerve MCV (79.2%; MD 3.78, 95% CrI 0.83 to 6.72) and Jiangtang Tongluo Tablet for peroneal nerve SCV (95.2%; MD 4.08, 95% CrI 2.38 to 5.78). Eight of the 19 trials made no mention of adverse-event monitoring, and none reported numerical laboratory safety data. The available information is insufficient to evaluate the safety of these add-on regimens.

Adding blood-activating, collateral-unblocking traditional Chinese medicine to mecobalamin was associated with improvement in TCSS and in nerve conduction velocity in patients with DPN. Certainty of evidence was very low for every comparison, however, and prediction intervals crossed the line of no effect for three outcomes, indicating that the direction of effect could change in a new study. The rankings are exploratory and hypothesis-generating: they are not a sufficient basis for inferring definite clinical efficacy or for choosing a formula for an individual patient, and they require confirmation in adequately powered, prospectively registered, blinded multicentre head-to-head trials.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42025123604.

Albumin-corrected fructosamine (AlbF) is a short-term glycemic marker that can substitute for HbA1c when HbA1c is unreliable. Studies have linked AlbF to diabetic retinopathy (DR), but it is not known whether the dose-response curve differs between men and women. We investigated this in 1,090 type 2 diabetes patients (433 men, 657 women) from a single Chinese center.

Restricted cubic splines were used to model the AlbF-DR relationship separately by sex, with threshold identification via segmented logistic regression. Models included age, BMI, diabetes duration, systolic blood pressure, HbA1c, HDL-C, and medications as covariates.

Each 10 μmol/g increase in AlbF raised DR risk in both sexes: men OR 1.83 (95% CI 1.39-2.41), women OR 1.58 (95% CI 1.26-1.99). The RCS curves told a different story. Men followed a linear pattern (P for nonlinearity = 0.751). Women showed a threshold near 62.0 μmol/g (P for nonlinearity < 0.001). Below that value, the OR was 2.57 (95% CI 1.74-3.81); above it, the association was no longer significant (OR 1.29, 95% CI 0.69-2.42; P for interaction < 0.001). Sensitivity analyses consistently reproduced this nonlinear pattern.

The AlbF-DR relationship is linear in men but follows a threshold model in women, with a change point near 62.0 μmol/g. Sex-specific risk modeling may improve DR stratification. Whether the threshold holds in practice will require prospective studies.

Diabetic foot infection (DFI) is a major cause of non-traumatic lower-limb amputation and is associated with poor survival outcomes. Identifying therapies that reduce progression to amputation is critical.

To evaluate the association between statin therapy and risk of amputation in patients with DFI, including assessment of dose-response effects.

A retrospective cohort study involving 376 patients presenting with DFI at a university hospital in Jordan between January 2020 and April 2024. The primary outcome was amputation severity (no amputation, minor amputation, major amputation), analyzed using multivariable ordinal logistic regression, adjusting for potential confounders; major amputation incidence was also examined as a secondary binary outcome for absolute risk reduction and number-needed-to-treat calculations.

Moderate-intensity statin therapy was associated with an absolute risk reduction (ARR) of 9.3% (NNT = 11) for major amputation, while high-intensity therapy was associated with an ARR of 14.3% (NNT = 7). In adjusted ordinal logistic regression models, both moderate-intensity (aOR 0.43, 95% CI 0.20-0.74, p = 0.004) and high-intensity statins (aOR 0.43, 95% CI 0.26-0.71, p = 0.001) were associated with lower odds of more severe amputation. A significant dose-response trend was observed, with major amputation rates decreasing from 21.9% in untreated patients to 12.6% and 7.6% in moderate- and high-intensity groups, respectively (p = 0.025). Subgroup analyses showed consistent associations across key clinical subgroups, including patients with advanced Wagner grades, peripheral arterial disease, and neuropathy.

Statin therapy was associated with lower odds of more severe amputation and a lower observed risk of major amputation in patients with diabetic foot infection. An ordered trend in risk reduction was observed across statin intensity levels, but moderate- and high-intensity statins did not differ significantly from one another, so these findings support an association with statin use rather than a confirmed dose-dependent gradient. Further randomized controlled trials are needed to confirm causality and evaluate long-term outcomes.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have become a key drug class in the treatment of Type 2 diabetes (T2D) due to their effectiveness in blood sugar control, but also for many other clinical indications because of beneficial effects on cardiovascular diseases and mortality. Therefore, the findings of a secondary analysis of the recent EMMY trial, in which acute myocardial infarction patients treated with empagliflozin had higher trimethylamine-N-oxide (TMAO) serum levels compared to placebo, were unexpected, as high TMAO concentrations in blood have previously been linked to adverse cardiovascular and mortality outcomes. In light of this, the aim of our study was to explore the effects of the SGLT-2 inhibitors empagliflozin and dapagliflozin on plasma concentrations and renal clearance (Cl_R) in a T2D patient setting.

Plasma and 24-h urine samples from two prospective, randomised, placebo-controlled, double-blind, cross-over trials with T2D patients (empagliflozin N = 69, NCT02471963; dapagliflozin N = 54, NCT02383238), taken at baseline and after each treatment with either SGLT-2 inhibitor or placebo, were measured for TMAO via LC-MS/MS.

After treatment with an SGLT-2 inhibitor, in the total of 123 patients, TMAO plasma levels were 11.5% higher compared to placebo (p = 0.006) and Cl_R of TMAO was reduced by 10.3% (p = 0.048) without any relevant change in its urinary excretion (p = 0.521). In the dapagliflozin trial, TMAO plasma concentration was 23.4% higher (p = 0.021), and Cl_R of TMAO was 22.6% lower (p = 0.025) after treatment with dapagliflozin compared to placebo. For empagliflozin, a similar trend was observed, but did not reach statistical significance.

Treatment with an SGLT-2 inhibitor was associated with a modest increase in plasma concentration of TMAO. Together with data from a previous trial, the present findings suggest a possible class effect of SGLT-2 inhibitors. Whether this effect impacts the overall clinical benefits of SGLT-2 inhibitors needs to be subject to further investigations.

http://www.

gov: NCT02471963 (registered 15th June 2015, retrospectively registered) and NCT02383238.