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Pictographs: feasibility and acceptability of a novel method of newborn identification to reduce wrong-patient errors in the NICU.

Wrong-patient errors cause serious harm in newborns. These errors involve ordering and administering tests, procedures, medications, and breast milk to an unintended patient. Newborns receiving care in neonatal intensive care units (NICUs) are at particularly high risk. Although more distinct newborn naming conventions as recommended by the Joint Commission significantly reduce wrong-patient orders, name similarities among multiple-birth infants and truncation of differentiating information in some electronic health record (EHR) systems contribute to this persistent increased risk. Accordingly, novel newborn identifiers are urgently needed. We propose Pictographs - images that are appealing, recognizable, and appropriate - to serve as visual identifiers for newborns in NICUs. Pictographs are selected by caregivers, uploaded into the EHR, and displayed at bedside. As part of a multicenter randomized controlled trial assessing effectiveness of Pictographs to prevent wrong-patient order errors, we initially evaluated feasibility and acceptability of Pictographs at two study sites. Pictographs as novel visual identifiers for newborns in the NICU were generally well received by caregivers and clinicians, and the vast majority of caregivers selected a Pictograph for their infant(s), which was posted at the bedside and uploaded into the EHR. Ordering clinicians - the primary target of the intervention to prevent wrong-patient errors - recognized the potential for Pictographs to provide a visual cue when placing orders, particularly for multiple-birth infants. Here, we describe the rationale, implementation, framework, feasibility, usefulness, and acceptability of Pictographs among key stakeholders. If found effective for preventing wrong-patient errors, Pictographs could be adopted as a patient safety solution in hospitals worldwide.

Female

Incidence and risk factors for malignancy in patients with incidental solitary pulmonary nodules: a systematic review and meta-analysis.

BACKGROUND: The increasing use of chest imaging has led to a higher detection rate of incidental solitary pulmonary nodules (SPNs), often causing patient anxiety. Determining the malignancy rate and associated risk factors is crucial for developing appropriate follow-up strategies to prevent overdiagnosis, overtreatment, or missed diagnoses. This meta-analysis aims to investigate the malignancy rate and risk factors in patients with incidental SPNs. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted up to June 30, 2025. Data on malignancy rates and potential risk factors were extracted from eligible studies. All pooled analyses were performed using a random-effects model. RESULTS: Fifty-four studies involving 19,985 patients were included. The pooled malignancy rate for incidental SPNs was 56.7% (95% CI: 51.5-62.0), with significant between-study heterogeneity (I2 = 98.5%, p&#x2009;<&#x2009;0.001). The pooled effect size showed a minimal change after adjustment for potential publication bias using the non-parametric Trim-and-Fill method (54.7%; 95%CI: 50.9-58.8). Risk factor analysis identified that older age, history of cancer, cigarette smoker, larger nodule diameter, spiculation, upper lobe location, lobulation, pleural indentation, vascular convergence, solid nodules, family history of cancer, and irregular or ill-defined margins were significantly associated with an increased risk of malignancy. Conversely, male sex, presence of calcification, and clear borders were significantly associated with a reduced risk of malignancy. CONCLUSION: This meta-analysis provides a comprehensive assessment of malignancy rates and risk factors in incidental SPNs. The high pooled malignancy rate should be interpreted considering the significant heterogeneity and the inclusion of a high proportion of retrospective studies and populations from high-risk regions. Nonetheless, these findings offer essential evidence for clinical risk stratification, supporting optimized follow-up and informed decision-making.

Humans

Longitudinal Prediction of Retinal Sensitivity Based on Disease Progression Quantified From Optical Coherence Tomography in Geographic Atrophy.

PURPOSE: The purpose of this study was to analyze the association between disease progression of geographic atrophy (GA) from optical coherence tomography (OCT) with retinal sensitivity (RS) in microperimetry (MP) over a 2-year follow-up period. METHODS: This is a longitudinal analysis of the OAKS Phase-III clinical trial. Both study and fellow eyes with GA that underwent imaging with the Spectralis OCT and consecutive MP examination were eligible. Pointwise quantification of ellipsoid zone (EZ) thickness, EZ and retinal pigment epithelium (RPE) loss from OCT volumes was correlated with localized RS. A longitudinal predictive model using a Markov Chain framework was implemented to predict RS change over time based on OCT biomarkers. The modeling of morphological and functional progression was based on the fellow-eye cohort. RESULTS: A total of 39,681 MP points from 406 patients were analyzed. In the fellow eye cohort, baseline (BSL) EZ thickness was positively associated with RS (0.3 decibel [dB]/&#xb5;m, P < 0.001). Decrease in EZ thickness between visits during follow-up was significantly associated with decrease in RS (0.1 dB / 1&#xa0;&#xb5;m change). RS was significantly lower in MP points within EZ loss during follow-up compared with MP points within the retina with measurable EZ (P < 0.001). The largest functional decline was observed within RPE loss, also associated with the highest probability of absolute scotoma (P < 0.001). Morphological progression to EZ and RPE loss was influenced by EZ thickness and the morphology of adjacent MP points (P < 0.001). CONCLUSIONS: Two exploratory endpoints were developed, namely quantification of EZ thickness and loss, and localized RS within high-risk OCT areas. RS decline during follow-up is associated with automatically quantified disease progression in OCT.

Humans

Respiratory-onset peripartum cardiomyopathy: a systematic review of diagnostic pitfalls and clinical outcomes.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) may initially present with prominent respiratory symptoms that resemble primary pulmonary disease, particularly in late pregnancy and the early postpartum period. In clinical practice, this presentation often triggers alternative diagnostic pathways, introducing delay at a time when rapid cardiac assessment is critical. Although respiratory-dominant presentations are repeatedly described across case-based and observational reports, they have not been systematically examined as a distinct diagnostic pathway within the PPCM literature. CONTENT: This PRISMA-guided systematic review synthesized evidence relating to respiratory-onset presentations of PPCM. Major databases and registers were searched comprehensively. Following screening of 589 records and full-text assessment of 145 reports, 49 studies met inclusion criteria. Twenty studies were qualitatively prioritized for narrative synthesis using ROBIS-informed methodological appraisal. Evidence was examined across diagnostic misclassification patterns, cardiopulmonary mechanisms, differential diagnoses, investigative strategies, and acute and longitudinal management considerations. SUMMARY: Respiratory-led presentations were commonly misattributed to asthma, pneumonia, pulmonary embolism, or perioperative causes, with diagnostic delay frequently reported. Across heterogeneous study designs, cardiogenic pulmonary edema with left-ventricular systolic dysfunction emerged as a recurring unifying mechanism. Early use of echocardiography, natriuretic peptides, and targeted imaging consistently aided differentiation from primary respiratory pathology. Severe clinical deterioration was often described in the context of delayed recognition. OUTLOOK: Respiratory-onset PPCM represents a high-risk diagnostic pathway rather than a discrete disease entity. Prospective registries, standardized diagnostic algorithms, and closer integration of obstetric and cardiopulmonary care are needed to refine early recognition and improve maternal outcomes.

Humans

Artificial intelligence in genitourinary oncology: publication trends and systematic review.

OBJECTIVE: To conduct an analysis of publication trends and a systematic review of randomized controlled trials (RCTs) to characterize the current state of artificial intelligence (AI) use in genitourinary (GU) oncology, as AI has emerged as a transformative tool in healthcare with potential applications in diagnostics, treatment planning, and prognostication. METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE; Ovid), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ultimate for studies related to AI and GU oncology, excluding non-English papers, non-human studies, review articles, and articles using AI solely for manuscript writing. Publication trends were analysed from 2013 to 2023 and categorized by study design and cancer type. RCTs were evaluated through systematic review using Covidence (Veritas Health Innovation Ltd, Melbourne, Victoria, Australia) for screening and data extraction. Two reviewers independently assessed all studies, with risk of bias (RoB) evaluated using the Cochrane RoB 2.0 tool. RESULTS: Of 2409 articles identified, 1220 met inclusion criteria. These included 962 retrospective articles, 175 prospective studies, 79 studies with combined retrospective/prospective methods, and four RCTs. Studies most commonly addressed prostate (n&#x2009;=&#x2009;923), renal (n&#x2009;=&#x2009;274), and urothelial (n&#x2009;=&#x2009;194) cancers. Publications grew from 14 in 2013 to 362 in 2023, with substantial acceleration in 2019. Four RCTs were identified - one in urothelial cancer and three in prostate cancer. Two RCTs evaluated AI-based diagnostics, demonstrating improved performance over conventional methods; the remaining two RCTs evaluated AI in prognostication and treatment planning, showing improved gains in imaging interpretation and operational efficiency. RoB varied across studies, primarily related to randomisation and deviations from intended interventions. CONCLUSIONS: Artificial intelligence research in GU oncology has grown, although high-level evidence from RCTs remains limited. Existing trials underscore AI's promise in diagnostics, prognostication, and treatment planning, and the rapidly evolving nature of this field warrants continued prospective investigation.

Humans

Flap Versus Tunneling for Horizontal Ridge Augmentation With FDBA and i-PRF: A Randomized Controlled Clinical Trial.

AIM: This study evaluated the efficacy of conventional flap and tunneling techniques for horizontal alveolar ridge augmentation using freeze-dried bone allograft (FDBA) particles combined with injectable platelet-rich fibrin (i-PRF). MATERIALS AND METHODS: Forty-five patients were randomly allocated to one of three groups (n&#x2009;=&#x2009;15 each): conventional flap (CF), tunneling with membrane (TM), or tunneling without membrane (TnM). Preoperative ridge width was measured via cone beam computed tomography (CBCT). All augmentation procedures incorporated FDBA and i-PRF; an absorbable collagen membrane was applied in the CF and TM groups. Follow-up assessments, including CBCT imaging and histomorphometric analysis, were conducted 6&#x2009;months postoperatively. For normally distributed data, ANOVA with Tukey's post hoc test and paired samples t-test were applied. Non-normally distributed data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. RESULTS: Statistical analysis was performed on 43 patients. All groups demonstrated an increase in ridge width after 6&#x2009;months. At the 2&#x2009;mm level, the mean width gain was 1.28&#x2009;mm (95% CI: 0.17 to 2.40) in the TM group, 2.85&#x2009;mm (95% CI: 1.80 to 3.89) in the TnM group, and 1.95&#x2009;mm (95% CI: 1.07 to 2.83) in the CF group. However, statistical analysis revealed no significant intergroup variation (p&#x2009;>&#x2009;0.05). Histomorphometric assessments similarly demonstrated comparable outcomes across all groups, with no statistically significant differences observed (p&#x2009;>&#x2009;0.05). CONCLUSION: Within the limitations of this study, the tunneling technique, regardless of membrane use, appears to be a clinically viable alternative to the conventional flap method for horizontal alveolar ridge augmentation. However, further studies with longer follow-up periods are required to substantiate these findings. TRIAL REGISTRATION: irct.behdasht.gov.ir identifier: IRCT 20101204005305N21.

Humans

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2&#xd7; liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans

Intramuscular Fat Infiltration and Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Intramuscular fat infiltration (IMFI) is considered to be closely associated with knee osteoarthritis (KOA); however, its overall association, muscle-specific involvement, and clinical relevance remain unclear. OBJECTIVE: To quantify the association between IMFI and KOA, identify affected muscle groups, and evaluate prognostic value. METHODS: We searched PubMed, Web of Science, Scopus, and Embase up to December 2025 for observational studies. Two reviewers independently screened, extracted data, and assessed bias (NOS/JBI). Pooled standardized mean differences (SMDs) were calculated using random-effects models, with subgroup and sensitivity analyses. RESULTS: Seventeen studies were included. IMFI was significantly higher in KOA patients than controls (SMD&#xa0;=&#xa0;0.63, 95% CI 0.41-0.85, I2&#xa0;=&#xa0;84.7%). Anatomically, the anterior thigh muscles (rectus femoris, vastus lateralis, vastus medialis) demonstrated a significant pooled effect (SMD&#xa0;=&#xa0;0.96, 95% CI 0.66-1.25, I2&#xa0;=&#xa0;3.2%) and showed the strongest pooled association, whereas posterior, medial, and composite measures did not demonstrate significant associations. At the individual muscle level, a single study reported a notable association for the semimembranosus (SMD&#xa0;=&#xa0;1.25, 95% CI 0.57-1.93); however, this finding is based on limited evidence and requires confirmation in future studies. Subgroup by imaging modality: CT demonstrated a significant association (SMD&#xa0;=&#xa0;0.59, 95% CI 0.28-0.90), while MRI and ultrasound did not show significant associations. Elevated IMFI was also associated with reduced muscle strength, higher KOA incidence, structural progression, and increased knee replacement risk. CONCLUSION: A moderate positive association exists between IMFI and KOA, with notable muscle-specific heterogeneity. Anterior thigh muscles show the strongest pooled association, whereas individual muscle findings require further confirmation. These findings suggest that IMFI may represent a promising potential marker warranting further prospective investigation for risk stratification, though causality and its role in modifying disease progression remain to be established.

Humans

The role of artificial intelligence in the diagnosis and prognosis of traumatic brain injury based on brain CT scans: a systematic review.

Traumatic brain injury (TBI) is a leading cause of emergency department visits and a major contributor to injury-related mortality and long-term neurological disability. Non-contrast computed tomography (CT) is the gold-standard imaging modality for the rapid diagnosis of TBI. Clinical outcomes depend strongly on early detection and prompt acute management. Artificial intelligence (AI)-based models may support faster automated identification of traumatic findings and early prediction of patient prognosis.&#xa0;A systematic literature search was conducted in PubMed/MEDLINE, Scopus, IEEE Xplore, ACM Digital Library, and the Cochrane Library in accordance with PRISMA 2020 guidelines to evaluate AI-based models for automated detection of TBI-related findings on CT and for prediction of clinical outcomes. Risk of bias and applicability were assessed using QUADAS-2 for diagnostic accuracy studies and PROBAST&#x2009;+&#x2009;AI for prediction model studies.&#xa0;Twenty-two studies were included. Sixteen studies evaluated diagnostic tasks and 10 evaluated prognostic outcomes, with four studies contributing to both categories. Diagnostic performance was generally high, with many studies reporting AUC values approaching or exceeding 0.90, particularly for larger lesion volumes.Prognostic performance was more variable, with moderate to high discrimination and substantial heterogeneity. Only 9 studies incorporated independent external validation, and performance was frequently lower in external cohorts. All prognostic model studies were judged to be at high overall risk of bias using PROBAST&#x2009;+&#x2009;AI, and most diagnostic accuracy studies also demonstrated high or unclear risk of bias in at least one QUADAS-2 domain, most frequently in patient selection.&#xa0;AI-based models applied to brain CT demonstrate strong technical performance for both diagnostic and prognostic tasks in TBI. However, most studies relied on retrospective designs and lacked independent external validation which limits models generalizability and raises concern for potential overfitting. Prospective, multicenter studies with standardized methodologies and rigorous external validation are required before widespread clinical implementation.

Humans

Exercise prehabilitation in head and neck cancer patients proposed for definitive chemoradiotherapy: The FIT4TREAT randomized controlled trial.

BACKGROUND: Patients with head and neck cancer (HNC) initially scheduled for definitive chemoradiotherapy (CRT) often experience early functional decline and deterioration in health-related quality of life (HRQoL) even before treatment initiation. Evidence for prehabilitation in this non-surgical setting remains limited. This study evaluated whether exercise prehabilitation (EP) initiated before CRT improves functional capacity compared with usual care (UC). METHODS: FIT4TREAT (ClinicalTrials.gov: NCT05418842) was a prospective, single-center, randomized clinical trial. Adults with HNC proposed for definitive CRT were randomly assigned (1:1) to EP or UC. EP consisted of supervised combined aerobic and resistance exercise performed three times per week from baseline until radiotherapy initiation. The primary outcome was the six-minute walk distance (6MWD) at the end of the pre-treatment period. Secondary outcomes included muscle strength, lower-limb functionality, body composition, and HRQoL assessed using the EORTC QLQ-C30 and QLQ-HN43. RESULTS: Between May 2021 and February 2025, 47 patients were enrolled; 40 were included in the primary analysis. After adjustment for baseline 6MWD and the randomization stratification variables, EP resulted in a significantly greater pre-treatment 6MWD than UC (adjusted between-group difference, 28.6&#xa0;m; 95&#xa0;% CI, 4.1-53.1; P&#xa0;=&#xa0;0.023). EP also improved lower-limb functionality (P&#xa0;<&#xa0;0.001) and was associated with better preservation in the QLQ-C30 summary score (P&#xa0;=&#xa0;0.008), social functioning (P&#xa0;=&#xa0;0.038) and body image (P&#xa0;=&#xa0;0.011). CONCLUSION: EP before definitive CRT improves functional capacity and may help preserve HRQoL in patients with HNC, supporting its potential integration into routine oncology care.

Humans

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms

Persistent cloaca without vaginal-common channel fistula: A Case series characterizing a rare phenotype.

INTRODUCTION: Persistent cloaca occurs in approximately 1 in 25,000 live births. Among patients with cloaca, the absence of a vaginal connection to the common channel represents a rare phenotype with distinct anatomic and management considerations. We describe the urologic, gynecologic, and surgical characteristics of this patient subset. METHODS: We performed a retrospective analysis of a single-institution cohort of patients with persistent cloaca managed at a quaternary-care children's hospital between 2019 and 2025. Patients were eligible if they underwent primary cloacal repair by our multidisciplinary team and met all three diagnostic criteria for absent vaginal-common channel fistula: no hydrocolpos on imaging, no identified vaginal opening on cystoscopy or cloacagram, and no visible lumen between m&#xfc;llerian and cloacal structures identified intraoperatively. RESULTS: Of 51 patients who underwent primary repair, 6 (12%) met criteria for absent vaginal-common channel fistula. All met criteria for VACTEGRLS association. Common channel length ranged from 1.1 to 7.0 cm and urethral length from 0.5 to 2.2 cm. Urologic anomalies were nearly universal: five patients (83%) had a solitary functional kidney and four (67%) had vesicoureteral reflux. All underwent posterior sagittal anorectoplasty (PSARP) for rectal repair with the common channel repurposed as the neourethra. Five (83%) underwent diagnostic laparoscopy during which the m&#xfc;llerian structures were examined but left in situ. At last follow-up (median 17.5 months, range 4-35 months), three patients (50%) had volitional voiding and three (50%) required assisted bladder emptying via vesicostomy or Mitrofanoff. CONCLUSION: Persistent cloaca without a vaginal-common channel fistula represents a rare but clinically distinct phenotype characterized by severe urologic anomalies. Recognition of this phenotype is essential for surgical planning and long-term urologic and gynecologic surveillance. Because there was no connection between the vagina and the urinary tract, delaying management of the m&#xfc;llerian structures did not adversely affect the urinary tract.

Humans

Data-centric, robust, and explainable multimodal deep learning for clinical decision support: A systematic review.

PURPOSE: Multimodal deep learning is increasingly proposed for clinical decision support (CDS) under a "data-centric" framing that prioritizes label quality, missing-modality robustness, distribution shift, calibration, and explainability. Prior reviews have examined multimodal medical AI, CDS, and data-centric methods separately, but none address their intersection. We mapped the modalities, fusion strategies, and data-centric and explainability techniques used in this recent literature, quantified how often each is implemented rather than merely mentioned, assessed deployment-relevant evidence (external validation, clinical-outcome measurement, equity), and formally appraised study-level risk of bias. METHODS: Following the PRISMA 2020 statement (PROSPERO CRD420261427815; registered retrospectively), we screened 150 records and included primary, clinical, multimodal studies that applied machine or deep learning to a decision-support task and reported at least one quantitative result. Two reviewers screened and extracted data with consensus adjudication. Each study was coded against pre-specified operational definitions, separating implemented or empirically evaluated techniques from those only mentioned. Study-level risk of bias was assessed with PROBAST + AI. Synthesis was narrative. RESULTS: Thirty-one studies met inclusion; 30 (97%) were published between 2024 and 2026, with a median of three modalities (range 2-6), most commonly structured EHR (71%) and imaging (39%). Data-centric techniques were frequently reported (74-84% across label-noise, distribution-shift, calibration, missing-modality and class-imbalance handling; equity 61%). However, external validation was reported in only 4/31 studies (13%), a clinical or provider outcome in 3/31 (10%), and no study reported routine deployment. Overall risk of bias was high in 27/31 studies (87%), driven by the analysis domain. CONCLUSION: Within this recent, self-selected slice of the field, technical robustness and explainability techniques are widely reported but rarely validated out-of-distribution or against clinical outcomes, and the underlying evidence is at high risk of bias. Progress requires external multi-site validation, clinical-outcome measurement, formal bias appraisal, and adherence to AI reporting standards (e.g., TRIPOD + AI) before deployment can be justified.

Deep Learning

Anatomy and Biomechanics of the Deltoid Ligament Complex in Healthy Ankles: Protocol for a Systematic Review and Meta-Analysis.

INTRODUCTION: Up to one in two individuals who have a history of an ankle injury will develop chronic ankle instability, which subsequently increases the risk of osteoarthritis development. Although lateral ankle ligament injuries are the most common, recent research shows that concomitant injuries to the deltoid (medial collateral) ligament complex may be more prevalent than previously recognised. However, the anatomy and biomechanics of the deltoid ligament complex are reported inconsistently in the literature. This systematic review will summarise current evidence on the anatomy and biomechanics of the deltoid ligament complex in healthy adult ankles. METHODS: Searches will be conducted in Scopus, MEDLINE, Embase, CINAHL and SPORTDiscus. Our search strategy will cover terms associated with 'deltoid ligament', 'anatomy' and 'biomechanics'. We will only include dissection and imaging studies published in English that report any of the listed clinically relevant properties of the deltoid ligament in healthy adult human ankles. Two reviewers will independently perform screening and assess study quality using the anatomical quality assessment (AQUA) tool. One reviewer will extract relevant data, which will be independently verified by co-authors. Primary outcomes include band prevalence, length, width, cross-sectional area, maximum and/or failure load and elastic modulus. If three or more studies report a primary outcome, we will conduct a meta-analysis and report findings as pooled means with 95% confidence intervals. If a meta-analysis is not feasible, outcomes will be summarised as a narrative analysis. Measures will be taken during data synthesis to address anticipated methodological heterogeneity across included studies, and pooled estimates will be interpreted with caution. DISCUSSION: This protocol details a systematic review that aims to summarise the anatomy and biomechanics of the deltoid ligament complex. Our findings will inform computational modelling, clinical management and biomechanics for ankle pathologies, as well as identifying research gaps and directions for future research. TRIAL REGISTRATION: PROSPERO: CRD420251142867.

Humans

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n&#x2009;=&#x2009;35) or muscle strength exercises (n&#x2009;=&#x2009;34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter&#x2122;) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system&#xae;. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD&#xa0;=&#xa0;-0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD&#xa0;=&#xa0;-0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans

One Year After a Cyberattack: Lessons Learned and Dosimetric Analysis of Contingency Radiotherapy Plans.

PURPOSE: Cyberattacks on health care institutions pose significant risks to patient care, particularly in radiotherapy departments, which are heavily reliant on digital systems. This study examines the impact of a ransomware attack on our hospital and evaluates the effectiveness of the contingency measures implemented to resume radiotherapy treatments. METHODS AND MATERIALS: Following the cyberattack, our radiotherapy department faced a complete shutdown. After an initial estimate considering a shutdown of several weeks, a contingency plan was executed, including manual patient data retrieval and collaboration with a backup hospital. Contingency plans were prepared and delivered within hours, despite a partial lack of information. These plans allowed some patients to restart treatment 3 days after the attack. A dosimetric analysis was performed for the contingency plans, including various pathologies, mainly glioblastoma, head and neck cancers, and lung cancer. We compared the original and contingency plans in terms of dose coverage to the clinical target volume, biological effective dose, and their clinical impact as assessed at the 1&#x2011;year follow&#x2011;up after the cyberattack. RESULTS: Treatments resumed within 12 days at our hospital. Patients with glioblastoma showed good target coverage because of generous margins, resulting in favorable outcomes. In head and neck cases, the lack of detailed imaging led to significant target volume misses, suggesting that more conservative initial treatments could have been beneficial. Lung cases demonstrated accurate peripheral lesion targeting but faced challenges in central lesions because of the absence of positron emission tomography information. In most cases, the approach of using a contingency plan, even with limited information, led to a higher biological effective dose than would have been achieved if treatment had been stopped until full recovery at our hospital. CONCLUSIONS: The study highlights the critical importance of robust contingency planning in radiotherapy departments, emphasizing the need for backup systems and tailored approaches based on tumor location and available diagnostic information. These lessons emphasize that preparedness for digital disruptions should not focus exclusively on information and technology infrastructure.

Humans