Neurogastroenterology & Motility

Background: Gastrointestinal (GI) motility disorders are prevalent, impose a significant burden, and are associated with disrupted spatial propagation of bioelectrical gastric slow waves. High-resolution endoscopic gastric mapping (EGM) is an emerging minimally invasive technique for imaging gastric electrical activity; however, EGM is performed alongside standard gastroscopy and requires procedural sedation, which may interact with gastric electrical activity, distorting clinical insights. This study explored the influence of procedural sedation on EGM-recorded slow-wave activity. Methods: EGM was performed for {approx}7 min in 32 patients undergoing upper GI endoscopy at two New Zealand hospitals. Endoscopists administered procedural sedation (fentanyl and midazolam) according to best clinical practice. The relationship between slow-wave amplitude and patient characteristics was then investigated using a variety of statistical techniques. Key Results: Gastric slow waves were detected in 30 of 32 patients who underwent EGM. Symptom scores and demographic measures were comparable between sites. Fentanyl (A, 93.4 {+/-} 13.7 g vs B, 137.5 {+/-} 33.7 g, p[≤]0.001) and midazolam (A, 5.0 {+/-} 0.9 mg vs B, 7.4 {+/-} 1.6 mg, p[≤]0.001) doses were higher at Hospital B than Hospital A. Correspondingly, slow-wave amplitudes were lower at Hospital B than Hospital A (A, 2.33 {+/-} 1.61 mV vs B, 0.86 {+/-} 1.01 mV, p=0.004). All other slow-wave metrics were consistent between hospitals. Combined sedative dose was negatively correlated with slow-wave amplitude (p=0.037). Conclusions & Inferences: Higher procedural sedative doses are associated with lower-amplitude gastric slow-waves. Procedural sedation dose and opiate administration should be carefully considered when interpreting GI electrophysiology measurements.

ABSTRACT Background: The esophageal String Test (EST) is emerging as a minimally invasive alternative for assessing disease activity in eosinophilic esophagitis (EoE), yet the molecular composition of its protein content remains unknown. Objective: To comprehensively characterize the esophageal EST proteome, define an EoE-associated luminal protein signature, and evaluate its biological and clinical relevance. Methods: EST samples were obtained from patients with active EoE, healthy controls (C) and patients with gastroesophageal reflux disease (GERD). Label-free proteomic profiling was performed by liquid chromatography-tandem mass spectrometry. Differential protein accumulation, principal component analysis (PCA), pathway annotation, comparison with published esophageal tissue and salivary proteomes, receiver operating characteristic (ROC) analyses and correlations with clinical disease activity were performed. Results: More than 3,000 proteins were identified in esophageal EST samples. Global proteomic profiling clearly separated patients with EoE from both C and GERD, whereas only limited differences were observed between the latter two groups. This enabled the identification of an EoE-associated luminal protein signature comprising inflammatory, epithelial, and tissue remodeling proteins. Comparison with published proteomic datasets indicated that the EST samples a complex esophageal luminal protein microenvironment containing proteins represented in esophageal mucosa and saliva, together with inflammatory and extracellular components. Several individual proteins showed high discriminatory performance in this exploratory cohort for distinguishing EoE from non-EoE subjects, and multiple proteins correlated with eosinophil counts and endoscopic measures of disease activity. Conclusions: This study demonstrates that the EST provides access to a complex esophageal luminal protein microenvironment and establishes a molecular framework for its minimally invasive characterization in EoE. KEYWORDS: eosinophilic esophagitis, esophageal string test, esophageal luminal protein signature

Pediatric endoscopy is performed only when clinically indicated, limiting access to healthy duodenal tissue. Biopsies with duodenal no pathologic abnormality (NPA) are often used as controls despite the presence of symptoms or inflammatory disease found elsewhere in the gastrointestinal (GI) tract. We characterized pediatric duodenal NPA tissue across clinical, histologic, cellular, and transcriptomic domains. Methods Archival duodenal NPA biopsies were obtained with clinical metadata and hematoxylin-and-eosin whole-slide images (WSIs). Duodenal mRNA-seq data were analyzed from a subset of patients with duodenal NPA. Clinical metadata and WSIs underwent machine-learning analysis, cell populations were quantified from WSIs, and RNA-seq data underwent differential expression and pathway-enrichment analyses. Results The primary cohort included 195 patients with duodenal NPA. Comparisons between patients with non-duodenal GI disease and those with no GI disease showed differences in inflammatory biomarkers and follow-up utilization. Unsupervised clinical clustering identified three clusters with partial enrichment for IBD with colonic inflammation and Eosinophilic Esophagitis (EoE) with esophageal inflammation. Supervised clinical classification showed modest discrimination. WSI clustering showed limited disease-status discrimination, and cell quantification showed no significant group differences. In the separate RNA-seq cohort of 43 patients, differential-expression and pathway-enrichment analyses identified transcriptional and pathway-level differences between disease-status groups. Conclusions This multi-level characterization indicates that pediatric duodenal NPA tissue should not be treated as a uniform control category. Clinical metadata and transcriptomics revealed clinical and molecular heterogeneity, while histologic and cell analyses showed limited disease-status separation, supporting a refined definition of control tissue.

Gastrointestinal dysfunction is a prominent feature of neurodevelopmental disorders and contributes significantly to visceral discomfort, but the specific etiology is unclear. In particular, it is unknown which cell types within central, autonomic or enteric nervous systems, gut muscle, epithelium or immune system are the principal drivers of gut dysfunction. We report that the Mecp2 mouse model of Rett syndrome, a neurodevelopmental disorder with profound gut dysmotility, exhibits impaired whole gut transit times and constipation in vivo as well as striking alterations to propagating neurogenic contractions in ex vivo colons. Selective elimination of Mecp2 in neurons, but not glia or smooth muscle, recapitulates these dysmotility phenotypes. Bulk RNA sequencing of colonic external muscle, containing the myenteric compartment of the enteric nervous system, showed significant expression changes in specific neurochemical signaling pathways. Pharmacological modulation of one, the M1 acetylcholine receptor, modified the aberrant neurogenic contractile phenotype in mutant mice and reproduced it in wild-type mice. These results identify disruptions to neuronal muscarinic signaling in the enteric nervous system in a mouse model of Rett syndrome and provide an experimental strategy to identify translationally relevant cellular and molecular pathways underlying gastrointestinal dysmotility in neurodevelopmental disorders.

Purpose: Posterior pharyngeal wall (PPW) thickening is a common structural manifestation of treatment-related internal lymphedema in patients with head and neck cancer and can be evaluated using lateral videofluoroscopic images acquired during modified barium swallow (MBS) studies. However, no standardized method currently exists for quantitative measurement. Methods: This two-phase methodological study first conducted a scoping review to characterize existing approaches to PPW thickness measurement and identify the principal factors contributing to variation in PPW thickness measurement. Eight studies were identified with variation observed across these measurement factors. An empirical reliability study was then performed using 107 MBS studies from 93 Head and Neck Cancer patients. Two independent raters annotated 10 anatomical landmarks on pre-swallow and post-swallow resting frames, and a computer-assisted algorithm quantitatively generated seven candidate PPW thickness measurements based on different vertebral reference points and measurement directions. Reliability was assessed intraclass correlation coefficients (ICCs). Results: Inter-rater reliability was highest for the measurement originating from the midpoint of C3 and extending perpendicular to the anterior C3 surface (ICC, 0.78; 95% CI, 0.72-0.83). Among the normalization references, C2-C4 vertebral length demonstrated greater reliability than C3 vertebral length, with an ICC of 0.88 (95% CI, 0.85-0.91). No significant differences were observed between pre-swallow and post-swallow PPW thickness measurements across the evaluated approaches. Conclusions: These findings provide a methodological foundation for more standardized and reliable quantification of PPW thickness, with potential to expand the role of MBS from the functional evaluation of swallowing to include quantitative characterization of pharyngeal structural abnormalities.

Objective: The Alimetry Gut-Brain Wellbeing (AGBW) Survey is a validated 10-item scale developed to assess mental health in patients with chronic gastroduodenal symptoms. While the original scale demonstrated strong psychometric properties overall, as part of an ongoing commitment to continuous instrument optimization, this study evaluated a revised, unidirectional version of the scale (AGBW-II) to enhance measurement precision. Methods: The psychometric properties of the revised AGBW-II were evaluated via an anonymous online questionnaire in a sample of 161 patients with chronic gastroduodenal symptoms. Score distributions, factor analysis, reliability, and validity were analyzed and compared with data from the validation study of the original scale (n= 311). Results: The AGBW-II total and subscale scores demonstrated robust reliability and validity, outperforming the original AGBW Survey. Notable improvements in the reliability and validity of the stress subscale were observed following item rewording. Confirmatory factor analysis verified the three-factor model separating the depression, stress, and anxiety subscales, with the AGBW-II showing improved model fit indices. Conclusions: The revised, unidirectional AGBW-II demonstrated improved reliability and validity, while maintaining the underlying psychometric properties of the original scale. Consequently, the AGBW-II provides a reliable, valid, and brief mental health assessment for patients with chronic gastroduodenal symptoms.

Background: Erythritol and xylitol, naturally present in fruits and vegetables, are widely used as alternative sweeteners with minimal glycemic and insulinemic effects. Both are also produced endogenously, with elevated plasma concentrations reported in metabolic disorders and cardiovascular disease. Recently, two interventional studies reported enhanced platelet aggregation after acute oral intake of erythritol or xylitol, raising concerns about potential prothrombotic effects. We investigated whether acute exposure to erythritol or xylitol increases platelet reactivity in healthy individuals. Methods: We conducted a randomized, single-blind, crossover study in 14 healthy participants who received erythritol (50 g), xylitol (33.5 g), or water. Platelet aggregation was assessed ex vivo, together with circulating markers of platelet activation (P-selectin), endothelial activation (sVCAM-1), and coagulation (D-dimer), as well as plasma erythritol and xylitol concentrations. Complementary in vitro experiments were performed using platelet-rich plasma from 11 healthy participants exposed to increasing concentrations of erythritol or xylitol, followed by assessment of platelet aggregation. Results: Despite substantial increases in circulating erythritol and xylitol concentrations following oral intake, neither erythritol nor xylitol increased ex vivo platelet aggregation compared with water. Consistently, no relevant changes were observed in P-selectin, sVCAM-1, or D-dimer concentrations. Direct in vitro exposure of platelet-rich plasma to increasing concentrations of erythritol or xylitol likewise did not enhance platelet aggregation. Conclusions: In healthy individuals, acute oral intake of erythritol or xylitol did not increase platelet aggregation or circulating markers of platelet activation, endothelial activation, or coagulation. These findings were supported by in vitro experiments showing no direct effect of erythritol or xylitol on platelet aggregation. Our results do not support an acute platelet-activating effect of erythritol or xylitol under the conditions studied. Registration: URL: https://clinicaltrials.gov/study/NCT04966299; Unique identifier: NCT04966299.

Looping is a major cause of difficult and painful insertion during unsedated colonoscopy, yet strategies are largely guided by trial and error; prolonged insertion may jeopardise completion, discourage future surveillance and is associated with lower adenoma detection. In this randomised trial of 141 patients, protocolised review of pre-existing abdominal-pelvic computed tomography (CT) anticipated colonic anatomy and shortened caecal intubation time by 136 s, while reducing pain, discomfort and operator workload and increasing willingness to repeat colonoscopy. Effects were largest in N-loop and alpha-loop configurations, which accounted for 83% of patients. Routinely acquired CT could support anatomy-informed colonoscope insertion especially when anesthesia services are limited or sedation poses an elevated risk.

Background: There is a growing availability of plant-based alternatives for bovine milk. However, plant-based drinks differ e.g. in protein quantity, protein quality and carbohydrate composition. Knowledge on the impact this has on digestion-related outcomes such as postprandial amino acid (AA) availability and gastric behavior is still limited. Additionally, data on milk alternatives with higher overall protein concentration are lacking. Objective: We aimed to compare the differences in postprandial AA profiles, glycemic response, and gastric behavior between bovine milk and plant-based drinks with or without added protein using representative commercial drinks. Methods: 12 healthy males participated in a randomized crossover study with three treatments. After an overnight fast, participants drank 750 ml of semi-skimmed milk (Milk), a standard oat-based drink (OBD) or an oat-based drink enriched with pea protein (OBD+Pea). Blood samples were taken for measurement of plasma AA, glucose, insulin and FGF21 over 5 hours. Gastric content changes were assessed using magnetic resonance imaging scans for Milk and OBD+Pea over 2 hours. Results: Compared with Milk, both oat-based drinks elicited lower 5-h total AA iAUC (OBD -169706; OBD+pea -139552 microM*min; both P<0.001) and EAA iAUC (OBD -91748; OBD+pea -78199; both P<0.001), with no differences between oat-based drinks. Gastric content volume was lower for OBD+Pea versus Milk from 60-120 min (range -48 - -84 ml, all P<0.001). Compared to Milk, OBD and OBD+Pea increased glucose more from 15-45 min (range 0.86 - 1.73 mmol/l, all P<0.001) and insulin from 30-60 min (1.84 - 2.14-fold, all P<0.001). Conclusions: Protein enrichment in plant-based milk alternatives can be a valuable strategy to increase protein content and improve amino acid composition. However, such products still show faster gastric emptying, lower postprandial essential amino acid and higher glycemic and insulinemic responses compared to bovine milk because of their different carbohydrate and protein content and quality.

NREM slow waves emerge from the synchronization of neuronal activity across multiple spatial scales. During childhood, local synchronization and large-scale propagation undergo distinct maturational trajectories, paralleling cortical synaptic remodeling and the maturation of long-range brain connectivity. How alterations in this local-to-global organization relate to arousal instability remains poorly understood. Here, we used 256-channel high-density EEG to characterize NREM oscillatory organization in 17 children with disorders of arousal (DOA) and 17 age- and sex-matched healthy controls. Children with DOA showed a marked dissociation between local synchronization and large-scale coordination: slow waves were locally larger, steeper and more synchronized, yet recruited the cortex less globally and exhibited a more spatially restricted distribution of origins. This phenotype preferentially involved Type 1 slow waves, a subtype associated with widespread cortical and subcortico-cortical recruitment and late developmental maturation. Children with DOA also showed reduced centro-posterior slow spindle density, providing convergent evidence for altered coordination of distributed NREM oscillations. These microstructural abnormalities occurred despite largely preserved conventional sleep architecture. Together, our findings reveal an altered local-to-global organization of NREM sleep in pediatric DOA and suggest that vulnerability to incomplete arousals may emerge when strong local synchronization is not matched by effective large-scale network coordination during brain development.

Background: Real-world evidence on food-as-medicine programs for irritable bowel syndrome (IBS) is scarce, and single-arm evaluations overstate improvement because of regression to the mean (RTM). We estimated change in the IBS Symptom Severity Scale (IBS-SSS, 0-500) in a multi-omics personalized digital health food-as-medicine program, unadjusted and RTM-corrected. Methods: Retrospective single-arm cohort. Of 15,933 members with a valid baseline, 2,254 had a follow-up reading and 1,683 one at least 14 days after baseline. Change at 4, 12 (primary) and 26 weeks was estimated by baseline severity stratum, unadjusted and RTM-corrected by analysis of covariance. A responder fell by at least 50 points (the minimal clinically important difference benchmark). Sensitivity analyses covered equity, inverse-probability weighting and tipping-point analyses for members without a reading in each landmark window, a negative-control stratum and medication. The association of weight loss and dietary nutrient density with symptom change was evaluated within and between members. Results: At 12 weeks (n = 430) IBS-SSS fell by 43.88 points unadjusted (95% confidence interval [CI] -52.44 to -35.32; p < 0.001) and by 47.73 RTM-corrected (-55.48 to -39.98; p < 0.001); 720 of 1,339 symptomatic members (53.8%; 95% CI 51.1 to 56.4) fell by at least 50 points. Larger improvement in more severe members persisted after RTM correction (severe stratum, n = 37: unadjusted -127.43, RTM-corrected -60.71, 95% CI -97.75 to -23.68, p = 0.001). A higher meal nutrient density was associated with lower IBS-SSS within a member's own trajectory (p = 0.018) while weight change was not (p = 0.361). Improvement was similar across groups in spite of baseline differences by age and sex: RTM-corrected 12-week change did not differ by age (p = 0.458), body-mass index (p = 0.328), sex (p = 0.749), income (p = 0.486) or ethnicity (p = 0.170). Estimates were robust to weighting for members without a reading in the landmark window (RTM-corrected estimates moved by less than 2 points), and the change of those members would have had to be 39 to 73 points worse than observed before the mean change reached zero. Baseline medication use and starting a GLP-1 receptor agonist did not explain symptom changes. Conclusions: IBS-SSS fell significantly among program participants, with steeper improvement in the more severe group, even after RTM correction. The improvement was comparable across socioeconomic characteristics, age and sex and robust to the confounders and missing-data assumptions evaluated. These associations from a self-selected single-arm cohort warrant replication in independent studies.

Introduction: Adipose tissue fibrosis has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and suboptimal weight loss after bariatric surgery. The objective was to characterize changes in adipose tissue fibrosis and extracellular matrix (ECM) components in adipose tissues from two abdominal fat compartments, subcutaneous and omental, in response to bariatric surgery; and determine the effect of weight loss on the association between adipose tissue fibrosis and MASLD feature changes with weight loss. Methods: Liver and adipose tissue biopsy samples were obtained before and after weight loss from patients who underwent two-stage bariatric surgery. Adipose tissue pericellular fibrosis was evaluated histologically with picrosirius red staining for collagen quantification and normalized to adipocyte count per microscope field. Transcript levels of ECM remodeling and inflammatory genes were measured by RNA sequencing in subcutaneous adipose tissue pre- and post-surgery. Results: At baseline, adipose tissue pericellular fibrosis did not associate with MASLD features, metabolic dysfunction-associated steatohepatitis or hepatic fibrosis in patients with severe obesity. Changes in liver histology after surgery were unrelated to changes in adipose tissue fibrosis. Transcripts for most genes involved in ECM remodeling and inflammation were downregulated in subcutaneous fat one year after bariatric surgery. Omental, but not subcutaneous, adipose tissue fibrosis decreased after surgery when adjusted for cell number (mean {+/-} SD: 0.41 {+/-} 0.12 vs 0.32 {+/-} 0.08 {micro}m2/cell, p<0.005). Higher subcutaneous adipose tissue fibrosis correlated with reduced weight loss (estimate {+/-} SE: -2.04 {+/-} 0.99, p<0.05) and BMI loss (-0.73 {+/-} 0.35, p<0.05), while increased omental adipose tissue fibrosis after weight loss was associated with worsening hepatic fibrosis (0.31 {+/-} 0.14, p<0.05). Conclusion: In individuals with severe obesity undergoing bariatric surgery, adipose tissue fibrosis is poorly correlated with MASLD features. Notably, pericellular fibrosis in subcutaneous abdominal, but not omental, adipose tissue was associated with a reduced weight-loss response to surgery.

Semi-occluded vocal tract (SOVT) exercises are widely used in voice training and therapy, but their immediate electroglottographic (EGG) effects remain incompletely characterized. In this pilot methodological study, six female community singers completed a no-straw baseline recording and then 1-min straw-phonation exercises with four straws (Household metal, Metal VoiceStraw, plastic, and paper), each followed by a no-straw EGG recording. Thirty 1s recordings were analyzed with a standardized pipeline including contact quotient (CQ), waveform skewness, contact-phase rise/fall timing, temporal skewness (s_t), a normalized derivative asymmetry index (NDAI), average-cycle morphology, and EGG spectral descriptors. Relative to baseline, group-mean CQ was higher after all four straws (by 0.027-0.058), waveform skewness and NDAI were lower, and the EGG spectral centroid was lower (by 9.6-15.3%). Contact-phase timing asymmetry did not change consistently: s_t exceeded baseline after three straws and fell below it after one, and the rise/fall ratio decreased in three to five of six participants depending on the straw. Four participants ranked the Metal VoiceStraw first and two ranked paper first. Because every straw condition followed the baseline, warm-up and order effects cannot be separated from straw effects. These hypothesis-generating results identify CQ, waveform skewness, and EGG spectral centroid as candidate endpoints for a larger controlled study

Pancreatic ductal adenocarcinoma (PDAC) arises within an extensively remodeled microenvironment, yet tissue markers that distinguish invasive carcinoma from precursor lesions remain limited. Integrating four single cell RNA sequencing atlases comprising 324,662 cells from 26 patients, we identified cancer associated fibroblast expansion, accumulation of C1QA+ immunoregulatory macrophages, and depletion of a dendritic cell compartment expressing plasmacytoid markers. Fibroblasts were enriched for extracellular matrix and PI3K AKT programs and macrophages for an antigen-presentation program. We then examined the protein level correlates of these populations in a tissue proteomic reference framework of 356 samples spanning non diseased pancreas, normal-adjacent tissue, low and high grade intraductal papillary mucinous neoplasms (IPMNs), IPMN associated invasive carcinoma, and PDAC, prioritizing proteins that changed monotonically across the six histopathologic reference groups or marked tumor enriched cell types. Despite depletion of plasmacytoid dendritic cells, the principal source of type I interferon, the interferon stimulated protein ISG15, expressed by both fibroblasts and macrophages, increased monotonically toward PDAC. In exploratory cross-validated benchmarking of PDAC versus low and high grade IPMN, excluding IPMN-associated invasive carcinoma (145 versus 56 samples), CATB+EPIPL achieved an AUC of 0.98, with a sensitivity of 92% at an achieved specificity of 92%, exceeding protein abundance models of diagnostic IHC-associated markers (S100P+IMP3+maspin+MSLN, 0.79) and refitted published IPMN progression combinations (<0.91). Against non diseased pancreas, candidate and comparator panels performed similarly (AUC 0.99 1.00). These biologically informed tissue protein panels warrant independent validation, including immunohistochemical evaluation of EUS guided fine needle biopsy specimens and measurement in blood.

BACKGROUND Primary sclerosing cholangitis (PSC) is characterized by multifocal biliary strictures on MRI/MRCP. However,we have observed that young PSC patients often displayed a marked intrahepatic bile duct visibility,sometimes with gallbladder enlargement, before developing biliary strictures. This study aimed to evaluatewhether this imaging pattern was associated with subsequent diagnosis of PSC. PATIENTS AND METHODS This retrospective two-center study included patients younger than 21 years who had a baseline liverMRI/MRCP, without biliary strictures. The endpoint was a definite diagnosis of large duct PSC during follow-up. The association of baseline imaging findings with the endpoint was evaluated by multivariable logisticregression, Cox models, and Kaplan-Meier analyses. RESULTS Ninety-four patients were included: 54% were women, the mean age was 16.7 years, and 23% had IBD. Overa mean follow-up of 7.75 years, 21 patients were subsequently diagnosed with large duct PSC after a mediantime of 5.60 years. Marked intrahepatic bile duct visibility and gallbladder enlargement displayed goodperformance to predict the subsequent diagnosis of PSC (AUC, 0.77 and 0.69, respectively). The presence ofboth signs displayed a specificity of 1.00. In multivariable analyses, marked intrahepatic bile duct visibility andgallbladder enlargement were independently associated with subsequent PSC diagnosis (OR 17.00 (95% CI,3.10-93.24; p = 0.001) and 16.08 (95% CI, 2.29-113.02; p = 0.005) respectively) and shorter time to diagnosis(HR 9.42 (95% CI, 2.50-35.59; p < 0.001) and 7.59 (95% CI, 2.03-28.41; p = 0.003) respectively). Survivalanalyses confirmed the association between these two imaging signs and the subsequent PSC diagnosis (HR7.78 (95% CI, 2.62-23.16; p < 0.001) and 3.85 (95% CI, 1.64-9.08; p < 0.001) respectively). CONCLUSIONS In young patients without biliary strictures, marked intrahepatic bile duct visibility and gallbladder enlargementon MRI/MRCP were strongly associated with subsequent diagnosis of large duct PSC.

Introduction: Resection margins in oral squamous cell carcinoma (OSCC) are frequently inadequate. This study investigated the accuracy and diagnostic performance of ex-vivo 7T MRI against histology. Methods: Fifty OSCC specimens underwent ex-vivo 7T MRI. Tumours were segmented on corresponding histology and twice on MRI: blinded to histology (radiologist segmentation; clinical practice) and using histology (histology-MR segmentation; MR-based ground truth). Resection margins were measured in five regions and compared with histology. Results: Anterior and posterior margins were generally smaller on MRI than on histology (maximum mean difference -2.5 mm), whereas cranial, caudal and deep margins were generally larger on MRI (mean differences <1 mm). For close margins (<5 mm), sensitivity was 95% for histology-MR segmentations and 91% for radiologist segmentations, with 75% specificity for both. Conclusion: Ex-vivo 7T MRI accurately measures resection margins and detects close margins with high sensitivity. A future clinical trial will determine whether intraoperative implementation reduces inadequate margins and adjuvant treatment.

Fibrotic strictures are among the most disabling complications of Crohn's disease, permanently narrowing the bowel and impairing motility, yet no approved therapy reverses them. Chronic inflammation alters pacemaker-network coupling, smooth-muscle excitability, and calcium-dependent contractility, while fibrosis thickens the bowel wall, narrows the lumen, and changes tissue mechanics. The relative contributions of these coupled electrical, contractile, and structural alterations to motility loss remain unclear. To address this gap, we develop an integrated electromechanical finite-element framework for fibrostenosing Crohn's disease that couples a fibrosis-driven growth model with a FitzHugh-Nagumo electromechanical model. A full-factorial 25 design of experiments is used to quantify the relative effects of electrical diffusivity, excitation threshold, peak active stress, wall stiffness, and hypertrophic remodeling on cyclic lumen-volume deformation. Motility is quantified by the standard deviation of lumen volume over one contraction cycle. Within the parameter ranges examined, increased wall stiffness emerged as the dominant contributor to motility loss, followed by impaired smooth-muscle contractility. Changes in excitation threshold, hypertrophic remodeling, and electrical diffusivity produced substantially smaller effects. Pairwise interactions were small relative to the dominant main effects, indicating that the mechanisms contributed largely through their individual effects. Our findings suggest that limiting wall stiffening while preserving smooth-muscle contractile function may provide a therapeutic strategy for maintaining intestinal motility in fibrostenosing Crohn's disease.

Background. Many Indian special newborn care units (SNCUs) cannot offer amplitude-integrated EEG (aEEG) or early MRI, so bedside judgement decides which newborns receive closer neurological attention. Earlier work found that asphyxiated newborns cry with a higher pitch and shorter phonation than healthy newborns, and a meta-analysis reported higher fundamental frequency, dysphonation and atypical melody in infants with neurological dysfunction, with wide differences between studies. Aim. To determine whether basic acoustic features of a smartphone-recorded pain cry (following a heel prick) can differentiate term newborns with HIE from control newborns. Also, to track changes in cry acoustics over the first 72 hours of life and evaluate their association with the clinical severity and short-term outcomes of encephalopathy. Design. A prospective, single centre diagnostic accuracy and cohort study in a tertiary SNCU. Three groups of term newborns are recorded: newborns with HIE, healthy comparators, and sick comparators who do not have HIE. Every newborn is recorded after the same stimulus, the first clinically indicated heel-prick. Newborns with HIE and sick comparators are recorded again at 24 hours, 72 hours and before discharge. A cry that is late or absent counts as a result and not as a missing value. Three clinicians blinded to group also classify the cries by listening, so the phone-based measures can be compared with the human ear. Analysis. The primary outcome is the area under the ROC curve of a logistic model with five pre-specified acoustic predictors. The target is 180 analyzable newborns (70 with HIE and 110 comparators). Reporting follows STARD and TRIPOD+AI. Relevance. In a South Asian trial, cooling did not reduce death or disability at 18 months and increased death alone. A cry tool in this setting is therefore proposed to help prioritize EEG, seizure surveillance, closer observation and referral. It is not proposed as a trigger for cooling. Keywords: neonatal encephalopathy; infant cry; acoustic analysis; smartphone; diagnostic accuracy; low-resource setting.

Background: Cervical spinal cord (CSC) compression and myelopathy are frequent, severe complications in mucopolysaccharidosis (MPS) types I and VI. Early detection is critical to prevent irreversible neurological deficits and preserve quality of life. This prospective study aimed to identify quantitative neuroimaging biomarkers of structural CSC damage and myelopathy in MPS I and VI. Methods: Structural and diffusion magnetic resonance imaging (MRI) of the CSC was analyzed in 17 MPS I patients, 3 MPS VI patients (19{+/-}7 years), and 19 case-matched healthy controls (20{+/-}7 years). CSC macrostructure (cross-sectional area, diameters) and microstructure (fractional anisotropy [FA], radial [RD], mean, axial diffusivities) were evaluated within and beyond the maximal compression areas. Results: MPS patients demonstrated reduced CSC cross-sectional area and anterior-posterior diameter at upper cervical levels, alongside widespread microstructural alterations (lower FA, higher RD) throughout the CSC versus controls (pFDR<0.05). Restricted foramen magnum space was associated with microstructural damage at lower cervical levels without overt macrostructural compression. Morphological and microstructural metrics were sensitive to CSC compression and myelopathy severity (pFDR<0.05). Lower CSC integrity correlated with more advanced growth retardation (p<0.001). Among patients receiving hematopoietic stem cell transplantation, earlier treatment correlated with preserved upper CSC morphology (p<0.05). Distinct neuroimaging phenotypes were observed across MPS genotypes (pFDR<0.05). Conclusions: CSC MRI provides candidate neuroimaging biomarkers for early detection and characterization of myelopathy in MPS I and VI. Structural damage extends beyond primary maximal compression areas, highlighting these markers for clinical monitoring and future therapeutic trials.

Background: Software tools can support MRI diagnosis of focal cortical dysplasias (FCDs) - subtle, surgically-treatable lesions that underlie drug-resistant focal epilepsy (DRFE). MELD-graph, a widely used open-source tool combining surface-based morphometry with a convolutional neural network, was developed using 1.5T and 3T MRI data. 7T MRI is increasingly used for lesion detection in DRFE. This study investigated whether MELD-graph is robust to domain shift at 7T. Methods: We collated paired 3T and 7T T1-weighted MRI, and FLAIR where available, from 23 patients with FCD (6 histologically-verified, 17 identified radiologically) and 39 healthy controls at four epilepsy centres. Manual lesion labels were used as ground truth. MELD-graph was run on 3T images, on 7T images with the default pipeline, and on 7T images with adaptations for 7T MRI (SPM bias-field correction, SynthStrip skull-stripping, sub-millimetric FreeSurfer reconstruction), with and without ComBat harmonisation. FCD detection performance and surface morphometry features were compared. Results: Sensitivity for FCD detection was 65% (15/23) at 3T, 48% (11/23) for 7T default and 52% (12/23) for 7T adapted, with Combat harmonisation. Among radiologically 3T-negative patients, 2/8 were detected at 3T and 3/8 at 7T; and among histologically confirmed FCD, 3/6 at 3T and 1/6 at 7T. Specificity was significantly lower at 7T (default 39%, adapted 45%) than 3T (76%). False-positives predominantly occurred in the basal temporal lobes. ComBat harmonisation improved specificity in all conditions and largely compensated for field-strength dependent differences in surface morphometry features. Adding FLAIR at 7T increased false-positive predictions. Conclusion: Sensitivity is comparable but specificity of MELD-graph is lower at 7T compared to 3T. Adaptations for 7T MRI can reduce segmentation errors but do not significantly improve FCD detection, while harmonisation improves performance. The adapted pipeline is released open-source. 7T MELD-graph outputs may inform radiologist review in challenging cases but require cautious interpretation.