Understanding how leaf water relations integrate with carbon economy is central to plant physiological ecology and to predictions of vegetation responses to environmental change, yet the degree of their coordination remains debated. We investigated relationships between leaf pressure-volume (PV) traits (leaf-specific capacitance at full turgor per dry mass (C*ft,mass), osmotic potential at the turgor loss point (πtlp), and other PV traits) and leaf economics spectrum (LES) traits (leaf nitrogen content, specific leaf area, and photosynthetic capacity) across temperate, subtropical, and tropical forests. These two suites of traits exhibited statistically partial coordination: C*ft,mass was tightly coupled with LES traits, whereas πtlp was independent of the LES framework, and this partial coupling was primarily driven by leaf saturated water content. Notably, coordination was strongest at the subtropical site, where conservative strategies strengthened the integration between PV and LES traits, thereby improving resource-use efficiency. This partial coupling provides insights into the multidimensional nature of plant functional strategies and the mechanisms underpinning species coexistence across forest types.
To evaluate the efficacy of partial orbital lobe dacryoadenectomy (POLD) in patients with refractory epiphora. Prospective interventional study. Tertiary eye care institute. Consecutive patients with refractory epiphora due to proximal lacrimal outflow system obstruction, multiple failed dacryocystorhinostomy, and postdacryocystectomy. All patients underwent preoperative assessment with Munk score, Schirmer-I Score, tear breakup time, corneal fluorescein staining, anterior segment OCT (AS-OCT), and CT scans of the orbit. Partial removal of the lacrimal gland orbital lobe under local anesthesia. Reduction in epiphora. Objective and subjective evaluation was repeated at postoperative 1-week, 1-month, and 3-month visits. Out of 17 patients enrolled, one had congenital punctal agenesis, three had acquired punctal effacement, and 13 had proximal bicanalicular obstruction. The mean age was 48.8 ± 18.6 years. All patients underwent POLD, with removal of 50-60% of the orbital lobe of the lacrimal gland. The mean follow-up duration was 5.7 months. At 3-month follow-up visit, the average reduction in Munk score was 60%, the average reduction in Schirmer-I value was 35.2%, and the average reduction in tear film height on AS-OCT was 35.9% (all statistically significant, P < 0.05), from the initial visit. None of the patients developed signs and symptoms of dry eye disease. POLD is an effective and safe procedure for patients with refractory epiphora in the short term. Further studies are needed to establish efficacy in the long term.
Randomized controlled trial has shown that dexmedetomidine does not significantly reduce postoperative acute kidney injury (AKI) in general partial nephrectomy (PN) populations. However, evidence remains limited in patients with high susceptibility to renal ischemia, such as those with a solitary kidney or pre-existing chronic kidney disease (CKD). We conducted a single-center retrospective cohort study including adult high-risk PN patients between 2015 and 2023. Eligible high-risk patients were those with a solitary kidney or pre-existing CKD. The study cohort was divided into dexmedetomidine-exposed and non-exposed groups. To balance baseline characteristics, inverse probability of treatment weighting (IPTW) was applied. The primary outcome was AKI incidence within 24 hours postoperatively, defined by KDIGO creatinine criteria. The study included 274 patients, with 82 assigned to the dexmedetomidine-exposed cohort and 192 to the non-exposed cohort. After IPTW adjustment, all baseline covariates were well balanced. Dexmedetomidine exposure was associated with significantly lower AKI incidence (23.9% versus 38.6%, P = 0.025), with a trend toward milder AKI staging. Intraoperative urine output was higher in the dexmedetomidine group (341 ± 183 versus 282 ± 188 mL, P = 0.022). Length of postoperative hospital stay, postoperative complications, ICU admission rate, percentage decrease in eGFR from baseline at 6-month follow-up, and incidence of a >20% decrease from baseline eGFR at 6-month follow-up did not differ significantly between the two groups. In high-risk PN patients with a solitary kidney or pre-existing CKD, intraoperative dexmedetomidine was associated with a clinically meaningful reduction in postoperative AKI. These findings suggest a potential renoprotective role of dexmedetomidine in this vulnerable surgical population, although this early renal benefit did not translate into long-term improvements in renal function.
While partial splenic artery embolization (PSE) has been effectively employed in treating portal hypertension, cirrhosis, and idiopathic thrombocytopenia, its combination with hepatic artery infusion chemotherapy (HAIC) for the management of chemotherapy-induced hypersplenism (CIH) has not been previously explored. This retrospective study aims to provide clinical insights into this potential therapeutic approach. We conducted a retrospective analysis involving patients with colorectal cancer liver metastases (CRLM) who received PSE in conjunction with HAIC (utilizing the FOLFOX regimen) to manage thrombocytopenia due to hypersplenism. Tumor response assessment followed the response evaluation criteria in solid tumors, while adverse reactions were categorized using the Common Terminology Criteria for Adverse Events (version 5.0). The primary objective was to attain a platelet (PLT) count of 100 × 10 9 /L, with secondary objectives encompassing evaluation of adverse events related to the combined therapy and its efficacy against liver metastases. From January 2018 to May 2023, 20 patients with CRLM and CIH were consecutively enrolled in this investigation, each undergoing PSE and HAIC. In total, PSE was performed 25 times. Median pre- and post-PSE PLT counts were 51 × 10 9 /L and 116 × 10 9 /L, respectively, with 80% of participants reaching the primary endpoint of a PLT count of ≥100 × 10 9 /L. Abdominal pain emerged as the most frequent postoperative complication, affecting 11 patients (44%). The objective response rate stood at 25%, while the disease-control rate was reported at 80%. The median progression-free survival was measured at 3.9 months, with a median overall survival of 13.8 months. The combination of PSE and HAIC (FOLFOX regimen) represents a safe and effective strategy for managing CIH and CRLM, demonstrating favorable outcomes in PLT count restoration and disease control.
Partial anomalous pulmonary venous drainage is an uncommon condition representing 0.6% of all congenital malformations that may be associated with an atrial septal defect. In the present report, we describe a modification of the Warden technique for surgical repair of partial anomalous pulmonary venous drainage with atrial septal defect by using a superior vena cava flap and a right atrial appendage flap to create a new tension-free cavoatrial continuity (neo right superior vena cava), along with redirection of the anomalous pulmonary veins to the left atrium through the atrial septal defect using an autologous pericardial patch. The patient had a favorable postoperative course, with no evidence of residual shunt or obstructive gradient across the anastomosis, and was discharged on postoperative day six. El drenaje venoso pulmonar anómalo parcial es una enfermedad poco frecuente que representa el 0,6% de todas las malformaciones congénitas; puede estar asociado a un defecto septal atrial. En el presente reporte describimos una modificación de la técnica de Warden para la reparación quirúrgica del drenaje venoso pulmonar anómalo parcial con defecto septal auricular, mediante la utilización de un colgajo de vena cava superior y de un colgajo de apéndice auricular derecho, para crear una nueva continuidad cavo-atrial sin tensión (neovena cava superior derecha), además del redireccionamiento de las venas pulmonares anómalas a través del defecto atrial mediante un parche de pericardio autólogo. El paciente presentó una evolución posoperatoria favorable, sin evidencia de cortocircuito residual ni gradiente obstructivo en la anastomosis, siendo dado de alta al sexto día posoperatorio.
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Mutations in Transglutaminase 6 (TG6) have been linked to a genetic form of spinocerebellar ataxia, namely SCA35. In recent years, several mutations associated with this disease have been identified. While some of them did not alter TG6 enzymatic activity, others induced a dominant-negative loss-of-function and altered subcellular localization. We previously observed that mutations identified in patients, which showed detrimental effects on neuronal viability in vitro, including mislocalization and activation of the unfolded protein response, were consistently characterized by a loss of TG6 enzymatic function. To investigate this effect in vivo, we re-derived Tgm6 knockout mice from the EMMA repository and performed behavioral characterization. We measured body weight and assessed motor performance using the rotarod, elevated beam/beam balance test, and ladder test, beginning at 1 month of age and continuing through 16 months of age. Here, we report that TG6 loss-of-function impairs motor coordination in male mice, suggesting a sex-specific function for this enzyme.
The relationship between cortical morphology and intelligence during adolescence has been widely studied, with existing literature reporting varying degrees of association across different modeling approaches. This study provides a comprehensive comparison of model performance in investigating the association between crystallized intelligence and cortical surface area using data from 11,351 subjects in the Adolescent Brain Cognitive Development (ABCD) study. We evaluate ten widely used models ranging from linear regression to graph convolutional networks across three covariate adjustment formulations: full (no adjustment), partial (age and sex adjusted), and total surface area (TSA) partial (age, sex, and TSA adjusted). Using bootstrap resampling with 50 iterations, we estimate the fraction of variance explained (FVE) for each model. Our results suggest that more complex models do not lead to higher FVE, with LASSO having the highest FVE of 15.9% (full formulation), Ridge at 10.5% (partial formulation), and Principal Component Regression (PCR) with 102 PCs at 2.5% (TSA partial formulation). Our results also reveal that the relationship between cortical surface area and crystallized intelligence is predominantly driven by global factors age, sex, and TSA, rather than by localized cortical surface area.
The application of fungi in forensic investigations remains limited, particularly in cases involving dismembered human remains. In this study, we characterized the mycobiome of a decomposing human body and a detached upper limb recovered from different locations using culture-dependent methods. A total of 23 fungal species were identified across four culture media and three incubation temperatures, including 20 species from the body and ten from the upper limb. The dominant taxa included Yarrowia lipolytica, Yarrowia deformans, Mucor hiemalis, and Geotrichum candidum. Notably, seven species were shared between the body and the detached limb, indicating partially preserved fungal signatures despite environmental differences. These findings suggest that fungal community profiles may serve as a complementary tool for associating separated human body parts and for assessing postmortem relocation. Additionally, 11 fungal species were identified on human remains for the first time (Acaulium album, Acaulium caviariforme, Akanthomyces lecanii, Dialonectria ullevolea, Fusarium acuminatum, Fusarium falsibabinda, Fusarium oxysporum, Fusarium redolens, Fusarium sacchari, Linnemannia hyalina, and Penicillium clavigerum), expanding current knowledge of postmortem fungal colonization in temperate climates. KEY POINTS: • The regional postmortem mycobiome of a corpse and a severed upper limb • Shared fungal species suggest partial preservation of mycobiome signatures • Fungal profiles as potential indicators for the identification of dismembered body parts.
Population aging poses significant challenges for community planning. While prior research has predominantly examined older adults as passive users of green spaces, less is known about how their direct involvement in green space regeneration is translated into active aging behavior. Drawing on place attachment theory, psychological ownership theory, self-determination theory, and meaning-making perspectives, this study proposes a process-based model in which participation fosters two psychological constructs-emotional imprint on place and sense of landscape ownership-that promote active aging behavior, with meaning in life incorporated as a moderator. Survey data were collected from 433 older adults aged 60 and above residing in Chinese communities with experience in green space regeneration initiatives. Partial least squares structural equation modeling (PLS-SEM) was used to estimate the measurement and structural models, with bootstrapping (5,000 resamples) for mediation analysis and a product-indicator approach for moderation. Perceived participation in green space regeneration exerts a significant positive effect on both emotional imprint on place (β = 0.647, p < 0.001) and sense of landscape ownership (β = 0.471, p < 0.001), and emotional imprint further predicts landscape ownership (β = 0.367, p < 0.001). Both constructs significantly predict active aging behavior (β = 0.290 and β = 0.275, both p < 0.01) and partially mediate the participation-behavior relationship. Meaning in life exhibits a dual moderating effect: it strengthens the emotional imprint-behavior link (β = 0.265, p < 0.001) but attenuates the landscape ownership-behavior link (β = -0.375, p < 0.001). The findings reveal a shift from ownership-based motivation to meaning-driven engagement in later life. By identifying psychological pathways linking participation and behavior, this study advances a place-based psychological perspective on active aging and provides practical implications for community planning that prioritize emotional connection and meaningful engagement over infrastructural provision alone.
Elevated muscle sympathetic nerve activity (MSNA) at high altitude is associated with blunted transduction of sympathetic signals to blood pressure in lowlanders and indigenous Andean highlanders. However, it is unclear whether this is due to reduced adrenergic communication or other factors (e.g. augmented dilatory signaling). Therefore, we quantified the contribution of α-adrenoreceptor activity to 1) resting systemic sympathetic transduction and 2) pressor responses to sympathoexcitation in acclimatizing lowlanders (9M, 4F) and Andean highlanders (15M) at 4,300m. MSNA (microneurography) and mean arterial pressure (MAP; finger photoplethysmography) were measured at rest, during maximal voluntary apnea, and with an α1-adrenergic agonist (phenylephrine) prior to and following partial α-adrenergic blockade (phentolamine). Sympathetic transduction was quantified as the slope of the relationship between MAP and total MSNA associated with sequences of sympathetic bursts. Transduction was attenuated in both lowlanders (0.0041±0.0037 to 0.0017±0.0017mmHg∙%-1, P=0.026) and highlanders (0.0033±0.0024 to 0.0008±0.0007mmHg∙%-1, P=0.005) under α-adrenergic blockade (main effect P<0.001) and was not different between groups (main effect P=0.276). However, pressor responses to apnea (lowlanders, +25±5mmHg; highlanders, +22±7mmHg) were unchanged following phentolamine (lowlanders, +25±8mmHg; highlanders, +20±8mmHg; main effect P=0.174) despite unchanged MSNA responses between conditions (main effect P=0.162). Highlanders exhibited reduced MSNA responses compared to lowlanders regardless of condition (main effect P=0.014). Partial α-adrenergic blockade reduced sympathetic transduction similarly in both groups. Yet, apnea responsiveness was maintained, achieved through lesser sympathoexcitation in highlanders. This suggests that resting blood pressure control is modulated primarily through α-adrenergic receptors in both populations, but pressor responses to stress may result from alternative mechanisms.
Dual-targeted therapy (DTT) combines medications with different anti-inflammatory mechanisms to manage immune-mediated conditions. We describe our experience of adding guselkumab (GUS) to upadacitinib (UPA) in complex inflammatory bowel disease (IBD). We reviewed our real-world registry of adult patients with IBD who had GUS added to UPA. Prospectively collected outcomes included clinical remission (Harvey-Bradshaw Index (HBI) < 5 or Simple Clinical Colitis Activity Index (SCCAI) < 3), biochemical remission (normalization of fecal calprotectin (FCP)/CRP), corticosteroid-free remission, and adverse events (AEs). Patient-reported activity of extraintestinal manifestations (EIMs) was retrospectively reviewed. We identified 11 patients with Crohn's disease (CD) and 4 with ulcerative colitis (UC) who added GUS to UPA for luminal inflammation (n = 12) and/or EIMs (n = 5). Five of nine patients with active CD achieved biochemical remission. Of the four with symptomatic CD (HBI > 5), two achieved clinical remission. Four patients received DTT for CD-associated EIMs and two had partial improvement of symptoms after GUS. All 3 patients who started DTT for active UC achieved clinical remission and one with active enteropathic arthropathy had partial improvement of symptoms after DTT. AEs included minor skin irritation, fatigue, and headaches. 14/15 patients remain on DTT after median 6 months' follow-up. The addition of GUS to UPA led to clinical remission in 50% and 100% of patients with CD and UC, and biochemical remission in 55.6% and 66.7% of patients with CD and UC, respectively. 60% noted improvement of their EIMs after adding GUS. No serious AEs were reported highlighting the safety of this DTT strategy.
The influence of repair of congenital heart defect (CHD) via a right subaxillary thoracotomy (RSAT) on postoperative pulmonary function and prognosis in small infants is a key consideration. Data were collected from infants who underwent ventricular septal defect (VSD) repair or VSD and atrial septal defect (ASD) between March 2020 and September 2024. Based on propensity score matching, 80 small infants (weight <5 kg and age <6 months) were selected, of which 40 underwent VSD repair or VSD, and ASD repair through an RSAT, while 40 underwent VSD repair or VSD and ASD repair through a standard median sternotomy (SMS). Perioperative respiratory parameters, morbidity, and mortality were compared to assess the influence of the RSAT approach on pulmonary function and postoperative outcomes in small infants. Primary outcome: there were no significant differences (p > 0.05) in the perioperative oxygenation index and alveolar-arterial oxygen gradient between the two surgical approaches. No significant differences were also observed between the two groups in the other respiratory parameters, including peak airway pressure, partial pressure of oxygen, and partial pressure of carbon dioxide. The operating time (150 ± 20 min vs. 163 ± 28 min; p < 0.05) was shorter in the RSAT group compared to the SMS group. There were no deaths in either group. The complication rate was low in both groups, with no significant difference between the groups (p > 0.05). Compared with SMS, the RSAT approach for the repair of congenital heart defects does not increase the risk of postoperative respiratory insufficiency and yields comparable outcomes in low-weight small infants.
Implanting a left ventricular assist device (LVAD) for end-stage heart failure with a giant left ventricular aneurysm is challenging, primarily owing to risks of unstable anchoring and inflow malalignment. A 68-year-old woman with a giant left ventricular aneurysm underwent bridge-to-transplant LVAD implantation, revascularization, and partial aneurysmectomy. A modified turtleneck technique secured the device. However, profound reverse remodeling caused delayed downward pump migration at 9 months, resulting in cerebral infarction. While the turtleneck technique provides reliable initial anchoring, dynamic postoperative geometric shifts pose ongoing risks. This case underscores the necessity of vigilant serial imaging to detect and manage late pump displacement. The modified turtleneck technique facilitates stable LVAD implantation in end-stage heart failure patients with giant left ventricular aneurysms. However, profound reverse remodeling postoperatively necessitates serial imaging surveillance to detect and manage delayed pump migration.
Laparoscopic Heller's myotomy (LHM) with a partial fundoplication is the standard surgical therapy for achalasia cardia. However, the ideal gastric extension of the myotomy remains controversial, as it may influence both symptom relief and post-operative gastro-oesophageal reflux disease (GORD). This study prospectively assessed the impact of gastric myotomy length on clinical outcomes after LHM with Dor fundoplication. In this prospective non-randomised comparative interventional study, patients undergoing LHM with Dor fundoplication were divided into three groups according to gastric myotomy length: Group A (<1.5 cm), Group B (1.5-2.5 cm) and Group C (>2.5 cm). The primary outcome was improvement in the Eckardt score at 1, 3 and 6 months postoperatively. The secondary outcomes included GORD incidence (Gastro-Oesophageal Reflux Disease Questionnaire [GORD-Q]), complications and re-intervention rates. Sixty-three patients were included ( n = 21 per group). All groups showed significant symptom improvement post-surgery. At 3 and 6 months, Groups B and C demonstrated greater Eckardt score improvement than Group A ( P = 0.012 and P < 0.01, respectively). Median GORD-Q scores were similar at 1 and 3 months but higher in Group C at 6 months ( P = 0.01). Re-intervention was most frequent in Group A (23.8%) due to persistent dysphagia ( P = 0.047). Operative time, hospital stay and complications did not differ significantly among the groups. Gastric myotomy beyond 1.5 cm improves symptom control after LHM with Dor fundoplication, but extension beyond 2.5 cm increases reflux risk. A length of 1.5-2.5 cm appears optimal for balancing dysphagia relief and reflux prevention.
The adoption and acceptance of parental control apps (PCAs) are threatened by many factors, even though mobile applications are at the forefront of mobile computing technologies. Existing studies indicate that PCA adoption can be improved by understanding users' behavioral intention and mindsets. Several adoption studies show that task features are among the most influential factors influencing users' perceptions of mobile applications. The role of PCA features, such as digital etiquette, cyberbullying, child tracking, and family values, remains largely unexamined in current research. Thus, by using task-technology fit (TTF) theory, this study examines how task-technology features and characteristics affect the behavioral intention of parents toward PCA adoption within the context of Saudi Arabia. To empirically test the proposed theoretical model, data were collected from 388 parents in Saudi Arabia. A multistage analysis, which consists of partial least squares structural equation modeling (PLS-SEM), partial least squares prediction algorithms (PLS-predict), and artificial neural networks (ANN), was employed to examine the outcome of PCA behavioral adoption. The results demonstrate that digital etiquette, cyberbullying, family values, and parental mediation significantly and positively influence TTF, whereas mobility, child tracking, and inappropriate online content do not have a significant impact. Furthermore, TTF was found to be a significant predictor of parents' behavioral intention toward PCA adoption. These findings can be utilized to enhance the design of PCAs and thus the user experience for both parents and children. Moreover, this study extends and contributes to the understanding of task features in the context of PCAs through the TTF model.
The rapid development of Artificial Intelligence (AI) is profoundly reshaping the creative industries and art design education. Understanding the factors influencing students' acceptance of Artificial Intelligence generated content is crucial for ensuring the sustainable application of this technology. This study investigated 630 Chinese university students majoring in art and design, adopting a combined variable-centered and person-centered approach to systematically examine the psychological mechanisms and heterogeneity of their intentions to use AI. Based on a serial mediation model, we hypothesized that general attitude toward AI itself and attitude toward using AI serve as mediators between distal antecedents (perceived usefulness, perceived ease of use, AI anxiety, creative self-efficacy) and AI usage intention. At the variable-centered level, hierarchical regression analysis and serial mediation analysis were used to test the predictive and indirect effects of perceived usefulness, perceived ease of use, AI anxiety, creative self-efficacy, general attitudes toward AI itself, and attitudes toward using AI on AI usage intention. At the person-centered level, latent profile analysis was employed to identify heterogeneous user groups based on AI usage intention across five design stages: creative ideation, material collection, visual element design, copywriting, and final modification and optimization. The study also examined differences in demographic and psychological variables across these profiles. Results indicated that the serial indirect effects of perceived usefulness, perceived ease of use, AI anxiety, and creative self-efficacy on usage intention via general attitude and usage attitude were significant, while their direct effects were non-significant, confirming full or partial mediation. General attitudes toward AI itself and attitudes toward using AI significantly and positively predicted usage intention in the hierarchical regression. Latent profile analysis identified three heterogeneous groups: Moderate Use Group, Low Use Group, and High Use Group. These three groups showed significant differences in grade level and key psychological variables, confirming the external validity of the profiles. The findings reveal the complexity of the psychological mechanisms underlying art design students' AI usage intention and the heterogeneous nature of their usage patterns, providing a theoretical basis and practical implications for integrating AI tools and implementing differentiated teaching strategies in art design education within the Chinese context.
Dupuytren disease (DD) is a fibroproliferative disorder that can result in progressive hand contractures and functional impairment. Multiple treatment options are available, ranging from minimally invasive procedures to surgical interventions. Current long-term trends in treatment utilization and reimbursement remain incompletely characterized. Understanding these trends is essential for clinical decision-making and resource allocation. A retrospective longitudinal analysis was conducted using Medicare data from 2005 to 2024. Treatment utilization and reimbursement data were extracted for current procedural terminology codes corresponding to percutaneous needle fasciotomy (PNF), open fasciotomy, collagenase Clostridium histolyticum injection (CCH) with manipulation, and fasciectomy-based procedures. Annual procedure volumes were normalized to Medicare enrollment. Reimbursement values were adjusted for inflation using the US Consumer Price Index. Temporal trends were assessed using the 2-tailed Mann-Kendall trend test. Utilization of surgical procedures declined significantly over the study period, whereas PNF and CCH demonstrated no individual temporal trends. When grouped as minimally invasive procedures, PNF and CCH showed an overall increase in utilization. A transient decline in utilization across all procedures occurred in 2020, followed by partial recovery in subsequent years. Normalized annual procedure volumes for DD demonstrated no significant temporal trend. Inflation-adjusted Medicare reimbursement per service declined significantly by 38% over the study period; fasciectomy-based procedures remained the highest reimbursed interventions and showed no significant temporal change. In contrast, reimbursement for PNF and CCH declined significantly over time. Over the past 2 decades, minimally invasive treatment of DD has become more common, whereas fasciectomy has been declining. Nevertheless, fasciectomy remains the most commonly performed treatment for DD. Decreasing inflation-adjusted reimbursement highlights growing economic pressures on health care and providers. Economic decision and analysis IV.
VEST was a multi-centre study of real-world use of vedolizumab in inflammatory bowel disease (IBD) in routine practice in the United Kingdom. To describe real-world indications, effectiveness, patient-reported outcomes and safety. Prospective observational cohort study at 22 centres. Patients receiving vedolizumab as part of standard care were included. Data were collected at infusion visits for activity indices (Harvey-Bradshaw Index (HBI) or partial Mayo Score (PMS)), physician global assessment (PGA), patient-reported quality-of-life and treatment perception (IBD-Control Questionnaire) and adverse events. Clinical response (Wk14) was defined as a reduction in HBI ⩾3 or PMS ⩾2, clinical remission as HBI ⩽4 or PMS ⩽1 and analysed using non-responder imputation. One-year persistence was defined as continuing on vedolizumab after an infusion at ⩾48 weeks. Biomarker and endoscopic data were not available. 364 patients, mean age: 48 years; 132 (36%) with Crohn's disease (CD), 224 (62%) with UC and 8 (2%) with IBD-U; 174 (48%) male; 142 (39%) receiving steroids at baseline (Wk0); 141 (39%) bio-naïve. At baseline, 279 (77%) had "active" disease. One-year persistence: 58% overall (54% for active disease). Among persistent cases (n = 212), median (IQR) IBD-Control-8 scores improved from 6 (3-10) at baseline to 14 (10-16) at post-induction (Wk14) and 1 year (p < 0.001 vs baseline). Corresponding scores for IBD-Control-VAS were: 50 (30-70), 80 (65-90) and 85 (70-95), respectively (p < 0.001 vs baseline). Each domain of IBD-Control-8 showed improvement. Baseline and post-induction health status (activity index, PGA or IBD-Control) were associated with 1-year persistence, but no significant associations were observed for disease type, duration, bio-naïve status or baseline steroids. Of those with active disease at Wk0, clinical remission rates were 29%, 30% and 38% for CD, UC and IBD-U, respectively, and steroid-free remission rates were 26%, 27% and 38%. Similar remission rates were observed at 1 year. Possible adverse events leading to treatment cessation were rare (3%). In routine clinical practice in the UK, vedolizumab demonstrated high levels of persistence. Similar rates of clinical response, remission and 1-year persistence were seen in UC and CD patients, and in bio-experienced versus naïve cases. Persistent cases experienced significant and sustained improvements in quality of life and treatment perception. Persistence does not imply anti-inflammatory efficacy, as biomarker data were not available. Vedolizumab in routine IBD practice: Persistence and patient-reported benefits This study (VEST) looked at how vedolizumab (a gut-selective biological treatment for inflammatory bowel disease (IBD)) works in everyday NHS practice across 22 UK hospitals. Unlike clinical trials, which have strict entry criteria, this study included all adults who started vedolizumab as part of routine care, including older patients, those usually excluded from trials and people with less severe disease. A total of 364 people took part: 224 with ulcerative colitis, 132 with Crohn’s disease, and 8 with IBD unclassified. Most had active symptoms when treatment began, and many had already tried other biological drugs. The main measure was “persistence,” meaning whether patients were still receiving vedolizumab one year later. Overall, 58% continued treatment (54% of those with active symptoms). Persistence rates were similar for Crohn’s disease and ulcerative colitis, and for people who were new to biologics versus those who had used them before. Among patients who remained on vedolizumab, symptoms and quality-of-life improved. By week 14, more patients were in clinical remission, using fewer steroids, and reporting better control of their condition. These findings were maintained at one year. Patient-reported outcomes “covering pain, sleep disturbance, fatigue, mood, and impact on daily activities” showed improvement across all areas. People with more severe symptoms at the start were less likely to stay on the drug, while better patient-reported control scores early in treatment predicted continuation. Vedolizumab was well tolerated. Possible drug-related side effects were uncommon (only 3% of patients stopped because of adverse events). In summary, this real-world UK study shows that vedolizumab was safe and is used across diverse patient groups with meaningful, lasting improvements observed in those remaining on treatment.
Optimizing plant height to enhance lodging resistance and facilitate mechanized harvesting is a critical breeding objective for cultivated hybrid sugarcane. However, the genetic dissection of this trait has been impeded by the complexity of the aneuploid sugarcane genome. To address this issue, we performed a k-mer-based genome-wide association study (GWAS) of 603 re-sequenced sugarcane accessions. We identified 138 quantitative trait loci (QTLs) linked to plant height. These included well-known regulators in the gibberellin and brassinosteroid pathways (e.g., GID1, DWF1) and genes involved in less-studied processes that might contribute to differences in plant height, such as sucrose and fatty acid biosynthesis (e.g., SUS6, ACC2). Using transcriptome data, we documented widespread, stable, allele-specific expression of plant height-related genes and unequal contributions among alleles: 35.02% of alleles accounted for 80% of total gene expression. We also detected substantial imbalances in both gene copy number and expression between the two progenitor-derived subgenomes. The expression bias between subgenomes was typically much smaller than the imbalance suggested by copy number alone, indicating partial buffering at the expression level. Crucially, at the population level, changes in both the dominant allele and subgenome bias of specific genes were associated with differences in plant height in cultivated sugarcane. Finally, we inferred an expression-based regulatory network for plant height-related genes and identified hub genes with possible direct and indirect roles in regulating plant height. Our findings shed light on the regulation of plant height in cultivated sugarcane and offer breeding targets for improved plant architecture.